US 11,053,243 B2
Inhibitors of hepatitis C virus replication
Craig A. Coburn, Novato, CA (US); Steven W. Ludmerer, North Wales, PA (US); Kun Liu, Boston, MA (US); Hao Wu, Shanghai (CN); Richard Soil, Shanghai (CN); Bin Zhong, Shanghai (CN); and Jian Zhu, Shanghai (CN)
Assigned to Merck Sharp & Dohme Corp., Rahway, NJ (US)
Filed by Merck Sharp & Dohme Corp., Rahway, NJ (US)
Filed on Mar. 25, 2020, as Appl. No. 16/829,878.
Application 14/473,117 is a division of application No. 13/260,684, granted, now 8,871,759, previously published as PCT/US2010/028653, filed on Mar. 25, 2010.
Application 16/829,878 is a continuation of application No. 15/800,172, filed on Nov. 1, 2017.
Application 15/800,172 is a continuation of application No. 15/272,669, filed on Sep. 22, 2016, abandoned.
Application 15/272,669 is a continuation of application No. 14/711,345, filed on May 13, 2015, abandoned.
Application 14/711,345 is a continuation of application No. 14/473,117, filed on Aug. 29, 2014, granted, now 9,090,661.
Claims priority of provisional application 61/247,318, filed on Sep. 30, 2009.
Claims priority of provisional application 61/163,958, filed on Mar. 27, 2009.
Prior Publication US 2020/0262836 A1, Aug. 20, 2020
Int. Cl. C07D 471/04 (2006.01); C07D 407/14 (2006.01); C07D 487/04 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 403/12 (2006.01); C07D 413/14 (2006.01); C07D 405/14 (2006.01); C07D 405/12 (2006.01); C07D 417/14 (2006.01); C07D 409/14 (2006.01); A61K 31/4985 (2006.01); A61K 31/4439 (2006.01); A61K 31/4184 (2006.01); A61K 31/423 (2006.01); A61K 31/4025 (2006.01); A61K 31/519 (2006.01); A61K 31/404 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 31/427 (2006.01); A61K 31/4245 (2006.01); A61K 31/475 (2006.01); A61K 31/536 (2006.01); A61K 31/4178 (2006.01); A61K 31/517 (2006.01); A61K 31/5386 (2006.01); A61K 31/553 (2006.01); A61K 31/437 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 31/404 (2013.01); A61K 31/4025 (2013.01); A61K 31/4178 (2013.01); A61K 31/4184 (2013.01); A61K 31/423 (2013.01); A61K 31/427 (2013.01); A61K 31/4245 (2013.01); A61K 31/437 (2013.01); A61K 31/4439 (2013.01); A61K 31/475 (2013.01); A61K 31/4985 (2013.01); A61K 31/506 (2013.01); A61K 31/517 (2013.01); A61K 31/519 (2013.01); A61K 31/536 (2013.01); A61K 31/5377 (2013.01); A61K 31/5386 (2013.01); A61K 31/553 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 407/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 487/04 (2013.01)] 12 Claims
 
1. A compound having structural formula (I):

OG Complex Work Unit Chemistry
and/or a pharmaceutically acceptable salt thereof, wherein:

OG Complex Work Unit Chemistry
is chosen from the group consisting of 9-membered bicyclic aryl ring systems that contain from 0 to 4 heteroatoms independently chosen from the group consisting of N, O and S, and that are substituted on C or N atoms by u substituents R1,
each R1 is independently chosen from the group consisting of hydrogen, halogen, —OR3a, —CN, —(CH2)0-6C(O)R3, —CO2R3a, —C(O)N(R3a)2, —SR3a, —S(O)R3a, —S(O2)R3a, —(CH2)0-6N(R3a)2, —N(R3a)SO2R3a, —N(R3a)CO2R3a, —N(R3a)C(O)R3, —N(R3a)COR3a, —N(R3a)C(O)N(R3a), C1-6alkyl, C3-8carbocycle containing from 0 to 3 heteroatoms chosen from N, O and S, and phenyl, and the C1-6alkyl, C3-8carbocycle and phenyl are substituted by from 0 to 3 substitutents independently chosen from the group consisting of hydrogen, halogen, —OR3a, —CN, —CO2R3a, —C(O)N(R3a)2, —N(R3a)2, —N(R3a)CO2R3a, —SR3a, —S(O)R3a, —S(O2)R3a, —N(R3a)SO2R3a, —N(R3a)CO2R3a, —N(R3a)C(O)N(R3a), C1-6alkyl, —O—C1-6alkyl, —S—C1-6alkyl, and C3-8cycloalkyl,
u is from 0 to 4,
each R3 is independently chosen from the group consisting of hydrogen, C1-6alkyl, —OH, —O—C1-6alkyl and C3-8cycloalkyl, and
each R3a is independently chosen from the group consisting of hydrogen, C1-6alkyl and C3-8cycloalkyl;

OG Complex Work Unit Chemistry
is a group chosen from 8- to 10-membered bicyclic ring systems, containing from 0 to 4 heteroatoms independently chosen from the group consisting of N, O and S, and substituted on C or N atoms by v substituents R2,
each R2 is independently chosen from the group consisting of hydrogen, halogen, —OR4a, —CN, —CO2R4a, —C(O)R4a, —C(O)N(R4a)2, —N(R4a)2, —N(R4a)COR4, —N(R4a)CO2R4a, —N(R4a)C(O)N(R4a), —N(R4a)SO2R4a, —SR4a, —S(O)R4a, —S(O2)R4a, C1-6alkyl substituted by from 0 to 4 R4 and C3-8cycloalkyl substituted by from 0 to 4 R4,
v is from 0 to 4,
each R4 is independently chosen from the group consisting of hydrogen, —OH, C1-6alkyl and C3-8cycloalkyl;
each R4a is independently chosen from the group consisting of hydrogen, C1-6alkyl and C3-8cycloalkyl;
such that said

OG Complex Work Unit Chemistry
and said

OG Complex Work Unit Chemistry
are taken together with one said substituent R1 and one said substituent R2 to form a 5- to 9-membered carbocyclic ring system represented by a group chosen from the group consisting of:

OG Complex Work Unit Chemistry
where
W is chosen from the group consisting of —(CH2)1-3—, —(CH2)0-2NH(CH2)0-2—, —(CH2)0-2N(C1-6alkyl)(CH2)0-2—, —(CH2)0-2O(CH2)0-2— and —(CH2)0-2C(O)(CH2)0-2—, where W is substituted by from 0 to 4 Rw, where each Rw is independently selected from C1-6alkyl and C3-8cycloalkyl;
each D is a group independently chosen from the group consisting of:
a single bond, or —N(R5)C(O)—
each R5 is hydrogen, and C1-6alkyl and
each E is a group independently chosen from the group consisting of:
a single bond, or
(c) a pyrrolidinyl derivative chosen from the group consisting of:

OG Complex Work Unit Chemistry
I is a bivalent group chosen from —C(O)—, and —CO2—,
each R8a is independently chosen from the group consisting of hydrogen, halogen, —OH, —OC1-6alkyl and C1-6alkyl, or two R8a may be taken together to form oxo,
each R8b is independently chosen from the group consisting of hydrogen, halogen, —OH, —OC1-6alkyl and C1-6alkyl, or two R8b may be taken together to form oxo,
each R8c is independently chosen from the group consisting of hydrogen and C1-6alkyl,
or any two groups selected from R8a, R8b and R8c may be taken together to form a spiro-bicyclic or bridged bicyclic ring;
each R9 is independently chosen from the group consisting of hydrogen, halogen, C1-6alkyl, —O—C1-6alkyl, —S—C1-6alkyl, —NH—C1-6alkyl and —NHC(O)—C1-6alkyl,
each R7 is independently chosen from the group consisting of hydrogen, C1-6alkyl and phenyl, and the C1-6alkyl and phenyl are substituted by from 0 to 3 substituents independently chosen from the group consisting of hydrogen, halogen, C1-6alkyl, —O—C1-6alkyl and —S—C1-6alkyl; and
each G is independently chosen from the group consisting of:
hydrogen, and C1-6alkyl having 0 to 4 substituents R11,
each R11 is independently chosen from the group consisting of:
—N(R10)2,
(o) aryl ring systems G′ chosen from the group consisting of:
5- to 7-membered monocyclic ring systems and;
each R10 is independently chosen from the group consisting of
hydrogen,
C1-6alkyl,
—C(O)R14,
—CO2R14, and
3- to 8-membered carbocycles containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S,
each R14 is independently chosen from the group consisting of hydrogen, C1-6alkyl, —(CH2)0-3C3-8cycloalkyl and phenyl.