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The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
July 1990,
Die Pharmazie,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
October 1995,
Farmaco (Societa chimica italiana : 1989),
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
May 1976,
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
January 1959,
Arzneimittel-Forschung,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
September 2019,
RSC advances,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
December 1978,
Il Farmaco; edizione scientifica,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
January 2008,
Beilstein journal of organic chemistry,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
April 1982,
Chemical & pharmaceutical bulletin,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
July 1975,
The Journal of organic chemistry,
E J Trybulski, and
R I Fryer, and
E Reeder, and
A Walser, and
J Blount
January 1988,
Polish journal of pharmacology and pharmacy,
