ZA200401538B - Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system. - Google Patents

Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system. Download PDF

Info

Publication number: ZA200401538B
Authority: ZA; South Africa
Prior art keywords: aliphatic; cycloalkyl; aryl; heteroaryl; heterocyclyl
Prior art date: 2001-10-24

Application number

ZA200401538A

Other languages

English (en)

Inventor

Robert B Perni

Janos Pitlik

John H Van Drie

Luc J Farmer

Original Assignee

Vertex Pharma

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.)

2001-10-24

Filing date

2004-01-01

Publication date

2005-04-25

2004-01-01 Application filed by Vertex Pharma filed Critical Vertex Pharma

2005-04-25 Publication of ZA200401538B publication Critical patent/ZA200401538B/en

Links

102000012479 Serine Proteases Human genes 0.000 title claims description 13
108010022999 Serine Proteases Proteins 0.000 title claims description 13
239000003112 inhibitor Substances 0.000 title claims description 11
108091005804 Peptidases Proteins 0.000 title claims description 8
239000004365 Protease Substances 0.000 title claims description 7
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title claims 4
241000711549 Hepacivirus C Species 0.000 title description 12
-1 1,2-methylenedioxy Chemical group 0.000 claims description 73
125000001931 aliphatic group Chemical group 0.000 claims description 71
229910052739 hydrogen Inorganic materials 0.000 claims description 63
239000001257 hydrogen Substances 0.000 claims description 60
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 55
150000001875 compounds Chemical class 0.000 claims description 52
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 51
125000001424 substituent group Chemical group 0.000 claims description 42
125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 41
125000001072 heteroaryl group Chemical group 0.000 claims description 40
125000000623 heterocyclic group Chemical group 0.000 claims description 40
125000003118 aryl group Chemical group 0.000 claims description 32
125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 25
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 25
125000005843 halogen group Chemical group 0.000 claims description 25
125000005842 heteroatom Chemical group 0.000 claims description 23
125000000753 cycloalkyl group Chemical group 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 20
229910052757 nitrogen Inorganic materials 0.000 claims description 19
125000002837 carbocyclic group Chemical group 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
238000000034 method Methods 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
208000015181 infectious disease Diseases 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
239000003443 antiviral agent Substances 0.000 claims description 7
125000004104 aryloxy group Chemical group 0.000 claims description 7
229910052796 boron Inorganic materials 0.000 claims description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 6
125000003396 thiol group Chemical group [H]S* 0.000 claims description 6
239000008280 blood Substances 0.000 claims description 4
210000004369 blood Anatomy 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
229940079322 interferon Drugs 0.000 claims description 4
239000012472 biological sample Substances 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
230000002519 immonomodulatory effect Effects 0.000 claims 4
210000001124 body fluid Anatomy 0.000 claims 3
102000005741 Metalloproteases Human genes 0.000 claims 2
108010006035 Metalloproteases Proteins 0.000 claims 2
108060004795 Methyltransferase Proteins 0.000 claims 2
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims 2
DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims 2
229960003805 amantadine Drugs 0.000 claims 2
239000010839 body fluid Substances 0.000 claims 2
229960000329 ribavirin Drugs 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
101000617550 Dictyostelium discoideum Presenilin-A Proteins 0.000 claims 1
229910019567 Re Re Inorganic materials 0.000 claims 1
101800001838 Serine protease/helicase NS3 Proteins 0.000 claims 1
239000002671 adjuvant Substances 0.000 claims 1
238000011109 contamination Methods 0.000 claims 1
125000000392 cycloalkenyl group Chemical group 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
125000006575 electron-withdrawing group Chemical group 0.000 claims 1
230000002401 inhibitory effect Effects 0.000 claims 1
239000000651 prodrug Substances 0.000 claims 1
229940002612 prodrug Drugs 0.000 claims 1
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims 1
150000003839 salts Chemical class 0.000 claims 1
239000000523 sample Substances 0.000 claims 1
239000011232 storage material Substances 0.000 claims 1
208000005176 Hepatitis C Diseases 0.000 description 7
108010076039 Polyproteins Proteins 0.000 description 6
241000700605 Viruses Species 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
208000006454 hepatitis Diseases 0.000 description 5
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
102000035195 Peptidases Human genes 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
231100000283 hepatitis Toxicity 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
238000012545 processing Methods 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
230000007017 scission Effects 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
230000003612 virological effect Effects 0.000 description 4
AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
102000014150 Interferons Human genes 0.000 description 3
108010050904 Interferons Proteins 0.000 description 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
206010073071 hepatocellular carcinoma Diseases 0.000 description 3
231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
235000019419 proteases Nutrition 0.000 description 3
125000003373 pyrazinyl group Chemical group 0.000 description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
238000011282 treatment Methods 0.000 description 3
230000029812 viral genome replication Effects 0.000 description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 2
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 2
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
206010019799 Hepatitis viral Diseases 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
108700010756 Viral Polyproteins Proteins 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
125000002527 bicyclic carbocyclic group Chemical group 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
208000010710 hepatitis C virus infection Diseases 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
125000006574 non-aromatic ring group Chemical group 0.000 description 2
230000008520 organization Effects 0.000 description 2
239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
125000002755 pyrazolinyl group Chemical group 0.000 description 2
125000003226 pyrazolyl group Chemical group 0.000 description 2
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
238000012552 review Methods 0.000 description 2
239000003001 serine protease inhibitor Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
201000001862 viral hepatitis Diseases 0.000 description 2
UERNRFHISLXQFU-DFWYDOINSA-N (2S)-5-oxopyrrolidine-2-carboxylic acid pyridine Chemical compound c1ccncc1.OC(=O)[C@@H]1CCC(=O)N1 UERNRFHISLXQFU-DFWYDOINSA-N 0.000 description 1
125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
FSUYMKXZLQOFQY-UHFFFAOYSA-N 3,4-dihydro-1,2-benzodithiine Chemical compound C1=CC=C2SSCCC2=C1 FSUYMKXZLQOFQY-UHFFFAOYSA-N 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
208000006154 Chronic hepatitis C Diseases 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
229940124771 HCV-NS3 protease inhibitor Drugs 0.000 description 1
241000725303 Human immunodeficiency virus Species 0.000 description 1
102000006992 Interferon-alpha Human genes 0.000 description 1
108010047761 Interferon-alpha Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
101800000515 Non-structural protein 3 Proteins 0.000 description 1
101800001020 Non-structural protein 4A Proteins 0.000 description 1
208000037581 Persistent Infection Diseases 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
JXVIIQLNUPXOII-UHFFFAOYSA-N Siduron Chemical compound CC1CCCCC1NC(=O)NC1=CC=CC=C1 JXVIIQLNUPXOII-UHFFFAOYSA-N 0.000 description 1
101900322197 Yellow fever virus Serine protease NS3 Proteins 0.000 description 1
SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 1
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
229940124277 aminobutyric acid Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
230000007423 decrease Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
231100000676 disease causative agent Toxicity 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
210000005069 ears Anatomy 0.000 description 1
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
239000012634 fragment Substances 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000004030 hiv protease inhibitor Substances 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
229940047124 interferons Drugs 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
239000007788 liquid Substances 0.000 description 1
208000018191 liver inflammation Diseases 0.000 description 1
230000007774 longterm Effects 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
LLYKPZOWCPVRPD-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine;n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=CC=N1 LLYKPZOWCPVRPD-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000000306 recurrent effect Effects 0.000 description 1
230000010076 replication Effects 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
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
230000006514 viral protein processing Effects 0.000 description 1
230000017613 viral reproduction Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1027—Tetrapeptides containing heteroatoms different from O, S, or N
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Virology (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

ZA200401538A 2001-10-24 2004-01-01 Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system. ZA200401538B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US34386201P	2001-10-24	2001-10-24

Publications (1)

Publication Number	Publication Date
ZA200401538B true ZA200401538B (en)	2005-04-25

Family

ID=23348006

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200401538A ZA200401538B (en)	2001-10-24	2004-01-01	Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system.

Country Status (10)

Country	Link
US (3)	US7241796B2 (de)
EP (2)	EP2402009A1 (de)
JP (2)	JP4460294B2 (de)
AT (1)	ATE539744T1 (de)
AU (1)	AU2002348414B2 (de)
CA (1)	CA2462163A1 (de)
MX (1)	MXPA04003825A (de)
NZ (1)	NZ531681A (de)
WO (1)	WO2003035060A1 (de)
ZA (1)	ZA200401538B (de)

Families Citing this family (58)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ298749B6 (cs) *	1996-10-18	2008-01-16	Vertex Pharmaceuticals Incorporated	Inhibitory serinových proteáz a farmaceutické prostředky s jejich obsahem
JP4806154B2 (ja) *	2000-04-03	2011-11-02	バーテックスファーマシューティカルズインコーポレイテッド	セリンプロテアーゼ、特にｃ型肝炎ウイルスｎｓ３プロテアーゼのインヒビター
SV2003000617A (es) *	2000-08-31	2003-01-13	Lilly Co Eli	Inhibidores de la proteasa peptidomimetica ref. x-14912m
NZ531681A (en) *	2001-10-24	2007-05-31	Vertex Pharma	Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system
JP2005535574A (ja) *	2002-04-11	2005-11-24	バーテックス　ファーマシューティカルズ　インコーポレイテッド	セリンプロテアーゼ、特にｈｃｖｎｓ３−ｎｓ４ａプロテアーゼのインヒビター
TW200510391A (en) *	2003-04-11	2005-03-16	Vertex Pharma	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
BRPI0412761A (pt) *	2003-07-18	2006-09-26	Vertex Pharma	inibidores de serino proteases, particularmente a protease ns3-ns4a do vhc
WO2005021584A2 (en) *	2003-08-26	2005-03-10	Schering Corporation	Novel peptidomimetic ns3-serine protease inhibitors of hepatitis c virus
PE20050374A1 (es) *	2003-09-05	2005-05-30	Vertex Pharma	Inhibidores de proteasas de serina, en particular proteasa ns3-ns4a del vhc
CA2538791A1 (en)	2003-09-18	2005-03-31	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
CA2541634A1 (en) *	2003-10-10	2005-04-28	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
US8187874B2 (en)	2003-10-27	2012-05-29	Vertex Pharmaceuticals Incorporated	Drug discovery method
EP1944042A1 (de)	2003-10-27	2008-07-16	Vertex Pharmceuticals Incorporated	Kombinationen für die HCV-Behandlung
WO2005067454A2 (en) *	2003-12-23	2005-07-28	Valeant Pharmaceuticals North America	Combination therapy for treating hepatitis c virus infection
KR20120090077A (ko)	2004-01-30	2012-08-16	얀센 알 앤드 디 아일랜드	Ｈｃｖｎｓ?３ 세린 프로테아제 저해제
EP2311851A3 (de) *	2004-02-04	2011-05-25	Vertex Pharmaceuticals Incorporated	Inhibitoren der Serinproteasen, insbesondere der HCV-NS3-NS4A-Protease
AU2005219824B2 (en) *	2004-02-27	2007-11-29	Merck Sharp & Dohme Corp.	Novel ketoamides with cyclic p4's as inhibitors of ns3 serine protease of hepatitis c virus
MY145081A (en) *	2004-02-27	2011-12-15	Schering Corp	Sulfur compounds as inhibitors of hepatitis c virus ns3 serine protease
US7192957B2 (en) *	2004-02-27	2007-03-20	Schering Corporation	Compounds as inhibitors of hepatitis C virus NS3 serine protease
CA2583472A1 (en) *	2004-10-01	2006-04-13	Chao Lin	Hcv ns3-ns4a protease inhibition
US7465537B2 (en) *	2005-05-01	2008-12-16	The Board Of Trustees Of The University Of Arkansas	Compounds and methods for inhibiting hepatitis C virus replication
CN101218224B (zh)	2005-05-13	2013-05-08	Viro化学制药公司	治疗或预防黄病毒感染的组合物和方法
US20070021434A1 (en) *	2005-06-24	2007-01-25	Migenix Inc.	Non-nucleoside anti-hepacivirus agents and uses thereof
PE20070211A1 (es)	2005-07-29	2007-05-12	Medivir Ab	Compuestos macrociclicos como inhibidores del virus de hepatitis c
CA2617679A1 (en) *	2005-08-02	2007-02-08	Steve Lyons	Inhibitors of serine proteases
CA2619659A1 (en) *	2005-08-19	2007-02-22	Vertex Pharmaceuticals Incorporated	Processes and intermediates
US8399615B2 (en)	2005-08-19	2013-03-19	Vertex Pharmaceuticals Incorporated	Processes and intermediates
AR055395A1 (es)	2005-08-26	2007-08-22	Vertex Pharma	Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c
US7964624B1 (en)	2005-08-26	2011-06-21	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases
CA2643688A1 (en)	2006-02-27	2007-08-30	Vertex Pharmaceuticals Incorporated	Co-crystals and pharmaceutical compositions comprising the same
WO2007109080A2 (en)	2006-03-16	2007-09-27	Vertex Pharmaceuticals Incorporated	Deuterated hepatitis c protease inhibitors
PT2104674E (pt)	2006-11-15	2013-07-26	Virochem Pharma Inc	Análogos de tiofeno para o tratamento ou prevenção de infeções por flavivírus
WO2008106058A2 (en)	2007-02-27	2008-09-04	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases
GEP20125645B (en) *	2007-02-27	2012-09-25	Vertex Pharma	Co-crystals and pharmaceutical compositions comprising the same
WO2009032198A1 (en)	2007-08-30	2009-03-12	Vertex Pharmaceuticals Incorporated	Co-crystals and pharmaceutical compositions comprising the same
CA2728226A1 (en)	2008-06-24	2010-01-21	Codexis, Inc.	Biocatalytic processes for the preparation of substantially stereomerically pure fused bicyclic proline compounds
JP2013512247A (ja)	2009-11-25	2013-04-11	バーテックスファーマシューティカルズインコーポレイテッド	フラビウイルス感染症の治療または予防のための５−アルキニル−チオフェン−２−カルボン酸誘導体およびそれらの使用
US20130072523A1 (en)	2009-12-24	2013-03-21	Vertex Pharmaceuticals Incorporated	Analogues for the treatment or prevention of flavivirus infections
TW201141857A (en)	2010-03-24	2011-12-01	Vertex Pharma	Analogues for the treatment or prevention of flavivirus infections
TW201139438A (en)	2010-03-24	2011-11-16	Vertex Pharma	Analogues for the treatment or prevention of flavivirus infections
WO2011119870A1 (en)	2010-03-24	2011-09-29	Vertex Pharmaceuticals Incorporated	Analogues for the treatment or prevention of flavivirus infections
MX2012010918A (es)	2010-03-24	2013-01-18	Vertex Pharma	Analogos para el tratamiento o prevencion de infecciones por flavivirus.
WO2011156545A1 (en)	2010-06-09	2011-12-15	Vertex Pharmaceuticals Incorporated	Viral dynamic model for hcv combination therapy
WO2011159826A2 (en)	2010-06-15	2011-12-22	Vertex Pharmaceuticals Incorporated	Hcv ns5b protease mutants
EP2585447A2 (de)	2010-06-28	2013-05-01	Vertex Pharmaceuticals Incorporated	Verbindungen und verfahren zur behandlung oder vorbeugung von flavivirus-infektionen
WO2012006070A1 (en)	2010-06-28	2012-01-12	Vertex Pharmaceuticals Incorporated	Compounds and methods for the treatment or prevention of flavivirus infections
JP2013531011A (ja)	2010-06-28	2013-08-01	バーテックスファーマシューティカルズインコーポレイテッド	フラビウイルス感染の処置または予防のための化合物および方法
MX2013001869A (es)	2010-08-17	2013-06-28	Vertex Pharma	Compuestos y metodos para el tratamiento o prevencion de infecciones virales por flaviviridae.
AU2012286853A1 (en)	2011-07-26	2013-05-02	Vertex Pharmaceuticals Incorporated	Thiophene compounds
WO2013016499A1 (en)	2011-07-26	2013-01-31	Vertex Pharmaceuticals Incorporated	Methods for preparation of thiophene compounds
US20130123276A1 (en)	2011-11-14	2013-05-16	Sven Ruf	Use of telaprevir and related compounds in atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases
EP2827876A4 (de)	2012-03-22	2015-10-28	Alios Biopharma Inc	Pharmazeutische kombinationen mit einem thionucleotidanalog
WO2014053533A1 (en)	2012-10-05	2014-04-10	Sanofi	Use of substituted 3-heteroaroylamino-propionic acid derivatives as pharmaceuticals for prevention/treatment of atrial fibrillation
TW201526899A (zh)	2013-02-28	2015-07-16	Alios Biopharma Inc	醫藥組成物
EP2899207A1 (de)	2014-01-28	2015-07-29	Amikana.Biologics	Neues Verfahren zum Testen von HCV-Proteasehemmung
US10728694B2 (en) *	2016-03-08	2020-07-28	Tinoq Inc.	Systems and methods for a compound sensor system
CA3224494A1 (en)	2021-07-09	2023-01-12	Koen Vandyck	Anti-viral compounds
WO2023043816A1 (en)	2021-09-17	2023-03-23	Aligos Therapeutics, Inc.	Anti-viral compounds for treating coronavirus, picornavirus, and norovirus infections

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5990276A (en)	1996-05-10	1999-11-23	Schering Corporation	Synthetic inhibitors of hepatitis C virus NS3 protease
EP0907659A1 (de)	1996-05-10	1999-04-14	Schering Corporation	Hepatitis c virus ns3 protease synthetische inhibitoren
CZ298749B6 (cs) *	1996-10-18	2008-01-16	Vertex Pharmaceuticals Incorporated	Inhibitory serinových proteáz a farmaceutické prostředky s jejich obsahem
GB9707659D0 (en)	1997-04-16	1997-06-04	Peptide Therapeutics Ltd	Hepatitis C NS3 Protease inhibitors
DE69829381T2 (de)	1997-08-11	2006-04-13	Boehringer Ingelheim (Canada) Ltd., Laval	Hepatitis c inhibitor peptide
EP1012180B1 (de)	1997-08-11	2004-12-01	Boehringer Ingelheim (Canada) Ltd.	Peptidanaloga mit inhibitorischer wirkung auf hepatitis c
DK1066247T3 (da) *	1998-03-31	2007-04-02	Vertex Pharma	Inhibitorer af serinproteaser, især hepatitis C virus NS3 protease
GB9812523D0 (en)	1998-06-10	1998-08-05	Angeletti P Ist Richerche Bio	Peptide inhibitors of hepatitis c virus ns3 protease
US6323180B1 (en) *	1998-08-10	2001-11-27	Boehringer Ingelheim (Canada) Ltd	Hepatitis C inhibitor tri-peptides
AR022061A1 (es) *	1998-08-10	2002-09-04	Boehringer Ingelheim Ca Ltd	Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos.
WO2001040262A1 (en) *	1999-12-03	2001-06-07	Bristol-Myers Squibb Pharma Company	Alpha-ketoamide inhibitors of hepatitis c virus ns3 protease
JP4806154B2 (ja)	2000-04-03	2011-11-02	バーテックスファーマシューティカルズインコーポレイテッド	セリンプロテアーゼ、特にｃ型肝炎ウイルスｎｓ３プロテアーゼのインヒビター
MXPA03000627A (es) *	2000-07-21	2004-07-30	Schering Corp	Nuevos peptidos como inhibidores de proteasa serina-ns3 del virus de la hepatitis c.
SV2003000617A (es) *	2000-08-31	2003-01-13	Lilly Co Eli	Inhibidores de la proteasa peptidomimetica ref. x-14912m
CA2449504A1 (en) *	2001-07-11	2003-01-23	Vertex Pharmaceuticals Incorporated	Bridged bicyclic serine protease inhibitors
NZ531681A (en) *	2001-10-24	2007-05-31	Vertex Pharma	Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system
JP2005535574A (ja) *	2002-04-11	2005-11-24	バーテックス　ファーマシューティカルズ　インコーポレイテッド	セリンプロテアーゼ、特にｈｃｖｎｓ３−ｎｓ４ａプロテアーゼのインヒビター

2002
- 2002-10-24 NZ NZ531681A patent/NZ531681A/en unknown
- 2002-10-24 CA CA002462163A patent/CA2462163A1/en not_active Abandoned
- 2002-10-24 AT AT02782236T patent/ATE539744T1/de active
- 2002-10-24 WO PCT/US2002/034248 patent/WO2003035060A1/en not_active Ceased
- 2002-10-24 MX MXPA04003825A patent/MXPA04003825A/es active IP Right Grant
- 2002-10-24 EP EP10178006A patent/EP2402009A1/de not_active Withdrawn
- 2002-10-24 EP EP02782236A patent/EP1441720B8/de not_active Expired - Lifetime
- 2002-10-24 JP JP2003537627A patent/JP4460294B2/ja not_active Expired - Fee Related
- 2002-10-24 US US10/280,940 patent/US7241796B2/en not_active Expired - Fee Related
- 2002-10-24 AU AU2002348414A patent/AU2002348414B2/en not_active Ceased
2004
- 2004-01-01 ZA ZA200401538A patent/ZA200401538B/en unknown
2007
- 2007-05-22 US US11/805,085 patent/US8486989B2/en not_active Expired - Fee Related
2009
- 2009-12-09 JP JP2009279701A patent/JP2010090150A/ja active Pending
2013
- 2013-05-29 US US13/904,109 patent/US20140010784A1/en not_active Abandoned

Also Published As

Publication number	Publication date
WO2003035060A1 (en)	2003-05-01
EP1441720B8 (de)	2012-03-28
MXPA04003825A (es)	2004-07-08
US8486989B2 (en)	2013-07-16
AU2002348414B2 (en)	2009-10-01
US7241796B2 (en)	2007-07-10
US20030134889A1 (en)	2003-07-17
ATE539744T1 (de)	2012-01-15
JP4460294B2 (ja)	2010-05-12
EP1441720B1 (de)	2012-01-04
JP2005526002A (ja)	2005-09-02
US20080045480A1 (en)	2008-02-21
EP2402009A1 (de)	2012-01-04
US20140010784A1 (en)	2014-01-09
NZ531681A (en)	2007-05-31
EP1441720A1 (de)	2004-08-04
CA2462163A1 (en)	2003-05-01
JP2010090150A (ja)	2010-04-22

Publication	Publication Date	Title
EP1441720B1 (de)	2012-01-04	Hemmer von serin-protease, insbesondere von hepatitis-c-virus-ns3-ns4a-protease, mit einem kondensierten ringsystem
EP1404704B1 (de)	2006-12-27	Verbrückte bizyklische serinproteaseinhibitoren
AU2002348414A1 (en)	2003-07-03	Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system
RU2440368C2 (ru)	2012-01-20	2-амидо-4-арилокси-1-карбонилпирролидиновые производные в качестве ингибиторов серинпротеаз, в частности протеазы ns3-ns4a hcv
AU2004274468B2 (en)	2009-07-23	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
ZA200408243B (en)	2006-07-26	Inhibitors of serine proteases, particularly hepatitus C virus NS3-NS4 protease
JP2007532474A (ja)	2007-11-15	セリンプロテアーゼ、特にｈｃｖのｎｓ３−ｎｓ４ａプロテアーゼの阻害剤
NZ544789A (en)	2010-01-29	Dithia-azaspiro-nonane and decane derivatives as inhibitors of serine proteases
AU2002320447B2 (en)	2007-04-19	Bridged bicyclic serine protease inhibitors
CN1906208B (zh)	2011-03-30	丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂
AU2002320447A1 (en)	2003-05-22	Bridged bicyclic serine protease inhibitors
HK1065322B (en)	2007-07-20	Bridged bicyclic serine protease inhibitors
AU2012202822A1 (en)	2012-06-07	Inhibitors of Serine Proteases, Particularly HCV NS3-NS4A Protease
HK1098164B (en)	2011-09-09	Inhibitors of serine proteases, particularly hcv ns3-ns4a protease