99293-95-5Relevant articles and documents
Molecular yardsticks. Rigid probes to define the spatial dimensions of the benzodiazepine receptor binding site
Martin,Trudell,Arauzo,Allen,LaLoggia,Deng,Schultz,Tan,Bi,Narayanan,Dorn,Koehler,Skolnick,Cook
, p. 4105 - 4117 (1992)
A series of rigid planar azadiindoles (8a, 8b, and 8d), benzannelated pyridodiindoles (11a, 11b, and 11d), and indolopyridoimidazoles (11c, 20, and 24) were synthesized from 4-oxo-1,2,3,4-tetrahydro-β-carboline 5 via the Fischer indole cyclization with the appropriate arylhydrazines. These analogues were employed as probes ('molecular yardsticks') to define the spatial dimensions of the lipophilic regions of the benzodiazepine receptor (BzR) binding cleft. Benzannelated indoles 11a-d and indolopyridoimidazoles 20 and 24 were important in establishing an area of negative interaction (S1, see Figure 6, part b) in the binding cleft common to the interactions of both inverse agonists and agonists. Data from this chemical and computer- assisted analysis of the pharmacophore (see Figure 6) indicates that inverse agonists and agonists bind to the same binding region, but the pharmacophoric descriptors required for the two activities are different, in keeping with previous studies with these planar ligands. However, the hydrogen bond donating site H1 and the lipophilic region L1 in the receptor binding site are common interactions experienced by both series of ligands. The low affinities of both indolo[3,2-c]carbazole (3a) and indolo[3,2-b]isoquinoline (3b) for the BzR are consonant with the requirements of a hydrogen bond acceptor interaction at donor site H1 and a hydrogen bond donor interaction at acceptor site A2 for potent inverse agonist activity in the β-carboline series. The hydrochloride salts of 1-aza- 8a (IC50 10.6 nM), 2-aza- 8b (IC50 51.5 nM), and 4-azadiindole 8d (IC50 11.2 nM) were found to be much more soluble in water than the corresponding salt of the parent diindole 2. Moreover, aza analogues 8a and 8b were shown to be partial inverse agonists with proconvulsant potencies comparable to that of the parent diindole 2.
Microbiological Transformations, Part 6. Microbiological Transformations of Acyl Derivatives of Indoline, 1,2,3,4-Tetrahydroquinoline, 1,2,3,4-Tetrahydroisoquinoline and 2,3,4,5-Tetrahydro-1H-1-benzazepine with the Fungus Cunninghamella elegans
Crabb, Trevor,Soilleux, Stephanie L.
, p. 1381 - 1386 (2007/10/02)
Incubation of N-benzoyl and N-(p-toluoyl)indoline with Cunninghamella elegans resulted in reductive cleavage with the formation of indoline and the corresponding benzyl alcohol.N-Acetylindoline underwent normal benzylic hydroxylation ond open chain analogues of N-(p-toluoyl)indolines were hydroxylated at the aryl methyl group by C. elegans.The fungus effected benzylic oxidation at the 4-position on N-benzoyl-1,2,3-tetrahydroquinoline and in N-benzoyl-1,2,3,4-tetrahydroisoquinoline derivatives.N-(p-Toluoyl)-1,2,3,4-tetrahydroquinoline and N-(p-ethylbenzoyl)-1,2,3,4-tetrahydroisoquinoline were, however, hydroxylated at the alternative 4'-benzylic position.Incubation of N-(p-toluoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine with C. elegans gave 5-hydroxy-N-(p-toluoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine
