NO329136B1 - Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom - Google Patents

Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom Download PDF

Info

Publication number: NO329136B1
Authority: NO; Norway
Prior art keywords: quinazolin; methyl; ylmethyl; aminopurin; tolyl
Prior art date: 2000-04-25

Application number

NO20025104A

Other languages

English (en)

Norwegian (no)

Other versions

NO20025104D0 (no

NO20025104L (no

Inventor

C Gregory Sowell

Edward A Kesicki

Chanchal Sadhu

Ken Dick

Jennifer Treiberg

Amy Oliver

Original Assignee

Icos Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-04-25

Filing date

2002-10-24

Publication date

2010-08-30

2002-10-24 Application filed by Icos Corp filed Critical Icos Corp

2002-10-24 Publication of NO20025104D0 publication Critical patent/NO20025104D0/no

2002-12-10 Publication of NO20025104L publication Critical patent/NO20025104L/no

2010-08-30 Publication of NO329136B1 publication Critical patent/NO329136B1/no

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 226
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 62
201000010099 disease Diseases 0.000 title claims abstract description 36
239000003814 drug Substances 0.000 title claims description 22
238000004519 manufacturing process Methods 0.000 title claims description 19
239000000825 pharmaceutical preparation Substances 0.000 title claims description 18
150000003246 quinazolines Chemical class 0.000 title 1
230000000694 effects Effects 0.000 claims abstract description 115
206010028980 Neoplasm Diseases 0.000 claims abstract description 20
230000004054 inflammatory process Effects 0.000 claims abstract description 19
206010061218 Inflammation Diseases 0.000 claims abstract description 18
201000011510 cancer Diseases 0.000 claims abstract description 15
-1 pyrdinyl Chemical group 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 26
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 18
GNWHRHGTIBRNSM-UHFFFAOYSA-N IC-87114 Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 GNWHRHGTIBRNSM-UHFFFAOYSA-N 0.000 claims description 13
150000002367 halogens Chemical class 0.000 claims description 10
239000000654 additive Substances 0.000 claims description 9
229940079593 drug Drugs 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
208000006673 asthma Diseases 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
208000026935 allergic disease Diseases 0.000 claims description 7
230000003394 haemopoietic effect Effects 0.000 claims description 7
208000032839 leukemia Diseases 0.000 claims description 7
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
XXXBRMHCEXRQRE-UHFFFAOYSA-N 2-[(2,6-diaminopurin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC(N)=NC(N)=C2N=C1 XXXBRMHCEXRQRE-UHFFFAOYSA-N 0.000 claims description 6
IWGAQSJFPSNTKF-UHFFFAOYSA-N 2-[(6-aminopurin-7-yl)methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=C(N)N=CN=C2N=C1 IWGAQSJFPSNTKF-UHFFFAOYSA-N 0.000 claims description 6
NIJYZONQYZIWKO-UHFFFAOYSA-N 2-[[(2-amino-7h-purin-6-yl)amino]methyl]-3-(2-chlorophenyl)-5-fluoroquinazolin-4-one Chemical compound C=12N=CNC2=NC(N)=NC=1NCC1=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1Cl NIJYZONQYZIWKO-UHFFFAOYSA-N 0.000 claims description 6
WPYVXMUPYRJJDY-UHFFFAOYSA-N 5-methyl-3-(2-methylphenyl)-2-(purin-7-ylmethyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=CN=CN=C2N=C1 WPYVXMUPYRJJDY-UHFFFAOYSA-N 0.000 claims description 6
XGBJKHZWQCGCDK-UHFFFAOYSA-N 5-methyl-3-(2-methylphenyl)-2-(purin-9-ylmethyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC=C2N=C1 XGBJKHZWQCGCDK-UHFFFAOYSA-N 0.000 claims description 6
GIMZHZAQQLFKDY-UHFFFAOYSA-N 5-methyl-3-(2-methylphenyl)-2-[(7h-purin-6-ylamino)methyl]quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CNC1=NC=NC2=C1N=CN2 GIMZHZAQQLFKDY-UHFFFAOYSA-N 0.000 claims description 6
NILGZRIBALJAAD-UHFFFAOYSA-N 5-methyl-3-(2-methylphenyl)-2-[1-(7h-purin-6-ylamino)ethyl]quinazolin-4-one Chemical compound N=1C=NC=2NC=NC=2C=1NC(C)C1=NC2=CC=CC(C)=C2C(=O)N1C1=CC=CC=C1C NILGZRIBALJAAD-UHFFFAOYSA-N 0.000 claims description 6
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
208000023275 Autoimmune disease Diseases 0.000 claims description 6
208000009329 Graft vs Host Disease Diseases 0.000 claims description 6
230000002917 arthritic effect Effects 0.000 claims description 6
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
208000024908 graft versus host disease Diseases 0.000 claims description 6
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
PGKGDAOZGPWYBX-UHFFFAOYSA-N 2-[(2-amino-6-chloropurin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC(N)=NC(Cl)=C2N=C1 PGKGDAOZGPWYBX-UHFFFAOYSA-N 0.000 claims description 5
XIIBYVZCAGZAPQ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-5-fluoroquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1Cl XIIBYVZCAGZAPQ-UHFFFAOYSA-N 0.000 claims description 5
VRZOWGGKIACNIC-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CC=C1Cl VRZOWGGKIACNIC-UHFFFAOYSA-N 0.000 claims description 5
VVRQFRVUVPOQPU-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-6,7-dimethoxyquinazolin-4-one Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CC=C1Cl VVRQFRVUVPOQPU-UHFFFAOYSA-N 0.000 claims description 5
AMYMIDIYTQOWGQ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chloropyridin-3-yl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CN=C1Cl AMYMIDIYTQOWGQ-UHFFFAOYSA-N 0.000 claims description 5
HHLQETOGUXOANM-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(cyclopropylmethyl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1CC1CC1 HHLQETOGUXOANM-UHFFFAOYSA-N 0.000 claims description 5
VKQSKJCTWBCERY-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-cyclohexyl-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1CCCCC1 VKQSKJCTWBCERY-UHFFFAOYSA-N 0.000 claims description 5
JDFQBHREQMPUEC-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-cyclopentyl-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1CCCC1 JDFQBHREQMPUEC-UHFFFAOYSA-N 0.000 claims description 5
MQGUQBFVGGNFBF-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-fluorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1F MQGUQBFVGGNFBF-UHFFFAOYSA-N 0.000 claims description 5
IOOGLFCOTPZWOV-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-methoxyphenyl)quinazolin-4-one Chemical compound COC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 IOOGLFCOTPZWOV-UHFFFAOYSA-N 0.000 claims description 5
HKGGEZVQRAZEDJ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 HKGGEZVQRAZEDJ-UHFFFAOYSA-N 0.000 claims description 5
LVMDQSBZDBGLET-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-phenylphenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1C1=CC=CC=C1 LVMDQSBZDBGLET-UHFFFAOYSA-N 0.000 claims description 5
XWHYLSLNUHYGHD-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-methyl-3-(2-propan-2-ylphenyl)quinazolin-4-one Chemical compound CC(C)C1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 XWHYLSLNUHYGHD-UHFFFAOYSA-N 0.000 claims description 5
CRAWDASOGPMBAA-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-6-chloro-3-(2-chlorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=C(Cl)C=C2C(=O)N1C1=CC=CC=C1Cl CRAWDASOGPMBAA-UHFFFAOYSA-N 0.000 claims description 5
PRNXFEYDFGYIMH-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-8-chloro-3-(2-chlorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=C(Cl)C=CC=C2C(=O)N1C1=CC=CC=C1Cl PRNXFEYDFGYIMH-UHFFFAOYSA-N 0.000 claims description 5
PMIJDQUGMZYEHH-UHFFFAOYSA-N 2-[1-[(2-fluoro-7h-purin-6-yl)amino]ethyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound N=1C(F)=NC=2NC=NC=2C=1NC(C)C1=NC2=CC=CC(C)=C2C(=O)N1C1=CC=CC=C1C PMIJDQUGMZYEHH-UHFFFAOYSA-N 0.000 claims description 5
NOYYMAUMYDJHSB-UHFFFAOYSA-N 2-[[(2-amino-7h-purin-6-yl)amino]methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CNC1=NC(N)=NC2=C1N=CN2 NOYYMAUMYDJHSB-UHFFFAOYSA-N 0.000 claims description 5
SCTILWQHMODCBQ-UHFFFAOYSA-N 2-[[(2-fluoro-7h-purin-6-yl)amino]methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CNC1=NC(F)=NC2=C1N=CN2 SCTILWQHMODCBQ-UHFFFAOYSA-N 0.000 claims description 5
QMMRTRAIDFEVAB-UHFFFAOYSA-N 2-[[6-(dimethylamino)purin-9-yl]methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound C1=NC=2C(N(C)C)=NC=NC=2N1CC1=NC2=CC=CC(C)=C2C(=O)N1C1=CC=CC=C1C QMMRTRAIDFEVAB-UHFFFAOYSA-N 0.000 claims description 5
UFPVKWSIZDJDCQ-UHFFFAOYSA-N 5-methyl-2-[[6-(methylamino)purin-9-yl]methyl]-3-(2-methylphenyl)quinazolin-4-one Chemical compound C1=NC=2C(NC)=NC=NC=2N1CC1=NC2=CC=CC(C)=C2C(=O)N1C1=CC=CC=C1C UFPVKWSIZDJDCQ-UHFFFAOYSA-N 0.000 claims description 5
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 5
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 5
206010014561 Emphysema Diseases 0.000 claims description 5
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 5
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 5
206010052779 Transplant rejections Diseases 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
CVLAPCOXQCXBJO-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-7-fluoroquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC(F)=CC=C2C(=O)N1C1=CC=CC=C1Cl CVLAPCOXQCXBJO-UHFFFAOYSA-N 0.000 claims description 4
FPMFIIHYOJIALC-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-cyclopropyl-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1CC1 FPMFIIHYOJIALC-UHFFFAOYSA-N 0.000 claims description 4
JDGRYIPYEMCXIZ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-chlorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1Cl JDGRYIPYEMCXIZ-UHFFFAOYSA-N 0.000 claims description 4
HNCVJZIXAKVYGJ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-6-bromo-3-(2-chlorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=C(Br)C=C2C(=O)N1C1=CC=CC=C1Cl HNCVJZIXAKVYGJ-UHFFFAOYSA-N 0.000 claims description 4
PXCXUJJZLMYBPT-UHFFFAOYSA-N 2-[[6-(benzylamino)purin-9-yl]methyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC(NCC=3C=CC=CC=3)=C2N=C1 PXCXUJJZLMYBPT-UHFFFAOYSA-N 0.000 claims description 4
MWFWIFXFNIZHHX-UHFFFAOYSA-N 2-[amino-(dimethylamino)-purin-9-ylmethyl]-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound C1=NC2=CN=CN=C2N1C(N)(N(C)C)C1=NC2=CC=CC(C)=C2C(=O)N1C1=CC=CC=C1C MWFWIFXFNIZHHX-UHFFFAOYSA-N 0.000 claims description 4
206010016654 Fibrosis Diseases 0.000 claims description 4
208000010191 Osteitis Deformans Diseases 0.000 claims description 4
208000001132 Osteoporosis Diseases 0.000 claims description 4
208000027868 Paget disease Diseases 0.000 claims description 4
206010003246 arthritis Diseases 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
230000004761 fibrosis Effects 0.000 claims description 4
208000027202 mammary Paget disease Diseases 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
239000012453 solvate Substances 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
BNQLOVCAZBJWHG-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-fluoro-2-[(7h-purin-6-ylamino)methyl]quinazolin-4-one Chemical compound O=C1C=2C(F)=CC=CC=2N=C(CNC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl BNQLOVCAZBJWHG-UHFFFAOYSA-N 0.000 claims description 3
201000005569 Gout Diseases 0.000 claims description 3
206010018634 Gouty Arthritis Diseases 0.000 claims description 3
206010025323 Lymphomas Diseases 0.000 claims description 3
208000034578 Multiple myelomas Diseases 0.000 claims description 3
XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 3
102100036056 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Human genes 0.000 claims description 3
101710204747 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Proteins 0.000 claims description 3
206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 3
230000000996 additive effect Effects 0.000 claims description 3
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
239000004305 biphenyl Substances 0.000 claims description 3
235000010290 biphenyl Nutrition 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 3
125000002757 morpholinyl group Chemical group 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
AHLCCIKVWYSPKZ-UHFFFAOYSA-N 5-methyl-2-[(2-methyl-6-oxo-3h-purin-7-yl)methyl]-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C(C(=O)NC(C)=N2)=C2N=C1 AHLCCIKVWYSPKZ-UHFFFAOYSA-N 0.000 claims description 2
JSJQJMOTACJJIC-UHFFFAOYSA-N 5-methyl-2-[(2-methyl-6-oxo-3h-purin-9-yl)methyl]-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C(N=C(C)NC2=O)=C2N=C1 JSJQJMOTACJJIC-UHFFFAOYSA-N 0.000 claims description 2
125000005059 halophenyl group Chemical group 0.000 claims description 2
201000000028 adult respiratory distress syndrome Diseases 0.000 claims 1
125000005037 alkyl phenyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 136
108091007960 PI3Ks Proteins 0.000 abstract description 41
102000038030 PI3Ks Human genes 0.000 abstract description 41
108010029485 Protein Isoforms Proteins 0.000 abstract description 31
102000001708 Protein Isoforms Human genes 0.000 abstract description 31
210000000265 leukocyte Anatomy 0.000 abstract description 28
208000035475 disorder Diseases 0.000 abstract description 26
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 abstract description 24
230000002401 inhibitory effect Effects 0.000 abstract description 22
230000001404 mediated effect Effects 0.000 abstract description 14
238000001727 in vivo Methods 0.000 abstract description 8
238000000338 in vitro Methods 0.000 abstract description 6
239000013543 active substance Substances 0.000 abstract description 5
230000010261 cell growth Effects 0.000 abstract description 5
230000004663 cell proliferation Effects 0.000 abstract description 4
230000036039 immunity Effects 0.000 abstract description 4
230000008569 process Effects 0.000 abstract description 3
210000004027 cell Anatomy 0.000 description 80
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 72
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 68
239000003112 inhibitor Substances 0.000 description 67
210000000440 neutrophil Anatomy 0.000 description 65
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 59
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 56
239000007787 solid Substances 0.000 description 56
239000000460 chlorine Substances 0.000 description 53
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
108090000765 processed proteins & peptides Proteins 0.000 description 43
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 42
239000000047 product Substances 0.000 description 39
102000004196 processed proteins & peptides Human genes 0.000 description 38
230000006870 function Effects 0.000 description 34
238000012360 testing method Methods 0.000 description 34
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
229920001184 polypeptide Polymers 0.000 description 31
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
210000003719 b-lymphocyte Anatomy 0.000 description 28
239000000203 mixture Substances 0.000 description 28
229910001868 water Inorganic materials 0.000 description 28
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 25
238000002474 experimental method Methods 0.000 description 25
239000003795 chemical substances by application Substances 0.000 description 24
230000005764 inhibitory process Effects 0.000 description 24
238000002360 preparation method Methods 0.000 description 23
238000001953 recrystallisation Methods 0.000 description 23
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 22
229960000583 acetic acid Drugs 0.000 description 22
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 21
102000004190 Enzymes Human genes 0.000 description 21
108090000790 Enzymes Proteins 0.000 description 21
102100026169 Phosphatidylinositol 3-kinase regulatory subunit alpha Human genes 0.000 description 21
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 21
238000004587 chromatography analysis Methods 0.000 description 21
229930024421 Adenine Natural products 0.000 description 20
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 20
229960000643 adenine Drugs 0.000 description 20
108090000623 proteins and genes Proteins 0.000 description 20
210000001519 tissue Anatomy 0.000 description 19
238000004458 analytical method Methods 0.000 description 18
230000015572 biosynthetic process Effects 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 17
229910006124 SOCl2 Inorganic materials 0.000 description 17
PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 17
239000000243 solution Substances 0.000 description 17
102000004169 proteins and genes Human genes 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
102000016387 Pancreatic elastase Human genes 0.000 description 15
108010067372 Pancreatic elastase Proteins 0.000 description 15
230000004913 activation Effects 0.000 description 15
AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 14
230000028023 exocytosis Effects 0.000 description 14
239000000543 intermediate Substances 0.000 description 14
230000005012 migration Effects 0.000 description 14
238000013508 migration Methods 0.000 description 14
230000035755 proliferation Effects 0.000 description 14
239000000725 suspension Substances 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
210000003651 basophil Anatomy 0.000 description 13
239000012043 crude product Substances 0.000 description 13
241001465754 Metazoa Species 0.000 description 12
210000001744 T-lymphocyte Anatomy 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 12
238000009472 formulation Methods 0.000 description 12
210000002997 osteoclast Anatomy 0.000 description 12
230000004044 response Effects 0.000 description 12
229960001340 histamine Drugs 0.000 description 11
208000028867 ischemia Diseases 0.000 description 11
229910000027 potassium carbonate Inorganic materials 0.000 description 11
230000001105 regulatory effect Effects 0.000 description 11
239000000126 substance Substances 0.000 description 11
108091003079 Bovine Serum Albumin Proteins 0.000 description 10
230000003197 catalytic effect Effects 0.000 description 10
238000013537 high throughput screening Methods 0.000 description 10
208000027866 inflammatory disease Diseases 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
102100040247 Tumor necrosis factor Human genes 0.000 description 9
125000003118 aryl group Chemical group 0.000 description 9
238000000605 extraction Methods 0.000 description 9
230000014509 gene expression Effects 0.000 description 9
238000004128 high performance liquid chromatography Methods 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
239000002609 medium Substances 0.000 description 9
239000002953 phosphate buffered saline Substances 0.000 description 9
235000015320 potassium carbonate Nutrition 0.000 description 9
239000013598 vector Substances 0.000 description 9
CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 8
206010063837 Reperfusion injury Diseases 0.000 description 8
239000002253 acid Substances 0.000 description 8
238000003556 assay Methods 0.000 description 8
210000004369 blood Anatomy 0.000 description 8
239000008280 blood Substances 0.000 description 8
230000006378 damage Effects 0.000 description 8
238000010790 dilution Methods 0.000 description 8
239000012895 dilution Substances 0.000 description 8
238000007911 parenteral administration Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
239000000758 substrate Substances 0.000 description 8
208000011580 syndromic disease Diseases 0.000 description 8
239000012981 Hank's balanced salt solution Substances 0.000 description 7
108010044467 Isoenzymes Proteins 0.000 description 7
102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 description 7
101710096503 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Proteins 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000000427 antigen Substances 0.000 description 7
102000036639 antigens Human genes 0.000 description 7
108091007433 antigens Proteins 0.000 description 7
238000012512 characterization method Methods 0.000 description 7
210000003630 histaminocyte Anatomy 0.000 description 7
230000003993 interaction Effects 0.000 description 7
239000002502 liposome Substances 0.000 description 7
239000007788 liquid Substances 0.000 description 7
238000005259 measurement Methods 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
239000003381 stabilizer Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
230000000451 tissue damage Effects 0.000 description 7
231100000827 tissue damage Toxicity 0.000 description 7
241000701447 unidentified baculovirus Species 0.000 description 7
101000873927 Homo sapiens Squamous cell carcinoma antigen recognized by T-cells 3 Proteins 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
229940124639 Selective inhibitor Drugs 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
230000001580 bacterial effect Effects 0.000 description 6
230000027455 binding Effects 0.000 description 6
239000000872 buffer Substances 0.000 description 6
238000005516 engineering process Methods 0.000 description 6
239000012634 fragment Substances 0.000 description 6
230000016784 immunoglobulin production Effects 0.000 description 6
230000002147 killing effect Effects 0.000 description 6
150000002632 lipids Chemical class 0.000 description 6
210000000056 organ Anatomy 0.000 description 6
210000002966 serum Anatomy 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
CNWINRVXAYPOMW-FCNJXWMTSA-N 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-biphosphate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCCC)COP(O)(=O)O[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H]1O CNWINRVXAYPOMW-FCNJXWMTSA-N 0.000 description 5
SZCPTRGBOVXVCA-UHFFFAOYSA-N 2-amino-6-chlorobenzoic acid Chemical compound NC1=CC=CC(Cl)=C1C(O)=O SZCPTRGBOVXVCA-UHFFFAOYSA-N 0.000 description 5
241000894006 Bacteria Species 0.000 description 5
241000283707 Capra Species 0.000 description 5
101001024630 Drosophila melanogaster RNA cytidine acetyltransferase Proteins 0.000 description 5
101000652705 Drosophila melanogaster Transcription initiation factor TFIID subunit 4 Proteins 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
229910004373 HOAc Inorganic materials 0.000 description 5
102000000588 Interleukin-2 Human genes 0.000 description 5
108010002350 Interleukin-2 Proteins 0.000 description 5
241000699666 Mus <mouse, genus> Species 0.000 description 5
108091034117 Oligonucleotide Proteins 0.000 description 5
101000996915 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Nucleoporin NSP1 Proteins 0.000 description 5
102100035748 Squamous cell carcinoma antigen recognized by T-cells 3 Human genes 0.000 description 5
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
230000001154 acute effect Effects 0.000 description 5
125000004414 alkyl thio group Chemical group 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
238000010171 animal model Methods 0.000 description 5
239000002585 base Substances 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
229940098773 bovine serum albumin Drugs 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000000969 carrier Substances 0.000 description 5
150000001768 cations Chemical class 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
239000012091 fetal bovine serum Substances 0.000 description 5
239000006260 foam Substances 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
208000015181 infectious disease Diseases 0.000 description 5
230000002757 inflammatory effect Effects 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
229930014626 natural product Natural products 0.000 description 5
239000003921 oil Substances 0.000 description 5
150000003905 phosphatidylinositols Chemical class 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
230000009467 reduction Effects 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000002904 solvent Substances 0.000 description 5
231100000419 toxicity Toxicity 0.000 description 5
230000001988 toxicity Effects 0.000 description 5
238000012384 transportation and delivery Methods 0.000 description 5
238000005406 washing Methods 0.000 description 5
QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 5
QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 5
KJQLFFHRDREFOS-UHFFFAOYSA-N 3-(2-chlorophenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound ClC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1CSC1=NC=NC2=C1NC=N2 KJQLFFHRDREFOS-UHFFFAOYSA-N 0.000 description 4
ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 4
102000004127 Cytokines Human genes 0.000 description 4
108090000695 Cytokines Proteins 0.000 description 4
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
UBXIJOJXUFYNRG-RJKBCLGNSA-N PIP[3'](17:0/20:4(5Z,8Z,11Z,14Z)) Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCC)COP(O)(=O)O[C@H]1C(O)C(O)C(O)[C@@H](OP(O)(O)=O)C1O UBXIJOJXUFYNRG-RJKBCLGNSA-N 0.000 description 4
108091000080 Phosphotransferase Proteins 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
206010040047 Sepsis Diseases 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 4
108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
238000002835 absorbance Methods 0.000 description 4
125000004442 acylamino group Chemical group 0.000 description 4
210000004712 air sac Anatomy 0.000 description 4
125000004183 alkoxy alkyl group Chemical group 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
125000003282 alkyl amino group Chemical group 0.000 description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
230000001684 chronic effect Effects 0.000 description 4
238000010367 cloning Methods 0.000 description 4
238000000576 coating method Methods 0.000 description 4
239000002299 complementary DNA Substances 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000011161 development Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 4
210000003714 granulocyte Anatomy 0.000 description 4
230000012010 growth Effects 0.000 description 4
150000002430 hydrocarbons Chemical group 0.000 description 4
230000004941 influx Effects 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
208000014674 injury Diseases 0.000 description 4
229940043355 kinase inhibitor Drugs 0.000 description 4
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
210000004698 lymphocyte Anatomy 0.000 description 4
210000002540 macrophage Anatomy 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000001301 oxygen Chemical group 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
102000020233 phosphotransferase Human genes 0.000 description 4
239000003757 phosphotransferase inhibitor Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
238000013207 serial dilution Methods 0.000 description 4
230000011664 signaling Effects 0.000 description 4
239000000600 sorbitol Substances 0.000 description 4
230000035886 specific defense system Effects 0.000 description 4
229910052717 sulfur Chemical group 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
229940104230 thymidine Drugs 0.000 description 4
238000001665 trituration Methods 0.000 description 4
DVVASDSBQCNZMX-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-5-fluoroquinazolin-4-one Chemical compound O=C1C=2C(F)=CC=CC=2N=C(CCl)N1C1=CC=CC=C1Cl DVVASDSBQCNZMX-UHFFFAOYSA-N 0.000 description 3
JMKJBXKMQTVCAL-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-6,7-dimethoxyquinazolin-4-one Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2N=C(CCl)N1C1=CC=CC=C1Cl JMKJBXKMQTVCAL-UHFFFAOYSA-N 0.000 description 3
OOUNOBBXGCWEJC-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-7-fluoroquinazolin-4-one Chemical compound C=1C(F)=CC=C(C2=O)C=1N=C(CCl)N2C1=CC=CC=C1Cl OOUNOBBXGCWEJC-UHFFFAOYSA-N 0.000 description 3
JVZXZCASXVUFSI-UHFFFAOYSA-N 2-amino-6-chloro-n-(2-methoxyphenyl)benzamide Chemical compound COC1=CC=CC=C1NC(=O)C1=C(N)C=CC=C1Cl JVZXZCASXVUFSI-UHFFFAOYSA-N 0.000 description 3
XHYVBIXKORFHFM-UHFFFAOYSA-N 2-amino-6-methylbenzoic acid Chemical compound CC1=CC=CC(N)=C1C(O)=O XHYVBIXKORFHFM-UHFFFAOYSA-N 0.000 description 3
YZZXESDKUSZLPY-UHFFFAOYSA-N 5-chloro-2-(chloromethyl)-3-(2-chlorophenyl)quinazolin-4-one Chemical compound ClCC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1Cl YZZXESDKUSZLPY-UHFFFAOYSA-N 0.000 description 3
DNNSMUVFFQHKQS-UHFFFAOYSA-N 5-chloro-2-(chloromethyl)-3-(2-fluorophenyl)quinazolin-4-one Chemical compound FC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CCl DNNSMUVFFQHKQS-UHFFFAOYSA-N 0.000 description 3
AXUFWQSIWXXQID-UHFFFAOYSA-N 6-bromo-2-(chloromethyl)-3-(2-chlorophenyl)quinazolin-4-one Chemical compound ClCC1=NC2=CC=C(Br)C=C2C(=O)N1C1=CC=CC=C1Cl AXUFWQSIWXXQID-UHFFFAOYSA-N 0.000 description 3
SVQSQAMAVITXTR-UHFFFAOYSA-N 6-chloro-2-(chloromethyl)-3-(2-chlorophenyl)quinazolin-4-one Chemical compound ClCC1=NC2=CC=C(Cl)C=C2C(=O)N1C1=CC=CC=C1Cl SVQSQAMAVITXTR-UHFFFAOYSA-N 0.000 description 3
DJHMFCFYNNIGCD-UHFFFAOYSA-N 8-chloro-2-(chloromethyl)-3-(2-chlorophenyl)quinazolin-4-one Chemical compound ClCC1=NC2=C(Cl)C=CC=C2C(=O)N1C1=CC=CC=C1Cl DJHMFCFYNNIGCD-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
229920000936 Agarose Polymers 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
229920001917 Ficoll Polymers 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
208000022559 Inflammatory bowel disease Diseases 0.000 description 3
108010028275 Leukocyte Elastase Proteins 0.000 description 3
102000016799 Leukocyte elastase Human genes 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
239000012828 PI3K inhibitor Substances 0.000 description 3
239000002033 PVDF binder Substances 0.000 description 3
206010057249 Phagocytosis Diseases 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
102000003923 Protein Kinase C Human genes 0.000 description 3
108090000315 Protein Kinase C Proteins 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
102000014128 RANK Ligand Human genes 0.000 description 3
108010025832 RANK Ligand Proteins 0.000 description 3
206010040070 Septic Shock Diseases 0.000 description 3
239000012190 activator Substances 0.000 description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
239000011324 bead Substances 0.000 description 3
230000008901 benefit Effects 0.000 description 3
238000010256 biochemical assay Methods 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
210000000988 bone and bone Anatomy 0.000 description 3
238000000423 cell based assay Methods 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
230000003399 chemotactic effect Effects 0.000 description 3
230000035605 chemotaxis Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000000470 constituent Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
239000008298 dragée Substances 0.000 description 3
210000002889 endothelial cell Anatomy 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
125000001188 haloalkyl group Chemical group 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
125000002768 hydroxyalkyl group Chemical group 0.000 description 3
210000000987 immune system Anatomy 0.000 description 3
238000011534 incubation Methods 0.000 description 3
230000006698 induction Effects 0.000 description 3
210000004969 inflammatory cell Anatomy 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
238000002955 isolation Methods 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
244000005700 microbiome Species 0.000 description 3
208000010125 myocardial infarction Diseases 0.000 description 3
229910052759 nickel Inorganic materials 0.000 description 3
230000035781 nonspecific defense system Effects 0.000 description 3
RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 3
230000008782 phagocytosis Effects 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
150000003916 phosphatidylinositol 3,4,5-trisphosphates Chemical class 0.000 description 3
229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 3
239000013612 plasmid Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229920002981 polyvinylidene fluoride Polymers 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
229910000160 potassium phosphate Inorganic materials 0.000 description 3
235000011009 potassium phosphates Nutrition 0.000 description 3
GUUBJKMBDULZTE-UHFFFAOYSA-M potassium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[K+].OCCN1CCN(CCS(O)(=O)=O)CC1 GUUBJKMBDULZTE-UHFFFAOYSA-M 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000002685 pulmonary effect Effects 0.000 description 3
230000010410 reperfusion Effects 0.000 description 3
238000012216 screening Methods 0.000 description 3
208000017520 skin disease Diseases 0.000 description 3
239000002002 slurry Substances 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
239000003826 tablet Substances 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
230000008733 trauma Effects 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
LOZWAPSEEHRYPG-UHFFFAOYSA-N 1,4-dithiane Chemical compound C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 2
AHVGFOUDKFEHLU-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-6,7-difluoroquinazolin-4-one Chemical compound O=C1C=2C=C(F)C(F)=CC=2N=C(CCl)N1C1=CC=CC=C1Cl AHVGFOUDKFEHLU-UHFFFAOYSA-N 0.000 description 2
RRWYRNYLKVRPBB-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-6-fluoroquinazolin-4-one Chemical compound O=C1C2=CC(F)=CC=C2N=C(CCl)N1C1=CC=CC=C1Cl RRWYRNYLKVRPBB-UHFFFAOYSA-N 0.000 description 2
ICEOJWILGIRYOK-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-7-nitroquinazolin-4-one Chemical compound C=1C([N+](=O)[O-])=CC=C(C2=O)C=1N=C(CCl)N2C1=CC=CC=C1Cl ICEOJWILGIRYOK-UHFFFAOYSA-N 0.000 description 2
MRRJOASXXQEGII-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)benzo[g]quinazolin-4-one Chemical compound ClCC1=NC2=CC3=CC=CC=C3C=C2C(=O)N1C1=CC=CC=C1Cl MRRJOASXXQEGII-UHFFFAOYSA-N 0.000 description 2
HYNQTSZBTIOFKH-UHFFFAOYSA-N 2-Amino-5-hydroxybenzoic acid Chemical compound NC1=CC=C(O)C=C1C(O)=O HYNQTSZBTIOFKH-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
XBBAOYPWNSDSCP-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-fluorophenyl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CC=C1F XBBAOYPWNSDSCP-UHFFFAOYSA-N 0.000 description 2
RXTIEVBLHKGDBF-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-benzyl-5-fluoroquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(F)=C2C(=O)N1CC1=CC=CC=C1 RXTIEVBLHKGDBF-UHFFFAOYSA-N 0.000 description 2
GMDVVVIIGZYKOU-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-butylquinazolin-4-one Chemical compound C1=CC=C2C(=O)N(CCCC)C(CN3C4=NC=NC(N)=C4N=C3)=NC2=C1 GMDVVVIIGZYKOU-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
ZHKRTXOCJARZJP-UHFFFAOYSA-N 2-amino-3-chloro-n-(2-chlorophenyl)benzamide Chemical compound NC1=C(Cl)C=CC=C1C(=O)NC1=CC=CC=C1Cl ZHKRTXOCJARZJP-UHFFFAOYSA-N 0.000 description 2
LWUAMROXVQLJKA-UHFFFAOYSA-N 2-amino-3-chlorobenzoic acid Chemical compound NC1=C(Cl)C=CC=C1C(O)=O LWUAMROXVQLJKA-UHFFFAOYSA-N 0.000 description 2
HJVAVGOPTDJYOJ-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C=C1OC HJVAVGOPTDJYOJ-UHFFFAOYSA-N 0.000 description 2
VXTOLCIPTYPJTC-UHFFFAOYSA-N 2-amino-5-bromo-n-(2-chlorophenyl)benzamide Chemical compound NC1=CC=C(Br)C=C1C(=O)NC1=CC=CC=C1Cl VXTOLCIPTYPJTC-UHFFFAOYSA-N 0.000 description 2
KTRRLGVJJDWQFY-UHFFFAOYSA-N 2-amino-5-chloro-n-(2-chlorophenyl)benzamide Chemical compound NC1=CC=C(Cl)C=C1C(=O)NC1=CC=CC=C1Cl KTRRLGVJJDWQFY-UHFFFAOYSA-N 0.000 description 2
XJIMZNJVUDAEBQ-UHFFFAOYSA-N 2-amino-6-chloro-n-(2-chlorophenyl)benzamide Chemical compound NC1=CC=CC(Cl)=C1C(=O)NC1=CC=CC=C1Cl XJIMZNJVUDAEBQ-UHFFFAOYSA-N 0.000 description 2
HTGHMLPSCLOYGP-UHFFFAOYSA-N 2-amino-6-chloro-n-(2-fluorophenyl)benzamide Chemical compound NC1=CC=CC(Cl)=C1C(=O)NC1=CC=CC=C1F HTGHMLPSCLOYGP-UHFFFAOYSA-N 0.000 description 2
SVEBDDDLGKFJQN-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-4,5-difluorobenzamide Chemical compound NC1=CC(F)=C(F)C=C1C(=O)NC1=CC=CC=C1Cl SVEBDDDLGKFJQN-UHFFFAOYSA-N 0.000 description 2
OVSVDAZFBZPTMF-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-4,5-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC(N)=C1C(=O)NC1=CC=CC=C1Cl OVSVDAZFBZPTMF-UHFFFAOYSA-N 0.000 description 2
LEBVKZMZJNRLNF-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-4-fluorobenzamide Chemical compound NC1=CC(F)=CC=C1C(=O)NC1=CC=CC=C1Cl LEBVKZMZJNRLNF-UHFFFAOYSA-N 0.000 description 2
RGXYBQQBETUUHQ-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-4-nitrobenzamide Chemical compound NC1=CC([N+]([O-])=O)=CC=C1C(=O)NC1=CC=CC=C1Cl RGXYBQQBETUUHQ-UHFFFAOYSA-N 0.000 description 2
UIGFETQEIGVKJP-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-5-fluorobenzamide Chemical compound NC1=CC=C(F)C=C1C(=O)NC1=CC=CC=C1Cl UIGFETQEIGVKJP-UHFFFAOYSA-N 0.000 description 2
AWHAQXRQOVWBKH-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-5-hydroxybenzamide Chemical compound NC1=CC=C(O)C=C1C(=O)NC1=CC=CC=C1Cl AWHAQXRQOVWBKH-UHFFFAOYSA-N 0.000 description 2
MKAUCPDIQZTGFU-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-6-fluorobenzamide Chemical compound NC1=CC=CC(F)=C1C(=O)NC1=CC=CC=C1Cl MKAUCPDIQZTGFU-UHFFFAOYSA-N 0.000 description 2
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
YPLRLMBBXGVXAN-UHFFFAOYSA-N 3-(2-chlorophenyl)-2-(1h-pyrazolo[3,4-d]pyrimidin-4-ylsulfanylmethyl)quinazolin-4-one Chemical compound ClC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1CSC1=NC=NC2=C1C=NN2 YPLRLMBBXGVXAN-UHFFFAOYSA-N 0.000 description 2
HTIJYCXXPTXUPT-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-methyl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl HTIJYCXXPTXUPT-UHFFFAOYSA-N 0.000 description 2
BMEYZFNEPNBJLV-UHFFFAOYSA-N 3-amino-n-(2-chlorophenyl)naphthalene-2-carboxamide Chemical compound NC1=CC2=CC=CC=C2C=C1C(=O)NC1=CC=CC=C1Cl BMEYZFNEPNBJLV-UHFFFAOYSA-N 0.000 description 2
GOFMHTSWWNYDRB-UHFFFAOYSA-N 5-chloro-2-(chloromethyl)-3-(2-methoxyphenyl)quinazolin-4-one Chemical compound COC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CCl GOFMHTSWWNYDRB-UHFFFAOYSA-N 0.000 description 2
KKPWLCWHIUUBIP-UHFFFAOYSA-N 5-chloro-2-(chloromethyl)-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CCl KKPWLCWHIUUBIP-UHFFFAOYSA-N 0.000 description 2
UNRIYCIDCQDGQE-UHFFFAOYSA-N 6-chloro-2-fluoro-7h-purine Chemical compound FC1=NC(Cl)=C2NC=NC2=N1 UNRIYCIDCQDGQE-UHFFFAOYSA-N 0.000 description 2
RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
HFWFBOCOXPEKBV-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(2-chloro-2-oxoethyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCC(=O)Cl)C3=CC=CC=C3C2=C1 HFWFBOCOXPEKBV-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
208000006386 Bone Resorption Diseases 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
101100440696 Caenorhabditis elegans cor-1 gene Proteins 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
206010010744 Conjunctivitis allergic Diseases 0.000 description 2
102000018832 Cytochromes Human genes 0.000 description 2
108010052832 Cytochromes Proteins 0.000 description 2
102000005768 DNA-Activated Protein Kinase Human genes 0.000 description 2
108010006124 DNA-Activated Protein Kinase Proteins 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
241000196324 Embryophyta Species 0.000 description 2
241000283074 Equus asinus Species 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
208000010496 Heart Arrest Diseases 0.000 description 2
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
241000238631 Hexapoda Species 0.000 description 2
241000282412 Homo Species 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
201000009906 Meningitis Diseases 0.000 description 2
206010027476 Metastases Diseases 0.000 description 2
241001529936 Murinae Species 0.000 description 2
108010038807 Oligopeptides Proteins 0.000 description 2
102000015636 Oligopeptides Human genes 0.000 description 2
102000004264 Osteopontin Human genes 0.000 description 2
108010081689 Osteopontin Proteins 0.000 description 2
WSLBJQQQZZTFBA-MLUQOLBVSA-N PIP[4'](17:0/20:4(5Z,8Z,11Z,14Z)) Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCC)COP(O)(=O)OC1C(O)C(O)C(OP(O)(O)=O)[C@@H](O)C1O WSLBJQQQZZTFBA-MLUQOLBVSA-N 0.000 description 2
102000035195 Peptidases Human genes 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
239000004365 Protease Substances 0.000 description 2
102000001253 Protein Kinase Human genes 0.000 description 2
206010037660 Pyrexia Diseases 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
241000191967 Staphylococcus aureus Species 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102000019197 Superoxide Dismutase Human genes 0.000 description 2
108010012715 Superoxide dismutase Proteins 0.000 description 2
206010042674 Swelling Diseases 0.000 description 2
230000006052 T cell proliferation Effects 0.000 description 2
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
NYTKGEDVBYLJGH-UHFFFAOYSA-N [2-(chloromethyl)-3-(2-chlorophenyl)-4-oxoquinazolin-6-yl] acetate Chemical compound O=C1C2=CC(OC(=O)C)=CC=C2N=C(CCl)N1C1=CC=CC=C1Cl NYTKGEDVBYLJGH-UHFFFAOYSA-N 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
239000000205 acacia gum Substances 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
235000010419 agar Nutrition 0.000 description 2
239000000556 agonist Substances 0.000 description 2
235000010443 alginic acid Nutrition 0.000 description 2
229920000615 alginic acid Polymers 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
208000002205 allergic conjunctivitis Diseases 0.000 description 2
230000007815 allergy Effects 0.000 description 2
230000003281 allosteric effect Effects 0.000 description 2
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000008499 blood brain barrier function Effects 0.000 description 2
230000017531 blood circulation Effects 0.000 description 2
210000001218 blood-brain barrier Anatomy 0.000 description 2
210000001185 bone marrow Anatomy 0.000 description 2
230000024279 bone resorption Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
150000001649 bromium compounds Chemical class 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
239000007975 buffered saline Substances 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
230000020411 cell activation Effects 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
230000036755 cellular response Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
230000001086 cytosolic effect Effects 0.000 description 2
210000004268 dentin Anatomy 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
239000008121 dextrose Substances 0.000 description 2
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
239000002158 endotoxin Substances 0.000 description 2
210000003979 eosinophil Anatomy 0.000 description 2
230000000763 evoking effect Effects 0.000 description 2
230000029142 excretion Effects 0.000 description 2
239000010685 fatty oil Substances 0.000 description 2
238000000855 fermentation Methods 0.000 description 2
230000004151 fermentation Effects 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
238000011010 flushing procedure Methods 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
210000002216 heart Anatomy 0.000 description 2
229960002897 heparin Drugs 0.000 description 2
229920000669 heparin Polymers 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
150000004694 iodide salts Chemical class 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
238000002372 labelling Methods 0.000 description 2
125000005647 linker group Chemical group 0.000 description 2
229920006008 lipopolysaccharide Polymers 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
210000003563 lymphoid tissue Anatomy 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000003550 marker Substances 0.000 description 2
MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 2
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
229960001428 mercaptopurine Drugs 0.000 description 2
230000009401 metastasis Effects 0.000 description 2
229960004452 methionine Drugs 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
238000002156 mixing Methods 0.000 description 2
238000010369 molecular cloning Methods 0.000 description 2
208000037890 multiple organ injury Diseases 0.000 description 2
208000031225 myocardial ischemia Diseases 0.000 description 2
210000004897 n-terminal region Anatomy 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
210000000944 nerve tissue Anatomy 0.000 description 2
230000011242 neutrophil chemotaxis Effects 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
150000002894 organic compounds Chemical class 0.000 description 2
230000003204 osmotic effect Effects 0.000 description 2
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
108060006633 protein kinase Proteins 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
238000004007 reversed phase HPLC Methods 0.000 description 2
238000012552 review Methods 0.000 description 2
239000000523 sample Substances 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
241000894007 species Species 0.000 description 2
230000009870 specific binding Effects 0.000 description 2
210000000952 spleen Anatomy 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
238000005556 structure-activity relationship Methods 0.000 description 2
230000004960 subcellular localization Effects 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000011593 sulfur Chemical group 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000008961 swelling Effects 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
230000003685 thermal hair damage Effects 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
230000001052 transient effect Effects 0.000 description 2
238000003828 vacuum filtration Methods 0.000 description 2
239000011534 wash buffer Substances 0.000 description 2
LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-N 0.000 description 1
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
JMIPINYUSIWLKU-REOHCLBHSA-N (2s)-2-aminopropanoyl chloride Chemical compound C[C@H](N)C(Cl)=O JMIPINYUSIWLKU-REOHCLBHSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
HKWJHKSHEWVOSS-OMDJCSNQSA-N 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)O[C@H]1[C@H](O)[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O HKWJHKSHEWVOSS-OMDJCSNQSA-N 0.000 description 1
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
BYIMEGGZJCPIMT-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CCl)N1C1=CC=CC=C1Cl BYIMEGGZJCPIMT-UHFFFAOYSA-N 0.000 description 1
NLGRBUCPQLUGRC-UHFFFAOYSA-N 2-(chloromethyl)-3-(2-chlorophenyl)-8-(trifluoromethyl)quinazolin-4-one Chemical compound FC(F)(F)C1=CC=CC(C2=O)=C1N=C(CCl)N2C1=CC=CC=C1Cl NLGRBUCPQLUGRC-UHFFFAOYSA-N 0.000 description 1
ZOTCSPSVHIKHBZ-UHFFFAOYSA-N 2-(chloromethyl)-5-methyl-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CCl ZOTCSPSVHIKHBZ-UHFFFAOYSA-N 0.000 description 1
YKOLZVXSPGIIBJ-UHFFFAOYSA-N 2-Isopropylaniline Chemical compound CC(C)C1=CC=CC=C1N YKOLZVXSPGIIBJ-UHFFFAOYSA-N 0.000 description 1
IBIHUDVRLLQWNN-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-morpholin-4-ylquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC=C2C(=O)N1N1CCOCC1 IBIHUDVRLLQWNN-UHFFFAOYSA-N 0.000 description 1
OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 1
UNLVJVQEDSDPIN-UHFFFAOYSA-N 2-amino-3-(trifluoromethyl)benzoic acid Chemical compound NC1=C(C(O)=O)C=CC=C1C(F)(F)F UNLVJVQEDSDPIN-UHFFFAOYSA-N 0.000 description 1
DGOZIZVTANAGCA-UHFFFAOYSA-N 2-amino-4,5-difluorobenzoic acid Chemical compound NC1=CC(F)=C(F)C=C1C(O)=O DGOZIZVTANAGCA-UHFFFAOYSA-N 0.000 description 1
LGPVTNAJFDUWLF-UHFFFAOYSA-N 2-amino-4-fluorobenzoic acid Chemical compound NC1=CC(F)=CC=C1C(O)=O LGPVTNAJFDUWLF-UHFFFAOYSA-N 0.000 description 1
CUKXRHLWPSBCTI-UHFFFAOYSA-N 2-amino-5-bromobenzoic acid Chemical compound NC1=CC=C(Br)C=C1C(O)=O CUKXRHLWPSBCTI-UHFFFAOYSA-N 0.000 description 1
IFXKXCLVKQVVDI-UHFFFAOYSA-N 2-amino-5-chlorobenzoic acid Chemical compound NC1=CC=C(Cl)C=C1C(O)=O IFXKXCLVKQVVDI-UHFFFAOYSA-N 0.000 description 1
ZZHQHVSOCFQYAE-UHFFFAOYSA-N 2-amino-6-chloro-n-(2-phenylphenyl)benzamide Chemical compound NC1=CC=CC(Cl)=C1C(=O)NC1=CC=CC=C1C1=CC=CC=C1 ZZHQHVSOCFQYAE-UHFFFAOYSA-N 0.000 description 1
RWSFZKWMVWPDGZ-UHFFFAOYSA-N 2-amino-6-fluorobenzoic acid Chemical compound NC1=CC=CC(F)=C1C(O)=O RWSFZKWMVWPDGZ-UHFFFAOYSA-N 0.000 description 1
XEQRGGIYCYXAPM-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-3-(trifluoromethyl)benzamide Chemical compound C1=CC=C(C(F)(F)F)C(N)=C1C(=O)NC1=CC=CC=C1Cl XEQRGGIYCYXAPM-UHFFFAOYSA-N 0.000 description 1
CTRTVLYAQBPGAI-UHFFFAOYSA-N 2-amino-n-(2-chlorophenyl)-6-methylbenzamide Chemical compound CC1=CC=CC(N)=C1C(=O)NC1=CC=CC=C1Cl CTRTVLYAQBPGAI-UHFFFAOYSA-N 0.000 description 1
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 description 1
229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
XJCQBQWPASYUHR-UHFFFAOYSA-N 2-phenylcyclohexa-2,4-diene-1,1-diamine Chemical compound NC1(N)CC=CC=C1C1=CC=CC=C1 XJCQBQWPASYUHR-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
XFXOLBNQYFRSLQ-UHFFFAOYSA-N 3-amino-2-naphthoic acid Chemical compound C1=CC=C2C=C(C(O)=O)C(N)=CC2=C1 XFXOLBNQYFRSLQ-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 1
XDCOYBQVEVSNNB-UHFFFAOYSA-N 4-[(7-naphthalen-2-yl-1-benzothiophen-2-yl)methylamino]butanoic acid Chemical compound OC(=O)CCCNCc1cc2cccc(-c3ccc4ccccc4c3)c2s1 XDCOYBQVEVSNNB-UHFFFAOYSA-N 0.000 description 1
UEALKTCRMBVTFN-UHFFFAOYSA-N 4-nitroanthranilic acid Chemical compound NC1=CC([N+]([O-])=O)=CC=C1C(O)=O UEALKTCRMBVTFN-UHFFFAOYSA-N 0.000 description 1
MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 1
HQLRWYJCOZVABA-UHFFFAOYSA-N 5-chloro-2-(chloromethyl)-3-(2-phenylphenyl)quinazolin-4-one Chemical compound ClCC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1C1=CC=CC=C1 HQLRWYJCOZVABA-UHFFFAOYSA-N 0.000 description 1
FPQMGQZTBWIHDN-UHFFFAOYSA-N 5-fluoroanthranilic acid Chemical compound NC1=CC=C(F)C=C1C(O)=O FPQMGQZTBWIHDN-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010001889 Alveolitis Diseases 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
244000144730 Amygdalus persica Species 0.000 description 1
206010003267 Arthritis reactive Diseases 0.000 description 1
206010003594 Ataxia telangiectasia Diseases 0.000 description 1
241000271566 Aves Species 0.000 description 1
201000001178 Bacterial Pneumonia Diseases 0.000 description 1
208000009137 Behcet syndrome Diseases 0.000 description 1
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
208000020084 Bone disease Diseases 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
244000056139 Brassica cretica Species 0.000 description 1
235000003351 Brassica cretica Nutrition 0.000 description 1
235000003343 Brassica rupestris Nutrition 0.000 description 1
206010006458 Bronchitis chronic Diseases 0.000 description 1
208000011691 Burkitt lymphomas Diseases 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
208000019300 CLIPPERS Diseases 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
241000700198 Cavia Species 0.000 description 1
102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
108091007958 Class I PI3Ks Proteins 0.000 description 1
101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
241000938605 Crocodylia Species 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010051392 Diapedesis Diseases 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
206010014824 Endotoxic shock Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
241000206602 Eukaryota Species 0.000 description 1
108091006020 Fc-tagged proteins Proteins 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
102000011652 Formyl peptide receptors Human genes 0.000 description 1
108010076288 Formyl peptide receptors Proteins 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
241000206672 Gelidium Species 0.000 description 1
206010018366 Glomerulonephritis acute Diseases 0.000 description 1
206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
208000003084 Graves Ophthalmopathy Diseases 0.000 description 1
102000009465 Growth Factor Receptors Human genes 0.000 description 1
108010009202 Growth Factor Receptors Proteins 0.000 description 1
208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
208000032843 Hemorrhage Diseases 0.000 description 1
208000032456 Hemorrhagic Shock Diseases 0.000 description 1
206010019728 Hepatitis alcoholic Diseases 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 description 1
101001059443 Homo sapiens Serine/threonine-protein kinase MARK1 Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010021138 Hypovolaemic shock Diseases 0.000 description 1
102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
206010023330 Keloid scar Diseases 0.000 description 1
FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
229930195722 L-methionine Natural products 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
206010069698 Langerhans' cell histiocytosis Diseases 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
208000019693 Lung disease Diseases 0.000 description 1
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
108090000988 Lysostaphin Proteins 0.000 description 1
102000043129 MHC class I family Human genes 0.000 description 1
108091054437 MHC class I family Proteins 0.000 description 1
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
206010064912 Malignant transformation Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
244000062730 Melissa officinalis Species 0.000 description 1
235000010654 Melissa officinalis Nutrition 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical class COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000000112 Myalgia Diseases 0.000 description 1
206010051606 Necrotising colitis Diseases 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
108091028043 Nucleic acid sequence Proteins 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
241001494479 Pecora Species 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 description 1
102100030264 Pleckstrin Human genes 0.000 description 1
102000010995 Pleckstrin homology domains Human genes 0.000 description 1
108050001185 Pleckstrin homology domains Proteins 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
241000288906 Primates Species 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
235000006040 Prunus persica var persica Nutrition 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
239000012979 RPMI medium Substances 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
206010039085 Rhinitis allergic Diseases 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
208000022639 SchC6pf-Schulz-Passarge syndrome Diseases 0.000 description 1
208000001364 Schopf-Schulz-Passarge syndrome Diseases 0.000 description 1
206010053879 Sepsis syndrome Diseases 0.000 description 1
206010049771 Shock haemorrhagic Diseases 0.000 description 1
201000010001 Silicosis Diseases 0.000 description 1
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
208000005392 Spasm Diseases 0.000 description 1
201000002661 Spondylitis Diseases 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
241000282887 Suidae Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 1
230000006044 T cell activation Effects 0.000 description 1
108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
101150106148 TOR1 gene Proteins 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
206010044248 Toxic shock syndrome Diseases 0.000 description 1
231100000650 Toxic shock syndrome Toxicity 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
244000098338 Triticum aestivum Species 0.000 description 1
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
206010046851 Uveitis Diseases 0.000 description 1
206010047115 Vasculitis Diseases 0.000 description 1
241000700605 Viruses Species 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
231100000851 acute glomerulonephritis Toxicity 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
208000002353 alcoholic hepatitis Diseases 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
201000010105 allergic rhinitis Diseases 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
230000003321 amplification Effects 0.000 description 1
208000007502 anemia Diseases 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
208000024998 atopic conjunctivitis Diseases 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000006472 autoimmune response Effects 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
230000008827 biological function Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
201000001531 bladder carcinoma Diseases 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
210000002798 bone marrow cell Anatomy 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
201000009267 bronchiectasis Diseases 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
230000009702 cancer cell proliferation Effects 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
210000000845 cartilage Anatomy 0.000 description 1
230000021164 cell adhesion Effects 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000032823 cell division Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000022534 cell killing Effects 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
210000002421 cell wall Anatomy 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000002975 chemoattractant Substances 0.000 description 1
229940070335 chlor-phen Drugs 0.000 description 1
125000000068 chlorophenyl group Chemical group 0.000 description 1
208000007451 chronic bronchitis Diseases 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
230000004087 circulation Effects 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
230000004186 co-expression Effects 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004624 confocal microscopy Methods 0.000 description 1
238000010276 construction Methods 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
230000004940 costimulation Effects 0.000 description 1
230000000139 costimulatory effect Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000002950 deficient Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
210000004443 dendritic cell Anatomy 0.000 description 1
238000001514 detection method Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000012154 double-distilled water Substances 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
238000007877 drug screening Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
206010014599 encephalitis Diseases 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
208000003401 eosinophilic granuloma Diseases 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000005713 exacerbation Effects 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
210000003414 extremity Anatomy 0.000 description 1
201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
230000027950 fever generation Effects 0.000 description 1
239000000835 fiber Substances 0.000 description 1
239000012997 ficoll-paque Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000002376 fluorescence recovery after photobleaching Methods 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
210000000224 granular leucocyte Anatomy 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
208000035474 group of disease Diseases 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000005347 halocycloalkyl group Chemical group 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
102000034345 heterotrimeric G proteins Human genes 0.000 description 1
108091006093 heterotrimeric G proteins Proteins 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
102000053508 human MARK1 Human genes 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
229940106780 human fibrinogen Drugs 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
229910052588 hydroxylapatite Inorganic materials 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000008105 immune reaction Effects 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000006054 immunological memory Effects 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000000411 inducer Substances 0.000 description 1
230000007574 infarction Effects 0.000 description 1
239000012678 infectious agent Substances 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
230000006749 inflammatory damage Effects 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical group O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000004073 interleukin-2 production Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
208000001286 intracranial vasospasm Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
208000011379 keloid formation Diseases 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000001821 langerhans cell Anatomy 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
230000003902 lesion Effects 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
206010024378 leukocytosis Diseases 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000000865 liniment Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
208000003747 lymphoid leukemia Diseases 0.000 description 1
238000012792 lyophilization process Methods 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000036212 malign transformation Effects 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
210000003574 melanophore Anatomy 0.000 description 1
238000002074 melt spinning Methods 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000005395 methacrylic acid group Chemical group 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000000329 molecular dynamics simulation Methods 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
210000005087 mononuclear cell Anatomy 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
235000010460 mustard Nutrition 0.000 description 1
230000035772 mutation Effects 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
KUHRIIPUCPOQMQ-UHFFFAOYSA-N n,n-diethyl-3-(ethyliminomethylideneamino)propan-1-amine Chemical compound CCN=C=NCCCN(CC)CC KUHRIIPUCPOQMQ-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
208000004995 necrotizing enterocolitis Diseases 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
230000003961 neuronal insult Effects 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
238000010606 normalization Methods 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
KZCOBXFFBQJQHH-UHFFFAOYSA-N octane-1-thiol Chemical compound CCCCCCCCS KZCOBXFFBQJQHH-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
102000027450 oncoproteins Human genes 0.000 description 1
108091008819 oncoproteins Proteins 0.000 description 1
238000005457 optimization Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
239000006072 paste Substances 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
229940067626 phosphatidylinositols Drugs 0.000 description 1
150000003906 phosphoinositides Chemical class 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
108010026735 platelet protein P47 Proteins 0.000 description 1
238000007747 plating Methods 0.000 description 1
208000008423 pleurisy Diseases 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229930001119 polyketide Natural products 0.000 description 1
125000000830 polyketide group Chemical group 0.000 description 1
229930001118 polyketide hybrid Natural products 0.000 description 1
125000003308 polyketide hybrid group Chemical group 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
230000026341 positive regulation of angiogenesis Effects 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000009696 proliferative response Effects 0.000 description 1
229940127293 prostanoid Drugs 0.000 description 1
150000003814 prostanoids Chemical class 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
238000004080 punching Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
238000011002 quantification Methods 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
230000005855 radiation Effects 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
102000016914 ras Proteins Human genes 0.000 description 1
108010014186 ras Proteins Proteins 0.000 description 1
239000002994 raw material Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
208000002574 reactive arthritis Diseases 0.000 description 1
239000003642 reactive oxygen metabolite Substances 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000003307 reticuloendothelial effect Effects 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
231100000241 scar Toxicity 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000028327 secretion Effects 0.000 description 1
230000001235 sensitizing effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
206010040560 shock Diseases 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
230000003393 splenic effect Effects 0.000 description 1
210000004988 splenocyte Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
210000004243 sweat Anatomy 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
210000001258 synovial membrane Anatomy 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000012385 systemic delivery Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
230000008685 targeting Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
229940124598 therapeutic candidate Drugs 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
206010043554 thrombocytopenia Diseases 0.000 description 1
230000009424 thromboembolic effect Effects 0.000 description 1
PYAOPMWCFSVFOT-UHFFFAOYSA-N tisopurine Chemical compound SC1=NC=NC2=C1C=NN2 PYAOPMWCFSVFOT-UHFFFAOYSA-N 0.000 description 1
230000009772 tissue formation Effects 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
101150049389 tor2 gene Proteins 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
231100000816 toxic dose Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000006168 tricyclic group Chemical group 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
239000006150 trypticase soy agar Substances 0.000 description 1
208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
238000005199 ultracentrifugation Methods 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
208000010570 urinary bladder carcinoma Diseases 0.000 description 1
230000007054 vacuolar protein processing Effects 0.000 description 1
239000002966 varnish Substances 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
201000005539 vernal conjunctivitis Diseases 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000011179 visual inspection Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/24—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one nitrogen and one sulfur atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/36—Sulfur atom
- C07D473/38—Sulfur atom attached in position 6
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Immunology (AREA)
Diabetes (AREA)
Rheumatology (AREA)
Pulmonology (AREA)
Orthopedic Medicine & Surgery (AREA)
Dermatology (AREA)
Neurology (AREA)
Cardiology (AREA)
Endocrinology (AREA)
Urology & Nephrology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Communicable Diseases (AREA)
Gastroenterology & Hepatology (AREA)
Ophthalmology & Optometry (AREA)
Pain & Pain Management (AREA)
Emergency Medicine (AREA)
Vascular Medicine (AREA)
Oncology (AREA)
Obesity (AREA)
Transplantation (AREA)
Epidemiology (AREA)

NO20025104A 2000-04-25 2002-10-24 Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom NO329136B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US19965500P	2000-04-25	2000-04-25
US23805700P	2000-10-05	2000-10-05
PCT/US2001/013315 WO2001081346A2 (en)	2000-04-25	2001-04-24	Inhibitors of human phosphatidyl-inositol 3-kinase delta

Publications (3)

Publication Number	Publication Date
NO20025104D0 NO20025104D0 (no)	2002-10-24
NO20025104L NO20025104L (no)	2002-12-10
NO329136B1 true NO329136B1 (no)	2010-08-30

Family

ID=26894992

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20025104A NO329136B1 (no)	2000-04-25	2002-10-24	Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom
NO20100777A NO20100777L (no)	2000-04-25	2010-05-28	Kinazolinoner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20100777A NO20100777L (no)	2000-04-25	2010-05-28	Kinazolinoner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom

Country Status (26)

Country	Link
US (2)	US6518277B1 (sr)
EP (3)	EP2223922B1 (sr)
JP (1)	JP4642309B2 (sr)
KR (1)	KR100785363B1 (sr)
CN (1)	CN1440408B (sr)
AT (1)	ATE502941T1 (sr)
AU (2)	AU5566701A (sr)
BR (1)	BRPI0110371B8 (sr)
CA (1)	CA2406278C (sr)
CY (1)	CY1117672T1 (sr)
DE (1)	DE60144277D1 (sr)
DK (3)	DK2223922T3 (sr)
EA (1)	EA008241B1 (sr)
ES (3)	ES2567260T3 (sr)
GE (1)	GEP20084317B (sr)
HR (1)	HRP20020838A2 (sr)
HU (1)	HU230554B1 (sr)
IL (3)	IL152275A0 (sr)
IS (1)	IS2822B (sr)
MX (1)	MXPA02010618A (sr)
NO (2)	NO329136B1 (sr)
NZ (1)	NZ522076A (sr)
PT (3)	PT1939203E (sr)
RS (1)	RS51458B (sr)
SI (2)	SI2223922T1 (sr)
WO (1)	WO2001081346A2 (sr)

Families Citing this family (217)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7230000B1 (en) *	1999-10-27	2007-06-12	Cytokinetics, Incorporated	Methods and compositions utilizing quinazolinones
US6545004B1 (en)	1999-10-27	2003-04-08	Cytokinetics, Inc.	Methods and compositions utilizing quinazolinones
US7671200B2 (en) *	1999-10-27	2010-03-02	Cytokinetics, Inc.	Quinazolinone KSP inhibitors
US6667300B2 (en) *	2000-04-25	2003-12-23	Icos Corporation	Inhibitors of human phosphatidylinositol 3-kinase delta
US6403588B1 (en)	2000-04-27	2002-06-11	Yamanouchi Pharmaceutical Co., Ltd.	Imidazopyridine derivatives
US6608053B2 (en) *	2000-04-27	2003-08-19	Yamanouchi Pharmaceutical Co., Ltd.	Fused heteroaryl derivatives
US7754208B2 (en)	2001-01-17	2010-07-13	Trubion Pharmaceuticals, Inc.	Binding domain-immunoglobulin fusion proteins
US20030133939A1 (en)	2001-01-17	2003-07-17	Genecraft, Inc.	Binding domain-immunoglobulin fusion proteins
US7829084B2 (en) *	2001-01-17	2010-11-09	Trubion Pharmaceuticals, Inc.	Binding constructs and methods for use thereof
IL149462A0 (en) *	2001-05-09	2002-11-10	Warner Lambert Co	Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor
US6689782B2 (en)	2001-07-16	2004-02-10	Essential Therapeutics, Inc.	Fungal efflux pump inhibitors
WO2003027321A2 (en) *	2001-09-24	2003-04-03	University Of Aarhus	Methods for diagnosis and treatment of diseases associated with altered expression of neurogranin
WO2003035048A2 (en) *	2001-10-26	2003-05-01	Novartis Ag	Methods for the treatment of osteoarthritis and compositions thereof
AU2002363429B2 (en) *	2001-11-07	2008-05-08	Merck & Co., Inc.	Mitotic kinesin inhibitors
AU2003213092A1 (en)	2002-02-15	2003-09-09	Smithkline Beecham Corporation	Syntheses of quinazolinones
AR038703A1 (es)	2002-02-28	2005-01-26	Novartis Ag	Derivados de 5-feniltiazol y uso como inhibidor de quinasa p i 3
US7381730B2 (en) *	2002-03-15	2008-06-03	Bristol-Myers Squibb Company	3-arylquinazoline derivatives as selective estrogen receptor beta modulators
US6900219B2 (en)	2002-04-04	2005-05-31	Cv Therapeutics, Inc.	ABCA-1 elevating compounds
JP2005530785A (ja) *	2002-05-09	2005-10-13	サイトキネティクス・インコーポレーテッド	化合物、組成物、及び方法
EP1503993A4 (en) *	2002-05-09	2006-05-03	Cytokinetics Inc	COMPOUNDS, METHODS AND COMPOSITIONS
EP1513820A4 (en)	2002-05-23	2006-09-13	Cytokinetics Inc	COMPOUNDS, COMPOSITIONS AND METHODS
EP1556357A4 (en)	2002-06-14	2006-09-13	Cytokinetics Inc	COMPOUNDS, COMPOSITIONS AND METHODS
US7943594B2 (en) *	2002-07-10	2011-05-17	Massachusetts Institute Of Technology	Solid-phase and solution-phase synthesis of glycosylphosphatidylinositol glycans
US7211580B2 (en) *	2002-07-23	2007-05-01	Cytokinetics, Incorporated	Compounds, compositions, and methods
AU2003262747A1 (en) *	2002-08-21	2004-03-11	Cytokinetics, Inc.	Compounds, compositions, and methods
AU2003293310B2 (en)	2002-09-30	2010-04-01	Bayer Intellectual Property Gmbh	Fused azole-pyrimidine derivatives
JP2006501306A (ja) *	2002-09-30	2006-01-12	サイトキネティクス・インコーポレーテッド	化合物、組成物および方法
US20040132732A1 (en) *	2002-10-21	2004-07-08	Wei Han	Quinazolinones and derivatives thereof as factor Xa inhibitors
JP2006510661A (ja) *	2002-12-06	2006-03-30	ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー	Ｐｉ３ｋの阻害剤としてのベンズオキサジン−３−オン類及びその誘導体
AU2003303231A1 (en) *	2002-12-20	2004-07-14	Warner-Lambert Company Llc	Benzoxazines and derivatives thereof as inhibitors of pi3ks
CA2518465A1 (en) *	2003-03-25	2004-10-14	Takeda San Diego, Inc.	Dipeptidyl peptidase inhibitors
US7429596B2 (en) *	2003-06-20	2008-09-30	The Regents Of The University Of California	1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof
EP1660486A4 (en)	2003-08-08	2006-12-13	Ulysses Pharmaceutical Product	HALOGENATED CHINAZOLINYL NITROFURANES AS ANTIBACTERIAL AGENTS
KR20060041309A (ko)	2003-08-13	2006-05-11	다케다 야쿠힌 고교 가부시키가이샤	４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도
US20050043239A1 (en) *	2003-08-14	2005-02-24	Jason Douangpanya	Methods of inhibiting immune responses stimulated by an endogenous factor
US20050054614A1 (en) *	2003-08-14	2005-03-10	Diacovo Thomas G.	Methods of inhibiting leukocyte accumulation
JP2007505121A (ja) *	2003-09-08	2007-03-08	武田薬品工業株式会社	ジペプチジルぺプチダーゼ阻害剤
WO2005030751A2 (en) *	2003-09-08	2005-04-07	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
NZ546611A (en)	2003-09-18	2010-02-26	Conforma Therapeutics Corp	Novel heterocyclic compounds as HSP90-inhibitors
WO2005041888A2 (en) *	2003-11-03	2005-05-12	Cytokinetics, Inc.	Pyrimidin-4-one compounds, compositions and methods
JP2007513154A (ja)	2003-12-08	2007-05-24	サイトキネティクス・インコーポレーテッド	化合物、組成物及び方法
CA2552664A1 (en) *	2004-01-08	2005-07-28	Michigan State University	Methods for treating and preventing hypertension and hypertension-related disorders
UA83416C2 (en) *	2004-02-13	2008-07-10	Баниу Фармасьютикал Ко., Лтд.	Fused ring 4-oxopyrimidine derivative
EP1724271A4 (en) *	2004-02-26	2013-01-23	Kyowa Hakko Kirin Co Ltd	PREVENTIVE AND / OR THERAPEUTIC AGENT AGAINST NEUTROPHIC INFLAMMATORY DISEASE
EA013427B1 (ru) *	2004-03-15	2010-04-30	Такеда Фармасьютикал Компани Лимитед	Ингибиторы дипептидилпептидазы
WO2005095360A1 (en)	2004-04-02	2005-10-13	Prana Biotechnology Limited	Neurologically-active compounds
AU2005239874A1 (en) *	2004-05-06	2005-11-17	Cancer Research Technology Limited	Compounds and compositions for treatment of cancer
WO2005112935A1 (en) *	2004-05-13	2005-12-01	Vanderbilt University	Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis
EP1761540B1 (en)	2004-05-13	2016-09-28	Icos Corporation	Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
CA2567883A1 (en) *	2004-05-25	2005-12-15	Icos Corporation	Methods for treating and/or preventing aberrant proliferation of hematopoietic cells
WO2005120511A1 (en) *	2004-06-04	2005-12-22	Icos Corporation	Methods for treating mast cell disorders
KR101300546B1 (ko) *	2004-08-24	2013-09-02	추가이 세이야쿠 가부시키가이샤	항 글리피칸 3 항체를 이용한 어쥬번트 요법
US20060079573A1 (en) *	2004-10-10	2006-04-13	Jakob Vinten-Johansen	Methods and compositions for preventing vasospasm
EP1831225A2 (en) *	2004-11-19	2007-09-12	The Regents of the University of California	Anti-inflammatory pyrazolopyrimidines
EP1828192B1 (en)	2004-12-21	2014-12-03	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
WO2006089106A2 (en) *	2005-02-17	2006-08-24	Icos Corporation	Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation
BRPI0609509A2 (pt)	2005-03-30	2010-04-13	Conforma Therapeutics Corp	composto ou um polimorfo, solvato, tautÈmero, enanciÈmero, pró-droga ou sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, uso do composto, polimorfo, solvato, tautÈmero, enanciÈmero, pró-droga ou sal farmaceuticamente aceitável
EP1903040A4 (en) *	2005-07-05	2010-08-04	Banyu Pharma Co Ltd	PROCESS FOR THE PREPARATION OF A 4 (3H) -CHINAZOLINONE DERIVATIVE
EP2295080A3 (en)	2005-07-25	2011-06-22	Emergent Product Development Seattle, LLC	B-cell reduction using CD37-specific and CD20-specific binding molecules
NZ565749A (en) *	2005-08-26	2010-12-24	Serono Lab	Pyrazine derivatives and use as PI3K inhibitors
US20070060529A1 (en) *	2005-09-14	2007-03-15	Christopher Ronald J	Administration of dipeptidyl peptidase inhibitors
AU2006290205B2 (en)	2005-09-14	2012-12-13	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors for treating diabetes
EP2073810B1 (en) *	2006-09-13	2011-08-31	Takeda Pharmaceutical Company Limited	Use of 2-6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethyl-4-fluoro-benzonitrile for treating diabetes, cancer, autoimmune disorders and hiv infection
CA2622642C (en) *	2005-09-16	2013-12-31	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
US20070087005A1 (en)	2005-10-14	2007-04-19	Lazar Gregory A	Anti-glypican-3 antibody
AU2006313701B2 (en)	2005-11-11	2012-05-31	Aeterna Zentaris Gmbh	Novel pyridopyrazines and their use as modulators of kinases
US8217042B2 (en)	2005-11-11	2012-07-10	Zentaris Gmbh	Pyridopyrazines and their use as modulators of kinases
EP1790342A1 (de)	2005-11-11	2007-05-30	Zentaris GmbH	Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege
CN103214484B (zh)	2005-12-13	2016-07-06	因塞特控股公司	作为两面神激酶抑制剂的杂芳基取代的吡咯并[2,3-b]吡啶和吡咯并[2,3-b]嘧啶
US20100029941A1 (en) *	2006-03-28	2010-02-04	Takeda Pharmaceutical Company Limited	Preparation of (r)-3-aminopiperidine dihydrochloride
EA200870409A1 (ru) *	2006-04-04	2009-04-28	Дзе Риджентс Оф Дзе Юниверсити Оф Калифорния	Антагонисты киназы pi3
GB0610242D0 (en)	2006-05-23	2006-07-05	Novartis Ag	Organic compounds
CN105837690A (zh) *	2006-06-12	2016-08-10	新兴产品开发西雅图有限公司	具有效应功能的单链多价结合蛋白
JP5193866B2 (ja) *	2006-08-08	2013-05-08	あすか製薬株式会社	キナゾリン誘導体
US8324383B2 (en)	2006-09-13	2012-12-04	Takeda Pharmaceutical Company Limited	Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
CA2663436A1 (en) *	2006-10-04	2008-04-10	Pfizer Products Inc.	Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists
KR20090075714A (ko)	2006-10-30	2009-07-08	노파르티스 아게	소염제로서의 헤테로시클릭 화합물
JP5313909B2 (ja)	2006-11-13	2013-10-09	アイコスコーポレイション	炎症性疾患および癌の処置のためのチエノピリミジノン
TW200838536A (en) *	2006-11-29	2008-10-01	Takeda Pharmaceutical	Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
US8093236B2 (en)	2007-03-13	2012-01-10	Takeda Pharmaceuticals Company Limited	Weekly administration of dipeptidyl peptidase inhibitors
HUE029236T2 (en)	2007-06-13	2017-02-28	Incyte Holdings Corp	(R) -3- (4- (7H-Pyrrolo [2,3-d] pyrimidin-4-yl) -1H-pyrazol-1-yl) -3-cyclopentylpropanenitrile Crystalline salts of Janus kinase inhibitor
UY31137A1 (es) *	2007-06-14	2009-01-05	Smithkline Beecham Corp	Derivados de quinazolina como inhibidores de la pi3 quinasa
GB2467670B (en) *	2007-10-04	2012-08-01	Intellikine Inc	Chemical entities and therapeutic uses thereof
WO2009058361A1 (en) *	2007-10-31	2009-05-07	Dynavax Technologies Corp.	Inhibition of type i ifn production
GEP20125635B (en) *	2007-11-13	2012-09-10	Icos Corp	Inhibitors of human phosphatidyl-inositol 3-kinase delta
CA2711558C (en)	2008-01-04	2016-12-13	Intellikine, Inc.	Phosphatidyl inositol-3 kinase inhibiting compounds
RU2513636C2 (ru) *	2008-01-04	2014-04-20	Интелликайн ЭлЭлСи	Некоторые химические структуры, композиции и способы
US8193182B2 (en)	2008-01-04	2012-06-05	Intellikine, Inc.	Substituted isoquinolin-1(2H)-ones, and methods of use thereof
JP5547099B2 (ja)	2008-03-14	2014-07-09	インテリカイン，エルエルシー	キナーゼ阻害剤および使用方法
US8993580B2 (en)	2008-03-14	2015-03-31	Intellikine Llc	Benzothiazole kinase inhibitors and methods of use
PT2132228E (pt)	2008-04-11	2011-10-11	Emergent Product Dev Seattle	Imunoterapia de cd37 e sua combinação com um quimioterápico bifuncional
US10517839B2 (en) *	2008-06-09	2019-12-31	Cornell University	Mast cell inhibition in diseases of the retina and vitreous
AU2009268611B2 (en)	2008-07-08	2015-04-09	Intellikine, Llc	Kinase inhibitors and methods of use
WO2010006072A2 (en)	2008-07-08	2010-01-14	The Regents Of The University Of California	Mtor modulators and uses thereof
JP5731978B2 (ja)	2008-09-26	2015-06-10	インテリカイン，エルエルシー	複素環キナーゼ阻害剤
CA2740885C (en)	2008-10-16	2018-04-03	The Regents Of The University Of California	Fused ring heteroaryl kinase inhibitors
US8476282B2 (en)	2008-11-03	2013-07-02	Intellikine Llc	Benzoxazole kinase inhibitors and methods of use
WO2010057047A1 (en) *	2008-11-13	2010-05-20	Trubion Pharmaceutics, Inc.	Cd37 immunotherapeutic combination therapies and uses thereof
US9492449B2 (en)	2008-11-13	2016-11-15	Gilead Calistoga Llc	Therapies for hematologic malignancies
KR20160091440A (ko)	2008-11-13	2016-08-02	길리아드 칼리스토가 엘엘씨	혈액 종양에 대한 요법
EP2365810A2 (en) *	2008-12-04	2011-09-21	The U.S.A. As Represented By The Secretary, Department Of Health And Human Services	Phosphatidylinositol-3-kinase p110 delta-targeted drugs in the treatment of cns disorders
WO2010092962A1 (ja)	2009-02-12	2010-08-19	アステラス製薬株式会社	へテロ環誘導体
CA2756347A1 (en)	2009-03-24	2010-09-30	Gilead Calistoga Llc	Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use
AU2010229468A1 (en)	2009-03-27	2011-10-13	Vetdc, Inc.	Pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy
WO2010110686A1 (en)	2009-03-27	2010-09-30	Pathway Therapeutics Limited	Pyrimidinyl and 1,3,5 triazinyl benzimidazoles and their use in cancer therapy
SG175259A1 (en) *	2009-04-20	2011-11-28	Gilead Calistoga Llc	Methods of treatment for solid tumors
EP2427195B1 (en)	2009-05-07	2019-05-01	Intellikine, LLC	Heterocyclic compounds and uses thereof
EP2445898A2 (en) *	2009-06-25	2012-05-02	Amgen, Inc	4h-pyrido[1,2-a]pyrimidin-4-one derivatives as pi3k inhibitors
US8486939B2 (en)	2009-07-07	2013-07-16	Pathway Therapeutics Inc.	Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy
AU2010276160A1 (en)	2009-07-21	2012-02-09	Gilead Calistoga Llc	Treatment of liver disorders with PI3K inhibitors
MY162604A (en)	2009-08-17	2017-06-30	Intellikine Llc	Heterocyclic compounds and uses thereof
WO2011047384A2 (en)	2009-10-16	2011-04-21	The Regents Of The University Of California	Methods of inhibiting ire1
GB0918249D0 (en)	2009-10-19	2009-12-02	Respivert Ltd	Compounds
WO2011049625A1 (en)	2009-10-20	2011-04-28	Mansour Samadpour	Method for aflatoxin screening of products
SG10201500895XA (en)	2009-11-05	2015-04-29	Rhizen Pharmaceuticals Sa	Chromen-4-one Derivatives As Kinase Modulators
EP3354652B1 (en)	2010-03-10	2020-05-06	Incyte Holdings Corporation	Piperidin-4-yl azetidine derivatives as jak1 inhibitors
AU2011255218B2 (en)	2010-05-21	2015-03-12	Infinity Pharmaceuticals, Inc.	Chemical compounds, compositions and methods for kinase modulation
AR084691A1 (es)	2010-05-21	2013-06-05	Incyte Corp	Formulacion de uso topico para un inhibidor de jak y metodo para tratar trastorno de la piel
EP3399026B1 (en)	2010-06-14	2024-06-26	The Scripps Research Institute	Reprogramming of cells to a new fate
EP2604601B1 (en)	2010-08-10	2016-02-24	Astellas Pharma Inc.	Hetero ring compound
RU2013114710A (ru)	2010-09-03	2014-10-10	Байер Интеллектуэль Проперти Гмбх	Замещенные конденсированные пиримидиноны и дигидропиримидиноны
EP2619209A1 (en)	2010-09-24	2013-07-31	Gilead Calistoga LLC	Atropisomers of pi3k-inhibiting compounds
WO2012044641A1 (en)	2010-09-29	2012-04-05	Pathway Therapeutics Inc.	1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy
UY33337A (es)	2010-10-18	2011-10-31	Respivert Ltd	DERIVADOS SUSTITUIDOS DE 1H-PIRAZOL[ 3,4-d]PIRIMIDINA COMO INHIBIDORES DE LAS FOSFOINOSITIDA 3-QUINASAS
JP2013545749A (ja)	2010-11-10	2013-12-26	インフィニティーファーマシューティカルズ，インコーポレイテッド	複素環化合物及びその使用
CA2818542A1 (en)	2010-11-19	2012-05-24	Incyte Corporation	Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
AU2012205669B2 (en)	2011-01-10	2015-08-20	Infinity Pharmaceuticals Inc.	Processes for preparing isoquinolinones and solid forms of isoquinolinones
EP2678016B1 (en)	2011-02-23	2016-08-10	Intellikine, LLC	Heterocyclic compounds and uses thereof
JP6130305B2 (ja)	2011-02-23	2017-05-17	インテリカイン，エルエルシー	キナーゼ阻害剤の組み合わせおよびそれらの使用
US20140213630A1 (en)	2011-03-08	2014-07-31	Thomas Diacovo	Methods and pharmaceutical compositions for treating lymphoid malignancy
EP2691384B1 (en)	2011-03-28	2016-10-26	MEI Pharma, Inc.	(alpha-substituted aralkylamino and heteroarylalkylamino) pyrimidinyl and 1,3,5-triazinyl benzimidazoles, pharmaceutical compositions containing them, and these compounds for use in treating proliferative diseases
CN102731525A (zh) *	2011-04-08	2012-10-17	上海艾力斯医药科技有限公司	苯并吗啉衍生物
EP2518070A1 (en)	2011-04-29	2012-10-31	Almirall, S.A.	Pyrrolotriazinone derivatives as PI3K inhibitors
RS58326B1 (sr)	2011-05-04	2019-03-29	Rhizen Pharmaceuticals S A	Nova jedinjenja kao modulatori proteinskih kinaza
MY165963A (en)	2011-06-20	2018-05-18	Incyte Holdings Corp	Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
JP6027610B2 (ja)	2011-07-19	2016-11-16	インフィニティーファーマシューティカルズ，インコーポレイテッド	複素環式化合物及びその使用
US9056877B2 (en)	2011-07-19	2015-06-16	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
EP2751093A1 (en)	2011-08-29	2014-07-09	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
MX370814B (es)	2011-09-02	2020-01-08	Univ California	Pirazolo[3,4-d]pirimidinas sustituidas y usos de las mismas.
EA025407B1 (ru)	2012-03-05	2016-12-30	Джилид Калистога Ллс	Полиморфная форма i (s)-2-(1-(9h-пурин-6-иламино)пропил)-5-фтор-3-фенилхиназолин-4(3h)-она
US8940742B2 (en)	2012-04-10	2015-01-27	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US8828998B2 (en)	2012-06-25	2014-09-09	Infinity Pharmaceuticals, Inc.	Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors
CN109970742A (zh)	2012-07-04	2019-07-05	理森制药股份公司	选择性PI3Kδ抑制剂
UY34893A (es)	2012-07-10	2014-02-28	Takeda Pharmaceutical	Derivados de azaindol
SG10202003090VA (en) *	2012-08-08	2020-05-28	Kbp Biosciences Co Ltd	PI3K δ INHIBITOR
MX2015003874A (es)	2012-09-26	2015-12-16	Univ California	Modulacion de ire1.
EA027277B1 (ru) *	2012-10-16	2017-07-31	Альмираль, С.А.	Производные пирроллотриазинона в качестве ингибиторов pi3k
KR102229478B1 (ko)	2012-11-01	2021-03-18	인피니티 파마슈티칼스, 인코포레이티드	Pi3 키나아제 동형단백질 조절인자를 사용하는 암의 치료
WO2014072937A1 (en)	2012-11-08	2014-05-15	Rhizen Pharmaceuticals Sa	Pharmaceutical compositions containing a pde4 inhibitor and a pi3 delta or dual pi3 delta-gamma kinase inhibitor
TWI761825B (zh)	2012-11-15	2022-04-21	美商英塞特控股公司	盧梭利替尼之緩釋性劑型
MX2015006191A (es) *	2012-11-16	2015-08-10	Merck Sharp & Dohme	Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana.
TW201441216A (zh)	2012-12-21	2014-11-01	Gilead Calistoga Llc	肌醇磷酯３－激酶的抑制劑
AU2013364070B2 (en)	2012-12-21	2016-10-27	Gilead Calistoga Llc	Isoquinolinone or quinazolinone phosphatidylinositol 3-kinase inhibitors
MX384910B (es)	2013-03-06	2025-03-14	Incyte Holdings Corp	Procesos e intermedios para hacer un inhibidor de jak.
AR095353A1 (es)	2013-03-15	2015-10-07	Respivert Ltd	Compuesto
JO3279B1 (ar)	2013-03-15	2018-09-16	Respivert Ltd	مشتقات 2-((4- امينو -3- (3- فلورو-5- هيدروكسي فينيل)-h1- بيرازولو [d-3,4] بيرمدين-1-يل )ميثيل )- 3- (2- تراي فلورو ميثيل ) بينزيل ) كوينازولين -4 (h3)- واحد واستخدامها كمثبطات فوسفواينوسيتايد 3- كاينيز
US9481667B2 (en)	2013-03-15	2016-11-01	Infinity Pharmaceuticals, Inc.	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
US20160024051A1 (en)	2013-03-15	2016-01-28	Infinity Pharmaceuticals, Inc.	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
TR201806822T4 (tr)	2013-06-14	2018-06-21	Gilead Calistoga Llc	Fosfatidilinositol 3-kinaz inhibitörleri.
CA2915418C (en)	2013-07-02	2022-05-03	Rhizen Pharmaceuticals Sa	Novel selective pi3k delta and/or gamma protein kinase inhibitors
UY35675A (es)	2013-07-24	2015-02-27	Novartis Ag	Derivados sustituidos de quinazolin-4-ona
SG11201600815WA (en)	2013-08-07	2016-03-30	Incyte Corp	Sustained release dosage forms for a jak1 inhibitor
EP3046921A4 (en)	2013-09-22	2017-02-22	Calitor Sciences, LLC	Substituted aminopyrimidine compounds and methods of use
US9751888B2 (en)	2013-10-04	2017-09-05	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
PE20160685A1 (es)	2013-10-04	2016-07-23	Infinity Pharmaceuticals Inc	Compuestos heterociclicos y usos de los mismos
US20150105383A1 (en)	2013-10-10	2015-04-16	Acetylon Pharmaceuticals, Inc.	HDAC Inhibitors, Alone Or In Combination With PI3K Inhibitors, For Treating Non-Hodgkin's Lymphoma
WO2015061204A1 (en)	2013-10-21	2015-04-30	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
WO2015095605A1 (en)	2013-12-20	2015-06-25	Gilead Calistoga Llc	Polymorphic forms of a hydrochloride salt of (s) -2-(9h-purin-6-ylamino) propyl) -5-fluoro-3-phenylquinazolin-4 (3h) -one
NZ720867A (en)	2013-12-20	2018-01-26	Gilead Calistoga Llc	Process methods for phosphatidylinositol 3-kinase inhibitors
AR099052A1 (es)	2014-01-09	2016-06-29	Takeda Pharmaceuticals Co	Derivados de azaindol
WO2015106014A1 (en)	2014-01-09	2015-07-16	Takeda Pharmaceutical Company Limited	Azaindole derivatives
SG10201808053XA (en)	2014-03-19	2018-10-30	Infinity Pharmaceuticals Inc	Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders
US20150320755A1 (en)	2014-04-16	2015-11-12	Infinity Pharmaceuticals, Inc.	Combination therapies
WO2015168079A1 (en)	2014-04-29	2015-11-05	Infinity Pharmaceuticals, Inc.	Pyrimidine or pyridine derivatives useful as pi3k inhibitors
WO2015181728A1 (en)	2014-05-27	2015-12-03	Rhizen Pharmaceuticals Sa	Improved forms of a pi3k delta selective inhibitor for use in pharmaceutical formulations
CA2952044C (en)	2014-06-13	2019-01-29	Gilead Sciences, Inc.	Phosphatidylinositol 3-kinase inhibitors
NZ726052A (en)	2014-06-13	2018-04-27	Gilead Sciences Inc	Phosphatidylinositol 3-kinase inhibitors
JP6455995B2 (ja)	2014-06-13	2019-01-23	ギリアードサイエンシーズ，インコーポレイテッド	ホスファチジルイノシトール３−キナーゼ阻害剤
US10308639B2 (en)	2014-06-13	2019-06-04	Gilead Sciences, Inc.	Phosphatidylinositol 3-kinase inhibitors
AU2015274635B2 (en) *	2014-06-13	2018-04-19	Gilead Sciences, Inc.	Phosphatidylinositol 3-kinase inhibitors
CN106459008A (zh)	2014-06-24	2017-02-22	吉利德科学公司	磷脂酰肌醇3‑激酶抑制剂
SG11201610770PA (en)	2014-07-04	2017-01-27	Lupin Ltd	Quinolizinone derivatives as pi3k inhibitors
US9708348B2 (en)	2014-10-03	2017-07-18	Infinity Pharmaceuticals, Inc.	Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof
HK1255034A1 (zh)	2015-07-01	2019-08-02	Crinetics Pharmaceuticals, Inc.	生长抑素调节剂及其用途
WO2017002934A1 (ja)	2015-07-01	2017-01-05	中外製薬株式会社	Ｇｐｃ３標的治療剤が有効である患者に投与されるｇｐｃ３標的治療剤
TWI649326B (zh)	2015-07-02	2019-02-01	瑞士商赫孚孟拉羅股份公司	苯并氧氮呯噁唑啶酮化合物及其製備方法
CN111848643A (zh)	2015-07-02	2020-10-30	豪夫迈·罗氏有限公司	苯并氧氮杂*噁唑烷酮化合物及其使用方法
MX392561B (es)	2015-08-21	2025-03-24	Morphosys Ag	Combinación sinérgica de un anticuerpo anti-cd19 y un inhibidor de fosfoinositida 3-quinasa para usarse en el tratamiento de linfoma no hodgkin, leucemia linfocítica crónica y/o leucemia linfoblástica aguda.
US10160761B2 (en)	2015-09-14	2018-12-25	Infinity Pharmaceuticals, Inc.	Solid forms of isoquinolinones, and process of making, composition comprising, and methods of using the same
KR102784293B1 (ko)	2015-09-21	2025-03-20	압테보 리서치 앤드 디벨롭먼트 엘엘씨	Cd3 결합 폴리펩타이드
WO2017103825A1 (en)	2015-12-18	2017-06-22	Lupin Limited	Quinolizinone derivatives as pi3k inhibitors
WO2017161116A1 (en)	2016-03-17	2017-09-21	Infinity Pharmaceuticals, Inc.	Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors
US10919914B2 (en)	2016-06-08	2021-02-16	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
MX391135B (es)	2016-06-24	2025-03-21	Infinity Pharmaceuticals Inc	Terapias de combinacion.
EP3272348A1 (en)	2016-07-21	2018-01-24	LEK Pharmaceuticals d.d.	Pharmaceutical composition comprising idelalisib
TW201825465A (zh)	2016-09-23	2018-07-16	美商基利科學股份有限公司	磷脂醯肌醇3-激酶抑制劑
TW201813963A (zh)	2016-09-23	2018-04-16	美商基利科學股份有限公司	磷脂醯肌醇3-激酶抑制劑
TW201815787A (zh)	2016-09-23	2018-05-01	美商基利科學股份有限公司	磷脂醯肌醇3-激酶抑制劑
WO2018057808A1 (en)	2016-09-23	2018-03-29	Gilead Sciences, Inc.	Benzimidazole derivatives and their use as phosphatidylinositol 3-kinase inhibitors
CN108239074B (zh) *	2016-12-26	2021-07-06	中国医学科学院药物研究所	喹唑啉类化合物及其制备方法、用途和药物组合物
AU2017389818B2 (en) *	2016-12-26	2022-04-07	Institute Of Materia Medica, Chinese Academy Of Medical Sciences	Quinazoline compound and preparation method, application, and pharmaceutical compostion thereof
EP3573619A4 (en)	2017-01-27	2020-10-28	SignalRX Pharmaceuticals, Inc.	THIENOPYRANONES AND FURANOPYRANONES AS KINASE, BROMODOMAIN AND CHECKPOINT INHIBITORS
EP3658560A4 (en)	2017-07-25	2021-01-06	Crinetics Pharmaceuticals, Inc.	SOMATOSTAT IN MODULATORS AND USES THEREOF
AU2018309739B2 (en) *	2017-07-31	2022-01-27	The Trustees Of Columbia University In The City Of New York	Compounds, Compositions, and Methods for Treating T-cell Acute Lymphoblastic Leukemia
WO2019036489A1 (en)	2017-08-14	2019-02-21	Mei Pharma, Inc.	COMBINATION THERAPY
US10596161B2 (en)	2017-12-08	2020-03-24	Incyte Corporation	Low dose combination therapy for treatment of myeloproliferative neoplasms
JP7393348B2 (ja)	2018-01-30	2023-12-06	インサイト・コーポレイション	（１－（３－フルオロ－２（トリフルオロメチル）イソニコチニル）ピぺリジン―４－オン）を作製するためのプロセス及び中間体
WO2019178596A1 (en)	2018-03-16	2019-09-19	Johnson Matthey Public Limited Company	Pyridine or n,n-dimethyl acetamide solvated solid state forms of solvated idelalisib, their use and preparation
CN113768934A (zh)	2018-03-30	2021-12-10	因赛特公司	使用jak抑制剂治疗化脓性汗腺炎
US20220112217A1 (en) *	2018-08-21	2022-04-14	Medshine Discovery Inc.	Pyrazolopyrimidine derivative and use thereof as pi3k inhibitor
EP3870173A4 (en)	2018-10-24	2022-06-22	Vanderbilt University	WDR5 INHIBITORS AND MODULATORS
CA3118493A1 (en)	2018-11-05	2020-05-14	Iovance Biotherapeutics, Inc.	Expansion of tils utilizing akt pathway inhibitors
CN111269231B (zh)	2018-12-04	2023-06-09	安徽中科拓苒药物科学研究有限公司	一种选择性PI3Kδ抑制剂及其用途
WO2020201073A1 (en) *	2019-03-29	2020-10-08	INSERM (Institut National de la Santé et de la Recherche Médicale)	Methods for the treatment of keloid, hypertrophic scars and/or hyperpigmentation disorders
US12577227B2 (en)	2019-06-04	2026-03-17	Vanderbilt University	WDR5 inhibitors and modulators
US11833155B2 (en)	2020-06-03	2023-12-05	Incyte Corporation	Combination therapy for treatment of myeloproliferative neoplasms
CN112830927A (zh) *	2021-03-04	2021-05-25	山西科灜科技有限公司	一种嘌呤喹唑啉酮衍生物及其制备方法

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1249281B (sr)	1963-05-18
DE2027645A1 (de) *	1970-06-05	1971-12-09	Byk Gulden Lomberg Chemische Fa bnk GmbH, 7750 Konstanz	Piperazinylalkyl chinazolon (4) den vate, Verfahren zu deren Herstellung und sie enthaltende Arzneimittel
DE2644265C2 (de) *	1976-09-30	1983-02-10	Bayer Ag, 5090 Leverkusen	Chinazoline
US4183931A (en)	1977-09-08	1980-01-15	Research Corporation	2-Ketoalkyl-4(3H)-quinazolinones
JPS55118918A (en) *	1979-03-06	1980-09-12	Mitsubishi Electric Corp	Production of quinazolone ring-containing epoxy resin
JPS55118917A (en) *	1979-03-06	1980-09-12	Mitsubishi Electric Corp	Production of quinazolone ring-containing epoxy resin
JPS6017375B2 (ja) *	1979-06-20	1985-05-02	三菱電機株式会社	ポリアミド樹脂の製造方法
US4703004A (en)	1984-01-24	1987-10-27	Immunex Corporation	Synthesis of protein with an identification peptide
US4782137A (en)	1984-01-24	1988-11-01	Immunex Corporation	Synthesis of protein with an identification peptide, and hybrid polypeptide incorporating same
US4851341A (en)	1986-12-19	1989-07-25	Immunex Corporation	Immunoaffinity purification system
US5011912A (en)	1986-12-19	1991-04-30	Immunex Corporation	Hybridoma and monoclonal antibody for use in an immunoaffinity purification system
GB9301000D0 (en) *	1993-01-20	1993-03-10	Glaxo Group Ltd	Chemical compounds
GB9404485D0 (en) *	1994-03-09	1994-04-20	Cancer Res Campaign Tech	Benzamide analogues
FI951367A7 (fi) *	1994-03-28	1995-09-29	Japan Energy Corp	Puriinijohdannaiset ja tulehdustautien tukahduttajat (suppressantit)
US5480906A (en)	1994-07-01	1996-01-02	Eli Lilly And Company	Stereochemical Wortmannin derivatives
FI970588L (fi) *	1994-08-12	1997-04-11	Pro Neuron Inc	Menetelmät verenmyrkytyksen tai tulehdussairauksien hoitamiseksi oksipuriininukleosideillä
US6043062A (en)	1995-02-17	2000-03-28	The Regents Of The University Of California	Constitutively active phosphatidylinositol 3-kinase and uses thereof
GB9611460D0 (en)	1996-06-01	1996-08-07	Ludwig Inst Cancer Res	Novel lipid kinase
US5858753A (en)	1996-11-25	1999-01-12	Icos Corporation	Lipid kinase
DE69723869T2 (de) *	1996-12-31	2004-04-22	Dr. Reddy's Laboratories Ltd.	Heterozyklische verbindungen, verfahren zu ihrer herstellung, pharmazeutische zusammensetzungen die diese enthalten und ihre anwendung in der behandlung von diabetis und verwandten krankheiten
GB9702701D0 (en) *	1997-02-01	1997-04-02	Univ Newcastle Ventures Ltd	Quinazolinone compounds
ID22711A (id) *	1997-02-28	1999-12-09	Pfizer Prod Inc	Atropisomer dari 3-aril-4(3h)-kinazolinon dan penggunaannya sebagai antagonis reseptor-ampa
IL125950A0 (en) *	1997-09-05	1999-04-11	Pfizer Prod Inc	Methods of administering ampa receptor antagonists to treat dyskinesias associated with dopamine agonist therapy
US5822910A (en)	1997-10-02	1998-10-20	Shewmake; I. W.	Fishing line tensioning device
EP1044004A1 (en)	1998-01-08	2000-10-18	The University Of Virginia Patent Foundation	A2a adenosine receptor agonists in combination with a type iv phosphodiesterase inhibitors
WO1999008501A2 (en)	1998-04-23	1999-02-25	Dr. Reddy's Research Foundation	New heterocyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them
US6100090A (en)	1999-06-25	2000-08-08	Isis Pharmaceuticals Inc.	Antisense inhibition of PI3K p85 expression
US6046049A (en)	1999-07-19	2000-04-04	Isis Pharmaceuticals Inc.	Antisense modulation of PI3 kinase p110 delta expression
EP1857443B1 (en)	2000-01-24	2012-03-28	AstraZeneca AB	Therapeutic morpholino-substituted compounds
AU2972701A (en)	2000-02-07	2001-08-14	Bristol Myers Squibb Co	3-aminopyrazole inhibitors of cyclin dependent kinases

2001
- 2001-04-24 DK DK10163434.3T patent/DK2223922T3/en active
- 2001-04-24 AU AU5566701A patent/AU5566701A/xx active Pending
- 2001-04-24 JP JP2001578436A patent/JP4642309B2/ja not_active Expired - Lifetime
- 2001-04-24 GE GEAP20024978A patent/GEP20084317B/en unknown
- 2001-04-24 CN CN01811654XA patent/CN1440408B/zh not_active Expired - Lifetime
- 2001-04-24 PT PT80064579T patent/PT1939203E/pt unknown
- 2001-04-24 EA EA200200990A patent/EA008241B1/ru not_active IP Right Cessation
- 2001-04-24 PT PT152009924T patent/PT3029041T/pt unknown
- 2001-04-24 CA CA2406278A patent/CA2406278C/en not_active Expired - Lifetime
- 2001-04-24 DK DK08006457.9T patent/DK1939203T3/en active
- 2001-04-24 WO PCT/US2001/013315 patent/WO2001081346A2/en not_active Ceased
- 2001-04-24 EP EP10163434.3A patent/EP2223922B1/en not_active Expired - Lifetime
- 2001-04-24 PT PT01928855T patent/PT1278748E/pt unknown
- 2001-04-24 SI SI200131048T patent/SI2223922T1/sl unknown
- 2001-04-24 SI SI200131072T patent/SI3029041T1/sl unknown
- 2001-04-24 MX MXPA02010618A patent/MXPA02010618A/es active IP Right Grant
- 2001-04-24 EP EP15200992.4A patent/EP3029041B1/en not_active Expired - Lifetime
- 2001-04-24 HR HRP20020838 patent/HRP20020838A2/hr not_active IP Right Cessation
- 2001-04-24 ES ES10163434.3T patent/ES2567260T3/es not_active Expired - Lifetime
- 2001-04-24 DK DK01928855.4T patent/DK1278748T3/da active
- 2001-04-24 AU AU2001255667A patent/AU2001255667C1/en not_active Expired
- 2001-04-24 BR BRPI0110371A patent/BRPI0110371B8/pt not_active IP Right Cessation
- 2001-04-24 IL IL15227501A patent/IL152275A0/xx unknown
- 2001-04-24 ES ES15200992T patent/ES2788383T3/es not_active Expired - Lifetime
- 2001-04-24 EP EP01928855A patent/EP1278748B1/en not_active Expired - Lifetime
- 2001-04-24 AT AT01928855T patent/ATE502941T1/de active
- 2001-04-24 NZ NZ522076A patent/NZ522076A/en unknown
- 2001-04-24 US US09/841,341 patent/US6518277B1/en not_active Expired - Lifetime
- 2001-04-24 HU HU0300497A patent/HU230554B1/hu unknown
- 2001-04-24 DE DE60144277T patent/DE60144277D1/de not_active Expired - Lifetime
- 2001-04-24 ES ES08006457.9T patent/ES2527754T3/es not_active Expired - Lifetime
- 2001-04-24 RS YUP-804/02A patent/RS51458B/sr unknown
- 2001-04-24 KR KR1020027014346A patent/KR100785363B1/ko not_active Expired - Lifetime
2002
- 2002-10-21 IS IS6585A patent/IS2822B/is unknown
- 2002-10-24 NO NO20025104A patent/NO329136B1/no not_active IP Right Cessation
2003
- 2003-01-06 US US10/337,192 patent/US6800620B2/en not_active Expired - Lifetime
2010
- 2010-05-28 NO NO20100777A patent/NO20100777L/no not_active Application Discontinuation
2014
- 2014-03-06 IL IL231360A patent/IL231360A/en active IP Right Grant
2016
- 2016-04-14 IL IL245146A patent/IL245146A0/en unknown
- 2016-05-31 CY CY20161100475T patent/CY1117672T1/el unknown

Also Published As

Publication number	Publication date
DK2223922T3 (en)	2016-06-06
HRP20020838A2 (en)	2004-12-31
NO20100777L (no)	2002-12-10
IS6585A (is)	2002-10-21
EP2223922B1 (en)	2016-03-02
AU5566701A (en)	2001-11-07
ES2567260T3 (es)	2016-04-21
NO20025104D0 (no)	2002-10-24
SI2223922T1 (sl)	2016-04-29
CN1440408B (zh)	2012-07-18
GEP20084317B (en)	2008-02-25
WO2001081346A3 (en)	2002-03-21
DK1278748T3 (da)	2011-04-18
EP1278748B1 (en)	2011-03-23
IL152275A0 (en)	2003-05-29
EP1278748A2 (en)	2003-01-29
BRPI0110371B8 (pt)	2021-05-25
RS51458B (sr)	2011-04-30
KR20020093077A (ko)	2002-12-12
HK1053308A1 (en)	2003-10-17
WO2001081346A2 (en)	2001-11-01
BRPI0110371B1 (pt)	2016-09-27
PT1278748E (pt)	2011-03-31
US6800620B2 (en)	2004-10-05
CA2406278A1 (en)	2001-11-01
DK1939203T3 (en)	2015-02-23
IL231360A (en)	2016-04-21
CA2406278C (en)	2012-06-05
EA200200990A1 (ru)	2003-06-26
PT1939203E (pt)	2015-02-04
JP4642309B2 (ja)	2011-03-02
HUP0300497A3 (en)	2004-10-28
IL245146A0 (en)	2016-06-30
US20030195211A1 (en)	2003-10-16
DE60144277D1 (de)	2011-05-05
US6518277B1 (en)	2003-02-11
EA008241B1 (ru)	2007-04-27
HU230554B1 (hu)	2016-12-28
ATE502941T1 (de)	2011-04-15
EP2223922A2 (en)	2010-09-01
SI3029041T1 (sl)	2020-08-31
PT3029041T (pt)	2020-05-13
EP2223922A3 (en)	2011-04-27
EP3029041B1 (en)	2020-03-04
AU2001255667C1 (en)	2016-06-09
NZ522076A (en)	2005-08-26
CN1440408A (zh)	2003-09-03
KR100785363B1 (ko)	2007-12-18
BR0110371A (pt)	2003-06-17
CY1117672T1 (el)	2017-05-17
IS2822B (is)	2013-02-15
EP3029041A1 (en)	2016-06-08
HUP0300497A2 (hu)	2003-06-28
ES2788383T3 (es)	2020-10-21
MXPA02010618A (es)	2004-05-05
ES2527754T3 (es)	2015-01-29
IL231360A0 (en)	2014-04-30
HRP20020838B1 (sr)	2012-12-31
NO20025104L (no)	2002-12-10
AU2001255667B2 (en)	2006-03-02
JP2003531209A (ja)	2003-10-21
YU80402A (sh)	2005-09-19

Legal Events

Date	Code	Title	Description
2021-05-10	MK1K	Patent expired

Publication	Publication Date	Title
US10695349B2 (en)	2020-06-30	Inhibitors of human phosphatidylinositol 3-kinase delta
DK1939203T3 (en)	2015-02-23	INHIBITORS OF HUMAN phosphatidyl-inositol 3-kinase DELTA ISOFORM
AU2002323426A1 (en)	2003-07-03	Inhibitors of human phosphatidyl-inositol 3-kinase delta
AU2001255667A1 (en)	2002-01-24	Inhibitors of human phosphatidyl-inositol 3-kinase delta
EP1939203B1 (en)	2014-11-19	Inhibitors of human phosphatidyl-inositol 3-kinase delta isoform
HK1224674B (en)	2021-01-29	Inhibitors of human phosphatidyl-inositol 3-kinase delta
HK1224674A1 (en)	2017-08-25	Inhibitors of human phosphatidyl-inositol 3-kinase delta
PL213200B1 (pl)	2013-01-31	Selektywne inhibitory PI3Kδ, kompozycje je zawierajace oraz ich zastosowania medyczne
HK1053308B (en)	2011-08-05	Inhibitors of human phosphatidyl-inositol 3-kinase delta