ChemInform Abstract: STUDIES ON COMPOUNDS WITH PSYCHOTROPIC ACTIVITY. VIII. SYNTHESIS AND SEDATIVE ACTIVITY OF SOME 9‐SUBSTITUTED DERIVATIVES OF 5‐PHENYLPYRROLO(2,1‐D)(1,5)BENZOTHIAZEPINE AND CIS‐4,5‐DIHYDRO‐4‐HYDROXY‐5‐PHENYLPYRROLO(2,1‐D)(1,5)BENZOTHIAZEPINE

Abstract

Auf dem im Formelschema angegebenen Wegen werden die Benzothiazepin‐Derivate (VII), (X), (XI) und (XII) hergestellt.

Cardiovascular Characterization of Pyrrolo[2,1-d][1,5]benzothiazepine Derivatives Binding Selectively to the Peripheral-Type Benzodiazepine Receptor (PBR): From Dual PBR Affinity and Calcium Antagonist Activity to Novel and Selective Calcium Entry Blockers

“…L-Type Calcium Channel Affinity of the PBR Ligands 3 and 7 − 20: In Vitro SAR Study. A series of pyrrolobenzothiazepines, recently described as potent and selective PBR ligands ( 3 , 7 − 20 ), 14d,e were examined for their ability to displace [ 3 H]nitrendipine binding to CCR in rat cortex and heart homogenates. Table summarizes the IC 50 s for the displacement of [ 3 H]PK 11195 and [ 3 H]nitrendipine binding in rat cortex, while Table summarizes the IC 50 s of a subset of compounds for the displacement of [ 3 H]nitrendipine in heart homogenate compared to rat brain.…”

“…The synthesis of pyrrolobenzothiazepinones 21 − 31 , which served as starting materials to obtain esters 54 − 68 , has been accomplished following an already published procedure (see ref a−e and references cited therein). As highlighted in Scheme , sodium borohydride reduction of the ketones 21 − 31 provided the alcohols 32 − 42 in 80−90% yield.…”

“…b The concentration of the tested compounds that inhibited [ 3 H]PK 11195 binding to rat cortex homogenate by 50% (IC 50 ) was determined by log−probit analysis with six concentrations of the displacers, each performed in triplicate. Values are the mean ± SE of at least three separate experiments, performed in triplicate, refs d,e for compounds 3 and 7 − 20 . NA = not active.…”

“…These observations, coupled with strong evidence of an interaction between L-type VOCC and PBR ligands in vitro , suggest that these latter compounds might represent novel potential therapeutic tools for cardiovascular diseases. 2b, We have recently developed a novel class of specific PBR ligands based on a pyrrolobenzothiazepine skeleton . In the light of the close relationship between PBR and the cardiovascular function and as part of our program aimed at developing novel cardioactive agents ( 6 ), we decided to further investigate our PBR ligands in order to define their cardiovascular activity.…”

1,5-Benzothiazepine, a versatile pharmacophore: A review

“…The NF-34, 17 and NF-44, 18, pyrrolo[2,1-d] [1,5]benzothiazepine-5-carboxamides have been synthesized and evaluated for their sedative action and were found to be potent sedative agents comparable to diazepam [60]. Three compounds from the series of 6-arylpyrrolo[2,1-d] [1,5]benzothiazepine derivatives were found most potent to displace [1,5]benzothiazepine 21 are most potent ligands in this series, specific for mitochondrial benzodiazepine receptor [61].…”