ZA200300161B - Pyrimidine derivatives. - Google Patents

Pyrimidine derivatives. Download PDF

Info

Publication number: ZA200300161B
Authority: ZA; South Africa
Prior art keywords: trifluoro; benzyloxymethyl; thiol; pyrrolidine; pyrimidin
Prior art date: 2000-07-19

Application number

ZA200300161A

Other languages

English (en)

Inventor

Johannes Aebi

Alexander Chucholowski

Daniel Bur

Henrietta Dehmlow

Original Assignee

Hoffmann La Roche

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.)

2000-07-19

Filing date

2003-01-07

Publication date

2004-04-07

2003-01-07 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2004-04-07 Publication of ZA200300161B publication Critical patent/ZA200300161B/en

Links

229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
150000003230 pyrimidines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 82
125000000217 alkyl group Chemical group 0.000 claims description 55
-1 diarylalkyl Chemical group 0.000 claims description 51
125000003118 aryl group Chemical group 0.000 claims description 47
229910052739 hydrogen Inorganic materials 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 35
238000006243 chemical reaction Methods 0.000 claims description 30
238000000034 method Methods 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 24
150000002367 halogens Chemical class 0.000 claims description 24
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
125000001072 heteroaryl group Chemical group 0.000 claims description 22
125000003710 aryl alkyl group Chemical group 0.000 claims description 19
201000010099 disease Diseases 0.000 claims description 17
150000002431 hydrogen Chemical group 0.000 claims description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 15
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
125000005129 aryl carbonyl group Chemical group 0.000 claims description 13
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
125000004663 dialkyl amino group Chemical group 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
102000048186 Endothelin-converting enzyme 1 Human genes 0.000 claims description 11
108030001679 Endothelin-converting enzyme 1 Proteins 0.000 claims description 11
206010019280 Heart failures Diseases 0.000 claims description 11
206010020772 Hypertension Diseases 0.000 claims description 11
208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 11
206010052779 Transplant rejections Diseases 0.000 claims description 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
230000001966 cerebroprotective effect Effects 0.000 claims description 11
239000000824 cytostatic agent Substances 0.000 claims description 11
230000001085 cytostatic effect Effects 0.000 claims description 11
238000010511 deprotection reaction Methods 0.000 claims description 11
150000002148 esters Chemical class 0.000 claims description 11
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210000000056 organ Anatomy 0.000 claims description 11
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WUEPMEXUMQVEGN-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;2,2,2-trifluoro-n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethylamino]ethyl]acetamide Chemical compound OC(=O)C(F)(F)F.FC(F)(F)C(=O)NCCNCCNC(=O)C(F)(F)F WUEPMEXUMQVEGN-UHFFFAOYSA-N 0.000 claims description 10
201000001320 Atherosclerosis Diseases 0.000 claims description 10
206010007559 Cardiac failure congestive Diseases 0.000 claims description 10
206010014824 Endotoxic shock Diseases 0.000 claims description 10
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206010003119 arrhythmia Diseases 0.000 claims description 10
208000006673 asthma Diseases 0.000 claims description 10
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
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125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
201000011461 pre-eclampsia Diseases 0.000 claims description 10
208000002815 pulmonary hypertension Diseases 0.000 claims description 10
125000004076 pyridyl group Chemical group 0.000 claims description 10
208000002249 Diabetes Complications Diseases 0.000 claims description 9
206010012655 Diabetic complications Diseases 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
206010060862 Prostate cancer Diseases 0.000 claims description 9
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 9
125000006193 alkinyl group Chemical group 0.000 claims description 9
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 9
125000004181 carboxyalkyl group Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
125000001544 thienyl group Chemical group 0.000 claims description 9
230000029663 wound healing Effects 0.000 claims description 9
230000000694 effects Effects 0.000 claims description 8
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000005120 alkyl cycloalkyl alkyl group Chemical group 0.000 claims description 7
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 7
125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 7
125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 7
239000011701 zinc Substances 0.000 claims description 7
229910052725 zinc Inorganic materials 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
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102000004157 Hydrolases Human genes 0.000 claims description 5
108090000604 Hydrolases Proteins 0.000 claims description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 5
125000004414 alkyl thio group Chemical group 0.000 claims description 5
125000005018 aryl alkenyl group Chemical group 0.000 claims description 5
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 5
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 5
150000003573 thiols Chemical class 0.000 claims description 5
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VYOCXHUFKWXORO-DLBZAZTESA-N (3r,5s)-1-(5-pyridin-4-ylpyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=CC(=CN=2)C=2C=CN=CC=2)C[C@H](S)C1 VYOCXHUFKWXORO-DLBZAZTESA-N 0.000 claims description 4
125000005116 aryl carbamoyl group Chemical group 0.000 claims description 4
125000003884 phenylalkyl group Chemical group 0.000 claims description 4
XRXDLCUAVFZZIZ-ZWKOTPCHSA-N (3r,5s)-1-(5-phenylpyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=CC(=CN=2)C=2C=CC=CC=2)C[C@H](S)C1 XRXDLCUAVFZZIZ-ZWKOTPCHSA-N 0.000 claims description 3
NQHHCMKGFMKOFU-DLBZAZTESA-N (3r,5s)-1-(6-phenylpyridazin-3-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=NC(=CC=2)C=2C=CC=CC=2)C[C@H](S)C1 NQHHCMKGFMKOFU-DLBZAZTESA-N 0.000 claims description 3
LDWBMEMUYZSWCV-ZVWHLABXSA-N (3r,5s)-1-pyrimidin-2-yl-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=CC=CN=2)C[C@H](S)C1 LDWBMEMUYZSWCV-ZVWHLABXSA-N 0.000 claims description 3
239000005711 Benzoic acid Substances 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000001769 aryl amino group Chemical group 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
238000006268 reductive amination reaction Methods 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
VKCDHWFZESIXBC-MCJVGQIASA-N (3r,5s)-1-(2-anilinopyrimidin-4-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=C(NC=3C=CC=CC=3)N=CC=2)C[C@H](S)C1 VKCDHWFZESIXBC-MCJVGQIASA-N 0.000 claims description 2
XPRQARNOXVFIAN-NWDGAFQWSA-N (3r,5s)-1-(2-methoxypyrimidin-4-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound COC1=NC=CC(N2[C@@H](C[C@@H](S)C2)COCC=2C(=CC(F)=C(F)C=2)F)=N1 XPRQARNOXVFIAN-NWDGAFQWSA-N 0.000 claims description 2
TVYWICRWPUGEFD-NWDGAFQWSA-N (3r,5s)-1-(4,6-dimethoxypyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound COC1=CC(OC)=NC(N2[C@@H](C[C@@H](S)C2)COCC=2C(=CC(F)=C(F)C=2)F)=N1 TVYWICRWPUGEFD-NWDGAFQWSA-N 0.000 claims description 2
ZBYVKAQKUFSUHI-VHSXEESVSA-N (3r,5s)-1-(4-amino-5-fluoropyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound C1=C(F)C(N)=NC(N2[C@@H](C[C@@H](S)C2)COCC=2C(=CC(F)=C(F)C=2)F)=N1 ZBYVKAQKUFSUHI-VHSXEESVSA-N 0.000 claims description 2
LFNXJOQDRKYPCI-LMRHVHIWSA-N (3r,5s)-1-(5-ethylpyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC(CC)=CN=C1N1[C@H](COCC=2C(=CC(F)=C(F)C=2)F)C[C@@H](S)C1 LFNXJOQDRKYPCI-LMRHVHIWSA-N 0.000 claims description 2
HHQGKVFJHXBAAD-JKSUJKDBSA-N (3r,5s)-1-(5-pyridin-2-ylpyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=CC(=CN=2)C=2N=CC=CC=2)C[C@H](S)C1 HHQGKVFJHXBAAD-JKSUJKDBSA-N 0.000 claims description 2
CDWMLPFDROZTPB-DLBZAZTESA-N (3r,5s)-1-(5-pyridin-3-ylpyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidine-3-thiol Chemical compound C1=C(F)C(F)=CC(F)=C1COC[C@H]1N(C=2N=CC(=CN=2)C=2C=NC=CC=2)C[C@H](S)C1 CDWMLPFDROZTPB-DLBZAZTESA-N 0.000 claims description 2
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229920003303 ion-exchange polymer Polymers 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
239000003446 ligand Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
229960004635 mesna Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000000369 oxido group Chemical group [*]=O 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
150000008379 phenol ethers Chemical class 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
FRYMCZDMUBETNT-DLBZAZTESA-N s-[(3r,5s)-1-(5-propylpyrimidin-2-yl)-5-[(2,4,5-trifluorophenyl)methoxymethyl]pyrrolidin-3-yl] ethanethioate Chemical compound N1=CC(CCC)=CN=C1N1[C@H](COCC=2C(=CC(F)=C(F)C=2)F)C[C@@H](SC(C)=O)C1 FRYMCZDMUBETNT-DLBZAZTESA-N 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

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- C07D401/02—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
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
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Animal Behavior & Ethology (AREA)
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Heart & Thoracic Surgery (AREA)
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Diabetes (AREA)
Ophthalmology & Optometry (AREA)
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Hematology (AREA)
Emergency Medicine (AREA)
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Obesity (AREA)
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ZA200300161A 2000-07-19 2003-01-07 Pyrimidine derivatives. ZA200300161B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP00114950		2000-07-19

Publications (1)

Publication Number	Publication Date
ZA200300161B true ZA200300161B (en)	2004-04-07

Family

ID=8169227

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200300161A ZA200300161B (en)	2000-07-19	2003-01-07	Pyrimidine derivatives.

Country Status (15)

Country	Link
US (1)	US6660738B2 (es)
EP (1)	EP1303507A1 (es)
JP (1)	JP3983662B2 (es)
KR (1)	KR100551853B1 (es)
CN (1)	CN1443184A (es)
AR (1)	AR030940A1 (es)
AU (1)	AU2001285836A1 (es)
BR (1)	BR0112656A (es)
CA (1)	CA2415681C (es)
MX (1)	MXPA03000504A (es)
PA (1)	PA8522201A1 (es)
PE (1)	PE20020484A1 (es)
UY (1)	UY26845A1 (es)
WO (1)	WO2002006271A1 (es)
ZA (1)	ZA200300161B (es)

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US8088737B2 (en)	2003-04-04	2012-01-03	Incyte Corporation	Compositions, methods and kits relating to Her-2 cleavage
CA2620333A1 (en)	2005-08-26	2007-03-01	Braincells, Inc.	Neurogenesis by muscarinic receptor modulation
EP2276750A2 (en) *	2008-03-27	2011-01-26	Auckland Uniservices Limited	Substituted pyrimidines and triazines and their use in cancer therapy
PE20151979A1 (es)	2013-01-23	2016-01-15	Astrazeneca Ab	Compuestos quimicos
PT3762368T (pt)	2018-03-08	2022-05-06	Incyte Corp	Compostos de aminopirazina diol como inibidores de pi3k-y
WO2020010003A1 (en)	2018-07-02	2020-01-09	Incyte Corporation	AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0182213B1 (en) *	1984-11-08	1990-09-26	Sumitomo Pharmaceuticals Company, Limited	Carbapenem compounds and production thereof
AU631671B2 (en) *	1989-08-04	1992-12-03	Banyu Pharmaceutical Co., Ltd.	2-(2-vinylpyrrolidinylthio)carbapenem derivatives
US5360798A (en) *	1991-07-04	1994-11-01	Shionogi Seiyaku Kabushiki Kaisha	Aminooxypyrrolidinylthiocarbapenem compounds
US5317016A (en) *	1991-08-20	1994-05-31	Shionogi Seiyaku Kabushiki Kaisha	Pyrrolidylthiocarbapenem derivative
PT848004E (pt) *	1995-07-31	2003-07-31	Shionogi & Co	Derivados pirrolidina tendo actividade inibidora da fosfolipase a2
WO1997041120A1 (en) *	1996-07-26	1997-11-06	Dr. Reddy's Research Foundation	Thiazolidinedione compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions thereof
BR9712792A (pt) *	1996-08-28	1999-12-14	Procter & Gamble	Inibidores de metaloprotease bidentada.
ATE293602T1 (de) *	1997-09-12	2005-05-15	Merck Frosst Canada Inc	2-aminopyridine als inhibitoren von cyclooxygenase-2
US6329418B1 (en) *	1998-04-14	2001-12-11	The Procter & Gamble Company	Substituted pyrrolidine hydroxamate metalloprotease inhibitors

2001
- 2001-07-12 WO PCT/EP2001/008059 patent/WO2002006271A1/en not_active Ceased
- 2001-07-12 JP JP2002512174A patent/JP3983662B2/ja not_active Expired - Lifetime
- 2001-07-12 KR KR1020037000727A patent/KR100551853B1/ko not_active Expired - Fee Related
- 2001-07-12 CA CA002415681A patent/CA2415681C/en not_active Expired - Fee Related
- 2001-07-12 MX MXPA03000504A patent/MXPA03000504A/es active IP Right Grant
- 2001-07-12 BR BR0112656-3A patent/BR0112656A/pt not_active IP Right Cessation
- 2001-07-12 CN CN01812970A patent/CN1443184A/zh active Pending
- 2001-07-12 AU AU2001285836A patent/AU2001285836A1/en not_active Abandoned
- 2001-07-12 EP EP01965123A patent/EP1303507A1/en not_active Withdrawn
- 2001-07-16 PA PA20018522201A patent/PA8522201A1/es unknown
- 2001-07-16 PE PE2001000709A patent/PE20020484A1/es not_active Application Discontinuation
- 2001-07-17 AR ARP010103414A patent/AR030940A1/es unknown
- 2001-07-17 UY UY26845A patent/UY26845A1/es not_active Application Discontinuation
- 2001-07-17 US US09/906,983 patent/US6660738B2/en not_active Expired - Fee Related
2003
- 2003-01-07 ZA ZA200300161A patent/ZA200300161B/en unknown

Also Published As

Publication number	Publication date
US20020055632A1 (en)	2002-05-09
UY26845A1 (es)	2002-01-31
CN1443184A (zh)	2003-09-17
AR030940A1 (es)	2003-09-03
CA2415681A1 (en)	2002-01-24
CA2415681C (en)	2008-05-20
WO2002006271A1 (en)	2002-01-24
JP2004504317A (ja)	2004-02-12
MXPA03000504A (es)	2003-06-24
US6660738B2 (en)	2003-12-09
EP1303507A1 (en)	2003-04-23
BR0112656A (pt)	2003-06-24
KR20030022289A (ko)	2003-03-15
JP3983662B2 (ja)	2007-09-26
AU2001285836A1 (en)	2002-01-30
PE20020484A1 (es)	2002-06-06
PA8522201A1 (es)	2002-04-25
KR100551853B1 (ko)	2006-02-13

Publication	Publication Date	Title
RU2288228C2 (ru)	2006-11-27	Ингибиторы металлопротеиназ, их применение и фармацевтические композиции на их основе
KR100859891B1 (ko)	2008-09-23	단백질 키나제 억제제로서 거울상이성질체적으로 순수한아미노헤테로아릴 화합물
KR100869393B1 (ko)	2008-11-21	단백질 키나제 억제제로서 피라졸-치환된 아미노헤테로아릴화합물
ES2908585T3 (es)	2022-05-03	Compuestos de N-((het)arilmetil)-heteroaril-carboxamidas como inhibidores de la calicreína plasmática
EP3612523B1 (en)	2021-06-09	Heteroarylcarboxamide derivatives as plasma kallikrein inhibitors
KR20070041495A (ko)	2007-04-18	폐쇄성 기도 질환의 치료를 위한 신규 히단토인 유도체
ZA200300167B (en)	2004-04-07	Pyrrolidine derivatives as inhibitors of endothelin-converting enzyme.
ZA200300161B (en)	2004-04-07	Pyrimidine derivatives.
ZA200300170B (en)	2004-04-07	Pyrrolidine derivatives as metalloprotease inhibitors.
US20080214495A1 (en)	2008-09-04	Heterocyclic Sulfonamide Derivatives as Inhibitors of Factor Xa
JP4533428B2 (ja)	2010-09-01	新規なピロリジン−３，４−ジカルボキサミド誘導体
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