Isoxazole estrogen receptor agonist and antagonist compounds having unexpected and surprising activity in modulating estrogen receptor activity are described. In addition, methods and compositions for treating or preventing estrogen receptor-mediated disorders are disclosed. The compounds, methods, and compositions of the invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Estrogen receptor modulators

https://www.arkat-usa.org/get-file/53632/

Chemistry and application of 4-oxo-4H-1-benzopyran-3-carboxaldehyde

Catalytic asymmetric transformations employing a-isothiocyanato compounds have recently been successful and have captured considerable attention as powerful methods for the synthesis of various kinds of useful chiral compounds. By using this kind of versatile reactant as the nucleophile, the enantioselective Aldol-type, Mannich-type, and Michael addition reactions have been developed to access the highly optically active b-hydroxy/amino-a-amino acid derivatives and spiro compounds. In a general mode of these reactions, the a-isothiocyanato compounds serve both as a nucleophile and electrophile; they are enolized by deprotonation at their a-carbon atom by a base catalyst and then nucleophilic attack at the electron-deficient double bonds (ketone/aldehyde, imine, or olefin). The anion (O, N, or C) generated in the addition process is subsequently quenched by the electron-deficient carbon atom in the isothiocyanate moiety. Based on the above-mentioned reaction course, we hypothesized that the enolized a-isothiocyanato compounds intermediate (Scheme 1, I1) might also be able to self-cyclize by trapping the oxygen anions of the enolate by the isothiocyanate. Thus, the enolized intermediate undergoes an equilibrium in a-isothiocyanate–thiooxazole (I2, I3) tautomerism. As the electrophiles employed in previous work were all restricted to electron-deficient double bonds, which prefer to undergo the nucleophilic attack by the enolate, no adducts of thiols were isolated. We envisaged that if a kind of appropriate electrophile were used to trap the thiooxazole intermediate (I2), not only the scope of reaction type of the versatile a-isothiocyanato compounds could be extended, but also a new methodology for the synthesis of useful 2-thiooxazole-containing organic molecules could be developed. To test our hypothesis, a-isothiocyanato imide 2 a was treated with tert-butoxycarbonyl (Boc) anhydride and 4-dimethylaminopyridine (DMAP) in the presence of catalytic N,N-diisopropylethylamine (DIPEA) at room temperature in CH2Cl2 (Scheme 2). To our delight, the product I3’ was isolated in 83 % yield, thus demonstrating the existence of the thiooxazole intermediate under the basic conditions. We

Catalytic enantioselective ring-opening reaction of meso-aziridines with α-isothiocyanato imides.

The synthesis of 4-oxo-4H-chromenes containing sulfur-nitrogen heterocyclic rings as well as their biological activities are reviewed.

Synthesis of Biologically Active 4-Oxo-4H-Chromene Derivatives Containing Sulfur-Nitrogen Heterocycles

The review is focused on recent developments of chemistry of synthetic analogs of natural compounds, isoflavone and homoisoflavone. The possible synthetic strategies to access heterocyclic analogs of these compounds starting from readily available 3-formylchromone and its derivatives (3-cyanochromone, 2-amino-3-formylchromone) and products of its condensation with simplest C- and N-nucleophiles are discussed. The structural features of the reaction products that depend on the nature of the reaction medium, structure of the starting compounds, and reagent ratio are considered. Particular attention is given to the application of the modern strategies of organic synthesis, namely green chemistry approaches, click reactions, domino reactions, etc. Examples of compounds of this group most promising for clinical application due to wide and pronounced pharmacological effects are given.

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Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone.

A few benzothiazepinyl chromones (II & IV) were prepared by the reaction of 2-amino benzenethiol with new types of chromonyl chalcones (I & III). One representative compound (IVb) was cleaved with hydrazine hydrate and with hydroxylamine hydrochloride to afford pyrazole (V) and isoxazole (VI) derivatives. The structures of these compounds were confirmed by their analytical and spectral analysis. Some of the above compounds were screened for their anti-microbial activity.

Synthesis and cleavage reactions of benzothiazepinyl chromone derivatives

2-Aminophenazin-3-ol (I) is treated with carbondisulfide in alkaline medium to furnish 2-mercapto(4:5)-phenazino oxazole (IIa). Treatment of IIa with alkyl/acyl halides gives the corresponding thioethers (IIb-i; k-o) and thioester (IIj). These are characterised by elemental, IR, PMR and mass spectral analysis. All the compounds synthesised have been screened for their antimicrobial activity.

R. B. Reddy

Papers

Synthesis and cleavage reactions of benzothiazepinyl chromone derivatives

Synthesis and antimicrobial activity of 2-substituted mercapto(4:5)-phenazino oxazole derivatives

Synthesis and Cleavage Reactions of Benzothiazepinylchromone Derivatives.

Synthesis of 3-Aryl-6-methyl-7-phenyl-8-oxo-2H,8H-pyrano(3,2-g)(1,4) benzoxazines as Potent Antimicrobial Agents.

Synthesis and Antimicrobial Activity of Imidazobenzothiadiazole Derivatives.