US2012009142A1PendingUtilityA1
Methods for treating hepatitis c
Est. expiryJul 14, 2024(expired)· nominal 20-yr term from priority
Inventors:Gary Mitchell KarpPeter Seongwoo HwangJames TakasugiHongyu RenRichard WildeAnthony TurpoffAlexander ArefolovGuangming ChenJeffrey Allen CampbellChristine EspirituConcetta FreundZhengxian GuTakashi Komatsu
A61P 31/14A61P 31/20A61K 31/4439A61K 31/405A61K 31/404A61P 1/16Y02A50/30
43
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
In accordance with the present invention, compounds that inhibit viral replication, preferably Hepatitis C Virus (HCV) replication, have been identified, and methods for their use provided. In one aspect of the invention, compounds useful in the treatment or prevention of a viral infection are provided. In another aspect of the invention, compounds useful in the treatment or prevention of HCV infection are provided.
Claims
exact text as granted — not AI-modified1 .- 41 . (canceled)
42 . A compound of Formula (I):
wherein:
X is: -cyano;
Y is:
amino optionally substituted with one or more C 1 to C 6 alkyl substituents;
—NHCOR e , where R e is:
—C 1 to C 6 alkyl;
cyclopropyl;
cyclobutyl;
cyclopentyl;
cyclohexyl; or
aryl optionally substituted with:
—C 1 to C 6 alkyl,
—C 1 to C 6 alkoxy,
cyano,
nitro, or
halogen;
—NHCOOR x , where R x is C 1 to C 6 alkyl;
—CH 2 O—R f , where R f is aryl;
—NR g R h , where R g is C 1 to C 6 alkyl or hydrogen and R h is aryl optionally substituted with C 1 to C 6 alkoxy;
where R cc is:
naphthalene,
5 or 6 membered heteroaryl,
aryl, optionally substituted with one or more of the following:
—C 1 to C 6 alkoxy,
hydroxy,
halogen,
—C 1 to C 6 alkyl, optionally substituted with cyano,
amino optionally substituted with one or more C 1 to C 6 alkyl substituents,
—NHPO(R x ) 2 , where R x is as defined above,
—NR ee CONR ff , where R ee is hydrogen or C 1 to C 6 alkyl, optionally substituted with halogen, and R ff is:
hydrogen,
—C 1 to C 6 haloalkyl,
—C 1 to C 6 haloalkoxy,
—C 1 to C 6 alkyl, or
—COR x , where R x is as defined above,
—NR gg COR hh , where R hh is:
hydrogen,
—C 1 to C 6 alkyl optionally substituted with:
—C 1 to C 6 alkoxy,
halogen, or
amino optionally substituted with one or more C 1 to C 6 alkyl substituents,
amino optionally substituted with one or more C 1 to C 6 alkyl substituents, where alkyl is optionally substituted with halogen,
5 or 6 membered heterocycle,
5 or 6 membered heteroaryl,
cyclopropyl,
cyclobutyl,
cyclopentyl, or
cyclohexyl,
and R gg is:
hydrogen,
—C 1 to C 6 alkyl,
—C 1 to C 6 haloalkyl,
—C 1 to C 6 haloalkoxy, or
—COR x , where R x is as defined above,
—C 1 to C 6 haloalkyl,
5 or 6 membered heterocycle optionally substituted with carboxy or oxo,
amino optionally substituted with one or more C 1 to C 6 alkyl substituents,
—NR ii SO 2 R x , where R x is as defined above, and R ii is:
hydrogen,
—C 1 to C 6 alkyl,
—C 1 to C 6 haloalkyl,
—C 1 to C 6 haloalkoxy,
—COR x , where R x is as defined above;
Z is:
hydrogen;
—C 1 to C 6 alkyl optionally substituted with:
—C 1 to C 6 alkoxy,
one or more halogen substituents, or
aryl;
aryl optionally substituted with C 1 to C 6 alkoxy or one or more C 1 to C 6 alkyl substituents;
R is hydrogen, halogen or C 1 to C 6 alkoxy;
R 1 is:
hydrogen;
hydroxy;
halogen;
—C 1 to C 6 haloalkyl;
nitro;
5 or 6 membered heteroaryl;
5 or 6 membered heterocycle;
—C 1 to C 6 alkoxy optionally substituted with:
one or more halogen substituents,
aryl, or
5 or 6 membered heterocycle;
aryl optionally substituted with C 1 to C 6 alkoxy;
—COR x , where R x is as defined above;
—C 1 to C 6 alkyl optionally substituted with di-C 1 to C 6 alkyl-amino or 5 or 6 membered heterocycle; or
R 1 joins together with R 2 to form:
R 2 is:
nitro;
hydrogen;
halogen;
hydroxy;
—C 1 to C 6 alkyl, optionally substituted with one or more halogen substituents;
amino;
—C 1 to C 6 alkoxy optionally substituted with:
one or more halogen substituents,
—OCOR x , where R x is as defined above,
di-C 1 to C 6 alkyl-amino optionally substituted with C 1 to C 6 alkoxy,
5 or 6 membered heterocycle optionally substituted with C 1 to C 6 alkyl,
5 or 6 membered heteroaryl, or
aryl;
—COOR x , where R x is as defined above;
—C 1 to C 6 haloalkyl;
amide optionally substituted with:
hydroxy, or
aryl;
5 or 6 membered heteroaryl;
—OCOR x , where R x is as defined above;
—NHCOR jj , where R jj is:
—C 1 to C 6 alkoxy, or
amino optionally substituted with one or more C 1 to C 6 alkyl substituents;
—OR kk , where R kk is 5 to 6 membered heteroaryl;
—NHSO 2 R x , where R x is as defined above; or
R 2 joins together with R 1 to form:
and,
R 3 is:
hydrogen; or
—CH 2 OCOR x , and R x is as defined above;
or a pharmaceutically acceptable salt thereof.
43 . The compound of claim 42 , wherein Y is selected from the group consisting of the following compounds:
44 . The compound of claim 42 , wherein Z is selected from the group consisting of -hydrogen; —C 1 to C 6 alkyl optionally substituted with: —C 1 to C 6 alkoxy, -one or more halogen substituents, or -aryl; and -aryl optionally substituted with C 1 to C 6 alkoxy.
45 . The compound of claim 42 , wherein Z is selected from the group consisting of -hydrogen; —C 1 to C 6 alkyl; and -aryl optionally substituted with C 1 to C 6 alkoxy.
46 . The compound of claim 42 , wherein R is hydrogen.
47 . The compound of claim 42 , wherein R 1 is selected from the group consisting of -hydrogen; -halogen; —C 1 to C 6 haloalkyl; -nitro; -5 or 6 membered heterocycle; —C 1 to C 6 alkoxy; -aryl optionally substituted with C 1 to C 6 alkoxy.
48 . The compound of claim 42 , wherein R 2 is selected from the group consisting of -nitro; -hydrogen; -halogen; -hydroxy; —C 1 to C 6 alkyl, optionally substituted with one or more halogen substituents; C 1 to C 6 alkoxy optionally substituted with: -one or more halogen substituents, —OCOR x , where R x is as defined above, -di-C 1 to C 6 alkyl-amino optionally substituted with C 1 to C 6 alkoxy, -5 or 6 membered heterocycle optionally substituted with C 1 to C 6 alkyl, or -5 or 6 membered heteroaryl; -amide; and —NHSO 2 R x , where R x is as defined above.
49 . The compound of claim 42 , wherein R 2 is selected from the group consisting of -nitro; -hydroxy; —C 1 to C 6 alkyl, optionally substituted with one or more halogen substituents; C 1 to C 6 alkoxy optionally substituted with: -one or more halogen substituents, or -amide.
50 . The compound of claim 42 , wherein R 3 is hydrogen.
51 . A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
52 . A pharmaceutical composition comprising the compound of claim 42 or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
53 . The pharmaceutical composition of claim 52 , further comprising one or more additional anti-viral agent selected from the group consisting of pegylated interferon, un-pegylated interferon, ribavirin or prodrugs or derivatives thereof, a glucosidase inhibitor, a protease inhibitor, a polymerase inhibitor, p7 inhibitors, an entry inhibitor, a fusion inhibitor, an anti-fibrotic, a caspase inhibitor, an inosine monophosphate dehydrogenase inhibitor, synthetic thymosin alpha 1, therapeutic vaccines, immunomodulators, a helicase inhibitor, a glycosidase inhibitor, a Toll-like receptor agonist and combinations thereof.
54 . A method for treating a viral infection in a subject in need thereof comprising administering an effective amount of the compound of claim 42 or pharmaceutically acceptable salt thereof to the subject.
55 . The method of claim 54 , wherein said viral infection is a Hepatitis C viral infection.
56 . A pharmaceutical composition comprising the compound of claim 51 or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
57 . The pharmaceutical composition of claim 56 , further comprising one or more additional anti-viral agent selected from the group consisting of pegylated interferon, un-pegylated interferon, ribavirin or prodrugs or derivatives thereof, a glucosidase inhibitor, a protease inhibitor, a polymerase inhibitor, p7 inhibitors, an entry inhibitor, a fusion inhibitor, an anti-fibrotic, a caspase inhibitor, an inosine monophosphate dehydrogenase inhibitor, synthetic thymosin alpha 1, therapeutic vaccines, immunomodulators, a helicase inhibitor, a glycosidase inhibitor, a Toll-like receptor agonist and combinations thereof.
58 . A method for treating a viral infection in a subject in need thereof comprising administering an effective amount of the compound of claim 51 or pharmaceutically acceptable salt thereof to the subject.
59 . The method of claim 58 , wherein said viral infection is a Hepatitis C viral infection.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.