Comparison of a new class of pyrrole containing benzodiazepine ligands to the pyrazoloquinolinones CGS 9896, 9895, and 8216.
Four pyrazoloquninolinone compounds, variations of known high affinity ligands for the GABA A/Benzodiazepine receptors (BDZRs), were synthesized and their affinities for BDZRs in cerebellum and spinal cord measured and compared to the parent compounds, CGS 8216, CGS 9895, and CGS 9896.  Using the techniques of computational chemistry, specific properties of both types of compounds were calculated and evaluated for the extent to which they fulfill the minimum postulated requirements for recognition of a cerebellum, "Type I", BDZR embodied in our current three dimensional pharmacophore. Additional properties were also calculated and examined as possible further determinants of recognition of the receptor subtype.
Schove
L T
LT
Molecular Research Institute, Palo Alto, CA 94304, USA.
Perez
J J
JJ
Maguire
P A
PA
Loew
G H
GH
D000818:Animals; D002531:Cerebellum / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D018755:GABA Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D008024:Ligands; D008956:Models, Chemical; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects; D013329:Structure-Activity Relationship
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D008024:Ligands; D011720:Pyrazoles; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one; C039232:2,5-dihydro-2-(4-methoxyphenyl)-3H-pyrazolo(4,3-c)quinolin-3-one; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one