TW520362B - Substituted pyrimidine compounds and pharmaceutical composition comprising same - Google Patents

Substituted pyrimidine compounds and pharmaceutical composition comprising same Download PDF

Info

Publication number: TW520362B
Authority: TW; Taiwan
Prior art keywords: amino; fluorophenyl; pyridyl; group; phenyl
Prior art date: 1996-12-05

Application number

TW086118244A

Other languages

English (en)

Chinese (zh)

Inventor

Ulrike D Spohr

Michael J Malone

Nathan B Mantlo

Original Assignee

Amgen 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.)

1996-12-05

Filing date

1997-12-04

Publication date

2003-02-11

1997-12-04 Application filed by Amgen Inc filed Critical Amgen Inc

2003-02-11 Application granted granted Critical

2003-02-11 Publication of TW520362B publication Critical patent/TW520362B/zh

Links

239000008194 pharmaceutical composition Chemical class 0.000 title claims abstract description 15
150000003230 pyrimidines Chemical class 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 149
238000000034 method Methods 0.000 claims abstract description 78
201000010099 disease Diseases 0.000 claims abstract description 38
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
150000003839 salts Chemical class 0.000 claims abstract description 23
238000011282 treatment Methods 0.000 claims abstract description 18
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
206010061218 Inflammation Diseases 0.000 claims abstract description 6
230000004054 inflammatory process Effects 0.000 claims abstract description 6
-1 Phenylthiomethyl Chemical group 0.000 claims description 746
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 256
125000000217 alkyl group Chemical group 0.000 claims description 203
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 164
125000003282 alkyl amino group Chemical group 0.000 claims description 110
150000001412 amines Chemical class 0.000 claims description 101
125000003277 amino group Chemical group 0.000 claims description 96
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 87
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 79
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 76
239000000203 mixture Substances 0.000 claims description 65
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 43
125000004076 pyridyl group Chemical group 0.000 claims description 40
125000001207 fluorophenyl group Chemical group 0.000 claims description 23
229910052736 halogen Inorganic materials 0.000 claims description 18
150000002367 halogens Chemical class 0.000 claims description 18
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
238000006467 substitution reaction Methods 0.000 claims description 14
229960004666 glucagon Drugs 0.000 claims description 13
230000000694 effects Effects 0.000 claims description 12
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 11
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 10
102000051325 Glucagon Human genes 0.000 claims description 10
108060003199 Glucagon Proteins 0.000 claims description 10
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 10
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 10
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 10
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
206010040070 Septic Shock Diseases 0.000 claims description 9
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 9
241000701022 Cytomegalovirus Species 0.000 claims description 8
206010006895 Cachexia Diseases 0.000 claims description 7
206010028289 Muscle atrophy Diseases 0.000 claims description 7
230000006378 damage Effects 0.000 claims description 7
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 6
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 6
102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 6
108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims description 6
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 6
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 6
206010063837 Reperfusion injury Diseases 0.000 claims description 6
208000006011 Stroke Diseases 0.000 claims description 6
230000001154 acute effect Effects 0.000 claims description 6
201000008482 osteoarthritis Diseases 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
208000011580 syndromic disease Diseases 0.000 claims description 6
206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
206010009900 Colitis ulcerative Diseases 0.000 claims description 5
206010020751 Hypersensitivity Diseases 0.000 claims description 5
206010040047 Sepsis Diseases 0.000 claims description 5
208000030886 Traumatic Brain injury Diseases 0.000 claims description 5
201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
241000700605 Viruses Species 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
210000004369 blood Anatomy 0.000 claims description 5
239000008280 blood Substances 0.000 claims description 5
208000019664 bone resorption disease Diseases 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
201000006417 multiple sclerosis Diseases 0.000 claims description 5
125000002347 octyl 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])[H] 0.000 claims description 5
125000006308 propyl amino group Chemical group 0.000 claims description 5
150000003180 prostaglandins Chemical class 0.000 claims description 5
230000036303 septic shock Effects 0.000 claims description 5
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 4
206010012442 Dermatitis contact Diseases 0.000 claims description 4
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
208000001132 Osteoporosis Diseases 0.000 claims description 4
206010037660 Pyrexia Diseases 0.000 claims description 4
206010039085 Rhinitis allergic Diseases 0.000 claims description 4
206010044248 Toxic shock syndrome Diseases 0.000 claims description 4
231100000650 Toxic shock syndrome Toxicity 0.000 claims description 4
201000010105 allergic rhinitis Diseases 0.000 claims description 4
230000007815 allergy Effects 0.000 claims description 4
206010003246 arthritis Diseases 0.000 claims description 4
208000010247 contact dermatitis Diseases 0.000 claims description 4
208000015181 infectious disease Diseases 0.000 claims description 4
230000000302 ischemic effect Effects 0.000 claims description 4
230000002265 prevention Effects 0.000 claims description 4
230000017702 response to host Effects 0.000 claims description 4
241000701161 unidentified adenovirus Species 0.000 claims description 4
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 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 3
241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 3
208000034578 Multiple myelomas Diseases 0.000 claims description 3
206010033557 Palpitations Diseases 0.000 claims description 3
206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
239000012528 membrane Substances 0.000 claims description 3
PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical group FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 3
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 3
208000010125 myocardial infarction Diseases 0.000 claims description 3
125000004344 phenylpropyl group Chemical group 0.000 claims description 3
241001529453 unidentified herpesvirus Species 0.000 claims description 3
YJVKLLJCUMQBHN-UHFFFAOYSA-N 2-pyridin-2-ylpyrimidine Chemical compound N1=CC=CC=C1C1=NC=CC=N1 YJVKLLJCUMQBHN-UHFFFAOYSA-N 0.000 claims description 2
LNPMZQXEPNWCMG-UHFFFAOYSA-N 4-(2-aminoethyl)aniline Chemical compound NCCC1=CC=C(N)C=C1 LNPMZQXEPNWCMG-UHFFFAOYSA-N 0.000 claims description 2
206010028980 Neoplasm Diseases 0.000 claims description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
208000026935 allergic disease Diseases 0.000 claims description 2
239000005557 antagonist Substances 0.000 claims description 2
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
201000011510 cancer Diseases 0.000 claims description 2
230000002490 cerebral effect Effects 0.000 claims description 2
229960005181 morphine Drugs 0.000 claims description 2
PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 1
VHJKDOLGYMULOP-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)ethanamine Chemical compound NCCC1=CC=C(Cl)C=C1Cl VHJKDOLGYMULOP-UHFFFAOYSA-N 0.000 claims 1
125000003070 2-(2-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
DLUYDWMBZSEZCU-UHFFFAOYSA-N 2-[(2,6-dichlorophenyl)methyl]-5-(4-fluorophenyl)-4-pyridin-4-ylpyrimidine Chemical compound C1=CC(F)=CC=C1C(C(=N1)C=2C=CN=CC=2)=CN=C1CC1=C(Cl)C=CC=C1Cl DLUYDWMBZSEZCU-UHFFFAOYSA-N 0.000 claims 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
AYUVXKSTUTVAMO-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(phenylsulfanylmethyl)-4-pyridin-4-ylpyrimidine Chemical compound C1=CC(F)=CC=C1C(C(=N1)C=2C=CN=CC=2)=CN=C1CSC1=CC=CC=C1 AYUVXKSTUTVAMO-UHFFFAOYSA-N 0.000 claims 1
CWEMLTMVMPIHTR-UHFFFAOYSA-N 5-(4-fluorophenyl)-n-(2-methoxyphenyl)-4-pyridin-4-ylpyrimidin-2-amine Chemical compound COC1=CC=CC=C1NC(N=C1C=2C=CN=CC=2)=NC=C1C1=CC=C(F)C=C1 CWEMLTMVMPIHTR-UHFFFAOYSA-N 0.000 claims 1
WAUSKYGFULPCPY-UHFFFAOYSA-N 5-(4-fluorophenyl)-n-(2-phenylethyl)-4-pyridin-4-ylpyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C(C(=N1)C=2C=CN=CC=2)=CN=C1NCCC1=CC=CC=C1 WAUSKYGFULPCPY-UHFFFAOYSA-N 0.000 claims 1
206010003210 Arteriosclerosis Diseases 0.000 claims 1
208000037260 Atherosclerotic Plaque Diseases 0.000 claims 1
206010014978 Epidemic pleurodynia Diseases 0.000 claims 1
240000005708 Eugenia stipitata Species 0.000 claims 1
235000006149 Eugenia stipitata Nutrition 0.000 claims 1
206010020772 Hypertension Diseases 0.000 claims 1
GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims 1
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HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims 1
229940094443 oxytocics prostaglandins Drugs 0.000 claims 1
125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
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MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 abstract 1
238000011049 filling Methods 0.000 description 169
125000001424 substituent group Chemical group 0.000 description 121
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 120
125000003545 alkoxy group Chemical group 0.000 description 118
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238000005481 NMR spectroscopy Methods 0.000 description 72
125000000623 heterocyclic group Chemical group 0.000 description 71
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 65
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238000006243 chemical reaction Methods 0.000 description 56
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IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
229930000223 plant secondary metabolite Natural products 0.000 description 1
231100000572 poisoning Toxicity 0.000 description 1
230000000607 poisoning effect Effects 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
238000000164 protein isolation Methods 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
235000008160 pyridoxine Nutrition 0.000 description 1
239000011677 pyridoxine Substances 0.000 description 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
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230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
210000005084 renal tissue Anatomy 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000007423 screening assay Methods 0.000 description 1
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
230000035807 sensation Effects 0.000 description 1
208000013223 septicemia Diseases 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
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229910000077 silane Inorganic materials 0.000 description 1
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239000000779 smoke Substances 0.000 description 1
239000000661 sodium alginate Chemical class 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
229910001948 sodium oxide Inorganic materials 0.000 description 1
RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
241000894007 species Species 0.000 description 1
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235000021286 stilbenes Nutrition 0.000 description 1
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239000005720 sucrose Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
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208000024891 symptom Diseases 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229910052715 tantalum Inorganic materials 0.000 description 1
GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
229960004906 thiomersal Drugs 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
150000003585 thioureas Chemical class 0.000 description 1
208000037816 tissue injury Diseases 0.000 description 1
238000004448 titration Methods 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
230000000699 topical effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000000165 tricyclic carbocycle group Chemical group 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
COHOGNZHAUOXPA-UHFFFAOYSA-N trimethyl(phenyl)stannane Chemical compound C[Sn](C)(C)C1=CC=CC=C1 COHOGNZHAUOXPA-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000005533 tritiation Methods 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
OBYIEPMKXIBQEV-UHFFFAOYSA-N undecyl hydrogen sulfate Chemical compound CCCCCCCCCCCOS(O)(=O)=O OBYIEPMKXIBQEV-UHFFFAOYSA-N 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
125000005289 uranyl group Chemical group 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
229940011671 vitamin b6 Drugs 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
239000011787 zinc oxide Substances 0.000 description 1
XLOMVQKBTHCTTD-UHFFFAOYSA-N zinc oxide Inorganic materials [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 1

Classifications

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- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- 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)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
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Orthopedic Medicine & Surgery (AREA)
Neurology (AREA)
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Pain & Pain Management (AREA)
Hematology (AREA)
Oncology (AREA)
Dermatology (AREA)
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Hospice & Palliative Care (AREA)
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TW086118244A 1996-12-05 1997-12-04 Substituted pyrimidine compounds and pharmaceutical composition comprising same TW520362B (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US3212896P	1996-12-05	1996-12-05
US5095097P	1997-06-13	1997-06-13

Publications (1)

Publication Number	Publication Date
TW520362B true TW520362B (en)	2003-02-11

Family

ID=26708010

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW086118244A TW520362B (en)	1996-12-05	1997-12-04	Substituted pyrimidine compounds and pharmaceutical composition comprising same

Country Status (4)

Country	Link
JP (1)	JP2002514195A (fr)
AR (1)	AR038955A1 (fr)
TW (1)	TW520362B (fr)
WO (1)	WO1998024782A2 (fr)

Families Citing this family (92)

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Publication number	Priority date	Publication date	Assignee	Title
US6613942B1 (en)	1997-07-01	2003-09-02	Novo Nordisk A/S	Glucagon antagonists/inverse agonists
US7045519B2 (en)	1998-06-19	2006-05-16	Chiron Corporation	Inhibitors of glycogen synthase kinase 3
DE69919707T2 (de) *	1998-06-19	2005-09-01	Chiron Corp., Emeryville	Glycogen synthase kinase 3 inhibitoren
AR023052A1 (es) *	1998-09-25	2002-09-04	Mitsuharu Yoshimura Milton	Derivados de pirimidona
US6548503B1 (en)	1998-11-04	2003-04-15	Smithkline Beecham Corporation	Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines
US6350744B1 (en)	1998-11-20	2002-02-26	Merck & Co., Inc.	Compounds having cytokine inhibitory activity
EP1140083A4 (fr)	1999-01-08	2004-01-02	Smithkline Beecham Corp	Nouveaux composes
US6503949B1 (en)	1999-05-17	2003-01-07	Noro Nordisk A/S	Glucagon antagonists/inverse agonists
US7122666B2 (en)	1999-07-21	2006-10-17	Sankyo Company, Limited	Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses
GB9927844D0 (en)	1999-11-26	2000-01-26	Glaxo Group Ltd	Chemical compounds
US6906067B2 (en)	1999-12-28	2005-06-14	Bristol-Myers Squibb Company	N-heterocyclic inhibitors of TNF-α expression
CA2396693A1 (fr) *	1999-12-28	2001-07-05	Stephen T. Wrobleski	Inhibiteurs de la cytokine, en particulier de tnf-alpha
GB0003224D0 (en) *	2000-02-11	2000-04-05	Glaxo Group Ltd	Chemical compounds
EP1136493A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-(thienopyridinyl)pyrimidones, 2-(furopyridinyl)pyrimidones, 2-(isoquinolinyl)pyrimidones, 2-(pyridoindolyl)pyrimidones et 2-(benzofuropyridinyl)pyrimidones
EP1136482A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-amino-3-(alkyl)-pyrimidone comme inhibiteurs de GSK3bêta
AU2001262150A1 (en) *	2000-03-23	2001-10-03	Mitsubishi Pharma Corporation	2-(nitrogen-heterocyclic)pyrimidone derivatives
EP1136489A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-[pipéridinyl]pyrimidinone
EP1136483A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-[pipérazinyl]pyrimidinone
WO2001070727A1 (fr) *	2000-03-23	2001-09-27	Sanofi-Synthelabo	Derives de 2-(arylalkylamino)pyrimidone et derives de 2-(heteroarylalkylamino)pyrimidone
EP1136485A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés d' aminophénylpyrimidinone
EP1136491A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-[(hétéroaryl)alkylamino]pyrimidinones
EP1136486A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-(indanylamino)pyrimidinone et de 2-(tétrahydronaphtalénylamino)pyrimidione
EP1136099A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-(indolylalkylamino)pyridone comme inhibiteurs de GSK3bêta
EP1136484A1 (fr) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	Dérivés de 2-(arylalkylamino)pyrimidine
AU2001252606B2 (en)	2000-04-26	2005-07-07	Eisai R&D Management Co., Ltd.	Medicinal compositions promoting bowel movement
CA2408408C (fr) *	2000-05-12	2013-07-09	Genzyme Corporation	Modulateurs de marquage du tnf-alpha
US6562807B2 (en)	2000-06-23	2003-05-13	Novo Nordisk A/S	Glucagon antagonists/inverse agonists
GB0021494D0 (en)	2000-09-01	2000-10-18	Glaxo Group Ltd	Chemical comkpounds
WO2002020495A2 (fr) *	2000-09-06	2002-03-14	Chiron Corporation	Inhibiteurs de glycogene-synthase kinase 3
US6670362B2 (en)	2000-09-20	2003-12-30	Pfizer Inc.	Pyridazine endothelin antagonists
WO2002040445A1 (fr)	2000-11-17	2002-05-23	Novo Nordisk A/S	Agonistes de glucagon/antagonistes inverses
US6821960B2 (en)	2000-11-17	2004-11-23	Noyo Nordisk Pharmaceuticals, Inc.	Glucagon antagonists/inverse agonists
US6706744B2 (en)	2000-11-17	2004-03-16	Novo Nordisk A/S	Glucagon antagonists/inverse agonists
GB0112802D0 (en)	2001-05-25	2001-07-18	Glaxo Group Ltd	Pyrimidine derivatives
GB0112810D0 (en)	2001-05-25	2001-07-18	Glaxo Group Ltd	Pyrimidine derivatives
GB0119477D0 (en) *	2001-08-09	2001-10-03	Glaxo Group Ltd	Pyrimidine derivatives
IL160701A0 (en)	2001-09-21	2004-08-31	Mitsubishi Pharma Corp	3-substituted-4-pyrimidone derivatives
CN1810802B (zh) *	2001-09-21	2011-04-27	三菱制药株式会社	3-取代的-4-嘧啶酮衍生物
EP1427720B1 (fr) *	2001-09-21	2009-03-04	Mitsubishi Tanabe Pharma Corporation	Derives de 3-substitue-4-pyrimidone
TWI330183B (fr) *	2001-10-22	2010-09-11	Eisai R&D Man Co Ltd
TWI301834B (en) *	2001-10-22	2008-10-11	Eisai R&D Man Co Ltd	Pyrimidone compound and pharmaceutical composition including the same
US6921762B2 (en)	2001-11-16	2005-07-26	Amgen Inc.	Substituted indolizine-like compounds and methods of use
US6762318B2 (en)	2001-12-03	2004-07-13	Novo Nordisk A/S	Glucagon antagonists
US6881746B2 (en)	2001-12-03	2005-04-19	Novo Nordick A/S	Glucagon antagonists/inverse agonists
TW200302728A (en)	2002-02-01	2003-08-16	Novartis Ag	Substituted amines as IgE inhibitors
EP1476428B1 (fr)	2002-02-22	2010-11-17	Pharmacia & Upjohn Company LLC	Derives de pyridyl sulfone utilises comme ligands du recepteur 5-ht6
AU2003221500B9 (en) *	2002-02-28	2008-11-20	Mitsubishi Pharma Corporation	Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl -6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one derivatives
AU2003216591A1 (en) *	2002-04-10	2003-10-20	Orichid Chemicals And Pharmaceuticals Limited	Amino substituted pyrimidinone derivatives useful in the treatment of inflammation and immunological
MXPA04011470A (es) *	2002-05-21	2005-02-14	Amgen Inc	Compuestos heterociclicos sustituidos y metodos de uso.
AU2003245989A1 (en)	2002-07-09	2004-01-23	Boehringer Ingelheim Pharma Gmbh And Co. Kg	Pharmaceutical compositions of anticholinergics and p38 kinase inhibitors in the treatment of respiratory diseases
DE60305053T2 (de)	2002-08-19	2006-08-31	Glaxo Group Ltd., Greenford	Pyrimidinderivate als selektive cox-2-inhibitoren
GB0221443D0 (en)	2002-09-16	2002-10-23	Glaxo Group Ltd	Pyridine derivates
JP4616003B2 (ja)	2002-12-16	2011-01-19	田辺三菱製薬株式会社	３−置換−４−ピリミドン誘導体
BRPI0406757A (pt) *	2003-02-06	2005-12-20	Basf Ag	Pirimidina, processo para preparar as mesmas, produto intermediário, agente pesticida, e, processo para combater fungos nocivos fitopatogênicos
TWI357408B (en)	2003-03-26	2012-02-01	Mitsubishi Tanabe Pharma Corp	3-substituted-4-pyrimidone derivatives
CA2531619A1 (fr)	2003-07-16	2005-01-27	Neurogen Corporation	Analogues de biaryl piperazinyl-pyridine
JP2007502300A (ja) *	2003-08-13	2007-02-08	カイロン　コーポレイション	Ｇｓｋ−３インヒビターおよびその使用
AU2004267096B2 (en) *	2003-08-20	2008-10-02	Amgen Inc.	Substituted pyrimdinone derivatives and methods of use
GB0323137D0 (en)	2003-10-03	2003-11-05	Chang Lisa C W	2,4,6- Trisubstituted pyrimidines and their different uses
JP4790703B2 (ja) *	2004-04-07	2011-10-12	武田薬品工業株式会社	環式化合物
US20060035893A1 (en)	2004-08-07	2006-02-16	Boehringer Ingelheim International Gmbh	Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders
MY145822A (en)	2004-08-13	2012-04-30	Neurogen Corp	Substituted biaryl piperazinyl-pyridine analogues
PE20060777A1 (es)	2004-12-24	2006-10-06	Boehringer Ingelheim Int	Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas
US8193206B2 (en)	2005-06-14	2012-06-05	Taigen Biotechnology Co., Ltd.	Pyrimidine compounds
EA015890B1 (ru) *	2005-06-14	2011-12-30	Тайджен Байотекнолоджи Ко. Лтд.	Производные пиримидина
ES2270715B1 (es)	2005-07-29	2008-04-01	Laboratorios Almirall S.A.	Nuevos derivados de pirazina.
WO2007022964A2 (fr)	2005-08-24	2007-03-01	Abbott Gmbh & Co. Kg	Composes guanidine a substitution hetaryl et utilisation en tant que partenaires de liaison pour des recepteurs de 5-ht5
ES2274712B1 (es)	2005-10-06	2008-03-01	Laboratorios Almirall S.A.	Nuevos derivados imidazopiridina.
WO2008045484A1 (fr)	2006-10-10	2008-04-17	Amgen Inc.	Composés de n-arylpyrazole à utiliser contre le diabète
EP1992344A1 (fr)	2007-05-18	2008-11-19	Institut Curie	P38 alpha comme cible therapeutique pour les maladies associées á une mutation de FGFR3
MX2010001020A (es) *	2007-07-26	2010-03-01	Novartis Ag	Derivados de pirimidina utiles para el tratamiento de condiciones inflamatorias o alergicas.
AU2008355098B2 (en) *	2008-04-21	2012-11-15	Gpcr Therapeutics, Inc	Heterocyclic compounds
WO2010056847A2 (fr)	2008-11-13	2010-05-20	Taigen Biotechnology Co., Ltd.	Formule lyophilisée
HRP20171587T1 (hr)	2010-10-18	2017-12-01	Cerenis Therapeutics Holding Sa	Spojevi, pripravci i postupci pogodni za mobilizaciju kolesterola
GB201106829D0 (en)	2011-04-21	2011-06-01	Proximagen Ltd	Heterocyclic compounds
AU2011346670B2 (en)	2010-12-23	2015-05-07	Pfizer Inc.	Glucagon receptor modulators
PH12013501557A1 (en)	2011-02-08	2019-06-03	Pfizer	Glucagon receptor modulator
RU2013157388A (ru)	2011-07-22	2015-08-27	Пфайзер Инк.	Хинолинильные модуляторы глюкагонового рецептора
AU2012335220B2 (en)	2011-11-11	2017-06-01	Pfizer Inc.	2-thiopyrimidinones
JP6454348B2 (ja)	2013-12-19	2019-01-16	サンシャイン・レイク・ファーマ・カンパニー・リミテッドＳｕｎｓｈｉｎｅＬａｋｅＰｈａｒｍａＣｏ．，Ｌｔｄ．	窒素複素環誘導体およびその医薬品への応用
TWI651310B (zh) *	2014-02-20	2019-02-21	日商日本煙草產業股份有限公司	三化合物及其醫藥用途
SG11201708407TA (en)	2015-05-05	2017-11-29	Pfizer	2-thiopyrimidinones
US20170057943A1 (en)	2015-08-17	2017-03-02	Japan Tobacco Inc.	Hydroxytriazine compounds and pharmaceutical use thereof
EP3372589B1 (fr) *	2015-10-29	2021-10-20	ASKA Pharmaceutical Co., Ltd.	Dérivé pyrimidine
TW202510883A (zh) *	2015-11-04	2025-03-16	德商默克專利有限公司	使用具有ｂｔｋ抑制活性之嘧啶及吡啶化合物治療癌症之方法
KR102780243B1 (ko) *	2015-11-17	2025-03-14	메르크 파텐트 게엠베하	Btk 억제 활성을 갖는 피리미딘 및 피리딘 화합물을 사용하여 다발성 경화증을 치료하는 방법
TW201811766A (zh)	2016-08-29	2018-04-01	瑞士商諾華公司	N-(吡啶-2-基)吡啶-磺醯胺衍生物及其用於疾病治療之用途
MX2022005810A (es) *	2019-11-12	2022-06-08	Genzyme Corp	Heteroarilaminosulfonamidas de 6 miembros para tratar enfermedades y afecciones mediadas por la actividad de regulador de la conductancia transmembrana de la fibrosis quistica (cftr) deficiente.
WO2021113809A1 (fr)	2019-12-05	2021-06-10	Genzyme Corporation	Arylamides et leurs procédés d'utilisation
WO2021113808A1 (fr)	2019-12-05	2021-06-10	Genzyme Corporation	Arylamides modulant cftr
WO2021113806A1 (fr)	2019-12-05	2021-06-10	Genzyme Corporation	Arylamides et leurs procédés d'utilisation
EP4626878A1 (fr)	2022-12-02	2025-10-08	Neumora Therapeutics, Inc.	Méthodes de traitement de troubles neurologiques

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1271116B (de) *	1965-05-04	1968-06-27	Bayer Ag	Verfahren zur Herstellung von 4-Hydroxypyrimidinen
BE759176A (fr) *	1969-11-20	1971-05-19	Sandoz Sa	Derives de la pyrimidine, leur preparation et medicaments contenant cesderives
US4438117A (en) *	1980-09-03	1984-03-20	E. I. Du Pont De Nemours And Company	2-Substituted thio-4,5-diarylpyrimidines
DE3319843A1 (de) *	1983-06-01	1984-12-06	Ali-Akbar Dipl.-Chem. Dr. 4300 Mülheim Pourzal	Verfahren zur herstellung von pyrimidinen aus nitrilen und alkinen
US4500533A (en) *	1983-06-22	1985-02-19	Eli Lilly And Company	2,4,5-Triaryl pyrimidines and a method of treating pain, fever, thrombosis, inflammation and arthritis
US5077142A (en) *	1989-04-20	1991-12-31	Ricoh Company, Ltd.	Electroluminescent devices
US5620999A (en) *	1994-07-28	1997-04-15	Weier; Richard M.	Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation
IL123950A (en) *	1995-10-06	2001-04-30	Merck & Co Inc	Substituted imidazoles having anti-cancer and cytokine inhibitory activity and pharmaceutical compositions containing them
WO1997016442A1 (fr) *	1995-10-31	1997-05-09	Merck & Co., Inc.	Pyrroles de pyridyle substitues, compositions contenant de tels composes et mode d'utilisation
US6096748A (en) *	1996-03-13	2000-08-01	Smithkline Beecham Corporation	Pyrimidine compounds useful in treating cytokine mediated diseases

1997
- 1997-12-04 JP JP52585098A patent/JP2002514195A/ja active Pending
- 1997-12-04 WO PCT/US1997/022390 patent/WO1998024782A2/fr not_active Ceased
- 1997-12-04 TW TW086118244A patent/TW520362B/zh not_active IP Right Cessation
- 1997-12-04 AR ARP970105716A patent/AR038955A1/es not_active Application Discontinuation

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WO1998024782A3 (fr)	1998-08-27
AR038955A1 (es)	2005-02-02
WO1998024782A2 (fr)	1998-06-11
JP2002514195A (ja)	2002-05-14

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CZ11996A3 (en)	1996-10-16	Tri-substituted imidazoles, process of their preparation, intermediates of the process, pharmaceutical preparation and the use of the compounds for various therapeutical applications
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EP2049515A2 (fr)	2009-04-22	Triazolyl pyridyl benzènesulfonamides en tant que modulateurs du ccr2 ou ccr9 pour le traitement l'athérosclérose
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