Benzo[1,4]oxazin-3-one, benzo[1,4]thiazin-3-one and quinolin-2-one urotensin II receptor antagonists

摘要

The invention is directed to benzo[1,4]oxazin-3-one, benzo[1,4]thiazin-3-one and quinolin-2-one Urotensin II receptor antagonists useful in treating or ameliorating a Urotensin-II mediated disorder. More specifically, the present invention relates to certain novel benzo[1,4]oxazin-3-one, benzo[1,4]thiazin-3-one and quinolin-2-one compounds and methods for preparing compounds, compositions, intermediates and derivatives thereof. Pharmaceutical compositions and methods for treating or ameliorating a Urotensin-II mediated disorder using compounds of the invention are also described.

主权项

1. A compound of Formula (I):wherein
Ring A is selected from the group consisting of piperidinyl, 8-aza-bicyclo[3.2.1]oct-2-enyl, 8-aza-bicyclo[3.2.1]octyl and 1,2,3,6-tetrahydro-pyridinyl; Y is selected from the group consisting of CH2, O and S; L1 is absent or is selected from the group consisting of —C(O)O—R1, —C(O)N(R5)—R1 and —NHC(O)—R1; L2 is C1-8alkyl; L3 is absent or is —C(O)N(R5)—R7; R1 is selected from the group consisting of C1-8alkyl, C1-8alkoxy, aryl, aryl-C1-8alkyl, C3-14cycloalkyl, C3-14cycloalkyl-C1-8alkyl, heterocyclyl, heterocyclyl-C1-8alkyl, heteroaryl and heteroaryl-C1-8alkyl, wherein C1-8alkyl is optionally substituted with one, two or three substituents each selected from the group consisting of C1-8alkoxy, halogen, hydroxy and —NHR6, wherein C1-8alkoxy is optionally substituted with one, two or three substituents each selected from the group consisting of C1-8alkoxy, halogen, hydroxy and —NHR6, wherein each instance of aryl is optionally substituted with one, two or three substituents each selected from the group consisting of C1-8alkyl, C1-8alkoxy, halogen and halo-C1-8alkyl, and wherein each instance of heterocyclyl is optionally substituted with oxo, C1-8alkyl-carbonyl, C1-8alkoxy-carbonyl, C1-8alkyl-N(R5)-carbonyl, aryl-carbonyl, aryl-C1-8alkyl-carbonyl, aryl-C1-8alkoxy-carbonyl, aryl-N(R5)-carbonyl, aryl-C1-8alkyl-N(R5)-carbonyl or aryl-C1-8alkyl-sulfonyl; R2 is one, two or three substituents each selected from the group consisting of hydrogen, C1-8alkyl, C1-8alkoxy and halogen; R3 is one, two or three substituents each selected from the group consisting of hydrogen and C1-4alkyl; R4 is one, two or three substituents each selected from the group consisting of hydrogen, C1-8alkyl, C1-8alkoxy, hydroxy and halogen; R5 is selected from the group consisting of hydrogen and C1-4alkyl; R6 is selected from the group consisting of C1-8alkyl-carbonyl, C1-8alkoxy-carbonyl, C1-8alkyl-N(R5)-carbonyl, aryl-carbonyl, aryl-C1-8alkyl-carbonyl, aryl-C1-8alkoxy-carbonyl, aryl-N(R5)-carbonyl, aryl-C1-8alkyl-N(R5)-carbonyl and aryl-C1-8alkyl-sulfonyl; and, R7 is selected from the group consisting of C1-8alkyl, aryl, aryl-C1-8alkyl, C3-14cycloalkyl, C3-14cycloalkyl-C1-8alkyl, heterocyclyl, heterocyclyl-C1-8alkyl, heteroaryl and heteroaryl-C1-8alkyl, and pharmaceutically acceptable salts, stereoisomers, tautomers, and esters thereof.