Synthesis and antihypertensive activity of 1,4-dihydropyridine derivatives with a 4-(disubstituted phenyl) ring and an aminoalkyl ester group: highly potent and long-lasting calcium antagonists.

New 1,4-dihydropyridine derivatives bearing a 4-(disubstituted phenyl) ring and an aminoethyl ester or an amino-2,2-dimethyl-propyl ester were synthesized and their antihypertensive activities were examined in normotensive rats and spontaneously hypertensive rats. The effects of phenyl substituents and ester groups on the antihypertensive activity are discussed. Several compounds showed a more potent antihypertensive activity than nicardipine and most compounds had a longer duration of action.

Antihypertensive effect of the new dihydropyridine calcium antagonist (+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedica rbo xylate hydrochloride in dogs.

The antihypertensive effect of TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate hydrochloride, CAS 96515-74-1), a new calcium antagonist, was investigated in normotensive dogs (NTD) and renal hypertensive dogs (RHD). By oral administration, the antihypertensive activity of TC-81 (ED20% was 0.09 mg/kg p.

Antihypertensive effect of the new calcium antagonist (+-)-3-(benzylmethylamino)-2,2-dimethylpropyl-methyl-4-(2-fluoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride in rats.

The antihypertensive effect of TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl-methyl-4-(2-f luoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride), a new calcium antagonist, was investigated in normotensive and hypertensive rats. By oral administration, the antihypertensive activity of TC-81 (ED20% in spontaneous hypertensive rats (SHR), DOCA-salt hypertensive rats and renal hypertensive rats were 0.37, 0.

Development of radioimmunoassay for TG-51, a new anti-ulcer drug, and its application.

A sensitive and specific radioimmunoassay for a new anti-ulcer drug TG-51 has been developed and applied to the evaluation of its pharmacokinetics in humans. The antiserum was raised in rabbits against an immunogen of N-Acetyl-TG-51 coupled to human serum albumin. The radioactive compound was prepared by acetylating TG-51 with 3H-Acetic anhydride.

Effect of TC-81, a new dihydropyridine derivative, on K(+)-induced contraction in rat aorta.

TC-81 (3-(N-benzyl-N-methylamino)-2,2-dimethylpropyl methyl-2,6-dimethyl-4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-pyridine- 3,5-dicarboxylate hydrochloride) is a new dihydropyridine derivative. The effects of TC-81 (10(-10)-10(-8) M) on high K(+)-induced contractions were investigated in isolated rat aorta, and the results were compared with those obtained with nicardipine, nifedipine, diltiazem and papaverine. All drugs produced concentration-dependent relaxation of K(+)-induced contractions.