title: Synthesis of 3,8,9-trisubstituted-1,7,9-triaza-fluorene-6-carboxylic acid derivatives as a new class of insulin secretagogues.
abstract: beta-Carbolines stimulate insulin secretion in a glucose-dependent manner, probably by acting on I(3)-binding site. Knowing the in vitro glucose-dependent insulinotropic potential of beta-carbolines, in this project, three series of substituted-triaza-fluorene-6-carboxylic acids (5a-v, 6a-t, and 7a-t) were designed (analogs of beta-carboline) as a new class of insulinotropic agents. The in vitro glucose-dependent insulinotropic activities of test compounds were evaluated using RIN5F assay. Interestingly, with respect to the control, test compounds showed concentration-dependent insulin release, only in presence of glucose load (16.7 mmol). Some of the test compounds from each series were found to be equipotent to standard compound (Harmane), indicating that the pyridine ring systems of substituted-triaza-fluorenes act as bioisosteres of benzene ring in beta-carbolines.
authors.affiliation: Zydus Research Center, Cadila Healthcare Ltd, Sarkhej-Bavala NH 8A, Moraiya, Ahmedabad, India. rajeshbahekar@zyduscadila.com
authors.forename: Rajesh H
authors.initials: RH
authors.lastname: Bahekar
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
authors.forename: Pradip A
authors.initials: PA
authors.lastname: Jadav
authors.forename: Ashish
authors.initials: A
authors.lastname: Goel
authors.forename: Dipam N
authors.initials: DN
authors.lastname: Patel
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Prajapati
authors.forename: Arun A
authors.initials: AA
authors.lastname: Gupta
authors.forename: Honey
authors.initials: H
authors.lastname: Modi
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Patel
mesh_terms: D000818:Animals; D001665:Binding Sites; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015394:Molecular Structure; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D007328:Insulin; D018341:Receptors, Adrenergic, alpha-2; D005947:Glucose