Reference

Process for preparation of catechol pyrazole derivatives and pharmaceutical composition containing the same

Process for preparation of catechol pyrazole derivatives and pharmaceutical composition containing the same. Jang, Myeong Sik; Jun, Hyeong Ok; Kim, Jong Hun; Lee, Geon Ho; Lee, Jae Mok; Min, In Gi; Ryu, Chun Seon; Song, Seok Beom (CJ Corp., S. Korea). Repub. Korean Kongkae Taeho Kongbo KR 2003046086 A 12 Jun 2003, No pp. given (Korean). (Korea, Republic Of). CODEN: KRXXA7. CLASS: ICM: C07D231-14. APPLICATION: KR 2001-76486 5 Dec 2001. DOCUMENT TYPE: Patent CA Section: 28 (Heterocyclic Compounds (More Than One Hetero Atom)) Section cross-reference(s): 63 Catechol pyrazole derivs., a prepn. process thereof and a pharmaceutical compn. contg. the same are provided, thereby inhibiting phosphodiesterase IV(PDE IV) or tumor necrosis factor(TNF), so that various diseases assocd. with PDE IV or TNF can be effectively treated. Catechol pyrazole derivs. represented by formula(1) and pharmaceutically acceptable salts thereof are provided, wherein R1 is methyl; R2 is C3-C7 cycloalkyl; R3 is hydrogen or alkyl, C1-C7 cycloalkyl or phenyl; and R4 is alkyl, 1 to 3 halogens substituted Me, Me ester or carboxylic acid. A process for prepg. catechol pyrazole derivs. comprises the steps of: reacting benzaldehyde(2) of which a hydroxyl group at C3 site is substituted by R1 with R2-A to prep. benzaldehyde(3) of which two hydroxyl groups are substituted by R1 and R2, resp.; reacting the benzaldehyde(3) with a compd. selected from Et trifluoroacetate, Et difluoroacetate, Et fluoroacetate, di-Et oxalate and di-Me oxalate to prep. dicarbonyl compd.(4); and reacting the dicarbonyl compd.(4) with alkylhydrazine to prep. a compd.(1).Except for chemicals metioned above, 459-72-3 and 302-01-2 are also used. .

Stereoselectivity of interaction of phosphoenolpyruvate analogs with various phosphoenolpyruvate-utilizing enzymes

Stereoselectivity of interaction of phosphoenolpyruvate analogs with various phosphoenolpyruvate-utilizing enzymes. Duffy, Thomas H.; Nowak, Thomas (Dep. Chem., Univ. Notre Dame, Notre Dame, IN 46556, USA). Biochemistry, 23(4), 661-70 (English) 1984. CODEN: BICHAW. ISSN: 0006-2960. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) The halogenated PEP analogs (Z)-phosphoenol-3-fluoropyruvate, (E)-phosphoenol-3-fluoropyruvate, and (Z)-phosphoenol-3-bromopyruvate were synthesized and purified. The analogs were characterized by 1H and by 19F NMR where applicable. Abs. stereoselectivity of the fluoro-PEP isomers as substrates with PEP carboxykinase, enolase, and pyruvate-phosphate dikinase was obsd. The Z isomer exhibited substrate activity with these enzymes, whereas no substrate activity was measured with the E isomer. Both isomers exhibited substrate activity with pyruvate kinase, however, with a substantial decrease in the Vmax/Km ratio compared with PEP as the substrate. A metal ion-dependent stereoselectivity of inhibition was measured for these analogs with PEP carboxykinase, enolase, and pyruvate kinase. The cation activator appeared to affect the specificity and thus the catalytic site of these enzymes. Proton longitudinal relaxation rate titrns. demonstrated that the dissocn. consts., K3, of the fluoro-PEP isomers from the enzyme-Mn complex agreed, in most cases, with the measured Ki values and that the analog binding resembled PEP binding. With PEP carboxykinase, the Ki 1 K3 for (E)-fluoro-PEP, suggesting that the binding of the E isomer was affected by the presence of the other substrates. The halogenated derivs. apparently undergo an enzyme-Mn-catalyzed Michael-type addn. reaction with the bromo-substituted analog decompg. 95-92-1 and 459-72-3 are just another two chemicals used in this study. much faster than the fluoro analogs. .