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Biomedical subjects

C Fukaya

Publications and source records attributed to C Fukaya.

49 records · Page 3Linked to original sources
PubMed1994

Novel potassium-channel openers: preparation and pharmacological evaluation of racemic and optically active N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives.

The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induced contraction of rat aorta, hypotensive activity in normotensive rats, and diuretic activity in spontaneously hypertensive rats. This led to further evaluation of compound (+/-)-10 and selection of (+)-N-(6-amino-3-pyridyl)-N'- [(1S,2R,4R)-bicyclo- [2.2.1]hept-2-yl]-N"-cyanoguanidine ((+)-10) (AL0670) for development as an antihypertensive agent. Although AL0670 is regarded as a pinacidil-type K(+)-channel opener, it showed different pharmacological and conformational profiles from pinacidil.

Animals↗
PubMed1994

Novel potassium channel openers: synthesis and pharmacological evaluation of new N-(substituted-3-pyridyl)-N'-alkylthioureas and related compounds.

This report describes the synthesis and pharmacological evaluation of a series of novel potassium channel openers related to the pinacidil-type compounds. Thioureas, cyanoguanidines, and pyridine N-oxides were systematically evaluated for their effects on both the inhibition of spontaneous mechanical activity in rat portal vein (in vitro) and their antihypertensive activity (in vivo), and the structure-activity relationship for this series of compounds was discussed. Good correlation between in vitro and iv antihypertensive activity was observed for these compounds. Among them, cyanoguanidines bearing a conformationally rigid unit such as a norbornyl group generally possessed potent activity in both in vitro and in vivo studies. Especially, N-(6-amino-3-pyridyl)-N'-cyano-N"-(1-methyl-2-norbornyl)guanidine (23d) was identified as a more potent potassium channel opener in vitro (EC100 = 3 x 10(-8) M) than pinacidil (EC100 = 10(-7) M).

4-Aminopyridine↗
PubMed1994

Massive intracerebral hematoma in a child with Klippel-Trenaunay syndrome.

The authors describe a child who suffered from massive intracerebral bleeding due to rupture of a cerebral arteriovenous malformation associated with Klippel-Trenaunay syndrome (KTS). Neurovascular lesions have been regarded as uncommon in KTS; however, our case may indicate the need for neurovascular scrutiny in patients with this syndrome.

Cerebral Hemorrhage↗
PubMed1991

Synthesis and pharmacological effects of optically active 2-[4-(4-benzhydryl-1-piperazinyl)phenyl]-ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate hydrochloride.

Optically active 2-[4-(4-benzhydryl-1-piperazinyl)phenyl]ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate [(S)-(+)-1 and (R)-(-)-1] hydrochlorides were synthesized with high optical purities from (R)-(-)- and (S)-(+)-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)- 3-pyridinecarboxylic acids [(R)-(-)-6 and (S)-(+)-6], which are available from (+/-)-6 by optical resolution using quinidine and cinchonidine, respectively. From pharmacological investigations of (S)-(+)-1 and (R)-(-)-1 such as the antihypertensive effect on spontaneously hypertensive rats and inhibition of [3H]nimodipine binding to rat cardiac membrane homogenate, the active form of 1 was defined to be the (4S)-(+)-enantiomer of 1.

Animals↗
PubMed1991

Inhibitory effect of 2-(E-2-alkenoylamino)ethyl alkyl sulfides on gastric ulceration in rats. II. Structure and activity relationships of 2-(E-n or Z-n-Decenoylamino)ethyl alkyl sulfides.

The analogues of 2-(E-n or Z-n-decenoylamino)ethyl carbamoylmethyl sulfide, including the modifications of sulfide portion, double bond in decenoyl chain and alkyl sulfide moiety, were synthesized and their inhibitory effects on stress-induced ulceration in rats were compared. Replacing the sulfura atom by methylene group or oxygen atom reduced the effect of potency. Saturation of the double bond in the decenoyl chain tended to reduce the anti-ulcerogenic activity in rats. There was no relationship between the position of double bond in decenoyl chain and the pharmacological activity. On the other hand, compounds with E-configuration showed stronger anti-ulcer activity than the corresponding Z-type of compounds. Among 9 kinds of S substituted alkyl groups for carbamoylmethyl, 2-(E-2-decenoylamino)ethyl 2-cyclohexylethyl sulfide showed the most potent anti-ulcerogenic activity in rats and also showed the lowest acute toxicity in mice.

Animals↗
PubMed1991

Quantitative structure-activity relationship of catechol derivatives inhibiting 5-lipoxygenase.

Various catechol derivatives (beta-substituted 3,4-dihydroxystyrenes, 1-substituted 3,4-dihydroxybenzenes, and 6-substituted 2,3-dihydroxynaphthalenes) were synthesized and their inhibition of 5-lipoxygenase was assayed. Their structure-activity relationships were examined quantitatively with substituent and structural parameters and regression analysis. The variations in the inhibitory activity were explained in bilinear hydrophobic parameter (log P) terms, and steric (molecular thickness) and electronic (proton nuclear magnetic resonance (1H-NMR) chemical shift of the proton adjacent to the catechol group) parameter terms. The hydrophobicity of the inhibitor molecule was important, and the optimum value of logP was about 4.3-4.6, beyond which inhibition did not increase further. A lower electron density of the aromatic ring containing the catechol group and the greater thickness of the lipophilic side chains were unfavorable to the activity. The results added a physicochemical basis for the selection of candidate compounds for developmental studies.

Catechols↗
PubMed1991

Periandradulcins A, B and C: phosphodiesterase inhibitors from Periandra dulcis Mart.

During the course of our screening of bioactive natural products, three new saponins named periandradulcins A (1), B (2) and C (3) were isolated as phosphodiesterase (PDE, EC 3.1.4.17) inhibitors from 80% MeOH extract of the roots of Periandra dulcis Mart. (Leguminosae) by a combination of column chromatography and reversed- and normal-phase high-performance liquid chromatography (HPLC). On the basis of 1H-, 13C- and two-dimensional nuclear magnetic resonance (NMR) spectral data and chemical evidence, their chemical structures were characterized as 3-O-beta-[alpha-L-rhamnopyranosyl(1----2)-beta-D-xylopyranosyl(1----2)-b eta-D- glucuronopyranosyl]-30-hydroxyl-25-formylolean-18-ene-22 beta-O-syringate, 3-O-beta-[alpha-L-rhamnopyranosyl(1----2)-beta-D- xylopyranosyl(1----2)-beta-D-glucuronopyranosyl]-22 beta-hydroxyl-25- formylolean-12-ene and 3-O-beta-[alpha-L-rhamnopyranosyl(1----2)-beta-D- glucopyranosyl(1----2)-beta-D-glucuronopyranosyl]-22 beta-hydroxyl-25-formylolean-18-ene, respectively. The concentrations of periandradulcins A, B and C required to give 50% inhibition (IC50 values) of PDE from bovine heart, were 0.033, 7.6 and 7.7 microM, respectively. Compound 1 was the most potent among the known PDE inhibitors; it inhibited PDE-I (IC50:0.0022 microM) twenty and forty times more effectively than PDE-II and -III, respectively.

Carbohydrate Sequence↗
PubMed1990

Novel 1,4-dihydropyridine calcium antagonists. I. Synthesis and hypotensive activity of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives.

A series of 4-(substituted pyridyl)-1,4-dihydropyridine derivatives were synthesized and their hypotensive effects examined. Several compounds, 2-(N-benzyl-N-methylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitro-2-pyridyl)-3,5-pyridinedicarboxylate (2b), its 4-(4-nitro-2-pyridyl) analogue (2g), 4-(3-trifluoromethyl-2-pyridyl) analogue (2c), 4-(2-trifluoromethyl-3-pyridyl) analogue (3e), 4-(4-cyano-2-pyridyl) analogue (2e), 4-(2-cyano-3-pyridyl) analogue (3d), and 4-(6-bromo-2-pyridyl) analogue (2i), were found to have a hypotensive activity parallel to that of nicardipine; 2c and 3e, in particular, had approximately twice the duration of nicardipine, and 2e had the most potent hypotensive activity of all the derivatives synthesized.

Animals↗
PubMed1989

Inhibitory activities and inhibition specificities of caffeic acid derivatives and related compounds toward 5-lipoxygenase.

Various caffeic acid derivatives were synthesized, and their effects on 5-lipoxygenase (5-LO), 12-lipoxygenase (12-LO) and prostaglandin (PG) synthase activities were investigated. Among them, caffeic acid octyl amide (5) and 1-(3,4-dihydroxyphenyl)-1-octen-3-one (11) showed very potent inhibitory activities toward 5-LO with IC50 values of 4.2 x 10(-8) and 3.5 x 10(-8) M, respectively. They were very selective inhibitors for 5-LO. Compound 11 showed non-competitive inhibition, and the two adjacent hydroxy groups attached to the benzene ring, as well as the hydrophobic alkyl side chain, were required for its strong binding to 5-LO.

Animals↗
PubMed1983

Selection of 53 PFC substances for better stability of emulsion and improved artificial blood substitutes.

In order to develop a new PFC emulsion which is better than Fluosol-DA as an artificial blood substitute, 53 different kinds of PFCs were evaluated from the aspects of toxicity, excretion rate and emulsion stability. From the results of the screening test, FMOQ was selected as the best material for a new emulsion. The half-life of FMOQ in the body of rats was calculated to be 7 days which was similar to FDC in Fluosol-DA, and its emulsion stabilized with the mixture of YPL and Pluronic F68 was stable at 4 degrees C for longer than 6 months. Rats extensively exchange-transfused with this emulsion survived well for a long period, indicating a high efficacy and low toxicity of this emulsion. In conclusion the FMOQ emulsion was selected to be a hopeful candidate for a second generation of artificial blood substitutes. This work was partially supported by NHLBI Contract NO1-HB-2927.

Animals↗