SK5862003A3 - Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents - Google Patents

Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents Download PDF

Info

Publication number: SK5862003A3
Authority: SK; Slovakia
Prior art keywords: isothiazole; ureido; bromo; pyrrolidin; difluorobenzyloxy
Prior art date: 2000-11-28

Application number

SK586-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Thomas G Gant

Glenn Robert Williams

Original Assignee

Pfizer Prod Inc

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.)

2000-11-28

Filing date

2001-11-19

Publication date

2004-05-04

2001-11-19 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2004-05-04 Publication of SK5862003A3 publication Critical patent/SK5862003A3/sk

Links

150000003839 salts Chemical class 0.000 title claims abstract description 47
BEPMYBTTZSNHPS-UHFFFAOYSA-N 1,2-thiazole-4-carboxamide Chemical compound NC(=O)C=1C=NSC=1 BEPMYBTTZSNHPS-UHFFFAOYSA-N 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 33
206010028980 Neoplasm Diseases 0.000 claims abstract description 29
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 22
241000124008 Mammalia Species 0.000 claims abstract description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
HXHAJRMTJXHJJZ-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 HXHAJRMTJXHJJZ-UHFFFAOYSA-N 0.000 claims abstract description 14
230000003463 hyperproliferative effect Effects 0.000 claims abstract description 13
150000001875 compounds Chemical class 0.000 claims description 81
238000001228 spectrum Methods 0.000 claims description 67
238000000634 powder X-ray diffraction Methods 0.000 claims description 66
PJXPORIRXYJDLD-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylic acid Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)O)=C1NC(=O)NCCCCN1CCCC1 PJXPORIRXYJDLD-UHFFFAOYSA-N 0.000 claims description 22
210000004027 cell Anatomy 0.000 claims description 19
238000011282 treatment Methods 0.000 claims description 16
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
210000002307 prostate Anatomy 0.000 claims description 8
210000000481 breast Anatomy 0.000 claims description 7
210000001072 colon Anatomy 0.000 claims description 6
210000004072 lung Anatomy 0.000 claims description 6
210000000496 pancreas Anatomy 0.000 claims description 6
210000003734 kidney Anatomy 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
210000003932 urinary bladder Anatomy 0.000 claims description 5
VQZTUZCKTWFBIF-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide;hydrobromide Chemical compound Br.S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 VQZTUZCKTWFBIF-UHFFFAOYSA-N 0.000 claims description 4
208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
210000003238 esophagus Anatomy 0.000 claims description 4
210000003128 head Anatomy 0.000 claims description 4
210000003739 neck Anatomy 0.000 claims description 4
210000001672 ovary Anatomy 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
210000002784 stomach Anatomy 0.000 claims description 4
208000013076 thyroid tumor Diseases 0.000 claims description 4
UNQAWZFKJZLETJ-LREBCSMRSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide;(2r,3r)-2,3-dihydroxybutanedioic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.N=1SC(NC(=O)NCCCCN2CCCC2)=C(C(=O)N)C=1OCC1=C(F)C=C(Br)C=C1F UNQAWZFKJZLETJ-LREBCSMRSA-N 0.000 claims description 3
208000009849 Female Genital Neoplasms Diseases 0.000 claims description 3
206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
BGFDYMMWVZICEI-UHFFFAOYSA-N acetic acid;3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound CC(O)=O.N=1SC(NC(=O)NCCCCN2CCCC2)=C(C(=O)N)C=1OCC1=C(F)C=C(Br)C=C1F BGFDYMMWVZICEI-UHFFFAOYSA-N 0.000 claims description 3
210000004556 brain Anatomy 0.000 claims description 3
208000029742 colonic neoplasm Diseases 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
208000025402 neoplasm of esophagus Diseases 0.000 claims description 2
208000025440 neoplasm of neck Diseases 0.000 claims description 2
208000023958 prostate neoplasm Diseases 0.000 claims description 2
208000003174 Brain Neoplasms Diseases 0.000 claims 1
208000008839 Kidney Neoplasms Diseases 0.000 claims 1
229910000042 hydrogen bromide Inorganic materials 0.000 claims 1
-1 hemi-citrate Chemical compound 0.000 abstract description 39
239000013078 crystal Substances 0.000 abstract description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract description 16
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 abstract description 16
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 abstract description 15
201000010099 disease Diseases 0.000 abstract description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
239000007787 solid Substances 0.000 description 26
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
239000000843 powder Substances 0.000 description 10
201000011510 cancer Diseases 0.000 description 8
239000000203 mixture Substances 0.000 description 8
238000012360 testing method Methods 0.000 description 8
108091003079 Bovine Serum Albumin Proteins 0.000 description 7
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
PCXTYKGTWQCNJI-UHFFFAOYSA-N 1,2-thiazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NSC=1 PCXTYKGTWQCNJI-UHFFFAOYSA-N 0.000 description 5
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 5
208000004403 Prostatic Hyperplasia Diseases 0.000 description 5
201000004681 Psoriasis Diseases 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
239000012458 free base Substances 0.000 description 5
238000011534 incubation Methods 0.000 description 5
238000005259 measurement Methods 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
238000003556 assay Methods 0.000 description 4
239000000872 buffer Substances 0.000 description 4
238000002050 diffraction method Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012091 fetal bovine serum Substances 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
239000003826 tablet Substances 0.000 description 4
NNPJZJJMQDXYGN-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide;hydrochloride Chemical compound Cl.S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 NNPJZJJMQDXYGN-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
208000026310 Breast neoplasm Diseases 0.000 description 3
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 3
241001465754 Metazoa Species 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 3
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
230000000340 anti-metabolite Effects 0.000 description 3
229940100197 antimetabolite Drugs 0.000 description 3
239000002256 antimetabolite Substances 0.000 description 3
239000002246 antineoplastic agent Substances 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 3
230000010261 cell growth Effects 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
238000011161 development Methods 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
238000009792 diffusion process Methods 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
238000002513 implantation Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
208000017169 kidney disease Diseases 0.000 description 3
208000020816 lung neoplasm Diseases 0.000 description 3
239000006166 lysate Substances 0.000 description 3
239000002609 medium Substances 0.000 description 3
201000001441 melanoma Diseases 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
230000011278 mitosis Effects 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
239000012679 serum free medium Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
229940095064 tartrate Drugs 0.000 description 3
210000004881 tumor cell Anatomy 0.000 description 3
230000004614 tumor growth Effects 0.000 description 3
201000001320 Atherosclerosis Diseases 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
229940123587 Cell cycle inhibitor Drugs 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
206010012689 Diabetic retinopathy Diseases 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
208000032612 Glial tumor Diseases 0.000 description 2
206010018338 Glioma Diseases 0.000 description 2
102000005720 Glutathione transferase Human genes 0.000 description 2
108010070675 Glutathione transferase Proteins 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
208000007766 Kaposi sarcoma Diseases 0.000 description 2
206010058467 Lung neoplasm malignant Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 2
206010033128 Ovarian cancer Diseases 0.000 description 2
208000016222 Pancreatic disease Diseases 0.000 description 2
206010061902 Pancreatic neoplasm Diseases 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical group CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
206010038933 Retinopathy of prematurity Diseases 0.000 description 2
206010039710 Scleroderma Diseases 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
102000004357 Transferases Human genes 0.000 description 2
108090000992 Transferases Proteins 0.000 description 2
108091008605 VEGF receptors Proteins 0.000 description 2
102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 2
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
230000002280 anti-androgenic effect Effects 0.000 description 2
230000003388 anti-hormonal effect Effects 0.000 description 2
239000000051 antiandrogen Substances 0.000 description 2
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
230000008901 benefit Effects 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
210000001109 blastomere Anatomy 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000013592 cell lysate Substances 0.000 description 2
208000037976 chronic inflammation Diseases 0.000 description 2
208000037893 chronic inflammatory disorder Diseases 0.000 description 2
239000003086 colorant Substances 0.000 description 2
239000010949 copper Substances 0.000 description 2
210000002889 endothelial cell Anatomy 0.000 description 2
125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
201000011066 hemangioma Diseases 0.000 description 2
102000055590 human KDR Human genes 0.000 description 2
206010020718 hyperplasia Diseases 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
208000002780 macular degeneration Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000001613 neoplastic effect Effects 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
208000008443 pancreatic carcinoma Diseases 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
201000001514 prostate carcinoma Diseases 0.000 description 2
102000016914 ras Proteins Human genes 0.000 description 2
108010014186 ras Proteins Proteins 0.000 description 2
238000010992 reflux Methods 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
208000017520 skin disease Diseases 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000001384 succinic acid Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
229940104230 thymidine Drugs 0.000 description 2
230000005747 tumor angiogenesis Effects 0.000 description 2
230000004862 vasculogenesis Effects 0.000 description 2
235000015041 whisky Nutrition 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 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical group CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
UNQAWZFKJZLETJ-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide 2,3-dihydroxybutanedioic acid Chemical compound OC(=O)C(O)C(O)C(O)=O.N=1SC(NC(=O)NCCCCN2CCCC2)=C(C(=O)N)C=1OCC1=C(F)C=C(Br)C=C1F UNQAWZFKJZLETJ-UHFFFAOYSA-N 0.000 description 1
ATXPSRAGQHXUCP-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.N=1SC(NC(=O)NCCCCN2CCCC2)=C(C(=O)N)C=1OCC1=C(F)C=C(Br)C=C1F ATXPSRAGQHXUCP-UHFFFAOYSA-N 0.000 description 1
ZKWZDRVZQCQGSK-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxylic acid hydrobromide Chemical compound Br.BrC1=CC(=C(COC2=NSC(=C2C(=O)O)NC(=O)NCCCCN2CCCC2)C(=C1)F)F ZKWZDRVZQCQGSK-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
238000010600 3H thymidine incorporation assay Methods 0.000 description 1
229920000936 Agarose Polymers 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
240000003291 Armoracia rusticana Species 0.000 description 1
235000011330 Armoracia rusticana Nutrition 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
108010006654 Bleomycin Proteins 0.000 description 1
206010006143 Brain stem glioma Diseases 0.000 description 1
241000283707 Capra Species 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
206010007953 Central nervous system lymphoma Diseases 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 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
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 1
238000012286 ELISA Assay Methods 0.000 description 1
239000004097 EU approved flavor enhancer Substances 0.000 description 1
208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
206010014733 Endometrial cancer Diseases 0.000 description 1
206010014759 Endometrial neoplasm Diseases 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
206010061968 Gastric neoplasm Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
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 1
239000012981 Hank's balanced salt solution Substances 0.000 description 1
206010019799 Hepatitis viral Diseases 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
206010061252 Intraocular melanoma Diseases 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
206010029098 Neoplasm skin Diseases 0.000 description 1
208000002471 Penile Neoplasms Diseases 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
208000007913 Pituitary Neoplasms Diseases 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
208000015634 Rectal Neoplasms Diseases 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
NFIQVTKOYPXSRQ-UHFFFAOYSA-N S(C)(=O)(=O)O.S(C)(=O)(=O)O.BrC1=CC(=C(COC2=NSC(=C2C(=O)O)NC(=O)NCCCCN2CCCC2)C(=C1)F)F Chemical compound S(C)(=O)(=O)O.S(C)(=O)(=O)O.BrC1=CC(=C(COC2=NSC(=C2C(=O)O)NC(=O)NCCCCN2CCCC2)C(=C1)F)F NFIQVTKOYPXSRQ-UHFFFAOYSA-N 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
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 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
201000005969 Uveal melanoma Diseases 0.000 description 1
201000003761 Vaginal carcinoma Diseases 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
206010047700 Vomiting Diseases 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
238000002083 X-ray spectrum Methods 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
208000024447 adrenal gland neoplasm Diseases 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
206010064930 age-related macular degeneration Diseases 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940046836 anti-estrogen Drugs 0.000 description 1
230000001833 anti-estrogenic effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
230000035578 autophosphorylation Effects 0.000 description 1
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
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 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
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
201000008275 breast carcinoma Diseases 0.000 description 1
239000012267 brine Substances 0.000 description 1
230000000711 cancerogenic effect Effects 0.000 description 1
229960004562 carboplatin Drugs 0.000 description 1
231100000357 carcinogen Toxicity 0.000 description 1
239000003183 carcinogenic agent Substances 0.000 description 1
229940097647 casodex Drugs 0.000 description 1
208000025997 central nervous system neoplasm Diseases 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
239000013043 chemical agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
208000024207 chronic leukemia Diseases 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000030944 contact inhibition Effects 0.000 description 1
239000003433 contraceptive agent Substances 0.000 description 1
230000002254 contraceptive effect Effects 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000006071 cream Substances 0.000 description 1
210000000448 cultured tumor cell Anatomy 0.000 description 1
208000030381 cutaneous melanoma Diseases 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000019264 food flavour enhancer Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
210000004013 groin Anatomy 0.000 description 1
230000012010 growth Effects 0.000 description 1
102000058223 human VEGFA Human genes 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229960001330 hydroxycarbamide Drugs 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000012444 intercalating antibiotic Substances 0.000 description 1
238000009830 intercalation Methods 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
201000005296 lung carcinoma Diseases 0.000 description 1
208000037841 lung tumor Diseases 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
201000004792 malaria Diseases 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
239000000463 material Substances 0.000 description 1
238000000691 measurement method Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
229940085033 nolvadex Drugs 0.000 description 1
201000002575 ocular melanoma Diseases 0.000 description 1
239000002674 ointment Substances 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical class O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
210000002990 parathyroid gland Anatomy 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
210000003899 penis Anatomy 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
102000013415 peroxidase activity proteins Human genes 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
201000008171 proliferative glomerulonephritis Diseases 0.000 description 1
108700042226 ras Genes Proteins 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
208000013718 rectal benign neoplasm Diseases 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
201000007444 renal pelvis carcinoma Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
238000011125 single therapy Methods 0.000 description 1
201000003708 skin melanoma Diseases 0.000 description 1
208000014680 small intestine neoplasm Diseases 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
230000003068 static effect Effects 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
230000026683 transduction Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
208000025421 tumor of uterus Diseases 0.000 description 1
210000003954 umbilical cord Anatomy 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
210000000626 ureter Anatomy 0.000 description 1
208000024722 urethra neoplasm Diseases 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
208000037965 uterine sarcoma Diseases 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
201000001862 viral hepatitis Diseases 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- 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
- A61P17/06—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
- 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
- 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
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Dermatology (AREA)
Rheumatology (AREA)
Hematology (AREA)
Cardiology (AREA)
Oncology (AREA)
Transplantation (AREA)
Vascular Medicine (AREA)
Emergency Medicine (AREA)
Pain & Pain Management (AREA)
Obesity (AREA)
Ophthalmology & Optometry (AREA)
Endocrinology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

SK586-2003A 2000-11-28 2001-11-19 Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents SK5862003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25351300P	2000-11-28	2000-11-28
PCT/IB2001/002193 WO2002044158A1 (en)	2000-11-28	2001-11-19	Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents

Publications (1)

Publication Number	Publication Date
SK5862003A3 true SK5862003A3 (en)	2004-05-04

Family

ID=22960587

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK586-2003A SK5862003A3 (en)	2000-11-28	2001-11-19	Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents

Country Status (49)

Country	Link
US (1)	US6831091B2 (de)
EP (1)	EP1337521B1 (de)
JP (2)	JP2004514714A (de)
KR (2)	KR20030059275A (de)
CN (1)	CN1231474C (de)
AP (1)	AP2001002358A0 (de)
AR (1)	AR031512A1 (de)
AT (1)	ATE340786T1 (de)
AU (2)	AU2002214204B2 (de)
BG (1)	BG107752A (de)
BR (1)	BR0115621A (de)
CA (1)	CA2430065C (de)
CR (1)	CR6963A (de)
CY (1)	CY1106240T1 (de)
CZ (1)	CZ20031315A3 (de)
DE (1)	DE60123461T2 (de)
DK (1)	DK1337521T3 (de)
DO (1)	DOP2001000288A (de)
EA (1)	EA005859B1 (de)
EC (1)	ECSP034628A (de)
EE (1)	EE200300247A (de)
ES (1)	ES2271086T3 (de)
GE (1)	GEP20053652B (de)
GT (1)	GT200100237A (de)
HN (1)	HN2001000268A (de)
HR (1)	HRP20030408A2 (de)
HU (1)	HUP0302553A3 (de)
IL (1)	IL155371A0 (de)
IS (1)	IS6788A (de)
MA (1)	MA26960A1 (de)
MX (1)	MXPA03004714A (de)
MY (1)	MY136686A (de)
NO (1)	NO325187B1 (de)
NZ (1)	NZ525788A (de)
OA (1)	OA12532A (de)
PA (1)	PA8533801A1 (de)
PE (1)	PE20020591A1 (de)
PL (1)	PL362079A1 (de)
PT (1)	PT1337521E (de)
SI (1)	SI1337521T1 (de)
SK (1)	SK5862003A3 (de)
SV (1)	SV2002000748A (de)
TN (1)	TNSN01167A1 (de)
TW (1)	TWI287542B (de)
UA (1)	UA74221C2 (de)
UY (1)	UY27039A1 (de)
WO (1)	WO2002044158A1 (de)
YU (1)	YU36403A (de)
ZA (1)	ZA200303341B (de)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA60365C2 (uk) *	1998-06-04	2003-10-15	Пфайзер Продактс Інк.	Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця
US8124630B2 (en)	1999-01-13	2012-02-28	Bayer Healthcare Llc	ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
EP2298311B1 (de)	1999-01-13	2012-05-09	Bayer HealthCare LLC	Omega-carboxyarylsubstituierte-Diphenyl-Harnstoffe als p38-Kinasehemmer
US7351834B1 (en)	1999-01-13	2008-04-01	Bayer Pharmaceuticals Corporation	ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
WO2003068229A1 (en)	2002-02-11	2003-08-21	Bayer Pharmaceuticals Corporation	Pyridine, quinoline, and isoquinoline n-oxides as kinase inhibitors
DK1478358T3 (da)	2002-02-11	2013-10-07	Bayer Healthcare Llc	Sorafenibtosylat til behandling af sygdomme kendetegnet ved unormal angiogenese
CA2493701A1 (en) *	2002-07-25	2004-02-05	Pfizer Products Inc.	Isothiazole derivatives useful as anticancer agents
EA200500234A1 (ru) *	2002-08-19	2005-08-25	Пфайзер Продактс Инк.	Комбинированная терапия гиперпролиферативных болезней
EP1636585B2 (de)	2003-05-20	2012-06-13	Bayer HealthCare LLC	Diaryl-harnstoffe mit kinasehemmender wirkung
PL1663978T3 (pl)	2003-07-23	2008-04-30	Bayer Healthcare Llc	Fluoropodstawiony omega-karboksyarylodifenylomocznik do leczenia i profilaktyki chorób i stanów
RU2317295C1 (ru) *	2003-10-27	2008-02-20	Мерк Энд Ко., Инк.	Соль антагониста ccr-2
US7572914B2 (en)	2003-12-19	2009-08-11	Takeda Pharmaceutical Company Limited	Kinase inhibitors
WO2005102327A1 (en) *	2004-04-20	2005-11-03	Pfizer Products Inc.	Dosage forms and methods of treatment using vegfr inhibitors
US7838524B2 (en)	2004-04-30	2010-11-23	Bayer Healthcare Llc	Substituted pyrazolyl urea derivatives useful in the treatment of cancer
TW200538104A (en) *	2004-05-17	2005-12-01	Pfizer Prod Inc	Phenyl derivatives for the treatment of abnormal cell growth
WO2006023931A2 (en)	2004-08-18	2006-03-02	Takeda San Diego, Inc.	Kinase inhibitors
EP1812439B2 (de)	2004-10-15	2017-12-06	Takeda Pharmaceutical Company Limited	Kinaseinhibitoren
US8119655B2 (en)	2005-10-07	2012-02-21	Takeda Pharmaceutical Company Limited	Kinase inhibitors
MY150647A (en)	2006-06-16	2014-02-14	Lundbeck & Co As H	1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a compound with combined serotonin reuptake, 5-ht3 and 5-ht1a activity for the treatment of cognitive impairment
US7932390B2 (en)	2006-06-29	2011-04-26	Hoffman-La Roche Inc.	Substituted thieno[3,2-C]pyridine carboxylic acid derivatives
JP2010505962A (ja)	2006-10-09	2010-02-25	武田薬品工業株式会社	キナーゼ阻害剤
MX2010001636A (es)	2007-08-14	2010-03-15	Hoffmann La Roche	Derivados de pirazolo[3,4-d]-pirimidina como agentes antiproliferativos.
WO2011073521A1 (en)	2009-12-15	2011-06-23	Petri Salven	Methods for enriching adult-derived endothelial progenitor cells and uses thereof
SG187592A1 (en)	2010-07-23	2013-03-28	Univ Boston	Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery
KR102433489B1 (ko) *	2013-03-14	2022-08-17	팬옵티카, 인크.	눈의 후안부로의 약물 전달을 위한 안구용 제제
AU2015317531B2 (en) *	2014-09-17	2020-11-19	Panoptica, Inc.	Ocular formulations for drug-delivery and protection of the anterior segment of the eye
KR20250121146A (ko) *	2022-12-28	2025-08-11	비양 테라퓨틱스 컴퍼니 리미티드	단백질 티로신 키나제 억제제 및 이의 의약적 용도
WO2026002126A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂及其眼用制剂
WO2026002142A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂的半琥珀酸盐晶型
WO2026002133A1 (zh) *	2024-06-27	2026-01-02	苏州必扬医药科技有限公司	一种蛋白酪氨酸激酶抑制剂的盐型

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA60365C2 (uk) *	1998-06-04	2003-10-15	Пфайзер Продактс Інк.	Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця

2001
- 2001-11-19 MX MXPA03004714A patent/MXPA03004714A/es active IP Right Grant
- 2001-11-19 WO PCT/IB2001/002193 patent/WO2002044158A1/en not_active Ceased
- 2001-11-19 IL IL15537101A patent/IL155371A0/xx unknown
- 2001-11-19 EE EEP200300247A patent/EE200300247A/xx unknown
- 2001-11-19 DK DK01982663T patent/DK1337521T3/da active
- 2001-11-19 EA EA200300424A patent/EA005859B1/ru not_active IP Right Cessation
- 2001-11-19 AP APAP/P/2001/002358A patent/AP2001002358A0/en unknown
- 2001-11-19 BR BR0115621-7A patent/BR0115621A/pt not_active Application Discontinuation
- 2001-11-19 SI SI200130630T patent/SI1337521T1/sl unknown
- 2001-11-19 UA UA2003054858A patent/UA74221C2/uk unknown
- 2001-11-19 OA OA1200300137A patent/OA12532A/en unknown
- 2001-11-19 EP EP01982663A patent/EP1337521B1/de not_active Expired - Lifetime
- 2001-11-19 HR HR20030408A patent/HRP20030408A2/hr not_active Application Discontinuation
- 2001-11-19 CN CNB018193285A patent/CN1231474C/zh not_active Expired - Fee Related
- 2001-11-19 PT PT01982663T patent/PT1337521E/pt unknown
- 2001-11-19 ES ES01982663T patent/ES2271086T3/es not_active Expired - Lifetime
- 2001-11-19 GE GE5216A patent/GEP20053652B/en unknown
- 2001-11-19 AU AU2002214204A patent/AU2002214204B2/en not_active Ceased
- 2001-11-19 SK SK586-2003A patent/SK5862003A3/sk unknown
- 2001-11-19 NZ NZ525788A patent/NZ525788A/en unknown
- 2001-11-19 HU HU0302553A patent/HUP0302553A3/hu unknown
- 2001-11-19 PL PL01362079A patent/PL362079A1/xx not_active Application Discontinuation
- 2001-11-19 DO DO2001000288A patent/DOP2001000288A/es unknown
- 2001-11-19 DE DE60123461T patent/DE60123461T2/de not_active Expired - Lifetime
- 2001-11-19 AU AU1420402A patent/AU1420402A/xx active Pending
- 2001-11-19 CZ CZ20031315A patent/CZ20031315A3/cs unknown
- 2001-11-19 YU YU36403A patent/YU36403A/sh unknown
- 2001-11-19 CA CA002430065A patent/CA2430065C/en not_active Expired - Lifetime
- 2001-11-19 JP JP2002546528A patent/JP2004514714A/ja not_active Withdrawn
- 2001-11-19 AT AT01982663T patent/ATE340786T1/de not_active IP Right Cessation
- 2001-11-19 KR KR10-2003-7007057A patent/KR20030059275A/ko not_active Ceased
- 2001-11-19 KR KR1020057022534A patent/KR20050116401A/ko not_active Abandoned
- 2001-11-26 PE PE2001001179A patent/PE20020591A1/es not_active Application Discontinuation
- 2001-11-26 UY UY27039A patent/UY27039A1/es not_active Application Discontinuation
- 2001-11-26 AR ARP010105484A patent/AR031512A1/es not_active Application Discontinuation
- 2001-11-26 MY MYPI20015382A patent/MY136686A/en unknown
- 2001-11-27 TN TNTNSN01167A patent/TNSN01167A1/fr unknown
- 2001-11-27 GT GT200100237A patent/GT200100237A/es unknown
- 2001-11-27 US US09/993,640 patent/US6831091B2/en not_active Expired - Lifetime
- 2001-11-27 SV SV2001000748A patent/SV2002000748A/es unknown
- 2001-11-27 TW TW090129315A patent/TWI287542B/zh active
- 2001-11-27 PA PA20018533801A patent/PA8533801A1/es unknown
- 2001-11-27 HN HN2001000268A patent/HN2001000268A/es unknown
2003
- 2003-04-14 IS IS6788A patent/IS6788A/is unknown
- 2003-04-22 BG BG107752A patent/BG107752A/bg unknown
- 2003-04-24 CR CR6963A patent/CR6963A/es not_active Application Discontinuation
- 2003-04-30 ZA ZA200303341A patent/ZA200303341B/en unknown
- 2003-05-13 MA MA27158A patent/MA26960A1/fr unknown
- 2003-05-27 NO NO20032388A patent/NO325187B1/no unknown
- 2003-05-28 EC EC2003004628A patent/ECSP034628A/es unknown
2006
- 2006-11-13 CY CY20061101645T patent/CY1106240T1/el unknown
2007
- 2007-10-29 JP JP2007279951A patent/JP4971946B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
IL155371A0 (en)	2003-11-23
NZ525788A (en)	2004-11-26
YU36403A (sh)	2006-08-17
MA26960A1 (fr)	2004-12-20
DE60123461T2 (de)	2007-02-15
WO2002044158A1 (en)	2002-06-06
EE200300247A (et)	2003-10-15
AR031512A1 (es)	2003-09-24
UY27039A1 (es)	2002-07-31
AU1420402A (en)	2002-06-11
HN2001000268A (es)	2002-01-30
MXPA03004714A (es)	2003-08-19
CA2430065A1 (en)	2002-06-06
EA005859B1 (ru)	2005-06-30
EP1337521B1 (de)	2006-09-27
ES2271086T3 (es)	2007-04-16
HUP0302553A2 (hu)	2003-11-28
HUP0302553A3 (en)	2009-03-30
NO20032388L (no)	2003-07-18
HK1059085A1 (en)	2004-06-18
PT1337521E (pt)	2006-12-29
AP2001002358A0 (en)	2001-12-31
PL362079A1 (en)	2004-10-18
KR20050116401A (ko)	2005-12-12
TNSN01167A1 (fr)	2005-11-10
TWI287542B (en)	2007-10-01
CY1106240T1 (el)	2011-06-08
MY136686A (en)	2008-11-28
PA8533801A1 (es)	2002-10-31
JP4971946B2 (ja)	2012-07-11
CN1231474C (zh)	2005-12-14
DK1337521T3 (da)	2007-01-29
GT200100237A (es)	2002-07-03
GEP20053652B (en)	2005-11-10
CN1476439A (zh)	2004-02-18
US20020151573A1 (en)	2002-10-17
BG107752A (bg)	2004-01-30
IS6788A (is)	2003-04-14
KR20030059275A (ko)	2003-07-07
EA200300424A1 (ru)	2003-10-30
UA74221C2 (uk)	2005-11-15
DE60123461D1 (de)	2006-11-09
SI1337521T1 (sl)	2006-12-31
BR0115621A (pt)	2003-09-02
DOP2001000288A (es)	2002-12-15
US6831091B2 (en)	2004-12-14
ATE340786T1 (de)	2006-10-15
JP2004514714A (ja)	2004-05-20
SV2002000748A (es)	2002-12-02
OA12532A (en)	2006-06-02
EP1337521A1 (de)	2003-08-27
CR6963A (es)	2003-11-25
AU2002214204B2 (en)	2007-05-24
NO325187B1 (no)	2008-02-11
CA2430065C (en)	2008-05-20
ECSP034628A (es)	2003-07-25
HRP20030408A2 (en)	2003-08-31
CZ20031315A3 (cs)	2004-04-14
NO20032388D0 (no)	2003-05-27
ZA200303341B (en)	2004-04-30
JP2008056692A (ja)	2008-03-13
PE20020591A1 (es)	2002-07-06

Publication	Publication Date	Title
US6831091B2 (en)	2004-12-14	Salt forms of 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide and method of production
AU2002214204A1 (en)	2002-08-15	Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents
EP1187826B1 (de)	2006-12-27	Als antikrebsmittel verwendbare heterocyklische derivate
AP1252A (en)	2004-02-25	N-[3-ethynylphenylamino]-6.7-bis9-Methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate.
PL201784B1 (pl)	2009-05-29	Pochodne benzimidazolu, ich zastosowanie i środek farmaceutyczny
HRP20050560A2 (en)	2006-02-28	Pyrrolopyrimidine derivatives
JP2021181467A (ja)	2021-11-25	Ｐｋｍ２調節因子およびそれらの使用方法
WO2003050108A1 (en)	2003-06-19	Salt forms of e-2-methoxy-n-(3-(4-(3-methyl-pyridin-3-yloxy)-phenylamino)-quinazolin-6-yl)-allyl)-acetamide, its preparation and its use against cancer
EP1527071A1 (de)	2005-05-04	Isothiazolderivate und ihre verwendung zur krebsbekämpfung
JP2009235057A (ja)	2009-10-15	血管新生阻害活性を有する新規インドール誘導体
HK1059085B (en)	2006-02-24	Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents
UA81915C2 (en)	2008-02-25	Novel venzoimidazole derivatives useful as antiproliferative agents