24370-84-1

Upstream product

• 103-45-7 acetic acid phenethyl ester 
• 674-82-8 4-methyleneoxetan-2-one 
• 60-12-8 2-phenylethanol 
• 122-97-4 3-Phenyl-1-propanol 
• 105-45-3 acetoacetic acid methyl ester 
• 5394-63-8 2,2,6-trimethyl-4H-1,3-dioxin-4-one 
• 42490-66-4 2,2,6-trimethyl-4H-1,3-dioxin-4-one 
• 1694-31-1 tert-butyl acetoacetate 

Downstream Products

• 1026427-03-1 3-Oxo-2-[1-(2-phenyl-3H-imidazol-4-yl)-meth-(Z)-ylidene]-butyric acid phenethyl ester 

Relevant academic research and scientific papers

NEW ANALOGS AS ANDROGEN RECEPTOR AND GLUCOCORTICOID RECEPTOR MODULATORS

The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of androgen receptor and/or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases, cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.

Enzymatic Synergism in the Synthesis of β-Keto Esters

Reaction of alcohols with ethyl and tert-butyl acetoacetate catalyzed by a combination of commercially available enzymes is shown to be a convenient method for the preparation of a range of acetoacetic acid derivatives. Systematic studies proved that the combination of two or more enzymes enhances the yield of the reaction. Application of the selected enzyme mixture for enzymatic transesterification of various β-keto esters provided the respective products in excellent yields up to 96% and quantitative within 24 and 48 hours, respectively. The presented methodology is simple and mild, and can be used to prepare acetoacetates from primary and secondary alcohols. Application of a selected enzyme mixture for enzyme-catalyzed esterification of various carboxylic acids provided the respective β-hydroxy esters in excellent yields up to 96% and quantitative within 24 and 48 hours, respectively.

An efficient synthesis of β-ketoesters via transesterification and its application in Biginelli reaction under solvent-free, catalyst-free conditions

A simple and efficient transesterification process for the synthesis of β-ketoester derivatives has been achieved by the reaction of methyl β-ketoester with higher alcohols at 110 C under solvent-free, catalyst-free conditions and its application in synthesis of 3,4-dihydropyrimidin-2(1H)-ones C-5 ester derivatives via Biginelli reaction has been described.

Efficient trans-acetoacylation mediated by ytterbium(III) triflate as a catalyst under solvent-free condition

A simple and efficient trans-acetoacylation method for the synthesis of β-keto ester derivatives has been described using ytterbium(III) triflate as a new catalyst under solvent-free condition. This method was found to be efficient and convenient for the synthesis of a wide variety of β-keto ester derivatives.

Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker

New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3′ of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists.

BF3OEt2: An efficient catalyst for transesterification of β-ketoesters

A facile and selective transesterification of β-ketoesters using BF3OEt2 as catalyst is described. The emphasis has been placed on the reaction of methyl acetoacetate with a series of alcohols of different structures, leading in all cases to good to excellent yields.

Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents

Tuberculosis is a leading infectious cause of death worldwide. Because of the concern of the resistance to most of the commonly used drugs displayed by the considered mycobacteria, most efforts have been done to introduce new anti-tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant anti-tubercular activity. In this study, we synthesized new derivatives of 1,4-dihydropyridines in which different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4 position. These asymmetric analogues were synthesized by a modified Hantzsh reaction using procedure reported by Meyer. The in vitro anti-tubercular activity of compounds against Mycobacterium tuberculosis was evaluated. The results indicate that the compounds containing aromatic esters are more potent than alkyl ones. The most potent aromatic compound (R = 3-phenylpropyl) exhibits comparable anti-tubercular activity (MIC = 1 μmol/ml) with reference compound isoniazide (INH) (MIC = 1 μmol/ml). Conformational analysis, SAR studies of these compounds showed that increasing in lipophilicity and rotable bonds of these compounds resulted in increasing anti-tubercular activity.

A nucleophilic Fe catalyst for transesterifications under neutral conditions

Carboxylic esters belong to the most important functional groups in organic chemistry. Strong efforts have been made in developing mild catalytic procedures for their preparation. Among the various methods developed to date, transesterifications have occupied an important space. In the present paper, a new catalytic method for this process based on the use of nucleophilic Fe(-II) complexes is presented. Evidence for the formation of an intermediate acyl Fe complex will be presented as well as investigations on scope and limitations.

Lipophilic 4-imidazoly-1,4-dihydropyridines: Synthesis, calcium channel antagonist activity and protection against pentylenetetrazole-induced seizure

A group of alkyl, cycloalkyl and aryl ester analogs of nifedipine, in which the o-nitrophenyl group at position 4 is replaced by a 2-phenyl-4(5)-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonist using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle, and the activity of 5a-d, 8b and 8f against pentylenetetrazole (PTZ)-induced seizure was assessed. The results for symmetrical esters showed that lengthening of the methylene chain in C3 and C5 ester substituents increased activity. When increasing of the length is accompanied by increasing the hindrance, the activity decreased. In contrast to symmetrical derivatives, comparison of the activities of asymmetrical esters showed that increasing the length of the methylene chain was accompanied by a decrease in their activity. The results demonstrate that 8a was more active, and 5c and 8f were similar in effect to that of the reference drug nifedipine. The time-course of anticonvulsant effect on PTZ-induced seizure threshold of said compounds was assessed and showed that increasing the lipophilicity decreases the time needed for maximum effect. Mice treated with intraperitoneal injection of 25 mg/kg of these derivatives all exhibited increase seizure threshold as compared with control.

Sustainable transesterification of β-ketoesters catalyzed by amine grafted on silica gel

Transesterification of β-ketoesters with various alcohols has been effected by N,N-diethylaminopropylated silica gel (NDEAP) as a catalyst in refluxing xylene. Generality of the reaction was demonstrated by successful transesterification of olefinic alcohols, tertiary alcohols and alcohols having acid- or base-sensitive substituents. The catalyst has been efficiently recycled more than five times without any re-activation.