A novel class of ligands specific for MBR receptors has been identified: 6-arylpyrrolo[2,1-d]- [1,5]benzothiazepine derivatives. The majority of newly synthesized esters 37–64 as well as some intermediate ketones showed micro- or nanomolar affinity for [3H]PK 11195 binding inhibition. A SAR study on 42 compounds and a molecular modeling approach led to a preliminary structural selectivity profile: the 6,7-double bond, the carbamoyloxy, alcanoyloxy, and mesyloxy side chains at the 7-position, and the prospective chloro substitution at the 4-position seemed to be the most important structural features improving affinity. Therefore, 7-[(dimethylcarbamoyl)oxy]- and 7-acetoxy-4-chloro-6-phenylpyrrolo[2,1-d] [1,5]benzothiazepine (43 and 57) were synthesized. With 7-[(dimethylcarbamoyl)oxy]-6-(p-methoxyphenyl)pyrrolo[2,1-d] [1,5]benzothiazepine (65), these were the most promising compounds with IC50s of respectively 9, 8, and 9 nM, under conditions where PK 11195 had an IC50 of 2 nM. © 1994, American Chemical Society. All rights reserved.

Fiorini, I., Nacci, V., Ciani, S.M., Garofalo, A., Campiani, G., Savini, L., et al. (1994). Novel Ligands Specific for Mitochondrial Benzodiazepine Receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine Derivatives. Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies. JOURNAL OF MEDICINAL CHEMISTRY, 37(10), 1427-1438 [10.1021/jm00036a007].

Novel Ligands Specific for Mitochondrial Benzodiazepine Receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine Derivatives. Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies

Fiorini, Isabella;Nacci, Vito;Campiani, Giuseppe;
1994-01-01

Abstract

A novel class of ligands specific for MBR receptors has been identified: 6-arylpyrrolo[2,1-d]- [1,5]benzothiazepine derivatives. The majority of newly synthesized esters 37–64 as well as some intermediate ketones showed micro- or nanomolar affinity for [3H]PK 11195 binding inhibition. A SAR study on 42 compounds and a molecular modeling approach led to a preliminary structural selectivity profile: the 6,7-double bond, the carbamoyloxy, alcanoyloxy, and mesyloxy side chains at the 7-position, and the prospective chloro substitution at the 4-position seemed to be the most important structural features improving affinity. Therefore, 7-[(dimethylcarbamoyl)oxy]- and 7-acetoxy-4-chloro-6-phenylpyrrolo[2,1-d] [1,5]benzothiazepine (43 and 57) were synthesized. With 7-[(dimethylcarbamoyl)oxy]-6-(p-methoxyphenyl)pyrrolo[2,1-d] [1,5]benzothiazepine (65), these were the most promising compounds with IC50s of respectively 9, 8, and 9 nM, under conditions where PK 11195 had an IC50 of 2 nM. © 1994, American Chemical Society. All rights reserved.
1994
Fiorini, I., Nacci, V., Ciani, S.M., Garofalo, A., Campiani, G., Savini, L., et al. (1994). Novel Ligands Specific for Mitochondrial Benzodiazepine Receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine Derivatives. Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies. JOURNAL OF MEDICINAL CHEMISTRY, 37(10), 1427-1438 [10.1021/jm00036a007].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/29739
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