Reference

GABA-mimetic activity and effects on diazepam binding of aminosulfonic acids structurally related to piperidine-4-sulfonic acid

GABA-mimetic activity and effects on diazepam binding of aminosulfonic acids structurally related to piperidine-4-sulfonic acid. Falch, Erik; Jacobsen, Poul; Krogsgaard-Larsen, Povl; Curtis, David R. (Dep. Chem., R. Dan. Sch. Pharm., Copenhagen DK-2100, Den.). J. Neurochem., 44(1), 68-75 (English) 1985.Several reagents such as 56-12-2 is used here. CODEN: JONRA9.In this article, certain chemicals are used. One of their cas registry numbers is 56-12-2 ISSN: 0022-3042. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 1 The relationship between structure, in vivo activity, and in vitro activity of some analogs of the GABA [56-12-2] agonist piperidine-4-sulfonic acid (P4S) [72450-62-5] was studied. The syntheses of 1,2,3,6-tetrahydropyridine-4-sulfonic acid (DH-P4S) [95596-29-5] and (RS)-pyrrolidin-3-yl-methanesulfonamide (PMSA-amide) [95596-30-8] are described. Like P4S, its unsatd. analog DH-P4S and the 5-ring isomer (RS)-pyrrolidin-3-yl-methanesulfonic acid (PMSA) [85310-67-4] were bicuculline methochloride (BMC)-sensitive inhibitors of the firing of neurons in the cat spinal cord. Whereas isonipecotic acid [498-94-2] was less potent than its unsatd. analog isoguvacine [64603-90-3] as a GABA mimetic and as an inhibitor of GABA binding, the opposite relative potencies of P4S and DH-P4S were obsd., P4S being proportionally more potent than DH-P4S. In contrast with P4S and DH-P4S, PMSA, which is an analog of the potent GABA uptake inhibitor and BMC-sensitive GABA-mimetic homo-b-proline [498-95-3], was a relatively weak inhibitor of GABA uptake in vitro. PMSA-amide was >2 orders of magnitude weaker than PMSA as an inhibitor of GABA binding and did not significantly affect GABA uptake in vitro. The effects of b-aminopropanesulfonic acid (3-APS) [3687-18-1], PMSA, P4S, and DH-P4S on the binding of 3H-labeled diazepam [439-14-5] in vitro at 30°, in the presence or absence of Cl-, were studied and compared with those of the structurally related amino acids GABA, homo-b-proline, isonipecotic acid, and isoguvacine. Under these conditions the aminosulfonic acids were weaker than the resp. amino acids in enhancing [3H1diazepam binding, the difference being more pronounced in the absence of Cl-. ..

1-(Alkenoyl)azacycloalkanecarboxylic acids and derivatives as protease inhibitors

1-(Alkenoyl)azacycloalkanecarboxylic acids and derivatives as protease inhibitors. Mueller, Richard August; Partis, Richard Allen (Searle, G. D., and Co., USA). Eur. Pat. Appl. EP 208279 A1 14 Jan 1987, 28 pp. DESIGNATED STATES: R: BE, CH, DE, FR, GB, IT, LI, NL, SE. (European Patent Organization) CODEN: EPXXDW. CLASS: ICM: C07D207-16. ICS: C07D211-60; A61K031-40; A61K031-445. APPLICATION: EP 86-109171 4 Jul 1986. PRIORITY: US 85-752873 8 Jul 1985. DOCUMENT TYPE: Patent CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 1 Title compds. I (R1 = C14-22 alkenoyl, alkadienoyl, alkapolyenoyl; R2 = H, Ph; R3 = H, C1-6 alkyl, alkali metal, alk. earth metal, NR4R5R6R7; R4-R7 = H, C1-6 alkyl, C2-4 hydroxyalkyl; m = 0-2; n = 1-5; m + n = 2-5), useful for prevention of degrdn. of elastin or other proteins, thus preventng or retarding the diseases caused by such degrdn., were prepd. by acylation of I (R1 = H) with R1X (X = halo). To L-proline and Et3N in CH2Cl2 was added (Z)-Me(CH2)7CH:CH(CH2)7COCl to give I [R1 = (Z)-Me(CH2)7CH:CH(CH2)7CO, R2, R3 = H, m = 0, n = 3) (II).In this experiment, several chemicals are used like 107432-41-7 and 498-94-2 II inhibited elastase and prolyl-4-hydroxylase with IC50 of 7.8 mcM and 4.4 mcM, resp. .