| 摘要 |
#CMT# #/CMT# Triazabenzo[a]naphtho[2,1,8-cde]azulene derivatives (I) are new. #CMT# : #/CMT# Triazabenzo[a]naphtho[2,1,8-cde]azulene derivatives of formula (I) are new. R 1H, 1-6C alkyl, 1-6C aminoalkyl or 1-6C hydroxyalkyl; R 2H; R 1+R 2 = a bond; R 3H; R 4H, Me, 3-6C alkyl, 1-6C aminoalkyl, 1-6C hydroxyalkyl, aryl(1-6C)alkyl or heterocycloalkyl(1-6C)alkyl; R 3+R 4a bond; R 5-R 8H, or R 5+R 6 and/or R 7+R 8 = O, S or NH; R 9H, halo, 1-6C alkyl (optionally substituted with Q), 1-6C alkoxy, OH, CN, NO 2, 1-6C polyhaloalkyl or NRR"; R, R" : H, 1-6C alkyl or 2-6C alkenyl; R 10, R 11H, halo, 1-6C alkyl, 1-6C alkoxy, OH, CN, NO 2, 1-6C polyhaloalkyl or NRR"; n : 0-4; m : 0-2; p : 0-3; X : NR 12; R 12H, 1-6C alkyl (optionally substituted with Q), 2-6C alkenyl (optionally substituted with Q), aryl(1-6C)alkyl, 1-6C polyhaloalkyl; aryl : optionally substituted phenyl or naphthyl; Q : halo, OH, 1-6C alkyl, 1-6C alkoxy, NH 2 or mono- or di(1-6C alkyl)amino. An independent claim is also included for a process for preparing (I). #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Antidepressant; Tranquilizer; Nootropic; Neuroprotective; Antiparkinsonian. #CMT#MECHANISM OF ACTION : #/CMT# Tyrosine hydroxylase inducer. Administering (5aRS,12aSR,12bSR,12cSR)-7-chloro-2,3,5a,10,12a,12b,12c-hexahydro-1H,4H-3a,9b,11-triazabenzo[a]naphtho[2,1,8-cde]azulene-10,12(5H,11H)-dione to mice by intraperitoneal injection (20 mg/kg) gave a 53% increase in tyrosine hydroxylase level in an anterior section of the locus coeruleus. #CMT#USE : #/CMT# (I) are tyrosine hydroxylase inducers useful for treatment of depression, anxiety, age-related memory disorders and neurodegenerative diseases, for palliative treatment of Parkinson's disease and for stress adaptation (all claimed). #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (claimed): The process comprises e.g. cyclizing an amide of formula (VII) in the presence of paraformaldehyde and acetic acid. #CMT#[Image]#/CMT# #CMT#SPECIFIC COMPOUNDS : #/CMT# 7 Compounds (I) are specifically claimed, e.g. (5aRS,12aSR,12bSR,12cSR)-7-chloro-2,3,4,5,5a,10,11,12a,12b,12c-decahydro-1H,12H-3a,9b,11-triazabenzo[a]naphtho[2,1,8-cde]azulen-12-one (Ia), (5aRS,12aSR,12bSR,12cSR)-7-chloro-2,3,5a,12a,12b,12c-hexahydro-1H,4H-3a,9b,11-triazabenzo[a]naphtho[2,1,8-cde]azulen-12-one, (12aRS,12bRS)-7-chloro-2,3,12a,12b-tetrahydro-1H,4H-3a,9b,11-triazabenzo[a]naphtho[2,1,8-cde]azulen-12-one, (5aRS,12aSR,12bSR,12cSR)-2,3,5a,12a,12b,12c-hexahydro-1H,4H-3a,9b,11-triazabenzo[a]naphtho[2,1,8-cde]azulen-12-one and (5aS,12aR,12bR,12cR)-2,3,5a,12a,12b,12c-hexahydro-1H,4H-3a,9b,11-triazabenzo[a]naphtho[2,1,8-cde]azulen-12-one-10,12-(5H,11H)-dione. |
