US 7,476,686 B2
Substituted aryl thioureas and related compounds; inhibitors of viral replication
Dawei Chen, Middletown, Conn. (US); Milind Deshpande, Madison, Conn. (US); Andrew Thurkauf, Ridgefield, Conn. (US); Avinash Phadke, Branford, Conn. (US); Xiangzhu Wang, Branford, Conn. (US); Yiping Shen, Branford, Conn. (US); Cuixian Liu, Branford, Conn. (US); Jesse Quinn, Windsor, Conn. (US); Junko Ohkanda, Gakuennishi-machi (Japan); and Shouming Li, Cheshire, Conn. (US)
Assigned to Achillion Pharmaceuticals, Inc., New Haven, Conn. (US)
Filed on Dec. 17, 2004, as Appl. No. 11/15,300.
Application 11/015300 is a continuation of application No. 10/716175, filed on Nov. 18, 2003, granted, now 7,094,807.
Claims priority of provisional application 60/427634, filed on Nov. 19, 2002.
Prior Publication US 2006/0014836 A1, Jan. 19, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/44 (2006.01); C07D 213/46 (2006.01)
U.S. Cl. 514—355  [546/316; 546/225; 546/152; 544/162; 548/146; 548/215; 548/469; 548/530; 549/49; 549/70; 549/357; 549/425; 549/462] 23 Claims
 
1. A compound of Formula 1

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein
A1 is an optionally substituted 6- membered heteroaryl group, an optionally substituted bicyclic heteroaryl group having a 5-membered heteroaryl ring fused to a phenyl ring, an optionally substituted partially unsaturated or aromatic heterocyclic group having two 6-membered rings, an optionally substituted 5- to 7-membered heterocycloalkyl group containing at least one nitrogen atom and 0 or 1 additional heteroatoms, an optionally substituted partially unsaturated 5- to 7-membered heterocycloalkyl group containing at least one nitrogen atom and 0 or 1 additional heteroatoms, a 6-membered heterocycloalkyl group fused to a phenyl or heteroaryl ring, or a fused or spiro 8 to 11-membered bicyclic heterocycloalkyl group containing at least one nitrogen atom and 0 to 3 additional heteroatoms;
A2is

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
t is 0 or 1;
X is O, S, NR, or absent, where R is hydrogen, optionally substituted C1-C6alkyl, or optionally substituted aryl(C0-C4alkyl);
Y is C1-C6 alkyl, C1-C6 alkyl substituted with C3-C7cycloalkyl, C2-C6alkenyl, C3-C7cycloalkyl, or absent;
Z is carbonyl or thiocarbonyl;
R1 and R2 are independently hydrogen, or
R1 and R2 are independently C1-C6alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, each of which is substituted with 0 to 3 substituents independently chosen from halogen, hydroxy, amino, C1-C4alkoxy, C1-C2haloalkyl, and C1-C2haloalkoxy, or
R1 and R2 are joined to form a 5- to 7-membered saturated or mono-unsaturated ring optionally containing one additional heteroatom chosen from N, S, and O, which 5- to 7-membered saturated or mono-unsaturated ring is substituted with 0 to 3 substituents independently chosen from halogen, hydroxy, amino, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C1-C2haloallcyl, and C1-C2haloalkoxy;
R10 is C1-C6alkyl;
R11 and R12 each represent 0 to 3 substituents independently chosen from halogen, hydroxy, cyano, C1-C6alkyl, C1-C6alkoxy, mono- and di-(C1-C6alkyl)amino, C2-C6alkanoyl, C1-C2haloalkyl, C1-C2haloalkoxy, and phenyl; and
R13 and R14 are independently chosen at each occurrence from hydrogen and C1-C4alkyl;
R15 is C4-C6alkoxy or C4-C6alkyl;
R17 represents 0 to 2 substituents independently chosen from halogen, methyl, and methoxy.