New indolizine and azaindolizine carboxamide derivatives, useful for treating e.g. schizophrenia and urinary incontinence, are ligands for serotinergic receptors

摘要

(Aza)indolizine derivatives (I) as free bases, salts, enantiomers and diastereomers are new. (Aza)indolizine derivatives of formula (I) as free bases, salts, enantiomers and diastereomers are new. A : saturated or aromatic 6-membered ring; B' : aromatic 5-membered ring, and A plus B' contain at most 3 ring-forming N atoms; Q 1, Q 2 and Q 3N, CH or CR 1; Q 4NR, CHR' 1 or CHR 1R' 1; Q 5, Q 6 and Q 7CHR' 1 or CR 1R' 1; R 1hydroxy, alkyl, alkoxy, alkylthio, alkenyl, alkynyl, phenyl, phenoxy, halo, trifluoromethyl, alkylcarbonyl, phenylcarbonyl, alkoxycarbonyl, cyano, nitro, amino, carboxy, sulfo, sulfamoyl, (alkyl)aminosulfonyl or alkylsulfonylamino; R' 1hydrogen when A is aromatic but is absent when A is saturated; R : hydrogen, alkyl, phenyl, alkylcarbonyl, phenylcarbonyl, phenylalkyl or phenylsulfonyl when A is saturated but is absent if A is aromatic; X : group (X1), bound to a C atom of an aromatic A or B'; Y' : bridging group; R 2-R 6hydrogen or substituents; and R 7hydrogen, alkyl or phenylalkyl. The full definitions are given in the DEFINITIONS - Full Definitions field. Independent claims are also included for the following: (1) preparation of (I) by reacting a heterocyclic free acid, or its halide or ester, with the appropriate amine; and (2) method for preparing pyrazolo[1,5-a]pyrimidine derivatives (X) by reacting an Rx-pyridine with O-(2,4-dinitrophenyl)hydroxylamine of formula (a) to an N-aminopyridinium salt, then cycloaddition reaction of this with R''OOC-Ctriple boundC-R'. Rx : 0-4, same or different, halo, alkyl, alkylcarbonyl, phenylcarbonyl, hydroxyalkyl, cyano, trifluoromethyl or alkoxycarbonyl, but position * is not substituted; R' : hydrogen, alkyl, phenyl or alkoxycarbonyl; and R'' : alkyl. [Image] [Image] [Image] [Image] ACTIVITY : Uropathic; Neuroleptic; Tranquilizer; Nootropic; Antiparkinsonian; Antiemetic; Vasotropic; Ophthalmological; Cerebroprotective. MECHANISM OF ACTION : 5-HT1a or D3 serotonergic receptors. Test methods are described but no results for individual compounds are given.