Synthesis of aza and carbocyclic β-carbolines for the treatment of alcohol abuse. Regiospecific solution to the problem of 3,6-disubstituted β- and aza-β-carboline specificity.
A novel two step protocol was developed to gain regiospecific access to 3-substituted β- and aza-β-carbolines, 3-PBC (1), 3-ISOPBC (2), βCCt (3), 6-aza-3-PBC (4) and 6-aza-3-ISOPBC (5). These β-carbolines (1-3) are potential clinical agents to reduce alcohol self-administration, especially 3-ISOPBC·HCl (2·HCl) which appears to be a potent anti-alcohol agent active against binge drinking in a rat model of maternally deprived (MD) rats. The method consists of two consecutive palladium-catalyzed reactions: a Buchwald-Hartwig amination followed by an intramolecular Heck-type cyclization in high yield.
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA. capncook@uwm.edu.
V V N
VV
Phani Babu Tiruveedhula
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA. capncook@uwm.edu.
Kashi Reddy
KR
Methuku
Center for Bimolecular Science and Engineering, Naval Research Laboratory, Code 6930, Washington, D. C. 20375, USA.
Jeffrey R
JR
Deschamps
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA. capncook@uwm.edu.
James M
JM
Cook
D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D063425:Binge Drinking / Q000188:drug therapy; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002384:Catalysis; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism
D001372:Aza Compounds; D002243:Carbolines; D010165:Palladium