27143-12-0

Pyrazoles bearing a 5-thiophenyl and a 4-cyano group were synthesised and tested for their affinity to the cannabinoid CB1 receptor showing in many cases single digit nanomolar Ki values and moderate to good selectivity towards the CB2 receptor. Some of these pyrazole ligands, such as 8g, displayed relatively low lipophilicity (experimental logP 90) suggesting that these compounds may behave as peripherally restricted CB1 ligands. Furthermore, 2-fluoroethyl carboxamides 8d, 8h and 8l are interesting candidates for further development into PET tracers. This journal is

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and anti

Chemokine receptor 2 (CXCR2) is the receptor of glutamic acid–leucine–arginine sequence-contained chemokines CXCs (ELR+ CXCs). In recent years, CXCR2-target treatment strategy has come a long way in cancer therapy. CXCR2 antagonists could block

The invention relates to a preparation method of mefenpyr-diethyl, which specifically comprises the following steps: (a) mixing ethyl 2-chloroacetoacetate, 2,4-dichloroaniline, inorganic acid and water, and then adding a sodium nitrite aqueous solution to form a reaction system, and performing diazotization and substitution reactions, so as to obtain ethyl 2-chloro-2-(2,4-dichlorobenzene diazo) acetoacetate; and (b) adding an inorganic base into the reaction system to adjust the pH value to 5-7, then adding a bicarbonate aqueous solution to carry out a hydrolysis reaction to obtain ethyl 2-chloro-2-(2,4-dichlorobenzylidenehydrazino)acetate, then sequentially adding a polymerization inhibitor, ethyl methacrylate and the bicarbonate aqueous solution to carry out cyclization, and carrying outpost-treatment to obtain the mefenpyr-diethyl. Compared with the prior art, the intermediate generated through diazotization and substitution is stable, the intermediate does not need to be separated, the method is easy and convenient to operate, reaction conditions are mild, sodium bicarbonate (or potassium bicarbonate) is used for hydrolysis, the raw material price is low, and the dosage is small.

The invention discloses a mefenpyr-diethyl impurity, a preparation method and applications thereof, wherein the molecular structural formula is represented by a formula I. The preparation method comprises: carrying out diazotization and a Japp-Klingemann reaction by using 2,4,-dichloroaniline, nitrite and ethyl 2-chloroacetoacetate as raw materials to obtain an intermediate, and carrying out a ring-closure reaction on the intermediate and ethyl methacrylate to obtain 1,5-bis(2,4-dichlorophenyl)-6-methyl-1H,5H-pyrazolo[5,1-c]-1,2,4-triazole-3,6,7a-triethyl tricarboxylate, wherein the yield reaches more than 40%. According to the invention, the method has advantages of mild reaction conditions, low energy consumption, high economic feasibility and high yield; and the substance has the application value in the influence on the efficacy of mefenpyr-diethyl by using the substance as the impurity and in the safety evaluation of the residual substance on agricultural products.

A series of novel 4-phenoxyquinoline derivatives containing 1,2,4-triazolone moiety were synthesized and evaluated for their in?vitro cytotoxic activity against four cancer cell lines (HT-29, H460, A549 and MKN-45). Most of the compounds exhibited moderate-to-significant cytotoxicity. Compounds 33, 37, 39, 44, 46, 47, 53, 55, 61, 64 and 66 were further examined for their inhibitory activity against c-Met kinase. The most promising compound 47 (with c-Met IC50value of 1.57?nM) showed remarkable cytotoxicity against HT-29, H460, A549 and MKN-45?cell lines with IC50values of 0.08?μM, 0.14?μM, 0.11?μM and 0.031?μM, respectively, and thus it was 1.1- to 2.3- fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.

OMAR analogs reference standards and their corresponding desmethylated precursors were synthesized from substituted anilines either in 4 and 5 steps with 27-32% and 24-31% yield, or in 3 and 4 steps with 21-30% and 19-28% yield, respectively. [11/su

A new and convenient one-step recyclization method for the synthesis of ethyl 1-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxylates is reported. Various ethyl chloro(2-arylhydrazinylidene)ethanoates react with thiazolidine-2,4-dione in the presence of potassium hydroxide to produce the 1-aryl-1,2,4-triazole derivatives in moderate to good yields. The procedure is economical, environmentally friendly and simple to perform. Georg Thieme Verlag Stuttgart - New York.

The synthesis, structure-activity relationship (SAR) studies and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles are described. The target compounds 6-18 represent a novel class of potent and selective CB1 r

The present invention relates to compounds of formula (I) wherein R1 represents a group R5O- in which R5 represents a C3-7alkyl group substituted by one or more fluoro or R5 represents a C3-7alkylsulphonyl group which is optionally substituted by one or more fluoro; R2 represents a C1-4alkyl group, hydroxy, fluoro, chloro or cyano wherein each R2 is independently selected when n is >1; R3 represents a) cyclohexyl optionally substituted by one or more of the following: hydroxy, fluoro, amino, mono or diC1-3alkylamino, carboxy or a C1-4alkoxycarbonyl group b) piperidino substituted by one or more hydroxy c) unsubstituted piperidino but only when one of the following applies: R4 represents cyano or R1 represents 3-fluoropropylsulphonyloxy or R1 represents 3,3,3-trifluoropropoxy or R1 represents 3-fluoropropoxy or R2 is methyl d) phenyl substituted by one or more of the following: hydroxy, halo or a C1-4alkyl group e) pyridyl substituted by a C1-4alkyl group or f) a C4-9alkyl group; R4 represents cyano or methyl; and n is 1, 2 or 3 and pharmaceutically acceptable salts thereof and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.

The invention relates to 4-cyanopyrazole-3-carboxamide derivatives of formula (I): in which R1, R2, R3, R4, R5, R6, R7, R8 are as described herein. Also disclosed and