New 7-substituted 3-nitropyrazolo(1,5-a)pyrimidine derivatives, useful to treat e.g. anxiety, epilepsy, sleep disorders and to induce sedation-hypnosis and anesthesia,are alpha-1 gamma-aminobutyric acid modulators

摘要

7-Substituted 3-nitropyrazolo[1,5-a]pyrimidine derivatives (I) are new. 7-Substituted 3-nitropyrazolo[1,5-a]pyrimidine derivatives of formula (I) and their salts are new. [Image] R 1phenyl, pyridyl, pyrimidinyl, triazinyl, pyridyl-N-oxide, thienyl, furyl, thiazolyl or oxazolyl (all optionally substituted by R 2) R 21-6C alkyl, 3-6C cycloalkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkoxy, CF 3, CN, SO 2R 3, NO 2, NHR 3, NR 3R 4, C(O)R 5, C(O)NHR 5, C(O)OR 5, NR 5C(X)R 6, NR 5SO 2R 6 or a substituted heterocycle of formula (a) or (b) R 3, R 41-6C alkyl, 3-6C cycloalkyl, aryl or heteroaryl R 5H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl or 3-6C cycloalkyl R 61-6C alkyl, 3-6C cycloalkyl, 1-6C alkoxy, 1-6C alkylamino, di(1-6C alkyl)amino, 1-6C alkoxy(1-6C alkyl), 1-6C alkylamino(1-6C alkyl), di(1-6C alkyl)amino(1-6C alkyl), optionally monosubstituted phenyl, furyl, thienyl, thiazolyl or pyridyl R 7H, 1-6C alkyl, 3-6C cycloalkyl, aryl or optionally substituted heteroaryl R 8H, 1-6C alkyl, CF 3, CN, CO-R 9 or SO 2R 9 R 9H, 1-6C alkyl, optionally substituted phenyl or optionally substituted heteroaryl X : O, S or NR 8 and n : 1-3. [Image] An independent claim is also included for the preparation of (I). ACTIVITY : Tranquilizer Anticonvulsant Hypnotic Sedative Anesthetic Muscular-Gen. MECHANISM OF ACTION : alpha 1 Gamma-aminobutyric acid (GABA-A) receptor modulator alpha 2 Gamma-aminobutyric acid receptor modulator. (I) were tested for alpha 1 GABA-A receptor modulatory activity using biological assays. The results showed that the inhibition constant of N-ethyl-N-[3-(3-nitropyrazolo[1,5-a]pyrimidin-7-yl)phenyl]methanesulfonamide was 11.1 nM.