115266-77-8Relevant academic research and scientific papers
Synthesis and in vitro activity of stereoisomers of a novel thromboxane receptor antagonist, (±)-(5Z)-7-[3-endo-[(phenylsulfonyl)amino]bicyclo[2.2.1]hept-2-exo-yl ]heptenoic acid
Ohtani,Narisada
, p. 1027 - 1031 (2007/10/02)
Three stereoisomers of S-145 (1) with variations at the side-chain junctions were synthesized. Endo-cis-isomer 10 and N-exo-trans isomer 18 were obtained via the common intermediate 5 having an endo-fused ring structure. Exo-cis isomer 28 was prepared via
Selective Reduction of Aryl Halides and α,β-Unsaturated Esters with Sodium Borohydride-Cuprous Chloride in Methanol and Its Application to Deuterium Labeling
Narisada, Masayuki,Horibe, Isao,Watanabe, Fumihiko,Takeda, Ken'ichi
, p. 5308 - 5313 (2007/10/02)
A reducing system, NaBH4-Cu2Cl2/MeOH, was developed for dehalogenation of aryl halides, conjugate reduction of α,β-unsaturated esters, and deuterium labeling in a chemo- and regioselective manner.These reactions proceeded without reduction of isolated olefins.The Cu2Cl2 is assumed to function as the catalyst which generates a transient species of copper hydride as an active reducing agent, on contact with NaBH4.Deuterium-labeling studies indicated that (i) the hydrogen which is transferred to the 4-position of methyl 4-iodobenzoate originates from MeOH and (ii) thehydrogens which were transferred to the α- and β-positions of the conjugated ester originate from MeOH and NaBH4, respectively.
Synthesis and in Vitro Activity of Various Derivatives of a Novel Thromboxane Receptor Antagonist, (+/-)-(5Z)-7-bicyclohept-2-exo-yl>heptenoic Acid
Narisada, Masayuki,Ohtani, Mitsuaki,Watanabe, Fumihiko,Uchida, Kiyohisa,Arita, Hitoshi,et al.
, p. 1847 - 1854 (2007/10/02)
Several sulfonyl derivatives (13a-t) of (+/-)-(5Z)-7-(3-endo-amonobicyclohept-2-exo-yl)heptenoic acid (VI) were synthesized via its methyl ester 10.Sulfonylation of 10 with 11a-t followed by saponification yielded 13a-t.Inhibitory concentrations (IC50) of the corresponding sodium salts 14a-t for platelet aggregation were measured with rat washed platelets (WP) and rabbit platelet-rich plasma (PRP).IC50 values of some derivatives for contraction of the rat aorta were also measured.The IC50 values for rat WP increased from 2.9 to 26 nM in the order of 14a, 14c, 14d, and 14b for derivatives with an arylsulfonyl residue, depending on the number of interventing methylene groups.Methyl derivative 14e exhibited a higher IC50 value than n-hexyl derivative 14f.Substitution with a p-methyl-, p-fluoro-, or p-chloro group in 14a retained or slightly reduced its IC50 value, while a p-n-pentyl or p-oxycarbonyl group augmented it significantly.The representative 14a supressed (15S)-15-hydroxy-11,9-(epoxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619) induced aggregation of human WP with an IC50 value of 7.7 nM, which corresponds well to the IC50 value of 3 nM obtained for each displacement by 14a of -U-46619 or (5Z,15ξ)-9α,11α-(dimethylmethano)-15-hydroxy-16-(3-iodo-4-hydroxyphenyl)-17,18,19,20-tetranor-13-aza-11a-carbathrombo-5-enoic acid (-PTA-OH) bound to human WP.Synthesis of thromboxane A2 (TxA2) in human WP stimulated by thrombin was not inhibited by 14a at a concentration up to 10 μM.From these observations, the corresponding acid 13a (S-145) was concluded to be potent TxA2 receptor antagonist.
