US 7,479,489 B2
Heterocyclic antiviral compounds
James F. Blake, Longmont, Colo. (US); Jay Bradford Fell, Longmont, Colo. (US); John P. Fischer, Longmont, Colo. (US); Robert Than Hendricks, San Carlos, Calif. (US); John E. Robinson, Commerce City, Colo. (US); Stacey Renee Spencer, Lyons, Colo. (US); and Peter J. Stengel, Longmont, Colo. (US)
Assigned to Roche Palo Alto LLC, Palo Alto, Calif. (US)
Filed on Aug. 22, 2005, as Appl. No. 11/208,962.
Claims priority of provisional application 60/677710, filed on May 04, 2005.
Claims priority of provisional application 60/603771, filed on Aug. 23, 2004.
Prior Publication US 2006/0040927 A1, Feb. 23, 2006
Int. Cl. C07D 417/02 (2006.01); A61K 31/5415 (2006.01)
U.S. Cl. 514—224.2  [544/52] 41 Claims
 
1. A compound according to formula I

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
wherein:
A is selected from the grouping consisting of A-1, A-2, A-3, A-4, A-5, A-6, A-7 and A-8;
X is CH or N;
X6 is —O—, —NR6— or X6 is absent;
R1 in each incidence is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, C1-6 alkoxy, optionally substituted phenyl, optionally substituted phenyl-C1-6 alkyl, C1-6hydroxyalkyl, C1-3 alkoxy-C1-6 alkyl, optionally substituted phenoxy, optionally substituted phenyl-C1-3 alkoxy, C1-6 heteroalkoxy, hydroxyl, halogen —X1(CH2)oCOR5, —(CH2)oCOR5, —X1(CH2)oSO2R7, —(CH2)oSO2R7, —X5C(═O)R9, —NR6SO2R7, —X4(CH2)rNRa′Rb′, —CO2R6, X4NRaRb, nitro, and cyano wherein said optionally substituted phenyl groups are substituted with one to three substituents independently selected from the group consisting of C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, phenoxy, C1-3 haloalkyl, hydroxy, halogen, NRaRb, cyano and nitro;
R2 is independently selected from the group consisting of C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, pyridinylmethyl, imidazolinylmethyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkyl, C1-6 heteroalkyl and phenyl-C1-3 alkyl said phenyl optionally substituted with one to three substituents independently selected from the group consisting of C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, phenoxy, C1-3 haloalkyl, hydroxy, halogen, NRaRb, cyano and nitro;
R3 in each incidence is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4alkyl, C1-6 alkoxy, halogen, R4 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4alkyl, C1-6 heteroalkyl, phenyl or phenyl-C1-4 alkyl said phenyl optionally substituted independently with one to three R3 radicals;
R4 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4alkyl, C1-6 heteroalkyl, phenyl or phenyl-C1-4 alkyl said phenyl optionally substituted independently with one to three R3 radicals;
R5 is hydroxyl, C1-6 alkoxy, —NRaRb, phenyl or C1-6 heteroalkoxy;
R6 is hydrogen or C1-6 alkyl;
R7 is C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, —NRaRb, —NR6(CH2)p-phenyl, —NHBoc, C1-6 heteroalkyl, —X2(CH2)oCOR5, optionally substituted isoxazole, phenyl or phenyl-C1-3 alkyl wherein said phenyl and said isoxazole are each optionally substituted independently with one to three C1-3 alkyl, C1-3 alkoxy, halogen, nitro or cyano;
R8 is R6 or C1-6 acyl;
R9 is C1-6 alkyl, C3-7 cycloalkyl, phenyl, NRaRb or OR4 wherein R4 is not hydrogen and said phenyl is optionally substituted with one to three R3 radicals;
R10 is phenyl or pyridinyl said phenyl and said pyridinyl are optionally substituted with one to three substituents selected from the group consisting of C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, halogen, NRaRb, cyano and nitro;
Ra and Rb are (i) independently hydrogen, C1-6 alkyl or C1-6 heteroalkyl, or (ii) taken together are (CH2)q, —(CH2)2OC(═O)— or (CH2)2X3(CH2)2;
Ra′ and Rb′ independently are (i) hydrogen, C1-6 alkyl or C1-6 heteroalkyl, or (ii) Ra′ is —SO2R4, —SO2NRaRb or —COR9 and Rb′ is hydrogen; or (iii) Ra′ and Rb′ taken together are (CH2)q or (CH2)2X3(CH2)2;
X1 is O, S(O)p, C(═O) or NR6;
X2 is NR6 or a bond;
X3 is —O—, C═O or NR8;
X4 is X1 or a bond;
X5 is NR6 or O;
m and n are independently zero to three;
o and r are independently one to six;
p is zero to two;
q is four to seven; and,
pharmaceutically acceptable salts thereof.