93250-22-7

Upstream product

• 75-05-8 acetonitrile 
• 552-89-6 2-nitro-benzaldehyde 
• 17729-59-8 tri-n-butyl(cyanomethyl)stannane 

Relevant academic research and scientific papers

N, N ′-Disubstituted thiourea and urea derivatives: Design, synthesis, docking studies and biological evaluation against nitric oxide synthase

The synthesis and biological evaluation of new types of N,N′-disubstituted thiourea and urea derivatives as inhibitors of both neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) are described. These compounds have been designed by reduction of the carbonyl group in the thiourea and urea kynurenamine derivatives 3 previously synthesized by our research group. The synthetic route performed to this new family also allows us to obtain the molecules 3 with less synthetic steps and higher global yield. Regarding the biological results, in general, the new derivatives 4a-q inhibit the neuronal NOS isoform better than the inducible one. Furthermore, thioureas exhibit higher inhibition than ureas for both isoenzymes. Among all the tested compounds, 4g shows significant nNOS (80.6%) and iNOS (76.6%) inhibition values without inhibiting eNOS. This molecule could be an interesting starting point for the design of new inhibitors with application in neurological disorders where both isoenzymes are implicated such as Parkinson's disease.

Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors

In search of new Nitric Oxide Synthase (NOS) inhibitor agents, two isosteric series of derivatives with an imidamide scaffold (one of them with a hydroxyl group and the other with a carbonyl one) were synthesized and evaluated on inducible (iNOS) and neuronal (nNOS) isoforms. These compounds have been designed by combining a kynurenamine framework with an amidine moiety in order to improve selectivity for the inducible isoform. In general, the in vitro inhibitory assays exhibited better inhibition values on the iNOS isoform, being the N-(3-(2-amino-5-methoxyphenyl)-3-hydroxypropyl)-4-(trifluoromethyl)benzimidamide 4i the most active inhibitor with the highest iNOS selectivity, without inhibiting eNOS. Docking studies on the two most active compounds suggest a different binding mode on both isozymes, supporting the experimentally observed selectivity towards the inducible isoform. Physicochemical in silico studies suggest that these compounds possess good drug-likeness properties.

1H and 13C NMR spectral assignment of N,N′-disubstituted thiourea and urea derivatives active against nitric oxide synthase

The 1H and 13C NMR resonances of seventeen N-alkyl and aryl-N′-[3-hydroxy-3-(2-nitro-5-substitutedphenyl)propyl]-thioureas and ureas (1–17), and seventeen N-alkyl or aryl-N′-[3-(2-amino-5-substitutedphenyl)-3-hydroxypropyl]-thioureas and ureas (18–34), designed as NOS inhibitors, were assigned completely using the concerted application of one- and two-dimensional experiments (DEPT, HSQC and HMBC). NOESY studies confirm the preferred conformation of these compounds. Copyright

STEREOSELECTIVE ALDOL CONDENSATIONS OF ORGANOTIN REAGENTS WITH ALDEHYDES

The reaction of the enolstannanes of cyclohexanone or propiophenone with various aldehydes under kinetic control (-78 deg C) gave predominately the threo aldols, diastereoselectivity as high as 95:5 being achived.At higher temperatures (+45 deg C) predominate erythro selectivity was observed.The enolstannane of propiophenone exists as an equilibrium mixture of O-Sn (probably the E-isomer) and C-Sn derivatives.Reaction at -78 deg C takes place rapidly with the O-Sn enolate, further reaction requiring isomerization of the C-Sn to the O-Sn enolate.The Pd catalyzed condensation of cyanomethyltributyltin with reactive aldehydes, such as nitrobenzaldehydes, took place at ambient temperatures in polar solvents to give high yields of condensation products.No reaction occured with aldehydes such as benzaldehyde.Only low stereoselectivity (10-34percent ee) was observed when (-)DIOP or (-)BPPM were utilized as chiral phosphine ligands.