Azolobenzazepine derivatives as neurologically active agents

Details Azolobenzazepine derivatives as neurologically active agents Azolobenzazepine derivatives as neurologically active agents

1998-09-03

2000-09-26

Berch, Mark L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

540521, 548255, 5483741, C07D48704, A61K 3155

Patent

active

061242810

DESCRIPTION:

BRIEF SUMMARY
The invention relates to azolobenzazepine derivatives, to pharmaceutical compositions containing the same and to the method of use thereof in the treatment of neuroloical disorders.
More specifically, the invention relates to compounds of the Formula I: ##STR2## wherein:
X is O or S;
R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently hydrogen, perfluorolower-alkyl, halogen, nitro is or cyano; and
C together with the carbon atoms to which it is attached forms a 5-membered aromatic heterocycle selected from the group consisting of: ##STR3## or tautomers thereof, wherein R is cyano, --C(O)OR.sup.5 (wherein R.sup.5 is hydrogen, lower-alkyl, lower-alkenyl, lower-alkynyl, cycloalkyl-lower-alkyl, phenyl, phenyl-lower-alkyl, phenyl-lower-alkynyl, lower-alkylthio-lower-alkyl, halo-lower-alkyl, trifluoromethyl-lower-alkyl, lower-alkoxy-lower-alkyl, hydroxy-lower-alkyl, lower-alkylamino, cycloalkylamino, or phenyl-lower-alkylamino), --C(O)NR.sup.6 R.sup.7 (wherein R.sup.6 and R.sup.7 are independently hvdrogen, phenyl, phenyl-lower-alkyl, lower-alkoxy-lower-alkyl, hydroxy-lower-alkyl, lower-alkyl, lower-alkoxy, hydroxy, or cycloalkyl, or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached form a 5- or 6-membered non-aromatic heterocycle selected from the group consisting of morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl and thiomorpholinyl), formyl, phenylcarbonyl, phenyl, lower-alkylcarbonyl, perfluorolower-alkyl, lower-alkoxy-carbonyl-lower-alkyl, carboxy-lower-alkyl, or phenyl-lower-alkylcarbonyl; wherein said phenyl, phenyl-lower-alkyl, phenyl-lower-alkynyl, phenyl-lower-alkyl-amino, phenylcarbonyl or phenyl-lower-alkylcarbonyl groups may optionally be substituted on the phenyl group thereof by one to three substituents, the same or different, selected from the group consisting of lower-alkyl, lower-alkoxy, halogen, hydroxy and trifluoromethyl; thereof; or a pharmaceutically acceptable base-addition salt of acidic members thereof; with the proviso that when C together with the carbon atoms to which it is attached forms a triazole ring, at least one of R.sup.1, R.sup.2, R.sup.3 or R.sup.4 must be other than hydrogen.
The compounds of the Formula I have been found to function as antagonists of the effects which excitatory amino acids, such as glutamate, have upon the NMDA receptor complex and are thus usefull in the treatment of neurological disorders.
Compounds within the ambit of Formula I above are those wherein:
X, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and C are as defined above; and
R is cyano, --C(O)OR (wherein R is hydrogen, lower-alkyl, lower-alkenyl, lower-alkynyl, cycloalkyl-lower-alkyl, phenyl, phenyl-lower-alkyl, phenyl-lower-alkynyl, lower-alkylthio- lower-alkyl, halo-lower-alkyl, trifluoromethyl-lower-alkyl, lower-alkylamino, cycloalkylamino, or phenyl-lower-alkyl-amino), --C(O)NR.sup.6 R.sup.7 (wherein R.sup.6 and R.sup.7 are independently hydrogen, phenyl, phenyl-lower-alkyl, lower-alkoxy-lower-alkyl, lower-alkyl, lower-alkoxy, hydroxy or cycloalkyl, or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached form a morpholinyl group), formyl, phenylcarbonyl, phenyl, lower-alkylcarbonyl, perfluorolower-alkyl, lower-alkoxy-carbonyl-lower-alkyl, or carboxy-lower-alkyl; wherein said phenyl, phenyl-lower-alkyl, phenyl-lower-alkynyl, phenyl-lower-alkylamino or phenylcarbonyl groups may optionally be substituted on the phenyl group thereof by one substituent selected from the group consisting of lower-alkyl, lower-alkoxy, halogen, hydroxy and trifluoromethyl.
Other compounds within the ambit of Formula I above are those wherein:
X, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and C are as defined above: and
R is cyano, --C(O)OR.sup.5 (wherein R.sup.5 is hydrogen, lower-alkyl, lower-alkenyl, lower-alkynyl, cycloalkyl-lower-alkyl, phenyl, phenyl-lower-alkyl, phenyl-lower-alkynyl, lower-alkylthio-lower-alkyl, halo-lower-alkyl, trifluoromethyl-lower-alkyl, lower-alkylamino, cycloalkylamino, or phenyl-lower-alkyl amino), --C(O)NR.sup.6 R.sup.7 (wherein R.sup.6 and

REFERENCES:
patent: 5686442 (1997-11-01), Ohtsuka et al.

Affiliated with

Also associated with

Rating

Azolobenzazepine derivatives as neurologically active agents does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Azolobenzazepine derivatives as neurologically active agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Azolobenzazepine derivatives as neurologically active agents will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2100338