303149-00-0

Upstream product

• 540758-03-0 N'-[1-(3-hydroxy-phenyl)-ethylidene]-hydrazinecarboxylic acid ethyl ester 
• 121-71-1 3-Hydroxyacetophenone 
• 1072880-58-0 (E)-ethyl 2-(1-(3-hydroxyphenyl)ethylidene)hydrazinecarboxylate 

Downstream Products

• 1072880-59-1 3-(1,2,3-thiadiazol-4-yl)phenyl cyclohexylcarbamate 
• 1072880-64-8 3-(1,2,3-thiadiazol-4-yl)phenyl isopropylcarbamate 
• 1072880-61-5 n-butylcarbamic acid 3-(1,2,3-thiadiazol-4-yl)phenyl ester 
• 1072880-66-0 3-(1,2,3-thiadiazol-4-yl)phenyl hexylcarbamate 
• 1072880-60-4 3-(1,2,3-thiadiazol-4-yl)phenyl cyclopentylcarbamate 
• 1072880-63-7 3-(1,2,3-thiadiazol-4-yl)phenyl phenylcarbamate 
• 1072880-67-1 3-(1,2,3-thiadiazol-4-yl)phenyl (4-phenyl-butyl)carbamate 
• 1072880-62-6 3-(1,2,3-thiadiazol-4-yl)phenyl benzylcarbamate 

Relevant academic research and scientific papers

3-Heterocycle-phenyl N-alkylcarbamates as FAAH inhibitors: Design, synthesis and 3D-QSAR studies

Carbamates are a well-established class of fatty acid amide hydrolase (FAAH) inhibitors. Here we describe the synthesis of meta-substituted phenolic N-alkyl/aryl carbamates and their in vitro FAAH inhibitory activities. The most potent compound, 3-(oxazol-2yl)phenyl cyclohexylcarbamate (2a), inhibited FAAH with a sub-nanomolar IC50 value (IC50=0.74 nM). Additionally, we developed and validated three-dimensional quantitative structure-activity relationships (QSAR) models of FAAH inhibition combining the newly disclosed carbamates with our previously published inhibitors to give a total set of 99 compounds. Prior to 3D-QSAR modeling, the degree of correlation between FAAH inhibition and in silico reactivity was also established. Both 3D-QSAR methods used, CoMSIA and GRID/GOLPE, produced statistically significant models with coefficient of correlation for external prediction (R2 PRED) values of 0.732 and 0.760, respectively. These models could be of high value in further FAAH inhibitor design.

The synthesis and biological evaluation of para-substituted phenolic N-alkyl carbamates as endocannabinoid hydrolyzing enzyme inhibitors

A series of para-substituted phenolic N-alkyl carbamates were evaluated for their FAAH and MGL inhibitory activities. The compounds were generally selective for FAAH, with IC50 values in the nM range, whereas inhibition of MGL required concentrations three orders of magnitude higher. The most potent compounds, dodecylcarbamic acid 4-(4,5-dihydrothiazol-2-yl)phenyl (12) and 4-(1,2,3-thiadiazol-4-yl)phenyl (26) esters, inhibited FAAH and MGL with IC50 values at the low-nanomolar (IC50s; 0.0063 and 0.012 μM) and the low-micromolar ranges (IC50s; 2.1 and 1.0 μM), respectively. Compound 26 also inhibited both FAAH-dependent AEA uptake and AEA hydrolysis (IC50; 0.082 μM) by intact RBL2H3 cells, and could also reduce 2-AG hydrolysis by these cells at concentrations ≥0.030 μM.

HETEROCYCLIC PHENYL CARBAMATES AS NOVEL FAAH-INHIBITORS

Fatty acid amide hydrolase inhibitors of the Formula (I) are provided, wherein R is a heterocyclic or heterocyclic carbonyl moiety and R' is a group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted

BETA-ADRENERGIC BLOCKING AGENTS IN THE 1,2,3-THIADIAZOLE SERIES

Novel 4-2,3 or 4(3-amino-2-hydroxypropoxy) phenyl!-and 5-2, 3 or 4(3-amino-2-hydroxypropoxy) phenyl!-1,2,3-thiadiazole derivatives which may be further substituted at the C-5 or C-4 position of the thiadiazole ring, respectively, by a lower alkyl, phenyl, trifluoromethyl, carboxy, alkoxycarbonyl, cyano or an aminocarbonyl group, and the pharmaceutically acceptable acid addition salts thereof and processes for the production of such compounds; 4-4(3-t-butylamino-2-hydroxypropoxy) phenyl!-1,2,3-thiadiazole and 5-4(3-t-butylamino-2-hydroxypropoxy) phenyl!-1,2,3-thiadiazole are representative of the class. These compounds possess cardiovascular activity and are useful for the treatment of abnormal heart conditions in mammals.