RU2448976C2 - Ингибиторы hcv/вич и их применение - Google Patents

Ингибиторы hcv/вич и их применение Download PDF

Info

Publication number
RU2448976C2
RU2448976C2 RU2008144299/04A RU2008144299A RU2448976C2 RU 2448976 C2 RU2448976 C2 RU 2448976C2 RU 2008144299/04 A RU2008144299/04 A RU 2008144299/04A RU 2008144299 A RU2008144299 A RU 2008144299A RU 2448976 C2 RU2448976 C2 RU 2448976C2
Authority
RU
Russia
Prior art keywords
alkyl
group
cycloalkyl
substituted
heterocyclyl
Prior art date
Application number
RU2008144299/04A
Other languages
English (en)
Other versions
RU2008144299A (ru
Inventor
Трикси БРАНДЛЬ (CH)
Трикси Брандль
Цзипин ФУ (US)
Цзипин Фу
Франсуа ЛЕНУАР (US)
Франсуа Ленуар
Дейвид Томас ПАРКЕР (US)
Дейвид Томас Паркер
Майкл ПАТЕЙН (US)
Майкл ПАТЕЙН
Бранко РАДЕТИЧ (US)
Бранко Радетич
Пракаш РАМАН (US)
Пракаш Раман
Паскаль РИГОЛЛЬЕ (FR)
Паскаль Риголлье
Мохиндра СИПЕРСАУД (US)
Мохиндра Сиперсауд
Оливер ЗИМИК (CH)
Оливер Зимик
Арегаен ЙИФРЮ (US)
Арегаен ЙИФРЮ
Руи ЧЖЭН (US)
Руи Чжэн
Original Assignee
Новартис Аг
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38617501&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=RU2448976(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Новартис Аг filed Critical Новартис Аг
Publication of RU2008144299A publication Critical patent/RU2008144299A/ru
Application granted granted Critical
Publication of RU2448976C2 publication Critical patent/RU2448976C2/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/96—Spiro-condensed ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • 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
    • C07D491/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
    • 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
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides 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
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Diabetes (AREA)
  • AIDS & HIV (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyridine Compounds (AREA)

Abstract

Представлены органические соединения формулы I, где радикалы указаны в описании, которые применимы для устранения, предупреждения или облегчения протекания одного или большего количества симптомов, связанных с HCV нарушениями. Также в настоящем изобретении описывается фармацевтическая композиция, обладающая ингибирующей активностью в отношении NS3-4 серинпротеазы HCV, включающая соединение формулы I и фармацевтически приемлемый носитель. 2 н.п. ф-лы, 25 пр., 2 табл.

Description

Текст описания приведен в факсимильном виде.
Figure 00000001
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
Figure 00000056
Figure 00000057
Figure 00000058
Figure 00000059
Figure 00000060
Figure 00000061
Figure 00000062
Figure 00000063
Figure 00000064
Figure 00000065
Figure 00000066
Figure 00000067
Figure 00000068
Figure 00000069
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
Figure 00000083
Figure 00000084
Figure 00000085
Figure 00000086
Figure 00000087
Figure 00000088
Figure 00000089
Figure 00000090
Figure 00000091
Figure 00000092
Figure 00000093
Figure 00000094
Figure 00000095
Figure 00000096
Figure 00000097
Figure 00000098
Figure 00000099
Figure 00000100
Figure 00000101
Figure 00000102
Figure 00000103
Figure 00000104
Figure 00000105
Figure 00000106
Figure 00000107
Figure 00000108
Figure 00000109
Figure 00000110
Figure 00000111
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115
Figure 00000116
Figure 00000117
Figure 00000118
Figure 00000119
Figure 00000120
Figure 00000121
Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125
Figure 00000126
Figure 00000127
Figure 00000128
Figure 00000129
Figure 00000130
Figure 00000131
Figure 00000132
Figure 00000133
Figure 00000134
Figure 00000135
Figure 00000136
Figure 00000137
Figure 00000138
Figure 00000139
Figure 00000140
Figure 00000141
Figure 00000142
Figure 00000143
Figure 00000144
Figure 00000145
Figure 00000146
Figure 00000147
Figure 00000148
Figure 00000149
Figure 00000150
Figure 00000151
Figure 00000152
Figure 00000153
Figure 00000154
Figure 00000155
Figure 00000156
Figure 00000157
Figure 00000158
Figure 00000159
Figure 00000160
Figure 00000161
Figure 00000162
Figure 00000163
Figure 00000164
Figure 00000165
Figure 00000166
Figure 00000167
Figure 00000168
Figure 00000169
Figure 00000170
Figure 00000171
Figure 00000172
Figure 00000173
Figure 00000174
Figure 00000175
Figure 00000176
Figure 00000177
Figure 00000178
Figure 00000179
Figure 00000180
Figure 00000181
Figure 00000182
Figure 00000183
Figure 00000184
Figure 00000185
Figure 00000186
Figure 00000187
Figure 00000188
Figure 00000189
Figure 00000190
Figure 00000191
Figure 00000192
Figure 00000193
Figure 00000194
Figure 00000195
Figure 00000196
Figure 00000197
Figure 00000198
Figure 00000199
Figure 00000200
Figure 00000201
Figure 00000202
Figure 00000203
Figure 00000204
Figure 00000205
Figure 00000206
Figure 00000207
Figure 00000208
Figure 00000209
Figure 00000210
Figure 00000211
Figure 00000212
Figure 00000213
Figure 00000214
Figure 00000215
Figure 00000216
Figure 00000217
Figure 00000218
Figure 00000219
Figure 00000220
Figure 00000221
Figure 00000222
Figure 00000223
Figure 00000224
Figure 00000225
Figure 00000226
Figure 00000227
Figure 00000228
Figure 00000229
Figure 00000230
Figure 00000231
Figure 00000232
Figure 00000233
Figure 00000234
Figure 00000235
Figure 00000236
Figure 00000237
Figure 00000238
Figure 00000239
Figure 00000240
Figure 00000241
Figure 00000242
Figure 00000243
Figure 00000244
Figure 00000245
Figure 00000246
Figure 00000247
Figure 00000248
Figure 00000249
Figure 00000250
Figure 00000251
Figure 00000252
Figure 00000253
Figure 00000254
Figure 00000255
Figure 00000256
Figure 00000257
Figure 00000258
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000263
Figure 00000264
Figure 00000265
Figure 00000266
Figure 00000267
Figure 00000268
Figure 00000269
Figure 00000270
Figure 00000271
Figure 00000272
Figure 00000273
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
Figure 00000289
Figure 00000290
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294
Figure 00000295
Figure 00000296
Figure 00000297
Figure 00000298
Figure 00000299
Figure 00000300
Figure 00000301
Figure 00000302
Figure 00000303
Figure 00000304
Figure 00000305
Figure 00000306
Figure 00000307
Figure 00000308
Figure 00000309
Figure 00000310
Figure 00000311
Figure 00000312
Figure 00000313
Figure 00000314
Figure 00000315
Figure 00000316
Figure 00000317
Figure 00000318
Figure 00000319
Figure 00000320
Figure 00000321
Figure 00000322
Figure 00000323
Figure 00000324
Figure 00000325

Claims (2)

1. Соединение формулы I:
Figure 00000326

или его фармацевтически приемлемая соль или его стереоизомер;
в которой у равен 1;
n равен 1;
R14 обозначает С(O);
R1 выбран из группы, включающей Н и С1-С4-алкил;
R2 выбран из группы, включающей С1-С4-алкил, С(O)С1-С4-алкил, С(O)ОС1-С4-алкил и С3-С6-циклоалкил-С0-С4-алкил;
или R1 и R2 вместе образуют циклопропановое кольцо, где циклопропановое кольцо может быть дополнительно замещено один или более раз;
W также выбран из группы, включающей С(O)-С(O)Н, C(=N-O-R24)-C(O)-аминогруппу, С(O)-С(O)-аминогруппу, C(O)NR24S(O)pR24, C(O)NR24S(O)pN(R24)2 и С(O)-[С(O)]а-гетероциклил, где гетероциклил может быть один или более раз независимо замещен арилом, C1-C4-алкилом, С1-С4-алкилом, замещенным одним или более атомами галогена, или С3-С6-циклоалкилом, где а равно 0 или 1, где каждый R24 независимо выбран из водорода или из группы, включающей С1-С4-алкил, С3-С6-циклоалкил-С0-С4-алкил, замещенный или незамещенный арил и замещенный или незамещенный гетероциклил, каждый из которых может быть один или более раз независимо замещен атомом галогена или C1-C4-алкилом;
V выбран из группы, включающей -Q1-Q2, где Q1 отсутствует, обозначает С(O), N(H), N(С1-С4-алкил), C=N(CN), C=N(SO2CH3), C=NCOH-C1-C4-алкил или C=N-COH, и Q2 обозначает водород или выбран из группы, включающей С1-С4-алкил, O-С1-С4-алкил, NH2, N(Н)-С1-С4-алкил, N(C1-C4-алкил)2, SО2-арил, SO2-С1-С4-алкил, С3-С6-циклоалкил-С0-С4-алкил, арил, гетероарил и гетероциклил, каждый из которых может быть один или более раз независимо замещен атомом галогена, С1-С4-алкилом, C1-C4-алкилом замещенным одним или более атомами галогена, или С3-С6-циклоалкилом;
р равен 0, 1 или 2;
R3 выбран из группы, включающей водород и С1-С4-алкил;
двухвалентный остаток:
Figure 00000327

выбран из группы, включающей:
Figure 00000328
,
Figure 00000329
,
Figure 00000330
,
Figure 00000331
,
Figure 00000332
,
Figure 00000333
,
Figure 00000334
,
Figure 00000335
,
Figure 00000336
,
Figure 00000337
Figure 00000338
,
Figure 00000339
,
Figure 00000340
,
Figure 00000341
,
Figure 00000342
,
Figure 00000343
,
R8, R9 и R10 каждый независимо выбран из группы, включающей водород, С1-С4-алкил и С3-С6-циклоалкил-С0-С4-алкил;
R11 обозначает Н;
R12 обозначает С3-С6-циклоалкил; и
R13 обозначает Н;
где арил означает 5- и 6-членные моно- или полициклические ароматические группы;
гетероциклил означает 5-10-членный ароматический или неароматический гетероциклил, содержащий от 1 до 4 гетероатомов, выбранных из О, N и S;
и
гетероарил означает моноциклическое или бициклическое кольцо, содержащее до 7 атомов в каждом кольце, в котором по меньшей мере одно кольцо является ароматическим и содержит от 1 до 4 гетероатомов, выбранных из О, N и S.
2. Фармацевтическая композиция, обладающая ингибирующей активностью в отношении NS3-4 серинпротеазы HCV, включающая соединение по п.1 и фармацевтически приемлемый носитель.
RU2008144299/04A 2006-04-11 2007-04-09 Ингибиторы hcv/вич и их применение RU2448976C2 (ru)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US79131806P 2006-04-11 2006-04-11
US60/791,318 2006-04-11
US86687406P 2006-11-22 2006-11-22
US60/866,874 2006-11-22

Publications (2)

Publication Number Publication Date
RU2008144299A RU2008144299A (ru) 2010-05-20
RU2448976C2 true RU2448976C2 (ru) 2012-04-27

Family

ID=38617501

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2008144299/04A RU2448976C2 (ru) 2006-04-11 2007-04-09 Ингибиторы hcv/вич и их применение

Country Status (27)

Country Link
US (4) US7825152B2 (ru)
EP (2) EP2007789B1 (ru)
JP (1) JP5167244B2 (ru)
KR (1) KR101059593B1 (ru)
CN (1) CN101466727B (ru)
AR (1) AR060405A1 (ru)
AU (1) AU2007249668B2 (ru)
BR (1) BRPI0710878A2 (ru)
CA (1) CA2643680A1 (ru)
CL (1) CL2007001005A1 (ru)
CR (1) CR10336A (ru)
EC (1) ECSP088811A (ru)
ES (1) ES2543840T3 (ru)
HK (1) HK1126798A1 (ru)
IL (1) IL194434A0 (ru)
MA (1) MA30392B1 (ru)
MX (1) MX2008013119A (ru)
MY (1) MY147247A (ru)
NO (1) NO20084749L (ru)
NZ (1) NZ571826A (ru)
PE (2) PE20080072A1 (ru)
RU (1) RU2448976C2 (ru)
SG (1) SG173368A1 (ru)
TN (1) TNSN08400A1 (ru)
TW (1) TWI341207B (ru)
UA (1) UA100666C2 (ru)
WO (1) WO2007133865A2 (ru)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2008001166A (es) 2005-07-25 2008-03-18 Intermune Inc Nuevos inhibidores macrociclicos de la replicacion del virus de hepatitis c.
MX2008004754A (es) 2005-10-11 2009-03-02 Intermune Inc Compuestos y metodos para inhibir la replicacion viral de hepatitis c.
JP5167244B2 (ja) 2006-04-11 2013-03-21 ノバルティス アーゲー Ｈｃｖ／ｈｉｖ阻害剤およびそれらの使用
RU2008152171A (ru) 2006-07-05 2010-08-10 Интермьюн, Инк. (Us) Новые ингибиторы вирусной репликации гепатита с
EA200971041A1 (ru) * 2007-05-10 2010-08-30 Интермьюн, Инк. Новые пептидные ингибиторы репликации вируса гепатита с
BRPI0817881A2 (pt) * 2007-10-10 2015-03-31 Novartis Ag Compostos orgânicos e seus usos
KR101367219B1 (ko) 2008-04-30 2014-03-14 지멘스 메디컬 솔루션즈 유에스에이, 인크. 기질 기재 ｐｅｔ 조영제
US20090285774A1 (en) * 2008-05-15 2009-11-19 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
US8188137B2 (en) 2008-08-15 2012-05-29 Avila Therapeutics, Inc. HCV protease inhibitors and uses thereof
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
EA201390532A1 (ru) * 2010-10-08 2013-09-30 Новартис Аг Композиции сульфамидых ингибиторов ns3, содержащие витамин е
CN103168029A (zh) * 2010-10-08 2013-06-19 诺瓦提斯公司 磺酰胺ns3抑制剂的盐和多晶型物
WO2013025858A1 (en) * 2011-08-16 2013-02-21 Glaxosmithkline Llc 5-benzyl-n-phenyethyl-1,3,4-oxadiazole-2-carboxamide derivatives
ES2607752T3 (es) * 2013-11-12 2017-04-03 Acousia Therapeutics Gmbh Compuestos nuevos para regeneración de células y tejidos terminalmente diferenciados
CN105769860A (zh) * 2016-04-18 2016-07-20 乔海灵 氯美噻唑作为预防和治疗肝脏及食管疾病药物的应用
EP3472151A4 (en) 2016-06-21 2020-03-04 Orion Ophthalmology LLC CARBOCYCLIC PROLINAMIDE DERIVATIVES
PL3472149T3 (pl) 2016-06-21 2024-02-12 Orion Ophthalmology LLC Heterocykliczne pochodne prolinamidu
CN109803953A (zh) * 2016-08-08 2019-05-24 西格纳姆生物科学公司 药物制剂及其用途
US12083099B2 (en) 2020-10-28 2024-09-10 Accencio LLC Methods of treating symptoms of coronavirus infection with viral protease inhibitors

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2004137480A (ru) * 2002-05-20 2005-08-10 Бристол-Маерс Сквибб Компани (Us) Ингибиторы вируса гепатита с
RU2004133044A (ru) * 2002-04-11 2006-01-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Ингибиторы сериновых протеаз, в частности, протеазы ns3-ns4a hcv
RU2006105002A (ru) * 2003-07-18 2006-08-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Ингибиторы сериновых протеаз, в частности, нс-3-нс4а протеазы

Family Cites Families (131)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3798209A (en) 1971-06-01 1974-03-19 Icn Pharmaceuticals 1,2,4-triazole nucleosides
USRE29835E (en) 1971-06-01 1978-11-14 Icn Pharmaceuticals 1,2,4-Triazole nucleosides
US4917888A (en) 1985-06-26 1990-04-17 Cetus Corporation Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation
US4766106A (en) 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
JP2514950B2 (ja) 1986-03-10 1996-07-10 エフ・ホフマン―ラ ロシユ アーゲー 化学修飾蛋白質，その製造法および中間体
US5041426A (en) 1987-12-21 1991-08-20 Brigham Young University Immune system enhancing 3-β-d-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and nucleotides
DE3803225A1 (de) * 1988-02-04 1989-08-17 Hoechst Ag Aminosaeureamide mit psychotroper wirkung, verfahren zu ihrer herstellung, sie enthaltende mittel und deren verwendung
KR0148748B1 (ko) 1988-09-16 1998-08-17 장 크라메르, 한스 루돌프 하우스 사이클로스포린을 함유하는 약학조성물
US5026687A (en) 1990-01-03 1991-06-25 The United States Of America As Represented By The Department Of Health And Human Services Treatment of human retroviral infections with 2',3'-dideoxyinosine alone and in combination with other antiviral compounds
DE69133617D1 (de) 1990-04-04 2009-07-23 Novartis Vaccines & Diagnostic Protease von Hepatitis C Virus
JPH05506230A (ja) 1990-04-06 1993-09-16 ジーンラブス　テクノロジイズ　インコーポレイテッド Ｃ型肝炎ウイルスエピトープ
CZ280909B6 (cs) 1990-11-02 1996-05-15 Novartis Ag Nové cyklosporiny
US5595732A (en) 1991-03-25 1997-01-21 Hoffmann-La Roche Inc. Polyethylene-protein conjugates
US5610054A (en) 1992-05-14 1997-03-11 Ribozyme Pharmaceuticals, Inc. Enzymatic RNA molecule targeted against Hepatitis C virus
US5382657A (en) 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
DK0627406T3 (da) 1992-10-21 1999-07-12 Taito Co 2-Amino-1,3-propandiolforbindelser og immunundertrykkende midler
DK1302468T3 (da) 1992-12-29 2009-03-02 Abbott Lab Fremgangsmåder og mellemprodukter til fremstilling af forbindelser, der inhiberer retroviral protease
WO1994019012A2 (en) 1993-02-24 1994-09-01 Wang Jui H Compositions and methods of application of reactive antiviral polymers
EP0773029A4 (en) 1993-07-19 1997-09-03 Tokyo Tanabe Co HEPATITIS C VIRUS PROLIFERATION INHIBITOR
JPH09506087A (ja) 1993-11-10 1997-06-17 エンゾン，インコーポレーテッド 改良されたインターフェロン−ポリマー複合体
DE4447588C2 (de) 1994-05-03 1997-11-20 Omer Osama Dr Dr Med Pflanzliches Arzneimittel zur Behandlung von chronischen und allergischen Rhino-Sino-Bronchitiden
DE69524962T4 (de) 1994-08-22 2003-08-28 Mitsubishi Pharma Corp., Osaka Benzolderivate und deren medizinische verwendung
DE4432623A1 (de) 1994-09-14 1996-03-21 Huels Chemische Werke Ag Verfahren zur Bleichung von wäßrigen Tensidlösungen
US5824784A (en) 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
JP3786447B2 (ja) 1995-03-31 2006-06-14 エーザイ株式会社 Ｃ型肝炎の予防・治療剤
US6037157A (en) 1995-06-29 2000-03-14 Abbott Laboratories Method for improving pharmacokinetics
US5908621A (en) 1995-11-02 1999-06-01 Schering Corporation Polyethylene glycol modified interferon therapy
US5807876A (en) 1996-04-23 1998-09-15 Vertex Pharmaceuticals Incorporated Inhibitors of IMPDH enzyme
US6054472A (en) 1996-04-23 2000-04-25 Vertex Pharmaceuticals, Incorporated Inhibitors of IMPDH enzyme
EP0914421A2 (en) 1996-02-29 1999-05-12 Immusol, Inc. Hepatitis c virus ribozymes
US5830905A (en) 1996-03-29 1998-11-03 Viropharma Incorporated Compounds, compositions and methods for treatment of hepatitis C
US5633388A (en) 1996-03-29 1997-05-27 Viropharma Incorporated Compounds, compositions and methods for treatment of hepatitis C
HUP0004421A3 (en) 1996-04-23 2002-10-28 Vertex Pharmaceuticals Inc Cam Urea derivatives and pharmaceutical compositions containing them, use thereof for the treatment of deseases mediated by impdh enzyme
US5990276A (en) 1996-05-10 1999-11-23 Schering Corporation Synthetic inhibitors of hepatitis C virus NS3 protease
US5891874A (en) 1996-06-05 1999-04-06 Eli Lilly And Company Anti-viral compound
US5837257A (en) 1996-07-09 1998-11-17 Sage R&D Use of plant extracts for treatment of HIV, HCV and HBV infections
JP3927630B2 (ja) 1996-09-27 2007-06-13 エーザイ・アール・アンド・ディー・マネジメント株式会社 ウイルス感染症の予防・治療剤
US5922757A (en) 1996-09-30 1999-07-13 The Regents Of The University Of California Treatment and prevention of hepatic disorders
HU227742B1 (en) 1996-10-18 2012-02-28 Vertex Pharma Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease
GB9623908D0 (en) 1996-11-18 1997-01-08 Hoffmann La Roche Amino acid derivatives
IL119833A (en) 1996-12-15 2001-01-11 Lavie David Hypericum perforatum extracts for the preparation of pharmaceutical compositions for the treatment of hepatitis
JP4327910B2 (ja) 1997-03-14 2009-09-09 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 Ｉｍｐｄｈ酵素のインヒビター
NZ500713A (en) 1997-04-04 2000-07-28 Yoshitomi Pharmaceutical 2-aminopropane-1,3-diol compounds and medicinal use thereof
US6004933A (en) 1997-04-25 1999-12-21 Cortech Inc. Cysteine protease inhibitors
KR100630506B1 (ko) 1997-06-30 2006-09-29 메르츠 파마 게엠베하 운트 코. 카가아 Ｎｍｄａ 수용체 길항물질로서의 1-아미노-알킬시클로헥산 화합물, 이를 함유하는 제약학적 조성물 및 이것으로 치료하는 방법
US6143715A (en) 1997-08-11 2000-11-07 Boehringer Ingelheim (Canada) Ltd. Hepatitis C inhibitor peptide analogues
CA2322008C (en) 1998-02-25 2011-06-28 Emory University 2'-fluoronucleosides
GB9806815D0 (en) 1998-03-30 1998-05-27 Hoffmann La Roche Amino acid derivatives
US6323180B1 (en) 1998-08-10 2001-11-27 Boehringer Ingelheim (Canada) Ltd Hepatitis C inhibitor tri-peptides
AU5475799A (en) 1998-08-10 2000-03-06 Centre National De La Recherche Scientifique Beta-l-2'-deoxy-nucleosides for the treatment of hepatitis
SK13332001A3 (sk) 1999-03-19 2002-02-05 Vertex Pharmaceuticals Incorporated Inhibítory IMPDH enzýmu a ich použitie
TR200102876T2 (tr) 1999-04-07 2006-12-21 Pfizer Products Inc. Bileşim tedavilerinde CYP2D6 önleyicilerinin kullanılması.
DE20015444U1 (de) 1999-09-06 2001-02-15 Innovationen zur Verbrennungstechnik GmbH, 38446 Wolfsburg Kraftfahrzeug-Verbrennungsmotor
WO2001032153A2 (en) 1999-11-04 2001-05-10 Shire Biochem Inc. Method for the treatment or prevention of flaviviridae viral infection using nucleoside analogues
EP1296690A2 (en) 2000-02-18 2003-04-02 Shire Biochem Inc. METHOD FOR THE TREATMENT OR PREVENTION OF i FLAVIVIRUS /i INFECTIONS USING NUCLEOSIDE ANALOGUES
CA2404639A1 (en) 2000-04-13 2001-10-25 Pharmasset, Ltd. 3'-or 2'-hydroxymethyl substituted nucleoside derivatives for treatment of hepatitis virus infections
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
NZ547204A (en) 2000-05-26 2008-01-31 Idenix Cayman Ltd Methods and compositions for treating flaviviruses and pestiviruses
US6875751B2 (en) 2000-06-15 2005-04-05 Idenix Pharmaceuticals, Inc. 3′-prodrugs of 2′-deoxy-β-L-nucleosides
KR100812578B1 (ko) 2000-07-13 2008-03-13 상꾜 가부시키가이샤 아미노알코올 유도체
US20020068702A1 (en) 2000-07-21 2002-06-06 Marguerita Lim-Wilby Novel peptides as NS3-serine protease inhibitors of hepatitis C virus
CN1446201A (zh) 2000-07-21 2003-10-01 先灵公司 用作丙型肝炎病毒ns3－丝氨酸蛋白酶抑制剂的新型肽
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
AU2001276988B2 (en) * 2000-07-21 2007-01-25 Dendreon Corporation Peptides as NS3-serine protease inhibitors of hepatitis C virus
WO2002018198A1 (en) 2000-08-28 2002-03-07 Roe Jae Ick Generator of two-wheeled vehicle and lighting system thereby
US20030008841A1 (en) 2000-08-30 2003-01-09 Rene Devos Anti-HCV nucleoside derivatives
SV2003000617A (es) 2000-08-31 2003-01-13 Lilly Co Eli Inhibidores de la proteasa peptidomimetica ref. x-14912m
AU2001285331B2 (en) 2000-08-31 2006-04-06 Merck & Co., Inc. Phosphate derivatives as immunoregulatory agents
DE60143672D1 (de) 2000-10-18 2011-01-27 Pharmasset Inc Modifizierte nukleoside zur behandlung von virusinfektionen und abnormaler zellulärer proliferation
BR0115447A (pt) 2000-11-20 2005-10-18 Bristol Myers Squibb Co Inibidores de tripeptìdeo de hepatite c
AR031905A1 (es) 2000-12-12 2003-10-08 Schering Corp Peptidos diarilicos como inhibidores de ns3-serina proteasa en hepatitis de virus c
WO2002048157A2 (en) 2000-12-13 2002-06-20 Bristol-Myers Squibb Pharma Company Imidazolidinones and their related derivatives as hepatitis c virus ns3 protease inhibitors
WO2002048116A2 (en) 2000-12-13 2002-06-20 Bristol-Myers Squibb Pharma Company Inhibitors of hepatitis c virus ns3 protease
JP2005502580A (ja) 2000-12-15 2005-01-27 フアーマセツト・リミテツド フラビウィルス感染治療用抗ウィルス薬
GEP20053601B (en) 2001-01-22 2005-08-10 Merck & Co Inc Nucleoside Derivatives as Inhibitors of RNA-Dependent RNA Viral Polymerase
DE10102928B4 (de) 2001-01-23 2004-03-04 Infineon Technologies Ag Viterbi-Decoder und Verfahren zur Decodierung
JP4012823B2 (ja) 2001-03-26 2007-11-21 ノバルティス アクチエンゲゼルシャフト ２−アミノ−誘導体
JP2002316985A (ja) 2001-04-20 2002-10-31 Sankyo Co Ltd ベンゾチオフェン誘導体
US6963012B2 (en) 2001-09-27 2005-11-08 Kyorin Pharmaceutical Co., Ltd. Diaryl ether derivative, addition salt thereof, and immunosuppressant
JP4217620B2 (ja) 2001-09-27 2009-02-04 杏林製薬株式会社 ジアリールスルフィド誘導体とその付加塩及び免疫抑制剤
US7138376B2 (en) * 2001-09-28 2006-11-21 Idenix Pharmaceuticals, Inc. Methods and compositions for treating hepatitis C virus using 4'-modified nucleosides
WO2003045968A1 (en) 2001-11-27 2003-06-05 Anadys Pharmaceuticals, Inc. 3-β-D-RIBOFURANOSYLTHIAZOLO[4,5-d]PYRIDIMINE NUCLEOSIDES AND USES THEREOF
WO2005003296A2 (en) 2003-01-22 2005-01-13 Human Genome Sciences, Inc. Albumin fusion proteins
US6973322B2 (en) 2001-12-22 2005-12-06 International Business Machines Corporation Personal travel agent using push services
ATE448193T1 (de) 2002-01-18 2009-11-15 Merck & Co Inc ßN-(BENZYL)AMINOALKYL CARBOXYLATE, PHOSPHINATE, PHOSPHONATE UND TETRAZOLE ALS EDG REZEPTORAGONISTENß
US7479504B2 (en) 2002-01-18 2009-01-20 Merck & Co., Inc. Edg receptor agonists
EP1467989B1 (en) * 2002-01-23 2009-09-23 Schering Corporation Proline compounds as ns3-serine protease inhibitors for use in treatment of hepatitis c virus infection
AU2003248748A1 (en) 2002-06-28 2004-01-19 Idenix (Cayman) Limited 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections
RU2375350C2 (ru) 2003-06-04 2009-12-10 Смитклайн Бичам Корпорейшн Азотсодержащие производные гетероарила
US7309717B2 (en) 2003-06-17 2007-12-18 Schering Corporation Process and intermediates for the preparation of (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylates or salts thereof
AU2004261667A1 (en) 2003-08-01 2005-02-10 Genelabs Technologies, Inc. Bicyclic imidazol derivatives against Flaviviridae
CN1867579A (zh) 2003-08-26 2006-11-22 先灵公司 丙肝病毒的新的肽模拟物ns3－丝氨酸蛋白酶抑制剂
EP1667694B1 (en) 2003-09-05 2010-04-28 Anadys Pharmaceuticals, Inc. Tlr7 ligands for the treatment of hepatitis c
AR045596A1 (es) 2003-09-05 2005-11-02 Vertex Pharma Inhibidores de proteasas de serina en particular proteasa ns3-ns4a del vhc
AU2004274468B2 (en) 2003-09-18 2009-07-23 Vertex Pharmaceuticals, Incorporated Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
NZ546663A (en) * 2003-10-10 2010-01-29 Vertex Pharma Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
AU2004285503A1 (en) * 2003-10-27 2005-05-12 Vertex Pharmaceuticals Incorporated Combinations for HCV treatment
EP1742913A1 (en) 2003-12-11 2007-01-17 Schering Corporation Inhibitors of hepatitis c virus ns3/ns4a serine protease
EP1711515A2 (en) 2004-02-04 2006-10-18 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
CN102816241B (zh) 2004-02-09 2015-07-22 人类基因科学公司 清蛋白融合蛋白
CA2557322A1 (en) * 2004-02-27 2005-09-15 Schering Corporation Inhibitors of hepatitis c virus ns3 protease
RU2428428C9 (ru) 2004-02-27 2012-03-10 Шеринг Корпорейшн Серусодержащие соединения, действующие как ингибиторы сериновой протеазы ns3 вируса гепатита с
JP2007525510A (ja) * 2004-02-27 2007-09-06 シェーリング　コーポレイション Ｃ型肝炎ウイルスｎｓ３セリンプロテアーゼのインヒビターとしての化合物
US7635694B2 (en) * 2004-02-27 2009-12-22 Schering Corporation Cyclobutenedione-containing compounds as inhibitors of hepatitis C virus NS3 serine protease
PE20050999A1 (es) * 2004-02-27 2005-12-01 Schering Corp Cetoamidas novedosas con p4 ciclicos como inhibidores de ns3 serina proteasa del virus de hepatitis c
AR048413A1 (es) * 2004-02-27 2006-04-26 Schering Corp Compuestos prolina 3,4- (ciclopentil) - fusionados , como inhibidores de serina proteasa ns3 del virus de la hepatitis c
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
US20080070852A1 (en) 2004-06-07 2008-03-20 Averett Devron R 3-Beta-D-Ribofuranosylthiazolo[ 4,5-D] Pyridimine Nucleosides and Uses Thereof
BRPI0511900A (pt) 2004-06-08 2008-01-22 Vertex Pharma composições farmacêuticas
EP2457896A1 (en) * 2004-07-12 2012-05-30 Idun Pharmaceuticals, Inc. Tripeptides as caspase modulators
CA2577812A1 (en) * 2004-08-27 2006-03-09 Schering Corporation Acylsulfonamide compounds as inhibitors of hepatitis c virus ns3 serine protease
UA88484C2 (ru) 2004-10-01 2009-10-26 Дебиофарм Са ПРИМЕНЕНИЕ [D-MeAla]3-[EtVal]4-ЦИКЛОСПОРИНА ДЛЯ ЛЕЧЕНИЯ ИНФЕКЦИИ ГЕПАТИТА С И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, КОТОРАЯ ВКЛЮЧАЕТ [D-MeAla]3-[EtVal]4-ЦИКЛОСПОРИН
NZ554514A (en) 2004-10-01 2010-10-29 Scynexis Inc 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis C infection
EP2374464A3 (en) 2004-10-01 2011-10-26 Vertex Pharmaceuticals Incorporated HCV N3S-NS4A protease inhibition
TW201424733A (zh) 2004-10-29 2014-07-01 Vertex Pharma 劑量型式
AU2006204917A1 (en) 2005-01-14 2006-07-20 Smithkline Beecham Corporation Indole derivatives for treating viral infections
WO2006130687A2 (en) 2005-06-02 2006-12-07 Schering Corporation Liver/plasma concentration ratio for dosing hepatitis c virus protease inhibitor
US20060276404A1 (en) 2005-06-02 2006-12-07 Anima Ghosal Medicaments and methods combining a HCV protease inhibitor and an AKR competitor
WO2006130626A2 (en) * 2005-06-02 2006-12-07 Schering Corporation Method for modulating activity of hcv protease through use of a novel hcv protease inhibitor to reduce duration of treatment period
WO2006130553A2 (en) 2005-06-02 2006-12-07 Schering Corporation Hcv protease inhibitors
CA2610167A1 (en) 2005-06-02 2006-12-07 Schering Corporation Administration of hcv protease inhibitors in combination with food to improve bioavailability
US7608592B2 (en) 2005-06-30 2009-10-27 Virobay, Inc. HCV 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
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
RU2008144294A (ru) 2006-04-11 2010-05-20 Новартис АГ (CH) Ингибиторы вируса гепатита с (hcv)
JP5167244B2 (ja) * 2006-04-11 2013-03-21 ノバルティス アーゲー Ｈｃｖ／ｈｉｖ阻害剤およびそれらの使用
WO2007120595A2 (en) 2006-04-11 2007-10-25 Novartis Ag Amines for the treatment of hcv
WO2007121124A2 (en) 2006-04-11 2007-10-25 Novartis Ag Hcv inhibitors comprising beta amino acids and their uses
BRPI0817881A2 (pt) * 2007-10-10 2015-03-31 Novartis Ag Compostos orgânicos e seus usos
US8512690B2 (en) * 2009-04-10 2013-08-20 Novartis Ag Derivatised proline containing peptide compounds as protease inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2004133044A (ru) * 2002-04-11 2006-01-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Ингибиторы сериновых протеаз, в частности, протеазы ns3-ns4a hcv
RU2004137480A (ru) * 2002-05-20 2005-08-10 Бристол-Маерс Сквибб Компани (Us) Ингибиторы вируса гепатита с
RU2006105002A (ru) * 2003-07-18 2006-08-27 Вертекс Фармасьютикалз Инкорпорейтед (Us) Ингибиторы сериновых протеаз, в частности, нс-3-нс4а протеазы

Also Published As

Publication number Publication date
CL2007001005A1 (es) 2008-07-11
UA100666C2 (ru) 2013-01-25
CA2643680A1 (en) 2007-11-22
TNSN08400A1 (en) 2010-04-14
US8445527B2 (en) 2013-05-21
AR060405A1 (es) 2008-06-11
MX2008013119A (es) 2008-10-21
MY147247A (en) 2012-11-14
EP2518079A3 (en) 2012-12-12
WO2007133865A3 (en) 2008-07-10
NO20084749L (no) 2008-11-10
HK1126798A1 (en) 2009-09-11
AU2007249668B2 (en) 2011-04-07
JP5167244B2 (ja) 2013-03-21
US20100331243A1 (en) 2010-12-30
RU2008144299A (ru) 2010-05-20
CR10336A (es) 2008-12-03
EP2518079A2 (en) 2012-10-31
US8211932B2 (en) 2012-07-03
NZ571826A (en) 2012-01-12
KR101059593B1 (ko) 2011-08-25
EP2007789A2 (en) 2008-12-31
CN101466727B (zh) 2012-10-17
EP2007789B1 (en) 2015-05-20
TW200815478A (en) 2008-04-01
IL194434A0 (en) 2011-08-01
PE20080072A1 (es) 2008-03-28
US20070286842A1 (en) 2007-12-13
SG173368A1 (en) 2011-08-29
MA30392B1 (fr) 2009-05-04
CN101466727A (zh) 2009-06-24
PE20121157A1 (es) 2012-09-14
US20130149281A1 (en) 2013-06-13
US20120231998A1 (en) 2012-09-13
JP2009533464A (ja) 2009-09-17
US7825152B2 (en) 2010-11-02
WO2007133865A2 (en) 2007-11-22
TWI341207B (en) 2011-05-01
KR20080111123A (ko) 2008-12-22
BRPI0710878A2 (pt) 2015-03-31
AU2007249668A1 (en) 2007-11-22
ECSP088811A (es) 2008-11-27
ES2543840T3 (es) 2015-08-24

Similar Documents

Publication Publication Date Title
RU2448976C2 (ru) Ингибиторы hcv/вич и их применение
RU2397168C2 (ru) Производные тиофена в качестве ингибиторов снк 1
RU2371433C2 (ru) Фенилзамещенные пирролидоны
AR047076A1 (es) Compuestos de pirrolotriazina como inhibidores de tirosina quinasas, composiciones farmaceuticas
EA200970461A1 (ru) ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ 3-ИЗОБУТИЛ-9,10-ДИМЕТОКСИ-1,3,4,6,7,11b-ГЕКСАГИДРО-2Н-ПИРИДО[2,1-a]ИЗОХИНОЛИН-2-ОЛА И СВЯЗАННЫЕ С НИМИ СПОСОБЫ
AR057380A1 (es) Compuestos quimicos derivados de 2-azetidinona y uso terapeutico de los mismos
HK1110868A1 (en) Heterocyclic compounds as ccr2b antagonists
AR054482A1 (es) Derivados de azetidinona para el tratamiento de hiperlipidemias
AR045595A1 (es) Composiciones utiles como inhibidores de proteinas quinasas
ECSP066760A (es) Derivado de 4-oxopirimidina de anillos condensados
EA200970510A1 (ru) Гетеромоноциклическое соединение и его применение
UY30118A1 (es) Compueto amina trisustituido
EA200702080A1 (ru) Полициклическое карбомоилпиридоновое производное, обладающее ингибиторной активностью в отношении интегразы вич
EA200800924A1 (ru) Новые соединения, обладающие ингибирующей активностью в отношении натрийзависимого транспортера
EA200702058A1 (ru) Новые фармацевтические соединения
PE20040937A1 (es) Derivados de piridazin-3(2h)-ona como inhibidores de fosfodiesterasa-4 (pde 4)
AR053120A1 (es) Aminopiridinas como inhibidores de beta secretasa
EA200401613A1 (ru) Лекарственное средство для лечения рака
RU2008125158A (ru) Гетероциклические соединения, обладающие ингибирующей активностью по отношению к 11-гидроксистероиддегидрогеназе 1 типа
RU2013119129A (ru) Органические соединения
BRPI0615248A2 (pt) derivado tendo atividade agonista de ppar
RU2017118335A (ru) Гетероциклическое производное, обладающее активирующей ampk активностью
AR110443A1 (es) Inhibidores de histona metiltransferasas
RU2006109004A (ru) 7-аминоалкилиденилгетероциклические хинолоны и нафтиридоны
CO6230986A2 (es) Compuesto de 4-piridinona y su uso para cancer

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20160410