SK2492003A3 - Peptidomimetic protease inhibitors - Google Patents

Peptidomimetic protease inhibitors Download PDF

Info

Publication number: SK2492003A3
Authority: SK; Slovakia
Prior art keywords: optionally substituted; compound; group; compound according; aryl
Prior art date: 2000-08-31

Application number

SK249-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Robert Edward Babine

Shu Hui Chen

Jason Eric Lamar

Nancy June Snyder

Xicheng David Sun

Mark Joseph Tebbe

Frantz Victor

Q May Wang

Yvonne Yee Mai Yip

Ivan Collado

Cristina Garcia-Paredes

Raymond Samuel Parker Iii

Ling Jin

Deqi Guo

John Irvin Glass

Original Assignee

Lilly Co Eli

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.)

2000-08-31

Filing date

2001-08-31

Publication date

2004-11-03

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26923261&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK2492003(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2001-08-31 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

2004-11-03 Publication of SK2492003A3 publication Critical patent/SK2492003A3/sk

Links

239000000816 peptidomimetic Substances 0.000 title abstract description 13
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 6
239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 6
150000001875 compounds Chemical class 0.000 claims abstract description 730
238000000034 method Methods 0.000 claims abstract description 124
102000014150 Interferons Human genes 0.000 claims abstract description 66
108010050904 Interferons Proteins 0.000 claims abstract description 66
230000000694 effects Effects 0.000 claims abstract description 53
238000002360 preparation method Methods 0.000 claims abstract description 43
239000003001 serine protease inhibitor Substances 0.000 claims abstract description 32
208000015181 infectious disease Diseases 0.000 claims abstract description 28
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
230000008569 process Effects 0.000 claims abstract description 14
239000003937 drug carrier Substances 0.000 claims abstract description 11
208000005176 Hepatitis C Diseases 0.000 claims abstract description 8
108091005804 Peptidases Proteins 0.000 claims abstract description 7
230000002401 inhibitory effect Effects 0.000 claims abstract description 7
230000004962 physiological condition Effects 0.000 claims abstract description 7
239000004365 Protease Substances 0.000 claims abstract description 5
-1 cyclyloxy Chemical group 0.000 claims description 491
125000000217 alkyl group Chemical group 0.000 claims description 143
125000001424 substituent group Chemical group 0.000 claims description 135
125000003118 aryl group Chemical group 0.000 claims description 129
241000711549 Hepacivirus C Species 0.000 claims description 127
125000001931 aliphatic group Chemical group 0.000 claims description 117
125000000464 thioxo group Chemical group S=* 0.000 claims description 105
125000001072 heteroaryl group Chemical group 0.000 claims description 104
239000002253 acid Substances 0.000 claims description 97
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229910052757 nitrogen Inorganic materials 0.000 claims description 71
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125000004433 nitrogen atom Chemical group N* 0.000 claims description 55
229940079322 interferon Drugs 0.000 claims description 52
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125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 43
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 43
125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 38
125000000623 heterocyclic group Chemical group 0.000 claims description 33
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238000010511 deprotection reaction Methods 0.000 claims description 30
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239000000651 prodrug Substances 0.000 claims description 30
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
125000003107 substituted aryl group Chemical group 0.000 claims description 26
229940122055 Serine protease inhibitor Drugs 0.000 claims description 25
101710102218 Serine protease inhibitor Proteins 0.000 claims description 25
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LCEFEIBEOBPPSJ-UHFFFAOYSA-N phenyl selenohypobromite Chemical compound Br[Se]C1=CC=CC=C1 LCEFEIBEOBPPSJ-UHFFFAOYSA-N 0.000 description 1
125000003884 phenylalkyl group Chemical group 0.000 description 1
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical group NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
125000005547 pivalate group Chemical group 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
230000020978 protein processing Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
MBVGZSSYNIBAKI-UHFFFAOYSA-N pyridine-2-carbothioic s-acid Chemical compound OC(=S)C1=CC=CC=N1 MBVGZSSYNIBAKI-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
150000003873 salicylate salts Chemical class 0.000 description 1
229940043230 sarcosine Drugs 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
229940083542 sodium Drugs 0.000 description 1
HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000001433 sodium tartrate Substances 0.000 description 1
229960002167 sodium tartrate Drugs 0.000 description 1
235000011004 sodium tartrates Nutrition 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
125000005717 substituted cycloalkylene group Chemical group 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
YSHDPXQDVKNPKA-UHFFFAOYSA-N tert-butyl 2-(benzhydrylideneamino)acetate Chemical group C=1C=CC=CC=1C(=NCC(=O)OC(C)(C)C)C1=CC=CC=C1 YSHDPXQDVKNPKA-UHFFFAOYSA-N 0.000 description 1
XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 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
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000006173 tetrahydropyranylmethyl group Chemical group 0.000 description 1
125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 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
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
150000003567 thiocyanates Chemical class 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 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
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
150000003952 β-lactams Chemical class 0.000 description 1

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SK249-2003A 2000-08-31 2001-08-31 Peptidomimetic protease inhibitors SK2492003A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US22939800P	2000-08-31	2000-08-31
US27764101P	2001-03-21	2001-03-21
PCT/US2001/026008 WO2002018369A2 (fr)	2000-08-31	2001-08-31	Inhibiteurs peptidomimetiques de protease

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Families Citing this family (241)

* 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
US6608027B1 (en)	1999-04-06	2003-08-19	Boehringer Ingelheim (Canada) Ltd	Macrocyclic peptides active against the hepatitis C virus
DE60111509T2 (de) *	2000-04-03	2006-05-11	Vertex Pharmaceuticals Inc., Cambridge	Inhibitoren von Serin-Proteasen, insbesondere der Hepatitis-C-Virus NS23-Protease
MY164523A (en)	2000-05-23	2017-12-29	Univ Degli Studi Cagliari	Methods and compositions for treating hepatitis c virus
JP5230052B2 (ja)	2000-05-26	2013-07-10	イデニクス（ケイマン）リミテツド	フラビウイルスおよびペスチウイルス治療のための方法および組成物
CZ303213B6 (cs)	2000-07-21	2012-05-23	Schering Corporation	Peptidové inhibitory serinové proteázy NS3 a farmaceutický prostredek
RU2003105221A (ru)	2000-07-21	2004-09-20	Шеринг Корпорейшн (US)	Новые пептиды, как ингибиторы ns3-серинпротеазы вируса гепатита с
US7244721B2 (en)	2000-07-21	2007-07-17	Schering Corporation	Peptides as NS3-serine protease inhibitors of hepatitis C virus
SV2003000617A (es)	2000-08-31	2003-01-13	Lilly Co Eli	Inhibidores de la proteasa peptidomimetica ref. x-14912m
GB2368339B (en)	2000-10-26	2002-09-18	Yissum Res Dev Co	Complex incorporating a plurality of antioxidants
EP1441720B8 (fr) *	2001-10-24	2012-03-28	Vertex Pharmaceuticals Incorporated	Inhibiteurs de la serine protease, en particulier de la protease ns3-ns4a du virus de l'hepatite c, integrant un systeme de cycles accoles
US7119072B2 (en)	2002-01-30	2006-10-10	Boehringer Ingelheim (Canada) Ltd.	Macrocyclic peptides active against the hepatitis C virus
US6642204B2 (en)	2002-02-01	2003-11-04	Boehringer Ingelheim International Gmbh	Hepatitis C inhibitor tri-peptides
US7091184B2 (en)	2002-02-01	2006-08-15	Boehringer Ingelheim International Gmbh	Hepatitis C inhibitor tri-peptides
NZ575692A (en)	2002-04-11	2009-10-30	Vertex Pharma	Inhibitors of Serine Proteases, Particularly Hepatitis C Virus NS3-NS4 Protease
EP1506172B1 (fr) *	2002-05-20	2011-03-30	Bristol-Myers Squibb Company	Inhibiteurs du virus de l'hepatite c
US7608600B2 (en)	2002-06-28	2009-10-27	Idenix Pharmaceuticals, Inc.	Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections
TW200500375A (en)	2002-06-28	2005-01-01	Idenix Cayman Ltd	Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae
WO2004026896A2 (fr) *	2002-09-23	2004-04-01	Medivir Ab	Inhibiteurs de la serine protease ns-3 du virus de l'hepatite c
US20050075279A1 (en)	2002-10-25	2005-04-07	Boehringer Ingelheim International Gmbh	Macrocyclic peptides active against the hepatitis C virus
ATE457716T1 (de)	2002-12-30	2010-03-15	Angiotech Int Ag	Wirkstofffreisetzung von schnell gelierender polymerzusammensetzung
AU2011203054B2 (en) *	2003-04-11	2012-04-26	Vertex Pharmaceuticals, Incorporated	Inhibitors of Serine Proteases, Particularly HCV NS3-NS4A Protease
CN100453553C (zh) *	2003-04-11	2009-01-21	沃泰克斯药物股份有限公司	丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂
CA2522577C (fr)	2003-05-21	2011-04-26	Boehringer Ingelheim International Gmbh	Composes inhibiteurs de l'hepatite c
CN100503628C (zh)	2003-05-30	2009-06-24	法莫赛特股份有限公司	修饰的氟化核苷类似物
CA2532664A1 (fr)	2003-07-18	2005-01-27	Vertex Pharmaceuticals Incorporated	Inhibiteurs de serines proteases, en particulier de la protease ns3-ns4a du vhc
TW201127828A (en) *	2003-09-05	2011-08-16	Vertex Pharma	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
US20050120398A1 (en) *	2003-09-12	2005-06-02	Vertex Pharmaceuticals Incorporated	Animal model for HCV infection
WO2005028502A1 (fr)	2003-09-18	2005-03-31	Vertex Pharmaceuticals, Incorporated	Inhibiteurs de serines proteases, en particulier de la protease ns3-ns4a du vhc
UY28525A1 (es)	2003-09-22	2005-04-29	Boehringer Ingelheim Int	Péptidos macrociclicos activos contra en virus de la hepatitis c
CN1906208B (zh) *	2003-10-10	2011-03-30	沃泰克斯药物股份有限公司	丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂
US7365092B2 (en) *	2003-10-10	2008-04-29	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
AU2004282148A1 (en)	2003-10-10	2005-04-28	Vertex Pharmaceuticals Incoporated	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
US7491794B2 (en)	2003-10-14	2009-02-17	Intermune, Inc.	Macrocyclic compounds as inhibitors of viral replication
WO2005043118A2 (fr)	2003-10-27	2005-05-12	Vertex Pharmaceuticals Incorporated	Methode de decouverte de medicament
EP1944042A1 (fr)	2003-10-27	2008-07-16	Vertex Pharmceuticals Incorporated	Combinaisons pour le traitement HCV
WO2005042570A1 (fr)	2003-10-27	2005-05-12	Vertex Pharmaceuticals Incorporated	Mutants resistant a la protease hcv ns3-ns4a
JP2007509950A (ja) *	2003-10-27	2007-04-19	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	Ｈｃｖ処置の組合せ剤
TW200518746A (en) *	2003-12-11	2005-06-16	Schering Corp	Novel inhibitors of hepatitis C virus NS3/NS4A serine protease
CA2549851C (fr)	2004-01-21	2012-09-11	Boehringer Ingelheim International Gmbh	Peptides macrocycliques actifs contre le virus de l'hepatite c
EP1711515A2 (fr) *	2004-02-04	2006-10-18	Vertex Pharmaceuticals Incorporated	Inhibiteurs de proteases serines, en particulier de la protease hcv ns3-ns4a
BRPI0508085A (pt) *	2004-02-27	2007-07-17	Schering Corp	compostos de enxofre como inibidores da ns3 serina protease do vìrus da hepatite c
WO2005085242A1 (fr) *	2004-02-27	2005-09-15	Schering Corporation	Nouveaux cetoamides a p4 cycliques en tant qu'inhibiteurs de la ns3 serine protease du virus de l'hepatite c
EP1730165A1 (fr) *	2004-02-27	2006-12-13	Schering Corporation	Inhibiteurs de la protease ns3 du virus de l'hepatite c
ES2328589T3 (es) *	2004-02-27	2009-11-16	Schering Corporation	Compuestos de la prolina 3,4(ciclopentil) fusionados como inhibidores de la proteasa serina ns3 del virus de la hepatitis c.
RU2373923C2 (ru) *	2004-06-08	2009-11-27	Вертекс Фармасьютикалз Инкорпорейтед	Фармацевтические композиции
ES2366478T3 (es)	2004-07-20	2011-10-20	Boehringer Ingelheim International Gmbh	Análogos peptídicos inhibidores de la hepatitis c.
UY29016A1 (es)	2004-07-20	2006-02-24	Boehringer Ingelheim Int	Analogos de dipeptidos inhibidores de la hepatitis c
RU2007116265A (ru)	2004-10-01	2008-11-10	Вертекс Фармасьютикалз Инкорпорейтед (Us)	Ингибирование протеазы ns3-ns4a вируса hcv
MY141025A (en)	2004-10-29	2010-02-25	Vertex Pharma	Dose forms
DK1865940T3 (da)	2005-03-21	2013-03-04	Virobay Inc	Alfaketoamidforbindelser som cysteinproteasehæmmere
EP1871365A2 (fr) *	2005-04-12	2008-01-02	Romark Laboratories, L.C.	Procedes pour traiter des maladies par interruption de la maturation de proteines, composes qui inhibent la fonction de chaperons moleculaires tels que des isomerases de disulfure proteiques ou qui interferent avec la glycosylation, compositions pharmaceutiques comprenant ces composes et procedes de
US7569600B2 (en)	2005-05-13	2009-08-04	Virochem Pharma Inc.	Compounds and methods for the treatment of prevention of Flavivirus infections
ES2572980T3 (es)	2005-06-02	2016-06-03	Merck Sharp & Dohme Corp.	Combinación de inhibidores de la proteasa del VHC con un tensioactivo
EP1891089B1 (fr)	2005-06-02	2014-11-05	Merck Sharp & Dohme Corp.	Inhibiteurs de protease du VHC en combinaison avec des aliments
WO2006130553A2 (fr) *	2005-06-02	2006-12-07	Schering Corporation	Methode destinee au traitement de troubles et de maladies ne repondant pas aux interferons, dans laquelle est utilise un inhibiteur de la protease du vhc
US20060276404A1 (en) *	2005-06-02	2006-12-07	Anima Ghosal	Medicaments and methods combining a HCV protease inhibitor and an AKR competitor
US7608592B2 (en)	2005-06-30	2009-10-27	Virobay, Inc.	HCV inhibitors
AU2006274862B2 (en)	2005-07-29	2012-03-22	Medivir Ab	Macrocyclic inhibitors of hepatitis C virus
TWI393723B (zh)	2005-07-29	2013-04-21	Tibotec Pharm Ltd	Ｃ型肝炎病毒之大環抑制劑（九）
EP1919898B1 (fr)	2005-07-29	2011-01-26	Tibotec Pharmaceuticals	Inhibiteurs macrocycliques du virus de l'hépatite c
RU2436787C2 (ru)	2005-07-29	2011-12-20	Тиботек Фармасьютикалз Лтд.	Макроциклические ингибиторы вируса гепатита с
WO2007014925A1 (fr)	2005-07-29	2007-02-08	Tibotec Pharmaceuticals Ltd.	Inhibiteurs macrocycliques du virus de l'hépatite c
PE20070210A1 (es)	2005-07-29	2007-04-16	Tibotec Pharm Ltd	Compuestos macrociclicos como inhibidores del virus de hepatitis c
JO2768B1 (en)	2005-07-29	2014-03-15	تيبوتيك فارماسيوتيكالز ليمتد	Large cyclic inhibitors of hepatitis C virus
PE20070211A1 (es)	2005-07-29	2007-05-12	Medivir Ab	Compuestos macrociclicos como inhibidores del virus de hepatitis c
CN101277950B (zh) *	2005-08-02	2013-03-27	弗特克斯药品有限公司	丝氨酸蛋白酶抑制剂
SG2014013338A (en) *	2005-08-19	2014-06-27	Vertex Pharma	Processes and intermediates
US8399615B2 (en)	2005-08-19	2013-03-19	Vertex Pharmaceuticals Incorporated	Processes and intermediates
US7964624B1 (en)	2005-08-26	2011-06-21	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases
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
EP1951748B1 (fr)	2005-11-11	2013-07-24	Vertex Pharmaceuticals, Inc.	Variantes du virus de l'hépatite c
US7705138B2 (en)	2005-11-11	2010-04-27	Vertex Pharmaceuticals Incorporated	Hepatitis C virus variants
JP4047365B2 (ja) *	2006-01-11	2008-02-13	生化学工業株式会社	シクロアルカンカルボキサミド誘導体及びその製造方法
JP3975226B2 (ja) *	2006-01-11	2007-09-12	生化学工業株式会社	シクロアルキルカルボニルアミノ酸誘導体及びその製造方法
ATE509941T1 (de) *	2006-01-11	2011-06-15	Seikagaku Kogyo Co Ltd	Cycloalkylcarbonylaminosäureester-derivat und herstellungsverfahren dafür
US8183413B2 (en)	2006-01-20	2012-05-22	Kaneka Corporation	Process for production of β-amino-α-hydroxy carboxamide derivative
CA2643688A1 (fr)	2006-02-27	2007-08-30	Vertex Pharmaceuticals Incorporated	Co-cristaux et compositions pharmaceutiques les comprenant
CN101460166B (zh) *	2006-03-06	2014-11-19	Abbvie公司	用于治疗c型肝炎病毒的利托那韦组合物及其用途
EP1993993A1 (fr)	2006-03-16	2008-11-26	Vertex Pharmaceuticals Incorporated	Procédés et intermédiaires pour la synthèse de composés stériques
US20070225297A1 (en)	2006-03-16	2007-09-27	Perni Robert B	Deuterated hepatitis C protease inhibitors
EA018811B1 (ru)	2006-03-20	2013-10-30	Вертекс Фармасьютикалз Инкорпорейтед	Способы получения твердой дисперсии лекарственного средства и твердые дисперсии лекарственного средства, полученные этим способом
WO2007111866A2 (fr) *	2006-03-23	2007-10-04	Schering Corporation	Combinaisons d'un ou plusieurs inhibiteurs de la protéase du vhc et d'un ou plusieurs inhibiteurs de cyp3a4, et méthodes de traitement associées
WO2007120595A2 (fr) *	2006-04-11	2007-10-25	Novartis Ag	Composés organiques et leurs utilisations
UA100666C2 (uk)	2006-04-11	2013-01-25	Новартіс Аг	Інгібітори нсv/віл та їх застосування
JP2009538327A (ja)	2006-05-23	2009-11-05	アイアールエム・リミテッド・ライアビリティ・カンパニー	チャネル活性化プロテアーゼ阻害剤である化合物および組成物
DE102006059317A1 (de) *	2006-07-04	2008-01-10	Evonik Degussa Gmbh	Verfahren zur Herstellung von β-Amino-α-hydroxy-carbonsäureamiden
EP1886685A1 (fr)	2006-08-11	2008-02-13	INSERM (Institut National de la Santé et de la Recherche Médicale)	Méthodes, utilisations et compositions pour la modulation de la réplication du HCV par activation ou inhibition du récepteur farnesoid X
US20120220520A1 (en) *	2006-10-17	2012-08-30	Van T Klooster Gerben Albert Eleutherius	Bioavailable combinations for hcv treatment
CN102675279A (zh)	2006-11-15	2012-09-19	Viro化学制药公司	用于治疗或预防黄病毒属感染的噻吩类似物
ES2470568T3 (es)	2006-11-17	2014-06-24	Janssen R&D Ireland	Inhibidores macroc�clicos del virus de la hepatitis C
WO2008073282A2 (fr)	2006-12-07	2008-06-19	Schering Corporation	Formulation de matrice sensible au ph
WO2008074035A1 (fr) *	2006-12-27	2008-06-19	Abbott Laboratories	Inhibiteurs de protéase du vhc et utilisations de ceux-ci
WO2008095058A1 (fr) *	2007-02-01	2008-08-07	Taigen Biotechnology Co. Ltd.	Inhibiteurs de la protéase du virus de l'hépatite c
BRPI0807087A2 (pt)	2007-02-08	2014-06-10	Tibotec Pharm Ltd	Inibidores de hcv macrocíclicos substituídos de pirimidina
BRPI0807483A2 (pt)	2007-02-09	2014-05-13	Irm Llc	Compostos e composições como inibidores de protease de ativação de canal
MX2009009182A (es)	2007-02-27	2009-09-04	Vertex Pharma	Co-cristales y composiciones farmaceuticas que los comprenden.
EP2134717A2 (fr)	2007-02-27	2009-12-23	Vertex Pharmceuticals Incorporated	Inhibiteurs de sérine protéases
WO2008127613A1 (fr) *	2007-04-11	2008-10-23	Scynexis, Inc.	Compositions pharmaceutiques inédites
EP2494991A1 (fr)	2007-05-04	2012-09-05	Vertex Pharmaceuticals Incorporated	Polythérapie pour le traitement de l'infection par VHC
KR101558403B1 (ko) *	2007-08-03	2015-10-07	바이오트론 리미티드	Ｃ형 간염 바이러스 조성물 및 방법
NZ583699A (en)	2007-08-30	2012-04-27	Vertex Pharma	Co-crystals of vx-950 (telaprevir) other components and pharmaceutical compositions comprising the same
DK2061513T3 (da)	2007-09-14	2011-11-21	Schering Corp	Fremgangsmåde til behandling af patienter med hepatitis C
US20090082366A1 (en) *	2007-09-26	2009-03-26	Protia, Llc	Deuterium-enriched telaprevir
AU2008309589B2 (en)	2007-10-10	2012-07-05	Novartis Ag	Spiropyrrolidines and their use against HCV and HIV infection
EP2215076A4 (fr)	2007-10-24	2012-05-02	Virobay Inc	Composés capables d'inhiber la protéase cathepsine s et la réplication du hcv
WO2009055335A2 (fr) *	2007-10-25	2009-04-30	Taigen Biotechnology Co., Ltd.	Inhibiteurs des protéases du vhc
AU2008339917B2 (en)	2007-12-24	2013-02-07	Tibotec Pharmaceuticals	Macrocyclic indoles as hepatitis C virus inhibitors
DE102008009761A1 (de)	2008-02-19	2009-08-27	Bayer Materialscience Ag	Verfahren zur Herstellung von Isocyanaten
EP2101173A1 (fr)	2008-03-14	2009-09-16	Vivalis	Procédé in vitro pour déterminer si un candidat destiné à un médicament pour une protéine cible est actif contre une variante de cette protéine
CN101580535B (zh) *	2008-05-16	2012-10-03	太景生物科技股份有限公司	丙型肝炎病毒蛋白酶抑制剂
AU2009271325A1 (en)	2008-06-24	2010-01-21	Merck Sharp & Dohme Corp.	Biocatalytic processes for the preparation of substantially stereomerically pure fused bicyclic proline compounds
US8569337B2 (en)	2008-07-23	2013-10-29	Vertex Pharmaceuticals Incorporated	Tri-cyclic pyrazolopyridine kinase inhibitors
WO2010014744A1 (fr) *	2008-07-29	2010-02-04	The Scripps Research Institute	Inhibiteurs d'une infection par le virus de l'hépatite c
US8188137B2 (en)	2008-08-15	2012-05-29	Avila Therapeutics, Inc.	HCV protease inhibitors and uses thereof
BRPI0922364A2 (pt)	2008-12-03	2017-08-29	Presidio Pharmaceuticals Inc	Composto, composição farmacêutica e uso de um composto
KR101784830B1 (ko)	2008-12-03	2017-10-16	프레시디오 파마슈티칼스, 인코포레이티드	Ｈｃｖｎｓ5ａ의 억제제
GB0900914D0 (en)	2009-01-20	2009-03-04	Angeletti P Ist Richerche Bio	Antiviral agents
EP2396028A2 (fr)	2009-02-12	2011-12-21	Vertex Pharmceuticals Incorporated	Polythérapie contre le hcv comprenant de l'interféron pégylé, de la ribavirine et de la telaprevir
PE20120773A1 (es)	2009-03-27	2012-07-19	Presidio Pharmaceuticals Inc	Anillos triciclicos fusionados sustituidos como inhibidores del virus de hepatitis c
US20110182850A1 (en)	2009-04-10	2011-07-28	Trixi Brandl	Organic compounds and their uses
US8512690B2 (en)	2009-04-10	2013-08-20	Novartis Ag	Derivatised proline containing peptide compounds as protease inhibitors
TW201113279A (en)	2009-06-23	2011-04-16	Gilead Sciences Inc	Pharmaceutical compositions useful for treating HCV
HRP20161025T1 (hr) *	2009-09-15	2016-11-04	Taigen Biotechnology Co., Ltd.	Inhibitori proteaze hcv-a
TWI404269B (zh) *	2009-09-18	2013-08-01	Advanced Connectek Inc	High speed plug connector
UA108211C2 (uk)	2009-11-04	2015-04-10	Янссен Рід Айрленд	Бензімідазолімідазольні похідні
MX2012006026A (es)	2009-11-25	2012-08-15	Vertex Pharma	Derivados de acido 5-alquinil-tiofen-2-carboxilico y usos para tratamiento o prevencion de infecciones por flavivirus.
AR079528A1 (es) *	2009-12-18	2012-02-01	Idenix Pharmaceuticals Inc	Inhibidores de arileno o heteroarileno 5,5-fusionado del virus de la hepatitis c
JP2013515746A (ja)	2009-12-24	2013-05-09	ヴァ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又は予防のための類似体
US20110178107A1 (en) *	2010-01-20	2011-07-21	Taigen Biotechnology Co., Ltd.	Hcv protease inhibitors
PL2528922T3 (pl)	2010-01-27	2018-01-31	Ab Pharma Ltd	Związki poliheterocykliczne jako inhibitory hcv
TW201130502A (en)	2010-01-29	2011-09-16	Vertex Pharma	Therapies for treating hepatitis C virus infection
WO2011112516A1 (fr)	2010-03-08	2011-09-15	Ico Therapeutics Inc.	Traitement et prévention de l'infection par le virus de l'hépatite c en utilisant des oligonucléotides antisens de la kinase c-raf
TW201200522A (en)	2010-03-24	2012-01-01	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
EP2550268A1 (fr)	2010-03-24	2013-01-30	Vertex Pharmaceuticals Incorporated	Analogues pour traiter ou prévenir les infections à flavivirus
CN102869657A (zh)	2010-03-24	2013-01-09	沃泰克斯药物股份有限公司	用于治疗或预防黄病毒感染的类似物
US8680071B2 (en)	2010-04-01	2014-03-25	Idenix Pharmaceuticals, Inc.	Compounds and pharmaceutical compositions for the treatment of viral infections
EP2575866A4 (fr)	2010-05-24	2013-10-16	Presidio Pharmaceuticals Inc	Inhibiteurs de ns5a du vhc
WO2011153423A2 (fr)	2010-06-03	2011-12-08	Vertex Pharmaceuticals Incorporated	Procédés et produits intermédiaires
WO2011156545A1 (fr)	2010-06-09	2011-12-15	Vertex Pharmaceuticals Incorporated	Modèle dynamique viral pour une polythérapie contre le vhc
WO2011159826A2 (fr)	2010-06-15	2011-12-22	Vertex Pharmaceuticals Incorporated	Mutants de la protéase ns5b du vhc
WO2012006070A1 (fr)	2010-06-28	2012-01-12	Vertex Pharmaceuticals Incorporated	Composés et méthodes de traitement ou de prévention d'infections à flavivirus
EP2585448A1 (fr)	2010-06-28	2013-05-01	Vertex Pharmaceuticals Incorporated	Composés et méthodes de traitement ou de prévention d'infections à flavovirus
UY33473A (es)	2010-06-28	2012-01-31	Vertex Pharma	Compuestos y métodos para el tratamiento o la prevencion de infecciones por flavivirus
WO2012009503A1 (fr)	2010-07-14	2012-01-19	Vertex Pharmaceuticals Incorporated	Composition pharmaceutique au goût agréable comprenant vx-950
WO2012020036A1 (fr)	2010-08-13	2012-02-16	F. Hoffmann-La Roche Ag	Inhibiteurs du virus de l'hépatite c
AU2011292040A1 (en)	2010-08-17	2013-03-07	Vertex Pharmaceuticals Incorporated	Compounds and methods for the treatment or prevention of Flaviviridae viral infections
EA025341B1 (ru)	2010-09-22	2016-12-30	Алиос Биофарма, Инк.	Замещенные аналоги нуклеотидов
AU2011311880B2 (en)	2010-10-08	2014-07-24	Novartis Ag	Vitamin E formulations of sulfamide NS3 inhibitors
US20140308242A1 (en)	2010-10-21	2014-10-16	Vertex Pharmaceuticals Incorporated	Biomarkers for hcv infected patients
US20130302282A1 (en)	2010-10-26	2013-11-14	Presidio Pharmaceuticals, Inc.	Inhibitors of Hepatitis C Virus
WO2012109646A1 (fr)	2011-02-11	2012-08-16	Vertex Pharmaceuticals Incorporated	Traitement du vhc chez des patients infectés par le vih
WO2012107589A1 (fr)	2011-02-11	2012-08-16	INSERM (Institut National de la Santé et de la Recherche Médicale)	Méthodes et compositions pharmaceutiques pour le traitement et la prévention des infections à vhc
WO2012123298A1 (fr)	2011-03-11	2012-09-20	F. Hoffmann-La Roche Ag	Composés antiviraux
EP2691409B1 (fr)	2011-03-31	2018-02-21	Idenix Pharmaceuticals LLC.	Composés et compositions pharmaceutiques pour le traitement d'infections virales
WO2012151319A1 (fr)	2011-05-02	2012-11-08	Virobay, Inc.	Inhibiteur de cathepsine pour le traitement du cancer des os et de la douleur provoquée par le cancer des os
EP2707347A1 (fr)	2011-05-13	2014-03-19	Vertex Pharmaceuticals Inc.	Procédés et intermédiaires
AU2012269643A1 (en)	2011-06-16	2014-02-06	AB Pharma Ltd.	Macrocyclic heterocyclic compound for inhibiting hepatitis C virus and preparation and use thereof
CN103732242A (zh)	2011-06-23	2014-04-16	迪格纳生物技术公司	用与IFN-α2b组合的IFN-α5在患者群体中治疗慢性丙型肝炎
US20120328565A1 (en)	2011-06-24	2012-12-27	Brinkman John A	Antiviral compounds
AU2012286853A1 (en)	2011-07-26	2013-05-02	Vertex Pharmaceuticals Incorporated	Thiophene compounds
WO2013016499A1 (fr)	2011-07-26	2013-01-31	Vertex Pharmaceuticals Incorporated	Procédés de préparation de composés du thiophène
JP2014526474A (ja)	2011-09-12	2014-10-06	アイディニ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	ウイルス感染の治療のための化合物および薬学的組成物
WO2013049382A2 (fr)	2011-09-27	2013-04-04	Kansas State University Research Foundation	Antiviraux à large spectre contre des protéases 3c ou 3c-associées du super-groupe des picornavirus-associés : picornavirus, calicivirus et coronavirus
WO2013053657A1 (fr)	2011-10-10	2013-04-18	F. Hoffmann-La Roche Ag	Composés antiviraux
IN2014CN02805A (fr)	2011-10-14	2015-07-03	Bristol Myers Squibb Co
ES2699226T3 (es)	2011-10-14	2019-02-08	Bristol Myers Squibb Co	Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa
CN103974938B (zh)	2011-10-14	2016-11-09	百时美施贵宝公司	作为因子xia抑制剂的经取代的四氢异喹啉化合物
US8492386B2 (en)	2011-10-21	2013-07-23	Abbvie Inc.	Methods for treating HCV
EP2583680A3 (fr)	2011-10-21	2013-06-12	Abbvie Inc.	Traitement seul (PSI-7977) ou combinatoire dans l'utilisation pour le traitement du VHC
US8466159B2 (en)	2011-10-21	2013-06-18	Abbvie Inc.	Methods for treating HCV
SE1450130A1 (sv)	2011-10-21	2014-05-07	Abbvie Inc	Förfaranden för att behandla hcv innefattande minst två direktverkande antivirala agenser, ribavirin men inte interferon
US9133170B2 (en)	2011-12-16	2015-09-15	Hoffmann-La Roche Inc.	Inhibitors of HCV NS5A
EA024297B1 (ru)	2011-12-20	2016-09-30	Рибосайенс Ллк	2',4'-дифтор-2'-метилзамещенные нуклеозидные производные в качестве ингибиторов репликации рнк вируса гепатита с
SG11201403086YA (en)	2011-12-20	2014-07-30	Hoffmann La Roche	4'-azido, 3'-fluoro substituted nucleoside derivatives as inhibitors of hcv rna replication
CA2858659A1 (fr)	2011-12-28	2013-07-04	Janssen R&D Ireland	Derives heterobicycliques en tant qu'inhibiteurs de vhc
WO2013116339A1 (fr)	2012-01-31	2013-08-08	Vertex Pharmaceuticals Incorporated	Formulations très puissantes de vx-950
ITMI20120192A1 (it)	2012-02-13	2013-08-14	Dipharma Francis Srl	Procedimento per la preparazione di un inibitore delle proteasi virali e suoi intermedi
MX357561B (es) *	2012-02-16	2018-07-13	Rqx Pharmaceuticals Inc	Antibióticos peptídicos lineales.
BR112014015582A8 (pt)	2012-02-24	2017-07-04	Hoffmann La Roche	compostos antivirais
ITMI20120359A1 (it)	2012-03-07	2013-09-08	Dipharma Francis Srl	Procedimento per la preparazione di intermedi utili nella preparazione di un inibitore delle proteasi virali
WO2013136265A1 (fr)	2012-03-13	2013-09-19	Dipharma Francis S.R.L.	Synthèse d'un intermédiaire d'un composé antiviral
ITMI20120391A1 (it) *	2012-03-13	2013-09-14	Dipharma Francis Srl	Procedimento per la sintesi di un intermedio ciclopropilammidico utile nella preparazione di un inibitore delle proteasi virali
US8916538B2 (en)	2012-03-21	2014-12-23	Vertex Pharmaceuticals Incorporated	Solid forms of a thiophosphoramidate nucleotide prodrug
HK1203356A1 (en)	2012-03-22	2015-10-30	艾丽奥斯生物制药有限公司	Pharmaceutical combinations comprising a thionucleotide analog
CA2872147A1 (fr)	2012-05-02	2013-11-07	Kansas State University Research Foundation	Composes macrocycliques et peptidomimetiques en tant qu'antiviraux a large spectre contre des proteases 3c ou de type 3c de picornavirus, calicivirus et coronavirus
ITMI20120800A1 (it) *	2012-05-10	2013-11-11	Dipharma Francis Srl	Procedimento per la preparazione di un intermedio utile nella preparazione di un inibitore delle proteasi virali
AR091192A1 (es)	2012-05-30	2015-01-21	Chemo Iberica Sa	Procedimiento multicomponente para la preparacion de compuestos biciclicos
CN103450066B (zh) *	2012-05-30	2017-03-15	博瑞生物医药（苏州）股份有限公司	特拉匹韦中间体的制备方法
US20140010783A1 (en)	2012-07-06	2014-01-09	Hoffmann-La Roche Inc.	Antiviral compounds
WO2014015217A1 (fr)	2012-07-19	2014-01-23	Vertex Pharmaceuticals Incorporated	Biomarqueurs pour patients infectés par le hcv
WO2014033667A1 (fr)	2012-08-30	2014-03-06	Ranbaxy Laboratories Limited	Procédé pour la préparation de télaprévir
WO2014045263A2 (fr) *	2012-09-24	2014-03-27	Dr. Reddy's Laboratories Limited	Procédé de préparation d'intermédiaires du télaprévir
JP6154473B2 (ja)	2012-10-12	2017-06-28	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	第ＸＩａ因子阻害剤の結晶形
WO2014059214A1 (fr)	2012-10-12	2014-04-17	Bristol-Myers Squibb Company	Composés de tétrahydroisoquinoléine à substitution guanidine et amine utilisés comme inhibiteurs du facteur xia
US9315519B2 (en)	2012-10-12	2016-04-19	Bristol-Myers Squibb Company	Guanidine substituted tetrahydroisoquinoline compounds as factor XIa inhibitors
WO2014068265A1 (fr)	2012-10-29	2014-05-08	Cipla Limited	Analogues de phosphonate antiviraux et leur procédé de préparation
ITMI20122036A1 (it)	2012-11-29	2014-05-30	Dipharma Francis Srl	Sintesi di un intermedio di un composto antivirale
WO2014096374A1 (fr)	2012-12-21	2014-06-26	Sandoz Ag	Procédé de synthèse de pyrrolidines et de pyrroles
MX2015009176A (es)	2013-01-23	2015-11-09	Hoffmann La Roche	Derivados de triazola antivirales.
CN103113288B (zh) *	2013-02-04	2015-05-20	苏州永健生物医药有限公司	一种八氢环戊烯并[c]吡咯羧酸衍生物的合成方法
WO2014134251A1 (fr)	2013-02-28	2014-09-04	Vertex Pharmaceuticals Incorporated	Compositions pharmaceutiques
WO2014135422A1 (fr)	2013-03-05	2014-09-12	F. Hoffmann-La Roche Ag	Composés antiviraux
ES2712699T3 (es)	2013-03-25	2019-05-14	Bristol Myers Squibb Co	Tetrahidroisoquinolinas que contienen azoles sustituidos como inhibidores del factor XIa
ITMI20130706A1 (it)	2013-04-30	2014-10-31	Dipharma Francis Srl	Procedimento per la preparazione di un inibitore delle proteasi virali e suoi intermedi
US20180200280A1 (en)	2013-05-16	2018-07-19	Riboscience Llc	4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication
MY186547A (en)	2013-05-16	2021-07-26	Riboscience Llc	4?-fluoro-2?-methyl substituted nucleoside derivatives
EA201592185A1 (ru)	2013-05-16	2016-05-31	Рибосайенс Ллк	4'-азидо, 3'-дезокси-3'-фторзамещенные нуклеозидные производные
CN104163851B (zh) *	2013-05-20	2019-03-05	湘北威尔曼制药股份有限公司	氟代的α-羰基类HCV NS3/4A丝氨酸蛋白酶抑制剂
CN103288671B (zh) *	2013-06-20	2014-10-29	上海步越化工科技有限公司	一种(3s)-3-氨基-n-环丙基-2-羟基己酰胺盐酸盐的合成方法
WO2014203224A1 (fr)	2013-06-21	2014-12-24	Ranbaxy Laboratories Limited	Procédé pour la préparation de télaprévir et d'intermédiaires de télaprévir
WO2014203208A1 (fr)	2013-06-21	2014-12-24	Ranbaxy Laboratories Limited	Procédé pour la préparation de télaprévir et d'intermédiaires de télaprévir
CN104292146B (zh) *	2013-06-24	2017-04-26	上海医药工业研究院	特拉匹韦中间体及其制备方法
CN104558106B (zh) *	2013-10-19	2019-12-10	广东东阳光药业有限公司	一种治疗丙肝药物的制备方法
CN104610272B (zh) *	2013-11-05	2017-03-29	上海唐润医药科技有限公司	环状黄酮或异黄酮类化合物及其用途
EP2899207A1 (fr)	2014-01-28	2015-07-29	Amikana.Biologics	Nouveau procédé pour tester l'inhibition de la protéase du HCV
TWI688564B (zh)	2014-01-31	2020-03-21	美商必治妥美雅史谷比公司	作為凝血因子ｘｉａ抑制劑之具有雜環p2'基團之巨環化合物
NO2760821T3 (fr)	2014-01-31	2018-03-10
CN104926712B (zh) *	2014-03-20	2018-03-23	上海医药工业研究院	合成特拉匹韦的中间体及其制备方法
CN104926831A (zh) *	2014-03-20	2015-09-23	上海医药工业研究院	合成特拉匹韦的中间体及其制备方法
US10240427B2 (en)	2014-07-07	2019-03-26	Halliburton Energy Services, Inc.	Downhole tools comprising aqueous-degradable sealing elements
WO2016036893A1 (fr)	2014-09-04	2016-03-10	Bristol-Myers Squibb Company	Diamides macrocycliques qui sont des inhibiteurs de fxia
US9453018B2 (en)	2014-10-01	2016-09-27	Bristol-Myers Squibb Company	Pyrimidinones as factor XIa inhibitors
EP3423469A1 (fr)	2016-03-04	2019-01-09	H. Hoffnabb-La Roche Ag	Nouveaux dérivés de trifluorométhylpropanamide utilisés comme inhibiteurs de htra1
WO2017148967A1 (fr)	2016-03-04	2017-09-08	F. Hoffmann-La Roche Ag	Nouveaux dérivés de difluorocétamide utilisés en tant qu'inhibiteurs de htra1
EA201892448A1 (ru)	2016-04-28	2019-06-28	Эмори Юниверсити	Алкинсодержащие нуклеотидные и нуклеозидные терапевтические композиции и связанные с ними способы применения
CN109476637B (zh)	2016-06-21	2022-02-01	奥瑞恩眼科有限责任公司	杂环脯氨酰胺衍生物
KR102512201B1 (ko) *	2016-06-21	2023-03-20	오리온 옵탈몰로지 엘엘씨	지방족 프롤린아미드 유도체
WO2017222914A1 (fr)	2016-06-21	2017-12-28	Inception 4, Inc.	Dérivés de prolinamide carbocycliques
CN109661389A (zh) *	2016-08-23	2019-04-19	豪夫迈·罗氏有限公司	作为htra1抑制剂的新型二氟酮酰胺衍生物
WO2019060740A1 (fr)	2017-09-21	2019-03-28	Riboscience Llc	Dérivés nucléosidiques à substitution 4'-fluoro-2'-méthyle utilisés comme inhibiteurs de la réplication de l'arn du vhc
CN109337537B (zh) *	2018-09-26	2022-10-25	河北晨阳工贸集团有限公司	一种起重机专用单组分水性面漆及其制备方法
CN110668538B (zh) *	2019-09-20	2021-10-22	济南大学	一种聚合氯化钛的制备方法
CN115960088B (zh) *	2020-07-31	2024-07-26	四川大学	一种新型冠状病毒主蛋白酶的抑制剂及其制备方法和用途
CN114057702B (zh) *	2020-07-31	2022-09-30	四川大学	一种新型冠状病毒主蛋白酶的抑制剂及其制备方法和用途
US12083099B2 (en)	2020-10-28	2024-09-10	Accencio LLC	Methods of treating symptoms of coronavirus infection with viral protease inhibitors
WO2023149981A1 (fr) *	2022-02-07	2023-08-10	Purdue Research Foundation	Composés pour le traitement du sars
CN114703003B (zh) *	2022-04-14	2023-04-28	上海绿晟环保科技有限公司	一种负载碳量子点的纳米材料润滑添加剂及其制备方法
CN115417790A (zh) *	2022-10-09	2022-12-02	山东大学	一类新型偶氮类发泡剂及合成方法
KR102829944B1 (ko)	2023-05-16	2025-07-03	최유성	하천 준설토 관리시스템

Family Cites Families (163)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3719667A (en)	1970-08-24	1973-03-06	Lilly Co Eli	Epimerization of 6-acylamido and 6-imido penicillin sulfoxide esters
US3840556A (en)	1971-05-28	1974-10-08	Lilly Co Eli	Penicillin conversion by halogen electrophiles and anti-bacterials derived thereby
DE3226768A1 (de)	1981-11-05	1983-05-26	Hoechst Ag, 6230 Frankfurt	Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung
DE3211676A1 (de)	1982-03-30	1983-10-06	Hoechst Ag	Neue derivate von cycloalka (c) pyrrol-carbonsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue cycloalka (c) pyrrol-carbonsaeuren als zwischenstufen und verfahren zu deren herstellung
US4499082A (en)	1983-12-05	1985-02-12	E. I. Du Pont De Nemours And Company	α-Aminoboronic acid peptides
FR2570695A1 (fr) *	1984-09-27	1986-03-28	Synthelabo	Diphenylazomethines a chaine ramifiee ou cyclique, leur preparation et leur application en therapeutique
FR2575753B1 (fr)	1985-01-07	1987-02-20	Adir	Nouveaux derives peptidiques a structure polycyclique azotee, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US5496927A (en)	1985-02-04	1996-03-05	Merrell Pharmaceuticals Inc.	Peptidase inhibitors
EP0204571B1 (fr) *	1985-06-07	1992-01-22	Ici Americas Inc.	Dérivés difluoro choisis
US4835168A (en)	1985-12-16	1989-05-30	Eli Lilly And Company	Thiadiazole antiviral agents
US5231084A (en)	1986-03-27	1993-07-27	Hoechst Aktiengesellschaft	Compounds having a cognition adjuvant action, agents containing them, and the use thereof for the treatment and prophylaxis of cognitive dysfuncitons
US5736520A (en)	1988-10-07	1998-04-07	Merrell Pharmaceuticals Inc.	Peptidase inhibitors
NZ235155A (en)	1989-09-11	1993-04-28	Merrell Dow Pharma	Peptidase substrates in which the carboxy terminal group has been replaced by a tricarbonyl radical
US5371072A (en) *	1992-10-16	1994-12-06	Corvas International, Inc.	Asp-Pro-Arg α-keto-amide enzyme inhibitors
EP0604182B1 (fr)	1992-12-22	2000-10-11	Eli Lilly And Company	Inhibiteurs de la protéase du VIH
KR100187990B1 (ko)	1992-12-29	1999-06-01	스티븐 에프. 웨인스톡	레트로바이러스성 프로테아제 억제 화합물 제조용 합성 중간체
US5384410A (en)	1993-03-24	1995-01-24	The Du Pont Merck Pharmaceutical Company	Removal of boronic acid protecting groups by transesterification
US5656600A (en) *	1993-03-25	1997-08-12	Corvas International, Inc.	α-ketoamide derivatives as inhibitors of thrombosis
US5672582A (en)	1993-04-30	1997-09-30	Merck & Co., Inc.	Thrombin inhibitors
IL110752A (en)	1993-09-13	2000-07-26	Abbott Lab	Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor
US5559158A (en)	1993-10-01	1996-09-24	Abbott Laboratories	Pharmaceutical composition
US5468858A (en)	1993-10-28	1995-11-21	The Board Of Regents Of Oklahoma State University Physical Sciences	N-alkyl and n-acyl derivatives of 3,7-diazabicyclo-[3.3.1]nonanes and selected salts thereof as multi-class antiarrhythmic agents
IL111991A (en)	1994-01-28	2000-07-26	Abbott Lab	Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent
HUT72440A (en)	1994-03-31	1996-04-29	Bristol Myers Squibb Co	Imidazole-containing inhibitors of farnesyl protein transferase and pharmaceutical compositions containing them
US5847135A (en)	1994-06-17	1998-12-08	Vertex Pharmaceuticals, Incorporated	Inhibitors of interleukin-1β converting enzyme
US5756466A (en)	1994-06-17	1998-05-26	Vertex Pharmaceuticals, Inc.	Inhibitors of interleukin-1β converting enzyme
US6420522B1 (en)	1995-06-05	2002-07-16	Vertex Pharmaceuticals Incorporated	Inhibitors of interleukin-1β converting enzyme
US5716929A (en)	1994-06-17	1998-02-10	Vertex Pharmaceuticals, Inc.	Inhibitors of interleukin-1β converting enzyme
US5861267A (en)	1995-05-01	1999-01-19	Vertex Pharmaceuticals Incorporated	Methods, nucleotide sequences and host cells for assaying exogenous and endogenous protease activity
US6037157A (en)	1995-06-29	2000-03-14	Abbott Laboratories	Method for improving pharmacokinetics
JPH09124691A (ja) *	1995-08-25	1997-05-13	Green Cross Corp:The	ペプチド化合物およびそれを含有する医薬組成物
JP2000500760A (ja)	1995-11-23	2000-01-25	メルクシヤープエンドドームリミテツド	スピロピペリジン誘導体およびタキキニン拮抗薬としてのその使用
US6054472A (en)	1996-04-23	2000-04-25	Vertex Pharmaceuticals, Incorporated	Inhibitors of IMPDH enzyme
US5807876A (en)	1996-04-23	1998-09-15	Vertex Pharmaceuticals Incorporated	Inhibitors of IMPDH enzyme
ZA972195B (en)	1996-03-15	1998-09-14	Du Pont Merck Pharma	Spirocycle integrin inhibitors
TR199802136T2 (xx)	1996-04-23	2001-06-21	Vertex Pharmaceuticals Incorporated	�MPDH enzimi inhibit�rleri olarak �re t�revleri.
US6127422A (en)	1996-05-06	2000-10-03	Eli Lilly And Company	Anti-viral method
US5990276A (en)	1996-05-10	1999-11-23	Schering Corporation	Synthetic inhibitors of hepatitis C virus NS3 protease
JPH11513890A (ja)	1996-05-10	1999-11-30	シェーリングコーポレイション	Ｃ型肝炎ウイルスｎｓ３プロテアーゼの合成インヒビター
CN1218479A (zh)	1996-05-17	1999-06-02	咨询卡有限公司	可固化的表面涂层组合物及其使用方法
US6245919B1 (en) *	1996-06-28	2001-06-12	Haruhiko Shinozaki	Cyclopropylglycine derivatives and agonists for metabotronic L-glutamate receptors
EP0913389A4 (fr) *	1996-06-28	2000-02-02	Nippon Chemiphar Co	Derives de cyclopropylglycine et agoniste du recepteur du l-glutamate du type a regulation metabolique
US6153579A (en)	1996-09-12	2000-11-28	Vertex Pharmaceuticals, Incorporated	Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex
US6046195A (en)	1996-09-25	2000-04-04	Merck Sharp & Dohme Ltd.	Spiro-azacyclic derivatives, their preparation and their use as tachykinin antagonists
JP2001502316A (ja)	1996-10-08	2001-02-20	コロラドステートユニバーシティリサーチファンデーション	触媒不斉エポキシ化
CZ298749B6 (cs)	1996-10-18	2008-01-16	Vertex Pharmaceuticals Incorporated	Inhibitory serinových proteáz a farmaceutické prostředky s jejich obsahem
GB9623908D0 (en)	1996-11-18	1997-01-08	Hoffmann La Roche	Amino acid derivatives
DE19648011A1 (de)	1996-11-20	1998-05-28	Bayer Ag	Cyclische Imine
ATE244717T1 (de)	1997-03-14	2003-07-15	Vertex Pharma	Inhibitoren des impdh-enzyms
GB9707659D0 (en)	1997-04-16	1997-06-04	Peptide Therapeutics Ltd	Hepatitis C NS3 Protease inhibitors
GB9708484D0 (en)	1997-04-25	1997-06-18	Merck Sharp & Dohme	Therapeutic agents
GB9711114D0 (en)	1997-05-29	1997-07-23	Merck Sharp & Dohme	Therapeutic agents
DK1003775T3 (da) *	1997-08-11	2005-05-30	Boehringer Ingelheim Ca Ltd	Hepatitis C-inhibitorpeptider
US6767991B1 (en)	1997-08-11	2004-07-27	Boehringer Ingelheim (Canada) Ltd.	Hepatitis C inhibitor peptides
WO1999007734A2 (fr)	1997-08-11	1999-02-18	Boehringer Ingelheim (Canada) Ltd.	Analogues de peptides inhibiteurs de l'hepatite c
US6183121B1 (en)	1997-08-14	2001-02-06	Vertex Pharmaceuticals Inc.	Hepatitis C virus helicase crystals and coordinates that define helicase binding pockets
US20040058982A1 (en)	1999-02-17	2004-03-25	Bioavailability System, Llc	Pharmaceutical compositions
US20020017295A1 (en)	2000-07-07	2002-02-14	Weers Jeffry G.	Phospholipid-based powders for inhalation
WO1999028482A2 (fr)	1997-11-28	1999-06-10	Schering Corporation	Complexes recombinants monocatenaires de la protease ns3 et du peptide co-facteur ns4a du virus de l'hepatite c (vhc)
EP1066247B1 (fr)	1998-03-31	2006-11-22	Vertex Pharmaceuticals Incorporated	Inhibiteurs de serine protease, particulierement de la protease ns3 du virus de l'hepatite c
US6518305B1 (en) *	1998-04-23	2003-02-11	Abbott Laboratories	Five-membered carbocyclic and heterocyclic inhibitors of neuraminidases
US6251583B1 (en)	1998-04-27	2001-06-26	Schering Corporation	Peptide substrates for HCV NS3 protease assays
GB9812523D0 (en)	1998-06-10	1998-08-05	Angeletti P Ist Richerche Bio	Peptide inhibitors of hepatitis c virus ns3 protease
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.
US6323180B1 (en)	1998-08-10	2001-11-27	Boehringer Ingelheim (Canada) Ltd	Hepatitis C inhibitor tri-peptides
DE19836514A1 (de)	1998-08-12	2000-02-17	Univ Stuttgart	Modifikation von Engineeringpolymeren mit N-basischen Gruppe und mit Ionenaustauschergruppen in der Seitenkette
US6117639A (en)	1998-08-31	2000-09-12	Vertex Pharmaceuticals Incorporated	Fusion proteins, DNA molecules, vectors, and host cells useful for measuring protease activity
US6025516A (en)	1998-10-14	2000-02-15	Chiragene, Inc.	Resolution of 2-hydroxy-3-amino-3-phenylpropionamide and its conversion to C-13 sidechain of taxanes
EP1027885B1 (fr)	1999-02-09	2008-07-09	Pfizer Products Inc.	Compositions de médicaments basiques avec une meilleure biodisponibilité
US20020042046A1 (en)	1999-02-25	2002-04-11	Vertex Pharmaceuticals, Incorporated	Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex
ES2405316T3 (es)	1999-03-19	2013-05-30	Vertex Pharmaceuticals Incorporated	Inhibidores de la enzima IMPDH
US6608027B1 (en)	1999-04-06	2003-08-19	Boehringer Ingelheim (Canada) Ltd	Macrocyclic peptides active against the hepatitis C virus
US7122627B2 (en)	1999-07-26	2006-10-17	Bristol-Myers Squibb Company	Lactam inhibitors of Hepatitis C virus NS3 protease
US20020183249A1 (en)	1999-08-31	2002-12-05	Taylor Neil R.	Method of identifying inhibitors of CDC25
CA2390349A1 (fr)	1999-12-03	2001-06-07	Bristol-Myers Squibb Pharma Company	Inhibiteurs d'alpha-cetoamides de la protease ns3 du virus de l'hepatite c
US6365380B2 (en) *	2000-02-23	2002-04-02	Pcbu Services, Inc.	Method for stereoselectively inverting a chiral center of a chemical compound using an enzyme and a metal catalyst
EP1261611A2 (fr)	2000-02-29	2002-12-04	Bristol-Myers Squibb Pharma Company	Inhibiteurs de la prot ase ns3 du virus de l'h patite c
DE60111509T2 (de)	2000-04-03	2006-05-11	Vertex Pharmaceuticals Inc., Cambridge	Inhibitoren von Serin-Proteasen, insbesondere der Hepatitis-C-Virus NS23-Protease
JP4748911B2 (ja)	2000-04-05	2011-08-17	シェーリングコーポレイション	Ｎ−環状ｐ２部分を含むｃ型肝炎ウイルスの大環状ｎｓ３‐セリンプロテアーゼ阻害剤
CN1432022A (zh)	2000-04-19	2003-07-23	先灵公司	含有烷基和芳基丙氨酸p2部分的丙型肝炎病毒的大环ns3－丝氨酸蛋白酶抑制剂
EP2289888A3 (fr)	2000-06-30	2011-07-13	Seikagaku Corporation	Amides d'acide expoxy-carboxylique, azides et amino-alcools et procédés de préparation d'alpha-ceto amides à l'aide de ces derniers
US20020068702A1 (en)	2000-07-21	2002-06-06	Marguerita Lim-Wilby	Novel peptides as NS3-serine protease inhibitors of hepatitis C virus
AR029851A1 (es)	2000-07-21	2003-07-16	Dendreon Corp	Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c
US7244721B2 (en)	2000-07-21	2007-07-17	Schering Corporation	Peptides as NS3-serine protease inhibitors of hepatitis C virus
AR034127A1 (es)	2000-07-21	2004-02-04	Schering Corp	Imidazolidinonas como inhibidores de ns3-serina proteasa del virus de hepatitis c, composicion farmaceutica, un metodo para su preparacion, y el uso de las mismas para la manufactura de un medicamento
RU2003105221A (ru)	2000-07-21	2004-09-20	Шеринг Корпорейшн (US)	Новые пептиды, как ингибиторы ns3-серинпротеазы вируса гепатита с
CZ303213B6 (cs)	2000-07-21	2012-05-23	Schering Corporation	Peptidové inhibitory serinové proteázy NS3 a farmaceutický prostredek
US6777400B2 (en)	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
SV2003000617A (es) *	2000-08-31	2003-01-13	Lilly Co Eli	Inhibidores de la proteasa peptidomimetica ref. x-14912m
US6939692B2 (en)	2000-09-12	2005-09-06	Degussa Ag	Nucleotide sequences coding for the pknB gene
US6846806B2 (en)	2000-10-23	2005-01-25	Bristol-Myers Squibb Company	Peptide inhibitors of Hepatitis C virus NS3 protein
CA2429359A1 (fr)	2000-11-20	2002-08-08	Bristol-Myers Squibb Company	Inhibiteurs du virus de l'hepatite c
CN1301994C (zh)	2000-12-12	2007-02-28	先灵公司	作为c型肝炎病毒ns3－丝氨酸蛋白酶抑制剂的二芳基肽
US6653295B2 (en)	2000-12-13	2003-11-25	Bristol-Myers Squibb Company	Inhibitors of hepatitis C virus NS3 protease
US6727366B2 (en)	2000-12-13	2004-04-27	Bristol-Myers Squibb Pharma Company	Imidazolidinones and their related derivatives as hepatitis C virus NS3 protease inhibitors
DZ3487A1 (fr)	2001-01-22	2002-07-25	Merck Sharp & Dohme	Derives de nucleoside comme inhibiteurs de l'arn polymerase virale d'arn-dependant
US20020187488A1 (en)	2001-01-30	2002-12-12	Chao Lin	Quantitative assay for nucleic acids
GB0102342D0 (en)	2001-01-30	2001-03-14	Smithkline Beecham Plc	Pharmaceutical formulation
JP4499990B2 (ja)	2001-03-27	2010-07-14	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	Ｈｃｖ感染に有用な組成物および方法
GB0107924D0 (en)	2001-03-29	2001-05-23	Angeletti P Ist Richerche Bio	Inhibitor of hepatitis C virus NS3 protease
WO2003003804A2 (fr)	2001-07-03	2003-01-16	Altana Pharma Ag	Procede de production de 3-phenylisoserine active au plan optique
JP4455056B2 (ja)	2001-07-11	2010-04-21	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	架橋二環式セリンプロテアーゼ阻害剤
US7029561B2 (en)	2001-07-25	2006-04-18	The United States Of America As Represented By The Secretary Of Commerce	Fluidic temperature gradient focusing
JP2003055389A (ja)	2001-08-09	2003-02-26	Univ Tokyo	錯体及びそれを用いたエポキシドの製法
US6824769B2 (en)	2001-08-28	2004-11-30	Vertex Pharmaceuticals Incorporated	Optimal compositions and methods thereof for treating HCV infections
EP1441720B8 (fr)	2001-10-24	2012-03-28	Vertex Pharmaceuticals Incorporated	Inhibiteurs de la serine protease, en particulier de la protease ns3-ns4a du virus de l'hepatite c, integrant un systeme de cycles accoles
MXPA04004657A (es)	2001-11-14	2004-08-13	Teva Pharma	Formas amorfas y cristalinas de potasio de losartan y proceso para su preparacion.
CA2369711A1 (fr)	2002-01-30	2003-07-30	Boehringer Ingelheim (Canada) Ltd.	Peptides macrocycliques qui agissent contre le virus de l'hepatite c
CA2369970A1 (fr)	2002-02-01	2003-08-01	Boehringer Ingelheim (Canada) Ltd.	Tri-peptides inhibiteur de l'hepatite c
US7091184B2 (en)	2002-02-01	2006-08-15	Boehringer Ingelheim International Gmbh	Hepatitis C inhibitor tri-peptides
AR038375A1 (es)	2002-02-01	2005-01-12	Pfizer Prod Inc	Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo
US6642204B2 (en)	2002-02-01	2003-11-04	Boehringer Ingelheim International Gmbh	Hepatitis C inhibitor tri-peptides
NZ575692A (en)	2002-04-11	2009-10-30	Vertex Pharma	Inhibitors of Serine Proteases, Particularly Hepatitis C Virus NS3-NS4 Protease
SG174624A1 (en)	2002-08-01	2011-10-28	Pharmasset Inc	Compounds with the bicyclo[4.2.1]nonane system for the treatment of flaviviridae infections
US20050075279A1 (en)	2002-10-25	2005-04-07	Boehringer Ingelheim International Gmbh	Macrocyclic peptides active against the hepatitis C virus
CA2413705A1 (fr)	2002-12-06	2004-06-06	Raul Altman	Utilisation de meloxicame avec un agent antiplaquettaire pour le traitement du syndrome coronarien aigu et de troubles connexes
US7601709B2 (en)	2003-02-07	2009-10-13	Enanta Pharmaceuticals, Inc.	Macrocyclic hepatitis C serine protease inhibitors
US7098231B2 (en)	2003-01-22	2006-08-29	Boehringer Ingelheim International Gmbh	Viral polymerase inhibitors
US7223785B2 (en)	2003-01-22	2007-05-29	Boehringer Ingelheim International Gmbh	Viral polymerase inhibitors
US20040180815A1 (en)	2003-03-07	2004-09-16	Suanne Nakajima	Pyridazinonyl macrocyclic hepatitis C serine protease inhibitors
BRPI0407587A (pt)	2003-02-18	2006-02-14	Pfizer	inibidores do vìrus da hepatite c, composições e tratamentos que os utilizam
EP1601685A1 (fr)	2003-03-05	2005-12-07	Boehringer Ingelheim International GmbH	Composes d'inhibition de l'hepatite c
JP4682140B2 (ja)	2003-03-05	2011-05-11	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	Ｃ型肝炎インヒビターペプチド類縁体
CN100453553C (zh)	2003-04-11	2009-01-21	沃泰克斯药物股份有限公司	丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂
CA2522577C (fr)	2003-05-21	2011-04-26	Boehringer Ingelheim International Gmbh	Composes inhibiteurs de l'hepatite c
CA2532664A1 (fr)	2003-07-18	2005-01-27	Vertex Pharmaceuticals Incorporated	Inhibiteurs de serines proteases, en particulier de la protease ns3-ns4a du vhc
WO2005018330A1 (fr)	2003-08-18	2005-03-03	Pharmasset, Inc.	Regime de dosage pour therapie contre flaviviridae
TW201127828A (en)	2003-09-05	2011-08-16	Vertex Pharma	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
US20050120398A1 (en)	2003-09-12	2005-06-02	Vertex Pharmaceuticals Incorporated	Animal model for HCV infection
WO2005028502A1 (fr)	2003-09-18	2005-03-31	Vertex Pharmaceuticals, Incorporated	Inhibiteurs de serines proteases, en particulier de la protease ns3-ns4a du vhc
US6933760B2 (en)	2003-09-19	2005-08-23	Intel Corporation	Reference voltage generator for hysteresis circuit
UY28525A1 (es)	2003-09-22	2005-04-29	Boehringer Ingelheim Int	Péptidos macrociclicos activos contra en virus de la hepatitis c
AU2004282148A1 (en)	2003-10-10	2005-04-28	Vertex Pharmaceuticals Incoporated	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
US7365092B2 (en)	2003-10-10	2008-04-29	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
AR045870A1 (es)	2003-10-11	2005-11-16	Vertex Pharma	Terapia de combinacion para la infeccion de virus de hepatitis c
WO2005043118A2 (fr)	2003-10-27	2005-05-12	Vertex Pharmaceuticals Incorporated	Methode de decouverte de medicament
JP2007509950A (ja)	2003-10-27	2007-04-19	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	Ｈｃｖ処置の組合せ剤
WO2005042570A1 (fr)	2003-10-27	2005-05-12	Vertex Pharmaceuticals Incorporated	Mutants resistant a la protease hcv ns3-ns4a
ATE442355T1 (de)	2003-10-28	2009-09-15	Vertex Pharma	Herstellung von 4,5-dialkyl-3-acylpyrrol-2- carbonsäurederivaten durch synthese nach fischer- fink und anschliebende acylierung
US20050119318A1 (en)	2003-10-31	2005-06-02	Hudyma Thomas W.	Inhibitors of HCV replication
US7132504B2 (en)	2003-11-12	2006-11-07	Bristol-Myers Squibb Company	Hepatitis C virus inhibitors
EP1689857A1 (fr)	2003-12-01	2006-08-16	Vertex Pharmaceuticals Incorporated	Compositions renfermant des cellules hepatiques foetales, et procedes utiles pour le traitement de l'infection par le vhc
CA2549851C (fr)	2004-01-21	2012-09-11	Boehringer Ingelheim International Gmbh	Peptides macrocycliques actifs contre le virus de l'hepatite c
EP1711515A2 (fr)	2004-02-04	2006-10-18	Vertex Pharmaceuticals Incorporated	Inhibiteurs de proteases serines, en particulier de la protease hcv ns3-ns4a
TWI368507B (en)	2004-02-20	2012-07-21	Boehringer Ingelheim Int	Viral polymerase inhibitors
US20050187192A1 (en)	2004-02-20	2005-08-25	Kucera Pharmaceutical Company	Phospholipids for the treatment of infection by togaviruses, herpes viruses and coronaviruses
ES2328589T3 (es)	2004-02-27	2009-11-16	Schering Corporation	Compuestos de la prolina 3,4(ciclopentil) fusionados como inhibidores de la proteasa serina ns3 del virus de la hepatitis c.
CN102225936B (zh)	2004-03-12	2013-09-11	弗特克斯药品有限公司	制备化合物的方法
PE20060309A1 (es)	2004-05-06	2006-04-13	Schering Corp	(1r,2s,5s)-n-[(1s)-3-amino-1-(ciclobutilmetil)-2,3-dioxopropil]-3-[(2s)-2[[[(1,1-dimetiletil)amino]carbonil]amino]-3,3-dimetil-1-oxobutil]-6,6-dimetil-3-azabiciclo[3.1.o]hexan-2-carboxamida como inhibidor de la ns3/ns4a serina proteasa del virus de l
RU2373923C2 (ru)	2004-06-08	2009-11-27	Вертекс Фармасьютикалз Инкорпорейтед	Фармацевтические композиции
EP1797111B1 (fr)	2004-08-27	2011-06-22	Schering Corporation	Composes d'acylsulfonamide inhibiteurs de la serine protease ns3 du virus de l'hepatite c
US7863274B2 (en)	2005-07-29	2011-01-04	Concert Pharmaceuticals Inc.	Deuterium enriched analogues of tadalafil as PDE5 inhibitors
CN101277950B (zh)	2005-08-02	2013-03-27	弗特克斯药品有限公司	丝氨酸蛋白酶抑制剂
SG2014013338A (en)	2005-08-19	2014-06-27	Vertex Pharma	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
US7705138B2 (en)	2005-11-11	2010-04-27	Vertex Pharmaceuticals Incorporated	Hepatitis C virus variants
CA2643688A1 (fr)	2006-02-27	2007-08-30	Vertex Pharmaceuticals Incorporated	Co-cristaux et compositions pharmaceutiques les comprenant
EP1993993A1 (fr)	2006-03-16	2008-11-26	Vertex Pharmaceuticals Incorporated	Procédés et intermédiaires pour la synthèse de composés stériques
US20070225297A1 (en)	2006-03-16	2007-09-27	Perni Robert B	Deuterated hepatitis C protease inhibitors
EA018811B1 (ru)	2006-03-20	2013-10-30	Вертекс Фармасьютикалз Инкорпорейтед	Способы получения твердой дисперсии лекарственного средства и твердые дисперсии лекарственного средства, полученные этим способом
US20070218138A1 (en)	2006-03-20	2007-09-20	Bittorf Kevin J	Pharmaceutical Compositions
PL2037887T3 (pl)	2006-05-31	2011-03-31	Vertex Pharma	Doustne preparaty o kontrolowanym uwalnianiu inhibitora enzymu konwertującego interleukinę 1 beta
EP2134717A2 (fr)	2007-02-27	2009-12-23	Vertex Pharmceuticals Incorporated	Inhibiteurs de sérine protéases

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- 2001-08-30 SV SV2001000617A patent/SV2003000617A/es not_active Application Discontinuation
- 2001-08-31 EP EP07012485A patent/EP1878720B1/fr not_active Expired - Lifetime
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2003
- 2003-02-25 EC EC2003004493A patent/ECSP034493A/es unknown
- 2003-02-27 IL IL154671A patent/IL154671A/en not_active IP Right Cessation
- 2003-02-27 NO NO20030928A patent/NO329929B1/no not_active IP Right Cessation
- 2003-02-27 ZA ZA200301641A patent/ZA200301641B/en unknown
2007
- 2007-01-31 EC EC2007007217A patent/ECSP077217A/es unknown
- 2007-05-30 JP JP2007143124A patent/JP2007284444A/ja active Pending
- 2007-08-30 IL IL185644A patent/IL185644A0/en unknown
2008
- 2008-09-08 US US12/231,982 patent/US8252923B2/en not_active Expired - Fee Related
2009
- 2009-07-20 CY CY20091100765T patent/CY1109216T1/el unknown
2010
- 2010-01-18 NO NO20100093A patent/NO20100093L/no not_active Application Discontinuation
- 2010-04-07 CL CL2010000330A patent/CL2010000330A1/es unknown
- 2010-07-12 NO NO20100999A patent/NO330807B1/no not_active IP Right Cessation
- 2010-10-25 JP JP2010238165A patent/JP5269035B2/ja not_active Expired - Fee Related
2011
- 2011-10-24 IL IL215892A patent/IL215892A/en not_active IP Right Cessation
- 2011-10-24 IL IL215891A patent/IL215891A/en not_active IP Right Cessation
- 2011-10-24 IL IL215890A patent/IL215890A0/en unknown
- 2011-11-10 US US13/293,812 patent/US20120064034A1/en not_active Abandoned
2012
- 2012-03-19 LU LU91960C patent/LU91960I2/fr unknown
- 2012-03-19 CY CY2012007C patent/CY2012007I2/el unknown
- 2012-03-19 DE DE201212000015 patent/DE122012000015I1/de active Pending
- 2012-04-03 NO NO2012006C patent/NO2012006I1/no unknown
- 2012-05-28 JP JP2012120678A patent/JP2012197289A/ja active Pending
- 2012-07-03 US US13/541,436 patent/US8529882B2/en not_active Expired - Fee Related
2014
- 2014-06-17 US US14/306,778 patent/US20140294763A1/en not_active Abandoned

Also Published As

Publication number	Publication date
EP1876173A1 (fr)	2008-01-09
ES2489115T3 (es)	2014-09-01
HRP20030139B1 (hr)	2015-08-28
PL211019B1 (pl)	2012-03-30
JP2007284444A (ja)	2007-11-01
EP1320540B1 (fr)	2009-05-13
DE122012000015I1 (de)	2012-05-24
US20100137583A1 (en)	2010-06-03
EP1878720B1 (fr)	2010-10-06
KR20110088600A (ko)	2011-08-03
CN103232381A (zh)	2013-08-07
NO330807B1 (no)	2011-07-18
CN1451014A (zh)	2003-10-22
NO2012006I1 (no)	2012-04-30
CL2010000330A1 (es)	2010-09-21
US20050197299A1 (en)	2005-09-08
MXPA03001780A (es)	2003-06-04
DK1320540T5 (da)	2012-05-29
UA81600C2 (en)	2008-01-25
NO2012006I2 (no)	2012-04-03
DE60138717D1 (de)	2009-06-25
WO2002018369A3 (fr)	2002-08-15
EP1958956A3 (fr)	2008-09-24
HUP0300855A2 (hu)	2003-10-28
EP1849797A3 (fr)	2008-01-23
KR20080104382A (ko)	2008-12-02
ES2325481T3 (es)	2009-09-07
EA011547B1 (ru)	2009-04-28
ATE483686T1 (de)	2010-10-15
US7820671B2 (en)	2010-10-26
HRP20030139B8 (hr)	2015-11-06
EP1958956B1 (fr)	2013-12-11
HK1057758A1 (en)	2004-04-16
IL215891A0 (en)	2011-12-29
ECSP077217A (es)	2007-04-26
CN100522991C (zh)	2009-08-05
AU2001288318B2 (en)	2007-09-06
TWI339661B (en)	2011-04-01
CN101633636A (zh)	2010-01-27
DK1320540T3 (da)	2009-07-27
EP2368901A1 (fr)	2011-09-28
EA200300318A1 (ru)	2004-02-26
AU8831801A (en)	2002-03-13
EP1320540A2 (fr)	2003-06-25
IL215892A (en)	2015-03-31
IL185644A0 (en)	2008-01-06
LU91960I2 (fr)	2012-05-21
KR100945975B1 (ko)	2010-03-09
WO2002018369A2 (fr)	2002-03-07
HK1114090A1 (en)	2008-10-24
CA2697205A1 (fr)	2002-03-07
US8252923B2 (en)	2012-08-28
PT1320540E (pt)	2009-07-14
TW201022243A (en)	2010-06-16
EA017556B1 (ru)	2013-01-30
HUP0300855A3 (en)	2012-01-30
EP1849797A2 (fr)	2007-10-31
ATE431358T1 (de)	2009-05-15
DZ3438A1 (fr)	2002-03-07
NZ541302A (en)	2007-04-27
HRP20030139A2 (en)	2005-04-30
EP1958956A2 (fr)	2008-08-20
TWI319763B (en)	2010-01-21
NO20030928D0 (no)	2003-02-27
KR20080007515A (ko)	2008-01-21
EP1878720A1 (fr)	2008-01-16
TW200918523A (en)	2009-05-01
KR20090120013A (ko)	2009-11-23
CN1869061A (zh)	2006-11-29
EP2368878A1 (fr)	2011-09-28
CN1869061B (zh)	2013-04-24
NZ569670A (en)	2010-03-26
ES2325481T9 (es)	2012-07-10
IL154671A (en)	2011-11-30
HK1163061A1 (en)	2012-09-07
CZ2003595A3 (cs)	2003-06-18
JP2012197289A (ja)	2012-10-18
NO20100093L (no)	2003-04-16
ZA200301641B (en)	2004-06-21
IL215891A (en)	2015-04-30
KR20080096718A (ko)	2008-10-31
AU2001288318C1 (en)	2002-03-13
NO20030928L (no)	2003-04-16
US20120064034A1 (en)	2012-03-15
KR20080104383A (ko)	2008-12-02
NO329929B1 (no)	2011-01-24
CA2419607C (fr)	2012-03-13
IL215890A0 (en)	2011-12-29
US8529882B2 (en)	2013-09-10
NO20100999L (no)	2003-04-16
AR030591A1 (es)	2003-08-27
IL154671A0 (en)	2003-09-17
CN102504014A (zh)	2012-06-20
ES2352804T3 (es)	2011-02-23
KR20080104384A (ko)	2008-12-02
EP1320540B9 (fr)	2012-03-21
EA200701869A1 (ru)	2008-02-28
JP5269035B2 (ja)	2013-08-21
KR100968295B1 (ko)	2010-07-07
JP4689938B2 (ja)	2011-06-01
WO2002018369A8 (fr)	2003-11-06
TWI359145B (en)	2012-03-01
BR0113666A (pt)	2005-09-27
EP2371839A1 (fr)	2011-10-05
DE20122915U1 (de)	2010-04-08
KR100876472B1 (ko)	2008-12-31
KR20030041981A (ko)	2003-05-27
KR20100043293A (ko)	2010-04-28
TWI359144B (en)	2012-03-01
CA2419607A1 (fr)	2002-03-07
CN101696232A (zh)	2010-04-21
ES2450815T3 (es)	2014-03-25
SV2003000617A (es)	2003-01-13
PE20020474A1 (es)	2002-06-18
CY2012007I1 (el)	2014-07-02
CA2697205C (fr)	2014-07-29
DE60143233D1 (de)	2010-11-18
EP2368877B1 (fr)	2014-05-07
CY1109216T1 (el)	2014-07-02
TW201022242A (en)	2010-06-16
US20120282219A1 (en)	2012-11-08
JP2004517047A (ja)	2004-06-10
SI1320540T1 (sl)	2009-10-31
CN101693672B (zh)	2014-11-12
IL215892A0 (en)	2011-12-29
TW201022244A (en)	2010-06-16
JP2011079835A (ja)	2011-04-21
TWI378927B (en)	2012-12-11
UA99895C2 (uk)	2012-10-25
EP2368877A1 (fr)	2011-09-28
PL365836A1 (en)	2005-01-10
KR20100042296A (ko)	2010-04-23
US20140294763A1 (en)	2014-10-02
CY2012007I2 (el)	2014-07-02
CN101693672A (zh)	2010-04-14
TW201022241A (en)	2010-06-16
DK1878720T3 (da)	2011-01-24
ECSP034493A (es)	2003-04-25
CN101633636B (zh)	2013-03-13

Legal Events

Date	Code	Title	Description
2012-08-06	TA4A	Addition of inventor(s)
2015-02-03	PC4A	Assignment and transfer of rights	Owner name: JANSSEN PHARMACEUTICA NV, BEERSE, BE Free format text: FORMER OWNER: VERTEX PHARMACEUTICALS INCORPORATED, BOSTON, MA, US Effective date: 20150126
2015-02-03	TE4A	Change of owner's address	Owner name: VERTEX PHARMACEUTICALS INCORPORATED, BOSTON, M, US Effective date: 20150126
2017-06-02	FB9A	Suspension of patent application procedure