	US 7,595,299 B2
	Peptides as NS3-serine protease inhibitors of hepatitis C virus
Anil Saksena, Upper Montclair, N.J. (US); Viyyoor M. Girijavallabhan, Parsippany, N.J. (US); Stephane L. Bogen, Somerset, N.J. (US); Raymond G. Lovey, West Caldwell, N.J. (US); Edwin Jao, Dayton, Md. (US); Frank Bennett, Cranford, N.J. (US); Jinping L. McCormick, Edison, N.J. (US); Haiyan Wang, Cranbury, N.J. (US); Russell E. Pike, Stanhope, N.J. (US); Yi-Tsung Liu, Morris Township, N.J. (US); Tin-Yau Chan, Edison, N.J. (US); Zhaoning Zhu, East Windsor, N.J. (US); Ashok Arasappan, Bridgewater, N.J. (US); Kevin X. Chen, Iselin, N.J. (US); Srikanth Venkatraman, Fords, N.J. (US); Tejal Parekh, Mountain View, Calif. (US); Patrick A. Pinto, Morris Plains, N.J. (US); Bama Santhanam, Bridgewater, N.J. (US); F. George Njoroge, Warren, N.J. (US); Ashit K. Ganguly, Upper Montclair, N.J. (US); Henry A. Vaccaro, South Plainfield, N.J. (US); Scott Jeffrey Kemp, San Diego, Calif. (US); Odile Esther Levy, San Diego, Calif. (US); Marguerita Lim-Wilby, La Jolla, Calif. (US); and Susan Y. Tamura, Santa Fe, N. Mex. (US)
Assigned to Schering Corporation, Kenilworth, N.J. (US); and Dendreon Corporation, Seattle, Wash. (US)
Filed on Mar. 24, 2005, as Appl. No. 11/89,192.
Application 11/089192 is a division of application No. 09/909012, filed on Jul. 19, 2001, granted, now 7,169,760, filed on Jan. 30, 2007.
Claims priority of provisional application 60/220107, filed on Jul. 21, 2000.
Prior Publication US 2005/0176648 A1, Aug. 11, 2005
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/00 (2006.01)

U.S. Cl. 514—17 [514/18; 514/616]

5 Claims

1. A method of inhibiting the hepatitis C virus NS3/NS4a serine protease, said method comprising administering to a patient in need of such treatment a pharmaceutical composition which composition comprises therapeutically effective amounts of a compound, including enantiomers, stereoisomers, rotamers and tautomers of said compound, and pharmaceutically acceptable salts or solvates of said compound, said compound having the general structure shown in Formula I:

wherein:

G, J and Y may be the same or different and are independently selected from the group consisting of the moieties: H, alkyl, alkyl-aryl, heteroalkyl, heteroaryl, aryl-heteroaryl, alkyl-heteroaryl, cycloalkyl, alkyloxy, alkyl-aryloxy, aryloxy, heteroaryloxy, heterocycloalkyloxy, cycloalkyloxy, alkylamino, arylamino, alkyl-arylamino, arylamino, heteroarylamino, cycloalkylamino and heterocycloalkylamino, with the proviso that Y maybe additionally optionally substituted with X¹¹or X¹²;

X¹¹is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, heterocyclyl, heterocyclylalkyl, aryl, alkylaryl, arylalkyl, heteroaryl, alkylheteroaryl, or heteroarylalkyl moiety, with the proviso that X¹¹may be additionally optionally substituted with X¹²;

X¹²is hydroxy, alkoxy, aryloxy, thio, alkylthio, arylthio, amino, alkylamino, arylamino, alkylsulfonyl, arylsulfonyl, alkylsulfonamido, arylsulfonamido, carboxy, carbalkoxy, carboxamido, alkoxycarbonylamino, alkoxycarbonyloxy, alkylureido, arylureido, halogen, cyano, or nitro, with the proviso that said alkyl, alkoxy, and aryl may be additionally optionally substituted with moieties independently selected from X¹²;

R¹is COR⁵wherein R⁵is COR⁷wherein R⁷is NHR¹⁰, wherein R¹⁰is selected from the group consisting of CH(R^1′)CONHCH(R^2′)COOR¹¹, CH(R^1′)CONHCH(R^2′)CONR¹²R¹³, CH(R^1′)CONHCH(R^2′)R′, CH(R^1′)CONHCH(R^2′)CONHCH(R^3′)COOR¹¹, CH(R^1′)CONHCH(R^2′)CONHCH(R^3′)CONR¹²R¹³, CH(R^1′)CONHCH(R^2′)CONHCH(R^3′)CONHCH(R^4′)COOR¹¹, CH(R^1′)CONHCH(R^2′)CONHCH(R^3′)CONHCH(R^4′)CONR¹²R¹³, CH(R^1′)CONHCH(R^2′)CONHCH(R^3′)CONHCH(R^4′)CONHCH(R^5′)COOR¹¹, and CH(R^1′)CONHCH(R^2′)CONHCH(R^3′)CONHCH(R^4′)CONHCH(R^5′)CONR¹²R¹³, wherein R^1′, R^2′, R^3′, R^4′, R^5′, R¹¹, R¹², and R¹³may be the same or different and are independently selected from a group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, alkyl-aryl, alkyl-heteroaryl, aryl-alkyl and heteroaralkyl;

Z is selected from O, N, or CH;

W maybe present or absent, and if W is present, W is selected from C═O, C═S, or SO₂; and

R′, R², R³and R⁴are independently selected from the group consisting of H; C1-C10 alkyl; C2-C10 alkenyl; C3-C8 cycloalkyl; C3-C8 heterocycloalkyl, alkoxy, aryloxy, alkylthio, arylthio, amino other than for R², amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro; oxygen, nitrogen, sulfur, or phosphorus atoms (with said oxygen, nitrogen, sulfur, or phosphorus atoms numbering zero to six); (cycloalkyl)alkyl and (heterocycloalkyl)alkyl, wherein said cycloalkyl is made of three to eight carbon atoms, and zero to six oxygen, nitrogen, sulfur, or phosphorus atoms, and said alkyl is of one to six carbon atoms; aryl; heteroaryl; alkyl-aryl; and alkyl-heteroaryl;

wherein said alkyl, heteroalkyl, alkenyl, heteroalkenyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl moieties may be optionally substituted, with said term “substituted” referring to optional and chemically-suitable substitution with one or more moieties selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, heterocyclic, halogen, hydroxy, thio, alkoxy, aryloxy, alkylthio, arylthio, amino, amido, ester, carboxylic acid, carbamate, urea, ketone, aldehyde, cyano, nitro, sulfonamide, sulfoxide, sulfone, sulfonylurea, hydrazide, and hydroxamate; with the proviso that R²is not arylalkyl or cyclohexylalkyl;.