97170-10-0Relevant articles and documents
Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates
Levin,Chen,Laakso,Du,Du,Venkatesan,Sandanayaka,Zask,Xu,Xu,Zhang,Skotnicki
, p. 4345 - 4349 (2007/10/03)
The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1′ group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-α production and a collagen-induced arthritis model.
N-Salicylideneamino acidato complexes of oxovanadium(IV). the cysteine and penicillamine complexes
Pessoa, Joao Costa,Calhorda, Maria J.,Cavaco, Isabel,Costa, Paulo J.,Correia, Isabel,Costa, Dina,Vilas-Boas, Luis F.,Felix, Vitor,Gillard, Robert D.,Henriques, Rui T.,Wiggins, Robert
, p. 2855 - 2866 (2007/10/03)
Oxovanadium(iv) complexes with ligands derived from the reaction of salicylaldehyde with L-cysteine and with D- and D,L-penicillamine are prepared. The compounds are characterised by elemental analysis, spectroscopy (UV-VIS, CD, EPR), TG, DSC and magnetic susceptibility measurements (9-295 K). We discuss several aspects related to the structure of these complexes in the solid state and in solution; in particular, the possibility of forming thiazolidine complexes, and their comparison with the characterised complexes is studied by molecular mechanics and density functional theory calculations. The solution structures depend on pH and solvent, and while with L-Cys the spectroscopic results show trends similar to those of the L-Ala and L-Ser systems up to ca. pH 8-9, where thiolate coordination starts being detected, the penicillamine system is quite distinct, namely thiolate coordination occurs for pH > 6.5. In the presence of salicylaldehyde and VIVO the desulfydration of cysteine proceeds rapidly, but no similar reaction occurs with penicillamine, although its decomposition is also activated. The DFT calculations do not indicate any energetic basis for this distinct reactivity, which possibly results from different complexes present in the Cys and Pen systems. In the cysteine system, the N-salicylidene dehydroalanine-VIVO complex V is believed to form in an intermediate stage of the desulfydration. Further, addition of several nucleophiles to the cysteine reaction mixtures produce amino acid derivatives by a Michael-type base-catalysed addition, a result compatible with the formation of V. The products of these reactions were analysed by TLC and HPLC, and in some cases isolated.
Synthesis of Optically Active 1,4-Thiazane-3-carboxylic Acid via Optical Resolution by Preferential Crystallization of (RS)2-Amino-3-[(2-chloroethyl)sulfanyl]propanoic Acid Hydrochloride
Shiraiwa, Tadashi,Tadokoro, Kohya,Tanaka, Haruyuki,Nanba, Keiichiro,Yokono, Noriyoshi,Shibazaki, Katsuyoshi,Kubo, Motoki,Kurokawa, Hidemoto
, p. 2382 - 2387 (2007/10/03)
Optically active 1,4-thiazane-3-carboxylic acid [TCA] was synthesized from cysteine via optical resolution by preferential crystallization. The intermediate (RS)-2-amino-3-[(2-chloroethyl)sulfanyl]propanoic acid hydrochloride [(RS)-ACS-HCl] was found to exist as a conglomerate based on its melting point, solubility and IR spectrum. (RS)-ACS·HCl was optically resolved by preferential crystallization to yield (R)- and (S)-ACS·HCl. (R)- and (S)-ACS·HCl thus obtained were recrystallized from a mixture of hydrochloric acid and 2-propanol, taking account of the solubility of (RS)-ACS·HCl, efficiently yielding both enantiomers in optically pure forms. (R)- and (S)-TCA were then respectively synthesized by the cyclization of (R)- and (S)-ACS·HCI in ethanol in the presence of triethylamine.
