Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors

摘要

The present invention relates to a series of compounds having antiviral activity, more specifically HIV (Human Immunodeficiency Virus) replication inhibiting properties. The invention also relates to methods for the preparation of such compounds, as well as to novel intermediates useful in one or more steps of such syntheses. The invention also relates to pharmaceutical compositions comprising an effective amount of such compounds as active ingredients. This invention further relates to the use of such compounds as medicines or in the manufacture of a medicament useful for the treatment of animals suffering from viral infections, in particular HIV infection. This invention further relates to methods for the treatment of viral infections in animals by the administration of a therapeutic amount of such compounds, optionally combined with one or more other drugs having anti-viral activity.

主权项

1. A compound according to formula (B),wherein,
each dotted line represents an optional double bond whereby maximally two non-adjacent dotted lines can form a double bond; n is selected from 0, 1, or 2; m is selected from 0, 1, 2, 3, 4, 5, or 6; R′ is independently selected from alkyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl;
wherein in the alkyl moiety of said alkyl, arylalkyl, or heterocycle-alkyl, one or more —CH3 or —CH2— is optionally replaced by one or more NH2, —NH—, —O—, or —S—, respectively;and wherein said alkyl, aryl, heterocycle, arylalkyl or heterocycle-alkyl can be unsubstituted or substituted with one or more Z1; R2a is independently selected from hydrogen, alkyl, alkynyl, arylalkyl, or heterocycle-alkyl and R2b is independently selected from alkyl, alkynyl, arylalkyl, or heterocycle-alkyl;
wherein in the alkyl moiety of said alkyl, arylalkyl, or heterocycle-alkyl, one or more —CH3 or —CH2— is optionally replaced by one or more NH2, —NH—, —O—, or —S—, respectively;and wherein said alkyl, alkynyl, arylalkyl, or heterocycle-alkyl can be unsubstituted or substituted with one or more Z′; R3 is independently selected from —COOH or —COOZ2; R4 is independently selected from hydroxyl or alkyl;
wherein in said alkyl, one or more —CH3 or —CH2— is optionally replaced by one or more —NH2, —NH—, —O—, or —S—, respectively;and wherein said alkyl can be unsubstituted or substituted with one or more Z1; each Z1 is independently selected from hydrogen, halogen, —OZ2, —SZ2, —S(O)Z3, —S(O)2Z3, —SO2NZ4Z5, trifluoromethyl, nitro, —NZ4Z5, —NZ2S(O)2Z3, cyano, —COOZ2, —C(O)NZ4Z5, —C(O)Z3, alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl;
and wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, or heterocycle-alkyl, one or more —CH3, —CH2—, —CH═ or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N═ or ≡N, respectively; or two Z1 on the same carbon atom can be taken together to form a 5, 6 or 7-membered spiro-cycloalkyl or a saturated spiro-heterocycle together with the (4, 5, 6, 7 or 8-membered unsaturated) ring they are attached to; or two Z1 on adjacent atoms can be taken together to form a 5, 6 or 7-membered cycloalkyl, aryl or heterocycle fused to the (4, 5, 6, 7, or 8-membered unsaturated) ring they are attached to; each Z2 is independently selected from hydrogen, alkyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl; and
wherein in said alkyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl, one or more —CH3, —CH2—, or —CH═ is optionally replaced by one or more —NH2, —NH—, —O—, —S—, or —N═, respectively; andwherein said alkyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl can be unsubstituted or substituted with alkyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; each Z3 is independently selected from hydroxyl, alkyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl; and
wherein in said alkyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl, one or more —CH3, —CH2—, or —CH═ is optionally replaced by one or more —NH2, —NH—, —O—, —S—, or —N═, respectively; andwherein said alkyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; each Z4 or Z5 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl; and
wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl, one or more —CH3, —CH2—, —CH═ or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S, —N═ or ≡N respectively; andwherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, or heterocycle-alkyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; andwherein Z4 and Z5, respectively, can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or —NH2;and a stereoisomer, tautomer, solvate, hydrate, salt, or pharmaceutically acceptable salt of any thereof.