MX2011010084A - Inhibidores de la replicacion del virus de la hepatitis c. - Google Patents
Inhibidores de la replicacion del virus de la hepatitis c.Info
- Publication number
- MX2011010084A MX2011010084A MX2011010084A MX2011010084A MX2011010084A MX 2011010084 A MX2011010084 A MX 2011010084A MX 2011010084 A MX2011010084 A MX 2011010084A MX 2011010084 A MX2011010084 A MX 2011010084A MX 2011010084 A MX2011010084 A MX 2011010084A
- Authority
- MX
- Mexico
- Prior art keywords
- pyrrolidin
- phenyl
- group
- amino
- alkyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 26
- 230000029812 viral genome replication Effects 0.000 title claims abstract description 17
- 241000711549 Hepacivirus C Species 0.000 title abstract description 103
- 150000001875 compounds Chemical class 0.000 claims abstract description 325
- 208000015181 infectious disease Diseases 0.000 claims abstract description 31
- 230000003612 virological effect Effects 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- -1 -OR6 Chemical group 0.000 claims description 322
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 290
- 125000000217 alkyl group Chemical group 0.000 claims description 280
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 237
- 229910052739 hydrogen Inorganic materials 0.000 claims description 196
- 239000001257 hydrogen Substances 0.000 claims description 195
- 150000002431 hydrogen Chemical class 0.000 claims description 151
- 125000001424 substituent group Chemical group 0.000 claims description 146
- 229910052757 nitrogen Inorganic materials 0.000 claims description 130
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 119
- 125000005842 heteroatom Chemical group 0.000 claims description 101
- 229910052736 halogen Inorganic materials 0.000 claims description 98
- 150000002367 halogens Chemical class 0.000 claims description 98
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 97
- 229910052760 oxygen Inorganic materials 0.000 claims description 92
- 229910052717 sulfur Inorganic materials 0.000 claims description 89
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 82
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 73
- 125000004432 carbon atom Chemical group C* 0.000 claims description 67
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 60
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 57
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 55
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 48
- VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 38
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 33
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 29
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 28
- 125000004076 pyridyl group Chemical group 0.000 claims description 28
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 27
- 239000000460 chlorine Chemical group 0.000 claims description 24
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 24
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 23
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 23
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 23
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 23
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 23
- 125000003386 piperidinyl group Chemical group 0.000 claims description 23
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 20
- 239000011737 fluorine Chemical group 0.000 claims description 19
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 229940124597 therapeutic agent Drugs 0.000 claims description 17
- 239000003443 antiviral agent Substances 0.000 claims description 16
- 125000002619 bicyclic group Chemical group 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 239000002955 immunomodulating agent Substances 0.000 claims description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 229940121354 immunomodulator Drugs 0.000 claims description 8
- 229960005475 antiinfective agent Drugs 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 229940124772 HCV-NS5B polymerase inhibitor Drugs 0.000 claims description 6
- 239000004599 antimicrobial Substances 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 101100295741 Gallus gallus COR4 gene Proteins 0.000 claims description 5
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 5
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 claims description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 claims description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 3
- 125000003466 9 membered carbocyclic group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
- OVPLZYJGTGDFNB-UHFFFAOYSA-N propan-2-yl carbamate Chemical compound CC(C)OC(N)=O OVPLZYJGTGDFNB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- NRZYYKACXDZFRF-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O.CC(C)(C)OC(N)=O NRZYYKACXDZFRF-UHFFFAOYSA-N 0.000 claims description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 2
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 claims description 2
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 2
- 230000002584 immunomodulator Effects 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 2
- QQBMEBQGVREZJL-CLYYUMCYSA-N N1C(CCC1)C(=O)NC1=CC=C(C=C1)C=1NC2=CC=C(C=C2C=1)NC(=O)[C@H]1N(CCC1)C([C@@H](C1=CC=CC=C1)NC(CC(C)(C)C)=O)=O Chemical compound N1C(CCC1)C(=O)NC1=CC=C(C=C1)C=1NC2=CC=C(C=C2C=1)NC(=O)[C@H]1N(CCC1)C([C@@H](C1=CC=CC=C1)NC(CC(C)(C)C)=O)=O QQBMEBQGVREZJL-CLYYUMCYSA-N 0.000 claims 4
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims 4
- VALPXRNQZYGXPS-UHFFFAOYSA-N benzyl pyrrolidine-1-carboxylate Chemical compound C1CCCN1C(=O)OCC1=CC=CC=C1 VALPXRNQZYGXPS-UHFFFAOYSA-N 0.000 claims 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 2
- 150000003857 carboxamides Chemical class 0.000 claims 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 2
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims 2
- HLWLVLTWDXOIHG-GITCGBDTSA-N (2S)-1-(1,3-oxazole-2-carbonyl)-N-[4-[5-(pyrrolidine-2-carbonylamino)-1H-indol-2-yl]phenyl]pyrrolidine-2-carboxamide Chemical compound N1C(CCC1)C(=O)NC=1C=C2C=C(NC2=CC=1)C1=CC=C(C=C1)NC(=O)[C@H]1N(CCC1)C(=O)C=1OC=CN=1 HLWLVLTWDXOIHG-GITCGBDTSA-N 0.000 claims 1
- HMFXPAYRNXTEFU-GEVKEYJPSA-N (2S)-1-(2-phenylacetyl)-N-[2-[4-(pyrrolidine-2-carbonylamino)phenyl]-1-benzofuran-5-yl]pyrrolidine-2-carboxamide Chemical compound N1C(CCC1)C(=O)NC1=CC=C(C=C1)C=1OC2=C(C=1)C=C(C=C2)NC(=O)[C@H]1N(CCC1)C(CC1=CC=CC=C1)=O HMFXPAYRNXTEFU-GEVKEYJPSA-N 0.000 claims 1
- MDXUCFMCJGQCHK-YNMFNDETSA-N (2S)-1-(pyridine-3-carbonyl)-N-[4-[6-(pyrrolidine-2-carbonylamino)-1H-benzimidazol-2-yl]phenyl]pyrrolidine-2-carboxamide Chemical compound N1C(CCC1)C(=O)NC1=CC2=C(NC(=N2)C2=CC=C(C=C2)NC(=O)[C@H]2N(CCC2)C(=O)C=2C=NC=CC=2)C=C1 MDXUCFMCJGQCHK-YNMFNDETSA-N 0.000 claims 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 claims 1
- SLVYYZMCQYMPCI-ZGTCLIOFSA-N 1-[(2r)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carboxamide Chemical compound O=C([C@H](N(C)C)C=1C=CC=CC=1)N1CCCC1C(N)=O SLVYYZMCQYMPCI-ZGTCLIOFSA-N 0.000 claims 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- BPPRJFYKDTZODQ-CPRJBALCSA-N C1(=CC=CC=C1)CCC(=O)N1[C@@H](CCC1)C(=O)NC=1C=C(C=CC1)C1=NC2=C(N1)C=CC(=C2)N2C(CCC2)C(=O)N Chemical compound C1(=CC=CC=C1)CCC(=O)N1[C@@H](CCC1)C(=O)NC=1C=C(C=CC1)C1=NC2=C(N1)C=CC(=C2)N2C(CCC2)C(=O)N BPPRJFYKDTZODQ-CPRJBALCSA-N 0.000 claims 1
- 235000002756 Erythrina berteroana Nutrition 0.000 claims 1
- 235000002753 Erythrina rubrinervia Nutrition 0.000 claims 1
- 244000088811 Erythrina rubrinervia Species 0.000 claims 1
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 claims 1
- SAIQVOBMHPXWCA-OBOZPERJSA-N N1C(CCC1)C(=O)NC1=CC=C(C=C1)C=1NC2=CC=C(C=C2C=1C1=CC=CC=C1)NC(=O)[C@H]1N(CCC1)C(CC1=CC=CC=C1)=O Chemical compound N1C(CCC1)C(=O)NC1=CC=C(C=C1)C=1NC2=CC=C(C=C2C=1C1=CC=CC=C1)NC(=O)[C@H]1N(CCC1)C(CC1=CC=CC=C1)=O SAIQVOBMHPXWCA-OBOZPERJSA-N 0.000 claims 1
- XGFDDSKFVULSJO-ACEFPKFPSA-N N1C(CCC1)C(=O)NC=1C=C2C=C(NC2=CC=1)C1=CC=C(C=C1)NC(=O)[C@H]1N(CCC1)C(CC1=CC=CC=C1)=O Chemical compound N1C(CCC1)C(=O)NC=1C=C2C=C(NC2=CC=1)C1=CC=C(C=C1)NC(=O)[C@H]1N(CCC1)C(CC1=CC=CC=C1)=O XGFDDSKFVULSJO-ACEFPKFPSA-N 0.000 claims 1
- 108091005804 Peptidases Proteins 0.000 claims 1
- 239000004365 Protease Substances 0.000 claims 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- 229940121357 antivirals Drugs 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims 1
- PZSNIHIFXLKWCD-UHFFFAOYSA-N ditert-butylcarbamic acid Chemical compound CC(C)(C)N(C(O)=O)C(C)(C)C PZSNIHIFXLKWCD-UHFFFAOYSA-N 0.000 claims 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims 1
- PQJFJRGZSZKPTF-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O.COC(N)=O PQJFJRGZSZKPTF-UHFFFAOYSA-N 0.000 claims 1
- HKKYCBGKXPTMPI-IOWSJCHKSA-N n-[4-[5-[5-[(2s)-1-[(2r)-2-(diethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1,3,4-oxadiazol-2-yl]-1h-indol-2-yl]phenyl]acetamide Chemical compound O1C([C@@H]2CCCN2C(=O)[C@H](N(CC)CC)C=2C=CC=CC=2)=NN=C1C(C=C1C=2)=CC=C1NC=2C1=CC=C(NC(C)=O)C=C1 HKKYCBGKXPTMPI-IOWSJCHKSA-N 0.000 claims 1
- 125000000286 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
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 claims 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- DAGOMDIEPJGKDZ-UHFFFAOYSA-N pyrrolo[2,3-c]pyridine Chemical compound C1=N[CH]C2=NC=CC2=C1 DAGOMDIEPJGKDZ-UHFFFAOYSA-N 0.000 claims 1
- PEVGKAAGTGDOGA-UHFFFAOYSA-N tert-butyl n-(2-oxo-1-phenylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C=O)C1=CC=CC=C1 PEVGKAAGTGDOGA-UHFFFAOYSA-N 0.000 claims 1
- LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 claims 1
- 101800001014 Non-structural protein 5A Proteins 0.000 abstract description 27
- 230000015572 biosynthetic process Effects 0.000 abstract description 16
- 230000002401 inhibitory effect Effects 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 239000000203 mixture Substances 0.000 description 180
- 239000000243 solution Substances 0.000 description 135
- 239000000047 product Substances 0.000 description 134
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 125
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 103
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
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- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229950002810 valopicitabine Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
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- 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
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- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US16395809P | 2009-03-27 | 2009-03-27 | |
| US24731809P | 2009-09-30 | 2009-09-30 | |
| PCT/US2010/028653 WO2010111483A1 (en) | 2009-03-27 | 2010-03-25 | Inhibitors of hepatitis c virus replication |
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| MX2011010084A true MX2011010084A (es) | 2011-10-14 |
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