THERAPEUTIC HYDROXYPYRIDINONES, HYDROXYPYRIMIDINONES AND HYDROXYPYRIDAZINONES

摘要

The invention provides compounds of formula (I): and salts and prodrugs thereof wherein R4, X1 and X2 have any of the meanings defined in the specification, as well as pharmaceutical compositions comprising the compounds or salts and methods for their use in therapy. The compounds have useful antiviral properties.;

主权项

1. A compound of formula I:wherein:
X1 is CR5 and X2 is CR6; or X1 is N and X2 is CR6; or X1 is CR5 and X2 is N; R4 is H, halo, cyano, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, aryl, heteroaryl, heterocycle, —NRaRb, —S(O)nRc, —S(O)nNRaRb, —N(Ry)S(O)nRc, —COORc, or —CONRaRb, wherein each (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle of R4 is optionally substituted with one or more groups independently selected from Rm; and wherein each aryl, heterocycle, and heteroaryl of R4 is optionally substituted with one or more groups independently selected from Rn; R5 is H, halo, cyano, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, aryl, heteroaryl, heterocycle, —NRaRb, —S(O)nRc, —N(Ry)S(O)nRc, —S(O)nNRaRb, —COORc, or —CONRaRb, wherein each (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle of R5 is optionally substituted with one or more groups independently selected from Rm; and wherein each aryl, heterocycle, and heteroaryl of R5 is optionally substituted with one or more groups independently selected from Rn; R6 is H, halo, cyano, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, aryl, heteroaryl, heterocycle, —NRaRb, —S(O)nRc, —N(Ry)S(O)nRc, —S(O)nNRaRb, —COORc, or —CONRaRb, wherein each (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle of R6 is optionally substituted with one or more groups independently selected from Rm; and wherein each aryl, heterocycle and heteroaryl of R6 is optionally substituted with one or more groups independently selected from Rn; each Ra and Rb is independently selected from hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C12)carbocycle, aryl, and heteroaryl, wherein each (C1-C6)alkyl, (C1-C6)alkanoyl, and (C3-C12)carbocycle of Ra and Rb is optionally substituted with one or more groups independently selected from Rm; and wherein each aryl and heteroaryl of Ra and Rb is optionally substituted with one or more groups independently selected from Rn; each Rc is independently selected from hydrogen, hydroxy, (C1-C6)alkyl, (C1-C6)alkanoyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C12)carbocycle, aryl, and heteroaryl, wherein each (C1-C6)alkyl, (C1-C6)alkanoyl, and (C3-C12)carbocycle of Rc is optionally substituted with one or more groups independently selected from Rm; and wherein each aryl and heteroaryl of Rc is optionally substituted with one or more groups independently selected from Rn; each Re and Rf is independently selected from hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C12)carbocycle, aryl, and heteroaryl; and each Rg is independently selected from hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C12)carbocycle, aryl, and heteroaryl; each Rm is independently selected from cyano, halo, nitro, hydroxy, oxo, carboxy, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy, heterocycleoxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —S(O)nNReRf, —COORg, and —CONReRf; wherein each heterocycle of Rm is optionally substituted with one or more groups independently selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, cyano, halo, nitro, hydroxy, oxo, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —COORg, and —CONReRf; and wherein each aryl and heteroaryl of Rm is optionally substituted with one or more groups independently selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, cyano, halo, nitro, hydroxy, carboxy, Rm1, aryloxy, heteroaryloxy, heterocycleoxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —S(O)nNReRf, (C1-C6)alkoxy, —COORg, and —CONReRf; each Rm1 is independently selected from aryl and heteroaryl, wherein any aryl and heteroaryl of Rm1 is optionally substituted with one or more groups independently selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, heterocycle, aryl, heteroaryl, cyano, halo, nitro, hydroxy, carboxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —S(O)nNReRf, (C1-C6)alkoxy, —COORg, and —CONReRf; each Rn is independently selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C12)carbocycle, aryl, heteroaryl, heterocycle, cyano, halo, nitro, hydroxy, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —S(O)nNReRf, —COORg, and —CONReRf; wherein each (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, heterocycle, and (C3-C12)carbocycle of Rn is optionally substituted with one or more groups independently selected from cyano, halo, nitro, hydroxy, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —COORg, and —CONReRf; wherein each aryl and heteroaryl of Rn is optionally substituted with one or more groups independently selected from cyano, halo, nitro, hydroxy, oxo, carboxy, aryl, heteroaryl, aryloxy, heteroaryloxy, heterocycleoxy, —NReRf, —S(O)nRg, —N(Ry)S(O)nRg, —COORg, —S(O)nNReRf, (C1-C6)alkoxy, and —CONReRf; each Ry is independently selected from hydrogen and (C1-C6)alkyl; and n is 0, 1, or 2; or a salt or prodrug thereof.