19376-57-9Relevant academic research and scientific papers
Structure-Activity Relationships for the Marine Natural Product Sintokamides: Androgen Receptor N-Terminus Antagonists of Interest for Treatment of Metastatic Castration-Resistant Prostate Cancer
Yan, Luping,Banuelos, Carmen A.,Mawji, Nasrin R.,Patrick, Brian O.,Sadar, Marianne D.,Andersen, Raymond J.
supporting information, p. 797 - 813 (2020/11/13)
Synthetic analogues of the marine natural product sintokamides have been prepared in order to investigate the structure-activity relationships for the androgen receptor N-terminal domain (AR NTD) antagonist activity of the sintokamide scaffold. An in vitro LNCaP cell-based transcriptional activity assay with an androgen-driven luciferase (Luc) reporter was used to monitor the potency of analogues. The data have shown that the chlorine atoms on the leucine side chains are essential for potent activity. Analogues missing the nonchlorinated methyl groups of the leucine side chains (C-1 and C-17) are just as active and in some cases more active than the natural products. Analogues with the natural R configuration at C-10 and the unnatural R configuration at C-4 are most potent. Replacing the natural propionamide N-terminus cap with the more sterically hindered pivaloylamide N-terminus cap leads to enhanced potency. The tetramic acid fragment and the methyl ether on the tetramic acid fragment are essential for activity. The SAR optimized analogue 76 is more selective, easier to synthesize, more potent, and presumed to be more resistant to proteolysis than the natural sintokamides.
ANDROGEN RECEPTOR MODULATORS AND METHODS FOR THEIR USE
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Page/Page column 49; 50, (2015/12/18)
Compounds having a structure of Structure I: or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R4, R6, Y1 and Y2 are as defined herein, and wherein at least one of R3 or R4 is a straight-chain C1-C6 haloalkyl, are provided. Uses of such compounds for treatment of various indications, including prostate cancer, as well as methods of treatment involving such compounds are also provided.
Asymmetric total synthesis of the gastroprotective microbial agent AI-77-B
Ghosh, Arun K.,Bischoff, Alexander,Cappiello, John
, p. 821 - 832 (2007/10/03)
An enantioselective total synthesis of the pseudopeptide microbial agent AI-77-B, which has shown potent antiulcerogenic properties, is described. The synthesis is convergent and involves the assembly of a dihydroisocoumarin fragment and a hydroxy amino acid. The dihydroisocoumarin derivative was synthesised by means of a Diels-Alder reaction between 1-methoxy-1,3-cyclohexadiene and an alkynyl ester derivative as the dienophile. The alkynyl ester was obtained stereoselectively by two different synthetic routes: (1) A stereoselective allylation of leucinal, and (2) a titanium enolate-mediated anti-aldol reaction with trichlorobutyraldehyde, a novel homopropargylaldehyde equivalent. The stereocentres of the hydroxy amino acid moiety were generated through a titanium enolate-mediated syn-aldol reaction, Curtius rearrangement, and application of Dondoni's aldehyde homologation. Condensation of the dihydroisocoumarin and hydroxy amino acid moieties and subsequent removal of the protecting groups furnished optically active AI-77-B. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
Catalyst Effects on Reactions of α,β-Unsaturated Ketones and Esters with Haloforms under Phase-Transfer Catalysis
Dehmlow, Eckehard V.,Wilkenloh, Juergen
, p. 582 - 588 (2007/10/02)
Reactions of acceptor-substituted alkenes with haloform/sodium hydroxide and PT-catalyst result in dihalocarbene additions competitive to Michael additions, with or without consecutive cyclization, and further reactions.Product compositions are strongly dependent on the nature of the phase-transfer catalyst: Sterically unhindered quarternary ammonium ions and benzo-crown ethers favour processes via carbenes, large delocalized (soft) cations foster primary Michael additions.Thus, tert-butyl cis-crotonate is dichlorocyclopropanated stereospecifically with NMe4Cl.The respective stereospecific CBr2 conversion is successful only with PhHgCBr3 .
FORMATION OF A REASONABLY STABILIZED TRICHLOROMETHYL ANION BY THE REACTION OF CHLOROFORM WITH ELECTROGENERATED BASE, AND ITS 1,4-ADDITION TO α,β-UNSATURATED CARBONYL COMPOUNDS
Shono, Tatsuya,Ishifune, Manabu,Ishige, Osamu,Uyama, Hiroshi,Kashimura, Shigenori
, p. 7181 - 7184 (2007/10/02)
A reasonably stabilized trichloromethyl anion (TCMA) was formed by the reaction of chloroform with an electrogenerated base prepared by the electroreduction of 2-pyrrolidone, and the addition of this TCMA to α,β-unsaturated esters gave the corresponding β-trichloromethyl esters in good yields.
Diaminotrihalopropyl triazines: and their methylol derivatives
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, (2008/06/13)
2,4-Diamino-6(3,3,3-tribromo-1-propyl)-1,3,5-triazine and 2,4-diamino-6(3,3,3-trichloro-1-propyl)-1,3,5-triazine were prepared by the reaction of the corresponding methyl or ethyl γ-tribromo-butyrate or methyl or ethyl γ-trichlorobutyrate with biguanide. The N-methylol derivatives of the diaminotrihalopropyl triazines were prepared by the reaction of the triazines with aqueous formaldehyde. Two pure tetramethylol derivatives were prepared, namely: 2,4-bis[bis(hydroxymethyl)amino]-6-(3,3,3-tribromo-1-propyl)-1,3,5-triazine and 2,4-bis[bis(hydroxymethyl)amino]-6-(3,3,3-trichloro-1-propyl)-1,3,5-triazine. The tetramethylol derivatives were used to impart durable flame retardancy and wrinkle recovery to cellulosic textiles, particularly to cotton. Flame-retardancy was also imparted to wool and to blends of cotton and polyester.
