A preparation of pyrido[1,2-a]pyrazine derivatives, useful for the treatment of schizophrenia and depression.

Abstract

The invention relates to a prepn. of pyrido[1,2-a]pyrazine derivs. of formula I [wherein: X is O, NH, or N(alkyl); Y is (CH2)0-1; Z is CHO, C(O)-alkoxy, SO2-alkoxy, Me, CH2OH, etc.; R1 and R2 are independently selected from H, halogen, (cyclo)alkyl, or alkoxy, etc.], useful for treating CNS or other disorders, including concurrent treatment of disorders such as schizophrenia and depression. Thus, e.g., II was prepd. via reaction of morpholine with (7R,9aS)-trans-methanesulfonic acid 6-(2-benzo[d]isoxazol-3-yl-octahydropyrido[1,2-a]pyrazin-7-ylmethoxy)-pyridin-2-ylmethyl ester (prepn. given). The prepd. compds. were detd. to be antagonists and/or inverse agonists of human D2, human 5-HT1B, and human 5-HT2A receptors. For instance, preferred compd. II exhibited Ki value of about 20 nM or less for at least two of the following receptors: D2, 5-HT1B, and 5-HT2A. [on SciFinder(R)]