ZA200602447B - Macrocyclic inhibitors of HCV NS3 serine protease - Google Patents
Macrocyclic inhibitors of HCV NS3 serine protease Download PDFInfo
- Publication number
- ZA200602447B ZA200602447B ZA200602447A ZA200602447A ZA200602447B ZA 200602447 B ZA200602447 B ZA 200602447B ZA 200602447 A ZA200602447 A ZA 200602447A ZA 200602447 A ZA200602447 A ZA 200602447A ZA 200602447 B ZA200602447 B ZA 200602447B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- group
- compound according
- aryl
- cycloalkyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 11
- 108010022999 Serine Proteases Proteins 0.000 title description 10
- 102000012479 Serine Proteases Human genes 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 95
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- -1 alkyi-aryl Chemical group 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 60
- 125000001072 heteroaryl group Chemical group 0.000 claims description 41
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 108091005804 Peptidases Proteins 0.000 claims description 16
- 239000004365 Protease Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
- 229940079322 interferon Drugs 0.000 claims description 13
- 125000001931 aliphatic group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- 102000014150 Interferons Human genes 0.000 claims description 10
- 108010050904 Interferons Proteins 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000003435 aroyl group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 230000007717 exclusion Effects 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000004202 carbamide Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 4
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229960000329 ribavirin Drugs 0.000 claims description 4
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
- 150000003457 sulfones Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 150000002678 macrocyclic compounds Chemical class 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 125000004076 pyridyl group Chemical class 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- 150000003456 sulfonamides Chemical class 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims 6
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 4
- FZRKAZHKEDOPNN-UHFFFAOYSA-N Nitric oxide anion Chemical group O=[N-] FZRKAZHKEDOPNN-UHFFFAOYSA-N 0.000 claims 2
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims 2
- 125000005594 diketone group Chemical group 0.000 claims 2
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims 2
- 150000004715 keto acids Chemical group 0.000 claims 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 102100030907 Aryl hydrocarbon receptor nuclear translocator Human genes 0.000 claims 1
- 101000690445 Caenorhabditis elegans Aryl hydrocarbon receptor nuclear translocator homolog Proteins 0.000 claims 1
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims 1
- 241001658031 Eris Species 0.000 claims 1
- 101100108327 Escherichia coli (strain K12) melA gene Proteins 0.000 claims 1
- 241000282326 Felis catus Species 0.000 claims 1
- 101000793115 Homo sapiens Aryl hydrocarbon receptor nuclear translocator Proteins 0.000 claims 1
- 101100454393 Homo sapiens LCOR gene Proteins 0.000 claims 1
- 235000007849 Lepidium sativum Nutrition 0.000 claims 1
- 244000211187 Lepidium sativum Species 0.000 claims 1
- 102100038260 Ligand-dependent corepressor Human genes 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 claims 1
- HSMNQINEKMPTIC-UHFFFAOYSA-N N-(4-aminobenzoyl)glycine Chemical compound NC1=CC=C(C(=O)NCC(O)=O)C=C1 HSMNQINEKMPTIC-UHFFFAOYSA-N 0.000 claims 1
- 241000712503 Sicyos pachycarpus Species 0.000 claims 1
- 239000002253 acid Chemical group 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims 1
- 239000013256 coordination polymer Substances 0.000 claims 1
- 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims 1
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims 1
- 235000015250 liver sausages Nutrition 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000005936 piperidyl group Chemical class 0.000 claims 1
- 235000008001 rakum palm Nutrition 0.000 claims 1
- 229910052761 rare earth metal Inorganic materials 0.000 claims 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 description 40
- 238000000034 method Methods 0.000 description 15
- 101710144111 Non-structural protein 3 Proteins 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 125000006413 ring segment Chemical group 0.000 description 10
- 229920001184 polypeptide Polymers 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 208000005176 Hepatitis C Diseases 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 125000005038 alkynylalkyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 241000709721 Hepatovirus A Species 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 108010076039 Polyproteins Proteins 0.000 description 2
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 description 2
- 241000534944 Thia Species 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 208000029570 hepatitis D virus infection Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- GFZMFCVDDFHSJK-UHFFFAOYSA-N 2-(methylideneamino)acetonitrile Chemical compound C=NCC#N GFZMFCVDDFHSJK-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 241001279686 Allium moly Species 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- WYVKPHCYMTWUCW-YUPRTTJUSA-N Cys-Thr Chemical group C[C@@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)N)O WYVKPHCYMTWUCW-YUPRTTJUSA-N 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 108010088842 Fibrinolysin Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 1
- 101001098529 Homo sapiens Proteinase-activated receptor 1 Proteins 0.000 description 1
- 101001077660 Homo sapiens Serine protease inhibitor Kazal-type 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 101100129514 Mus musculus Mbip gene Proteins 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 102100037136 Proteinase-activated receptor 1 Human genes 0.000 description 1
- 108010049219 RNA-dependent ATPase Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 125000005513 benzoazaindolyl group Chemical group 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108700012707 hepatitis C virus NS3 Proteins 0.000 description 1
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 1
- 125000005312 heteroarylalkynyl group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- 102000057815 human SPINK1 Human genes 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000001786 wide angle neutron scattering Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
- C07D245/04—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
-
- 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
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- 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
- 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
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-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
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0217—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -C(=O)-C-N-C(=O)-N-C-C(=O)-
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Manufacturing & Machinery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ceramic Engineering (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Inorganic Chemistry (AREA)
- Structural Engineering (AREA)
- Materials Engineering (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US50663703P | 2003-09-26 | 2003-09-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200602447B true ZA200602447B (en) | 2007-09-26 |
Family
ID=34393181
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200602447A ZA200602447B (en) | 2003-09-26 | 2006-03-24 | Macrocyclic inhibitors of HCV NS3 serine protease |
Country Status (21)
Country | Link |
---|---|
US (1) | US7592419B2 (pt) |
EP (1) | EP1664092B1 (pt) |
JP (2) | JP4525982B2 (pt) |
KR (1) | KR20060085248A (pt) |
CN (1) | CN1894274A (pt) |
AR (1) | AR046166A1 (pt) |
AT (1) | ATE497505T1 (pt) |
AU (1) | AU2004276281A1 (pt) |
BR (1) | BRPI0414814A (pt) |
CA (1) | CA2540031A1 (pt) |
CO (1) | CO5680449A2 (pt) |
DE (1) | DE602004031298D1 (pt) |
EC (1) | ECSP066456A (pt) |
IL (1) | IL174459A0 (pt) |
MX (1) | MXPA06003455A (pt) |
NO (1) | NO20061822L (pt) |
PE (1) | PE20050953A1 (pt) |
RU (1) | RU2006113880A (pt) |
TW (1) | TWI280964B (pt) |
WO (1) | WO2005030796A1 (pt) |
ZA (1) | ZA200602447B (pt) |
Families Citing this family (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ335276A (en) | 1996-10-18 | 2000-09-29 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis C virus (HCV) NS3 (Non Structural Protein 3) protease |
US7176208B2 (en) * | 2003-04-18 | 2007-02-13 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors |
US20110150835A1 (en) * | 2003-09-26 | 2011-06-23 | Schering Corporation | Macrocyclic Inhibitors of Hepatitis C Virus NS3 Serine Protease |
MX2007015270A (es) * | 2005-06-02 | 2008-02-21 | Schering Corp | Combinacion de inhibidores de proteasa de virus de la hepatitis c con un agente tensioactivo. |
PL1891089T3 (pl) | 2005-06-02 | 2015-05-29 | Merck Sharp & Dohme | Inhibitory proteazy HCV w połączeniu z pokarmem |
US20070237818A1 (en) * | 2005-06-02 | 2007-10-11 | Malcolm Bruce A | Controlled-release formulation of HCV protease inhibitor and methods using the same |
NZ594105A (en) * | 2005-07-25 | 2013-02-22 | Intermune Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
US8399615B2 (en) | 2005-08-19 | 2013-03-19 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
JP5203203B2 (ja) * | 2005-08-19 | 2013-06-05 | 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 | 製造工程および中間体 |
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 |
ATE493409T1 (de) * | 2005-10-11 | 2011-01-15 | Intermune Inc | Verbindungen und verfahren zur inhibierung der replikation des hepatitis-c-virus |
NZ568324A (en) | 2005-11-11 | 2012-01-12 | Vertex Pharma | Hepatitis C virus variants |
US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
US7816348B2 (en) | 2006-02-03 | 2010-10-19 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US9526769B2 (en) * | 2006-06-06 | 2016-12-27 | Enanta Pharmaceuticals, Inc. | Macrocylic oximyl hepatitis C protease inhibitors |
AR061629A1 (es) * | 2006-06-26 | 2008-09-10 | Enanta Pharm Inc | Quinoxalinil macrociclicos inhibidores de serina proteasa del virus de la hepatitis c. proceso de obtencion y composiciones farmaceuticas |
CA2656816A1 (en) * | 2006-08-04 | 2008-02-14 | Enanta Pharmaceuticals, Inc. | Tetrazolyl macrocyclic hepatitis c serine protease inhibitors |
US7662779B2 (en) * | 2006-08-11 | 2010-02-16 | Enanta Pharmaceuticals, Inc. | Triazolyl macrocyclic hepatitis C serine protease inhibitors |
EP2054388A4 (en) | 2006-08-17 | 2009-10-28 | Boehringer Ingelheim Int | VIRAL POLYMERASE HEMMER |
US8003604B2 (en) * | 2006-11-16 | 2011-08-23 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US20100120716A1 (en) * | 2006-12-06 | 2010-05-13 | Phenomix Corporation | Macrocyclic hepatitis c serine protease inhibitors and uses therefor |
WO2008073282A2 (en) | 2006-12-07 | 2008-06-19 | Schering Corporation | Ph sensitive matrix formulation |
PL2118098T3 (pl) * | 2007-02-01 | 2015-03-31 | Janssen Sciences Ireland Uc | Postacie polimorficzne makrocyklicznego inhibitora HCV |
JP2010519266A (ja) * | 2007-02-20 | 2010-06-03 | ノバルティス アーゲー | Hcvns3プロテアーゼ阻害剤としての大員環化合物 |
US20090005387A1 (en) * | 2007-06-26 | 2009-01-01 | Deqiang Niu | Quinoxalinyl macrocyclic hepatitis c virus serine protease inhibitors |
CA2693997C (en) | 2007-08-03 | 2013-01-15 | Pierre L. Beaulieu | Viral polymerase inhibitors |
WO2009073713A1 (en) * | 2007-12-05 | 2009-06-11 | Enanta Pharmaceuticals, Inc. | Oximyl macrocyclic derivatives |
JP2011506472A (ja) * | 2007-12-14 | 2011-03-03 | エナンタ ファーマシューティカルズ インコーポレイテッド | 大環状オキシミルc型肝炎セリンプロテアーゼ阻害剤 |
CN101903351B (zh) | 2007-12-19 | 2014-09-10 | 贝林格尔.英格海姆国际有限公司 | 病毒聚合酶抑制剂 |
EP2268619A4 (en) * | 2008-03-20 | 2012-04-04 | Enanta Pharm Inc | FLUORINATED MACROCYCLIC COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS |
SG175692A1 (en) * | 2008-04-15 | 2011-11-28 | Intermune Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
US20090285773A1 (en) * | 2008-05-15 | 2009-11-19 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
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 |
CN102046648A (zh) * | 2008-05-29 | 2011-05-04 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
AU2009303483A1 (en) * | 2008-10-15 | 2010-04-22 | Intermune, Inc. | Therapeutic antiviral peptides |
US20100272674A1 (en) * | 2008-12-04 | 2010-10-28 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
MX2011007195A (es) | 2009-01-07 | 2013-07-12 | Scynexis Inc | Derivado de ciclosporina para el uso en el tratamiento de infección de virus de hepatitis c (vhc) y virus de inmunodeficiencia humana (vih). |
WO2010138791A1 (en) | 2009-05-29 | 2010-12-02 | Schering Corporation | Antiviral compounds composed of three linked aryl moieties to treat diseases such as hepatitis c |
US8232246B2 (en) * | 2009-06-30 | 2012-07-31 | Abbott Laboratories | Anti-viral compounds |
WO2011034518A1 (en) * | 2009-09-15 | 2011-03-24 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
TW201116540A (en) * | 2009-10-01 | 2011-05-16 | Intermune Inc | Therapeutic antiviral peptides |
CA2782024A1 (en) | 2009-11-25 | 2011-06-03 | Schering Corporation | Fused tricyclic compounds and derivatives thereof useful for the treatment of viral diseases |
JP2013515068A (ja) | 2009-12-22 | 2013-05-02 | メルク・シャープ・アンド・ドーム・コーポレーション | ウイルス性疾患の治療のための縮合三環式化合物およびその使用方法 |
US20110178107A1 (en) * | 2010-01-20 | 2011-07-21 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
SG183526A1 (en) | 2010-03-09 | 2012-09-27 | Merck Sharp & Dohme | Fused tricyclic silyl compounds and methods of use thereof for the treatment of viral diseases |
AU2011286276A1 (en) | 2010-07-26 | 2013-01-24 | Merck Sharp & Dohme Corp. | Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases |
WO2012050848A1 (en) | 2010-09-29 | 2012-04-19 | Schering Corporation | Fused tetracycle derivatives and methods of use thereof for the treatment of viral diseases |
BR112013016480A2 (pt) | 2010-12-30 | 2016-09-20 | Abbvie Inc | macrocíclo da fenantridina inibadores da protease da serina da hepatite c |
US8937041B2 (en) | 2010-12-30 | 2015-01-20 | Abbvie, Inc. | Macrocyclic hepatitis C serine protease inhibitors |
CN103415530A (zh) | 2011-03-09 | 2013-11-27 | Jitsubo株式会社 | 新型的含有非肽性交联结构的交联肽、以及该交联肽的合成方法和用于该方法的新型有机化合物 |
JP2014515023A (ja) | 2011-04-13 | 2014-06-26 | メルク・シャープ・アンド・ドーム・コーポレーション | 2’−置換ヌクレオシド誘導体およびウイルス疾患の処置のためのその使用方法 |
WO2012142075A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
WO2013033900A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases |
WO2013033899A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases |
WO2013033901A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases |
WO2013039876A1 (en) | 2011-09-14 | 2013-03-21 | Merck Sharp & Dohme Corp. | Silyl-containing heterocyclic compounds and methods of use thereof for the treatment of viral diseases |
CN102617705B (zh) * | 2012-02-16 | 2014-12-31 | 上海纬诺医药科技有限公司 | 抑制丙肝病毒复制的大环类化合物 |
US9365615B2 (en) | 2013-09-09 | 2016-06-14 | Jitsubo Co., Ltd. | Cross-linked peptides containing non-peptide cross-linked structure, method for synthesizing cross-linked peptides, and novel organic compound used in method |
US10167298B2 (en) | 2013-10-30 | 2019-01-01 | Merck Sharp & Dohme Corp. | Pseudopolymorphs of an HCV NS5A inhibitor and uses thereof |
EP3089757A1 (en) | 2014-01-03 | 2016-11-09 | AbbVie Inc. | Solid antiviral dosage forms |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5698390A (en) | 1987-11-18 | 1997-12-16 | Chiron Corporation | Hepatitis C immunoassays |
JPH02500880A (ja) | 1987-11-18 | 1990-03-29 | カイロン コーポレイション | Nanbvの診断用薬およびワクチン |
DE69133402T2 (de) | 1990-04-04 | 2004-11-11 | Chiron Corp. (N.D.Ges.D. Staates Delaware), Emeryville | Protease von hepatitis-c-virus |
US5922757A (en) | 1996-09-30 | 1999-07-13 | The Regents Of The University Of California | Treatment and prevention of hepatic disorders |
NZ335276A (en) | 1996-10-18 | 2000-09-29 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis C virus (HCV) NS3 (Non Structural Protein 3) protease |
GB9623908D0 (en) | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
ES2234144T3 (es) | 1997-08-11 | 2005-06-16 | Boehringer Ingelheim (Canada) Ltd. | Analogos de peptidos inhibidores de la hepatitis c. |
US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
AR022061A1 (es) | 1998-08-10 | 2002-09-04 | Boehringer Ingelheim Ca Ltd | Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos. |
UA74546C2 (en) * | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
JP4806154B2 (ja) | 2000-04-03 | 2011-11-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | セリンプロテアーゼ、特にc型肝炎ウイルスns3プロテアーゼのインヒビター |
SK14192002A3 (sk) | 2000-04-05 | 2003-03-04 | Schering Corporation | Makrocyklické zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie |
US6914122B2 (en) * | 2000-04-19 | 2005-07-05 | Schering Corporation | Macrocyclic NS-3 serine protease inhibitors of hepatitis C virus comprising alkyl and aryl alanine P2 moieties |
WO2002008251A2 (en) | 2000-07-21 | 2002-01-31 | Corvas International, Inc. | Peptides as ns3-serine protease inhibitors of hepatitis c virus |
PL206255B1 (pl) * | 2000-07-21 | 2010-07-30 | Dendreon Corporationdendreon Corporation | Inhibitor proteazy wirusa zapalenia wątroby C, zawierająca go kompozycja farmaceutyczna i zastosowanie inhibitora do wytwarzania leku do leczenia chorób związanych z HCV oraz zastosowanie do wytwarzania kompozycji do stosowania w kombinowanej terapii |
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 |
HUP0303358A3 (en) * | 2000-07-21 | 2005-10-28 | Schering Corp | Novel peptides as ns3-serine protease inhibitors of hepatitis c virus and pharmaceutical compositions containing them |
US7244721B2 (en) * | 2000-07-21 | 2007-07-17 | Schering Corporation | 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 |
EP1343807B1 (en) | 2000-12-12 | 2009-04-29 | Schering Corporation | Diaryl peptides as ns3-serine protease inhibitors of hepatits c virus |
KR20040077767A (ko) * | 2002-01-23 | 2004-09-06 | 쉐링 코포레이션 | C형 간염 바이러스 감염 치료용 ns3-세린 프로테아제억제제로서의 프롤린 화합물 |
WO2004072243A2 (en) | 2003-02-07 | 2004-08-26 | Enanta Pharmaceuticals, Inc. | Macrocyclic hepatitis c serine protease inhibitors |
JP4778893B2 (ja) * | 2003-04-18 | 2011-09-21 | エナンタ ファーマシューティカルズ インコーポレイテッド | キノキサリニル大環状のc型肝炎セリンプロテアーゼ阻害剤 |
-
2004
- 2004-09-23 CA CA002540031A patent/CA2540031A1/en not_active Abandoned
- 2004-09-23 EP EP04784827A patent/EP1664092B1/en active Active
- 2004-09-23 US US10/948,367 patent/US7592419B2/en not_active Expired - Fee Related
- 2004-09-23 PE PE2004000928A patent/PE20050953A1/es not_active Application Discontinuation
- 2004-09-23 AU AU2004276281A patent/AU2004276281A1/en not_active Abandoned
- 2004-09-23 KR KR1020067005941A patent/KR20060085248A/ko not_active Application Discontinuation
- 2004-09-23 AR ARP040103438A patent/AR046166A1/es unknown
- 2004-09-23 AT AT04784827T patent/ATE497505T1/de not_active IP Right Cessation
- 2004-09-23 WO PCT/US2004/031136 patent/WO2005030796A1/en active Application Filing
- 2004-09-23 BR BRPI0414814-2A patent/BRPI0414814A/pt not_active IP Right Cessation
- 2004-09-23 JP JP2006528146A patent/JP4525982B2/ja not_active Expired - Fee Related
- 2004-09-23 MX MXPA06003455A patent/MXPA06003455A/es unknown
- 2004-09-23 CN CNA2004800349233A patent/CN1894274A/zh active Pending
- 2004-09-23 RU RU2006113880/04A patent/RU2006113880A/ru not_active Application Discontinuation
- 2004-09-23 DE DE602004031298T patent/DE602004031298D1/de active Active
- 2004-09-23 TW TW093128803A patent/TWI280964B/zh not_active IP Right Cessation
-
2006
- 2006-03-21 IL IL174459A patent/IL174459A0/en unknown
- 2006-03-24 ZA ZA200602447A patent/ZA200602447B/en unknown
- 2006-03-24 CO CO06029608A patent/CO5680449A2/es not_active Application Discontinuation
- 2006-03-24 EC EC2006006456A patent/ECSP066456A/es unknown
- 2006-04-25 NO NO20061822A patent/NO20061822L/no not_active Application Discontinuation
-
2009
- 2009-07-03 JP JP2009159346A patent/JP2009275048A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
BRPI0414814A (pt) | 2006-11-14 |
EP1664092B1 (en) | 2011-02-02 |
ECSP066456A (es) | 2006-09-18 |
ATE497505T1 (de) | 2011-02-15 |
EP1664092A1 (en) | 2006-06-07 |
TW200526687A (en) | 2005-08-16 |
WO2005030796A1 (en) | 2005-04-07 |
KR20060085248A (ko) | 2006-07-26 |
JP4525982B2 (ja) | 2010-08-18 |
DE602004031298D1 (de) | 2011-03-17 |
NO20061822L (no) | 2006-06-22 |
AR046166A1 (es) | 2005-11-30 |
JP2007534627A (ja) | 2007-11-29 |
IL174459A0 (en) | 2006-08-01 |
US20050119168A1 (en) | 2005-06-02 |
CO5680449A2 (es) | 2006-09-29 |
RU2006113880A (ru) | 2007-11-20 |
CN1894274A (zh) | 2007-01-10 |
US7592419B2 (en) | 2009-09-22 |
JP2009275048A (ja) | 2009-11-26 |
MXPA06003455A (es) | 2006-05-31 |
AU2004276281A1 (en) | 2005-04-07 |
TWI280964B (en) | 2007-05-11 |
PE20050953A1 (es) | 2005-11-19 |
CA2540031A1 (en) | 2005-04-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200602447B (en) | Macrocyclic inhibitors of HCV NS3 serine protease | |
ZA200304382B (en) | Diaryl peptides as NS3-Serine protease inhibitors of hepatitis C virus. | |
AU2003207625B2 (en) | Proline compounds as NS3-serine protease inhibitors for use in treatment of hepatites C virus infection | |
ZA200405304B (en) | Novel peptides as NS3-serine protease inhibitors of hepatitis C virus | |
ZA200210311B (en) | Novel petides as NS3-serine protease inhibitors of hepatitis C virus. | |
CN100509784C (zh) | 丙型肝炎病毒ns3/ns4a丝氨酸蛋白酶的抑制剂 | |
ES2401661T3 (es) | Inhibidores de serina proteasas | |
EA012650B1 (ru) | ПРИМЕНЕНИЕ [D-MeAla]-[EtVal]-ЦИКЛОСПОРИНА ДЛЯ ЛЕЧЕНИЯ ИНФЕКЦИИ ГЕПАТИТА С И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ВКЛЮЧАЮЩАЯ [D-MeAla]-[EtVal]-ЦИКЛОСПОРИН | |
US20040259934A1 (en) | Inhibiting Coronaviridae viral replication and treating Coronaviridae viral infection with nucleoside compounds | |
MX2014015846A (es) | Inhibidores de virus de hepatitis c. | |
EP3294717B1 (en) | Methods of preparing inhibitors of influenza viruses replication | |
ZA200207845B (en) | Macrocyclic NS3-serine protease inhibitors of hepatitis C virus comprising N-cyclic P2 moieties. | |
EP1879575A2 (en) | Thiazole compounds and methods of use | |
ZA200208014B (en) | Macrocyclic NS3-serine protease inhibitors of hepatitis C virus comprising alkyl and aryl alanine P2 moieties. | |
AU2005222056A1 (en) | Novel compounds as inhibitors of hepatitis C virus NS3 serine protease | |
CA2557247A1 (en) | Compounds as inhibitors of hepatitis c virus ns3 serine protease | |
AU2005219824A1 (en) | Novel ketoamides with cyclic p4's as inhibitors of ns3 serine protease of hepatitis c virus | |
JP2011157369A (ja) | セリンプロテアーゼ、特にhcvns3‐ns4aプロテアーゼの阻害剤 | |
CN104936949A (zh) | 用于治疗丙型肝炎的squaric衍生物 | |
WO2006100106A1 (en) | 3-carboxy pyrroles as anti-viral agents | |
ES2688554T3 (es) | Compuestos de azabenzofurano que contienen ciano para el tratamiento de la hepatitis C | |
JP2016510746A (ja) | C型肝炎の治療のための化合物 | |
WO2016133970A1 (en) | Benzofurans substituted with primary benzamide as hcv inhibitors | |
EP3890731A1 (en) | Compounds for the treatment of arenavirus infection | |
JP2016515105A (ja) | C型肝炎の処置のためのピリミジン化合物 |