114636-29-2Relevant articles and documents
Exploring Derivatives of Quinazoline Alkaloid l-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors
Ahmad, Mudassier,Aga, Mushtaq A.,Bhat, Javeed Ahmad,Kumar, Brijesh,Rouf, Abdul,Capalash, Neena,Mintoo, Mubashir Javeed,Kumar, Ashok,Mahajan, Priya,Mondhe, Dilip Manikrao,Nargotra, Amit,Sharma, Parduman Raj,Zargar, Mohmmad Afzal,Vishwakarma, Ram A.,Shah, Bhahwal Ali,Taneja, Subhash Chandra,Hamid, Abid
, p. 3484 - 3497 (2017/05/05)
l-Vasicine is a quinazoline alkaloid with an electron dense ring and additional functionalities in its structure. Employing target oriented synthesis (TOS) based on in silico studies, molecules with significant docking scores containing different derivatives of l-vasicine as caps were synthesized. Interestingly, one molecule, i.e., 4a, which contained 3-hyroxypyrrolidine as a cap group and a six carbon long aliphatic chain as a linker was found to inhibit HDACs. 4a showed more specificity toward class I HDAC isoforms. Also 4a was found to be less cytotoxic toward normal cell lines as compared to cancer cell lines. 4a inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency.
1-SUBSTITUTED-3-PYRROLIDINE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS
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Page 15, (2008/06/13)
This invention generally relates to the derivatives of 1 -substituted-3 -pyrroli dines having the structure of Formula (I): The compounds of this invention can function as..muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to a process for the preparation of the compounds of the present invention. pharmaceutical compositions containing the compounds of the present invention and the methods for treating the diseases mediated through muscarinic receptors.
Stereocontrolled dopamine receptor binding and subtype selectivity of clebopride analogues synthesized from aspartic acid
Einsiedel, Juergen,Weber, Klaus,Thomas, Christoph,Lehmann, Thomas,Huebner, Harald,Gmeiner, Peter
, p. 3293 - 3296 (2007/10/03)
Employing the achiral 4-aminopiperidine derivative clebopride as a lead compound, chiral analogues were developed displaying dopamine receptor binding profiles that proved to be strongly dependent on the stereochemistry. Compared to the D1 receptor, the t
Synthesis and structure-activity relationships of naphthamides as dopamine D3 receptor ligands
Huang,Luedtke,Freeman,Wu,Mach
, p. 1815 - 1826 (2007/10/03)
A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D2 and D3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1- alkylp
Fluoronaphthyridines and -quinolines as Antibacterial Agents. 5. Synthesis and Antimicrobial Activity of Chiral 1-tert-Butyl-6-fluoro-7-substituted-naphthyridones
Cesare, P. Di,Bouzard, D.,Essiz, M.,Jacquet, J. P.,Ledoussal, B.,et al.
, p. 4205 - 4213 (2007/10/02)
A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3-carboxylic acids has been prepared.These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position.In this paper we report the full details of the asymmetric synthesis of this series of compounds.Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity.Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.
Asymmetric Synthesis and Properties of the Enantiomers of the Antibacterial Agent 7-(3-Aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic Acid Hydrochloride
Rosen, Terry,Chu, Daniel T. W.,Lico, Isabella M.,Fernandes, Prabhavathi B.,Shen, Linus,et al.
, p. 1586 - 1590 (2007/10/02)
Compound 1 is a potent member of the quinoloecarboxylic acid class of antibacterial agents and is currently undergoing clinical evaluation.We have developed efficient asymmetric syntheses of the enantiomers of this agent.The S-(+) enantiomer 1a is 1-2 log2 dilutions more active than the R-(-) enantiomer 1b against aerobic bacteria and 1-2 or more log2 dilutions more active against anaerobic bacteria in vitro.The enantiomer 1a shows significantly better in vivo activity in a Pseudomonas aeruginosa mouse protection model compared to racemic 1.Coupled with the improved solubility profile of 1a relative to racemic material, these features may be of practical significance from a clinical standpoint.
