New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives

Sonnet, Pascal; Dallemagne, Patrick; Guillon, Jean; Enguehard, Cécile; Stiebing, Silvia; Tanguy, Julien; Bureau, Ronan; Rault, Syl­vain; Auvray, Pierrı̈ck; Moslemi, Safa; Sourdaine, Pascal; Séralini, Gilles‐Éric

doi:10.1016/s0968-0896(00)00024-9

Cited by 122 publications

(52 citation statements)

References 25 publications

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“…Dihydropyrrolizinone derivatives were thus obtained, among which the most potent compound was 9 (IC 50 ¼ 0.65 mM), which even though did not reach the potency of the leads, still showed the feasibility of a new ring system. 60 An important observation regarding the indolizinone and pyrrolizinone derivatives like 8 and 9 is that they are chiral compounds, but no attempt of resolution of the enantiomers was reported. Unfortunately, basing any SAR or mechanistic consideration on the activity of the racemates may seriously question the relevance of possible conclusions.…”

mentioning

confidence: 99%

Nonsteroidal aromatase inhibitors: Recent advances

Recanatini

Cavalli

Valenti

2002

Medicinal Research Reviews

106

102

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Aromatase is the cytochrome P450 enzyme responsible for the last step of estrogen biosynthesis, and aromatase inhibitors constitute an important class of drugs in clinical use for the treatment of breast cancer. Nonsteroidal aromatase inhibitors (NSAIs) are competitive inhibitors of aromatase, which bind to the enzyme active site by coordinating the iron atom present in the heme group of the P450 protein. Presently, third generation NSAIs are in use, and research efforts are being carried out both to identify new molecules of therapeutic interest and to clarify the mechanism of action. In this article, we present a survey of the compounds that have been recently reported as NSAIs, to provide a broad view on the general structure-activity relationships of the class. Moreover, starting from the current knowledge of the mechanistic aspects of aromatase action and from recent theoretical work on the molecular modeling of both enzyme and inhibitors, we try to indicate a way to integrate these different studies in view of a more general understanding of the aromeatase-inhibitor system. Finally, some aspects regarding the possible future development of the field are considered briefly.

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confidence: 99%

Nonsteroidal aromatase inhibitors: Recent advances

Recanatini

Cavalli

Valenti

2002

Medicinal Research Reviews

106

102

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“…Indolizine derivatives containing a variety of functional groups are being used due to their interesting biological activities like antibacterial [5], antiviral and antileishmanial [6], antiinflamatory [7], analgesic [8], antitumor [9], antioxidant [10], aromatase inhibitory [11], calcium entry blocking [12], and histamine H 3 receptor antagonist [13] and also evaluated as agrochemical [14]. As such, the indolizines are important synthetic targets for developing new pharmaceuticals or agrochemicals.…”

Section: Introductionmentioning

confidence: 99%

Amberlite–IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: Antibacterial and antifungal evaluation of the products

Hazra

Mondal

Maity

et al. 2011

European Journal of Medicinal Chemistry

189

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“…Indolizine derivatives have been found to possess a variety of biological activities such as anti-inflammatory [10], antiviral [11], aromatase inhibitory [12], analgesic and antitumor [13] activities. A brief survey of the Cambridge Structural Database (Version 5.33; [14]) revealed a scarcity of precise crystallographic data on octahydroindolizine ring systems.…”

Section: Introductionmentioning

confidence: 99%

Spectral Analysis and Crystal Structure of Spiro[2.2”] Acenaphthene-1”-One-Spiro[3.3’]-5’-(2,3-Dichlorophenyl Methylidene)-1’-Methylpiperidin-4’-One-4- (2,3-Dichlorophenyl) Octahydroindolizine

Priya¹,

Suresh²,

Sivakumar³

et al. 2012

CSTA

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The crystal structure of spiro[2.2"]acenaphthene-1"-onespiro[3.3']-5'-(2,3-dichlorophenylmethylidene)-1'-methylpiperidin-4'-one-4-(2,3-dichorophenyl) octahydroindolizine was elucidated by single crystal X-ray diffraction. The title compound C 37 H 30 Cl 4 N 2 O 2 , crystallizes in the orthorhombic system, space group P2 1 2 1 2 1 with a = 8.4610(4) Å, b = 16.0926(6) Å, c = 23.8997(11) Å and Z = 4. The central piperidine ring adopts twisted conformation, the piperidine of octahydroindolizine ring is in chair conformation and the pyrrole ring is in slightly twisted envelope conformation. Details of the synthesis, NMR, crystal structure determination and intra-and intermolecular interactions of the compound are given.

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New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives

Cited by 122 publications

References 25 publications

Nonsteroidal aromatase inhibitors: Recent advances

Nonsteroidal aromatase inhibitors: Recent advances

Amberlite–IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: Antibacterial and antifungal evaluation of the products

Spectral Analysis and Crystal Structure of Spiro[2.2”] Acenaphthene-1”-One-Spiro[3.3’]-5’-(2,3-Dichlorophenyl Methylidene)-1’-Methylpiperidin-4’-One-4- (2,3-Dichlorophenyl) Octahydroindolizine

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