Substituted spiro[5H-Thieno[2,3-c]Pyran-7,4’-Piperidine compound

Abstract

An ORL-1 receptor antagonist of the formula: wherein R1 is fluoro or chloro; R2a and R2b are each hydrogen or are each fluoro; R3 is hydrogen, methyl, hydroxymethyl, or (C1-C3) alkoxymethyl; R4 is selected from the group consisting of fluoro, chloro, cyano, cyanomethyl, (C1-C3) alkyl, cyclopropyl, hydroxymethyl, methoxy, cyclopropylmethoxy, am inocarbonylmethoxy, (C1-C3) alkoxymethyl, cyclopropyloxymethyl, cyclopropylmethoxymethyl, 1-hydroxy-l-methylethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl, dimethylaminocarbonyloxymethyl, aminocarbonyl, am inocarbonylmethyl, -CH2NR5R6, hydroxyimine, methoxyimine, morpholin-4-yl, morpholin-4-ylmethyl, Ar1, -CH2 Ar1, tetrahydrofuran-2-yl, 3-oxomorpholin-4-ylmethyl, 2-oxopyrrolidin-1-ylmethyl, and 2-oxopiperidin-1 -ylmethyl; R5 is hydrogen, C1-C3 alkyl, cyanomethyl, -C(O)CH3, or aminocarbonylmethyl; R6 is hydrogen or methyl; and Ar1 is a moiety selected from the group consisting of imidizol-1-yl, imidizol-2-yl, pyrazol-lyl, 1,2,3-triazol-1 -yl; 1,2,3-triazol-2-y1; 1,2,4-triazol-1- yl, isoxazol-3-yl, oxazol-5-yl, and 3-methyl-1,2,4-oxadiazol-5-yl; and methods for its preparation are described.