Synthesis and pharmacological evaluation of 1-isopropyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel antihypertensive agents

A series of 1-isopropyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and their bradycardic activities were evaluated in isolated guinea pig right atria. Structure-activity relationship studies revealed that the introduction of an appropriate substituent and its position on the 1,2,3,4-tetrahydroisoquinoline ring are essential for potent in vitro activity. Furthermore, the tether between the piperidyl moiety and the terminal aromatic ring is important for potent antihypertensive activity. Oral administration of 6-fluoro-1-isopropyl-2-{[1-(2-phenylethyl)piperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline (3b) to spontaneously hypertensive rats (SHR) elicited antihypertensive effects without inducing reflex tachycardia, which is often caused by traditional L-type Ca2? channel blockers.     

Synthesis and pharmacological evaluation of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents

We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels for a series of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives. Structure-activity relationship studies have revealed that the isopropyl substituent at the benzylic position plays an important role in exerting potent inhibitory activity, and the absolute configuration of the benzylic position was found to be opposite that of mibefradil, which was first launched as a new class of T-type Ca(2+) channel blocker. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-1-[2-(3-methoxyphenyl)ethyl]piperidine-4-carboxamide (17f) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, an adverse effect often caused by traditional L-type Ca(2+) channel blockers.     

Dimensional stability of regenerated cellulose film in relation to orientations of crystalline and noncrystalline phases

The dimensional stability of regenerated cellulose film on swelling with water is discussed in relation to the biaxial orientation of the two kinds of structural units, cellulose II crystallites and noncrystalline chain segments, and their anisotropic swelling (anisotropic absorption of water). Considerable dimensional stability in the plane of the film but enormous instability of thickness on swelling in water of some commercial cellophanes is qualitatively interpreted in terms of the planar orientation of crystal (101) planes along the film surface and the orientation of the noncrystalline chain segments parallel to the film surface. The dimensional changes on swelling from the completely dry state to 10% moisture regain were further interpreted quantitatively in terms of the degrees of biaxial orientation of the two kinds of structural units and their degrees of anisotropic swelling by modifying the Hermans monophase model for crystalline and noncrystalline biphase structures. The following degrees of anisotropic swelling of the structural units were thus obtained: q_{c, [101]} = 0.40%, q_{c, [101 ]} = ?0.33%, and q_a = 2.42%.     

Structure of thiotropocin,a new sulfur-containing 7-membered antibiotic

The structure of a new antibiotic thiotropocin is described.     

Measurements of Liquid-Phase Adsorption under High Pressure

Adsorption equilibria at about 1000 atm were measured for aqueous solutions of aromatic compounds. No significant difference between the isotherms at atmospheric pressure and at 1000 atm was found for nitrobenzene and ethylbenzene on activated carbon fiber. The decrease in the amount adsorbed due to the solubility increase with pressure and the increase in the amount adsorbed caused by compression of the adsorbed phase were considered to cancel each other. On the other hand, pressure had a marked effect on the adsorption of L-phenylalanine on a macroreticular adsorbent, resulting in a 1.5 to 2 times larger amount adsorbed at 1500 atm. The pressure effect was greater with larger amounts adsorbed. This implies that the molar volume of the adsorbed state is smaller than those of the pure state and dissolved state, and varies with the amount adsorbed.