1,4-dihydropyridine derivatives and optically active 1,4-dihydropyridine derivatives with the following formula, having vasodilating activity based on calcium antagonism, and PAF antaognism, and methods of producing the same are disclosed: ##STR1## wherein (*) indicates a chiral center in the case of the optically active 1,4-dihydropyridine derivatives.

BACKGROUND OF THE INVENTION 
The present invention relates to 1,4-dihydropyridine derivatives and 
optically active 1,4-dihydropyridine derivatives having (a) vasodilating 
activity based on calcium antagonism and (b) PAF antagonism, and methods 
of producing the optically active 1,4-dihydropyridine derivatives. 
Generally it is known that 1,4-dihydropyridine derivatives are useful as 
remedies for diseases of circulatory system such as remedies for ischemic 
heart disease, cerebral circulatory disease and hypertension, since the 
1,4-dihydropyridine derivatives have vasodilating activity based on the 
calcium antagonism thereof. 
It has been reported that it is essential that the 1,4-dihydropyridine 
derivatives have a 3,5-diester structure in order that the 
1,4-dihydropyridine derivatives exhibit the above-mentioned actions. 
Representative examples of such 1,4-dihydropyridine derivatives are 
1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylic acid 
dimethyl ester (Generic name: "NIFEDIPINE" as described in U.S. Pat. No. 
3,644,627) and 
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic 
acid-3-[2-(N-benzyl-N-methylamino)ethyl]ester-5-methyl ester hydrochloride 
(Generic name: "NICARDIPINE" as described in Japanese Patent Publication 
55-45075). 
Furthermore, as the conventional methods of producing optically active 
1,4-dihydropyridine-3-carboxylate derivatives, there are known, for 
instance, (a) a method comprising the steps of subjecting 
1,4-dihydropyridine-3-carboxylic acid derivatives to optical resolution to 
obtain optically active 1,4-dihydropyridine-3-carboxylic acid derivatives, 
(refer to T. Shibanuma et al., Chem. Pharm. Bull. 28, 2809 (1980)) to 
1,4-dihydropyridine-3,5dicarboxylate derivatives and (b) a method of 
subjecting diastereomers of 1,4-dihydropyridine-3,5-dicarboxylate 
derivatives to optical resolution (refer to Japanese Laid-Open Patent 
Application 56-36455). 
Platelet-activating factor (PAF) is produced by many types of 
pre-phlogocytes, platelet and liver, liberated, and exhibits not only 
strong platelet aggregation activity, but also biological activities in a 
wide range, which are induced directly or through the liberation of other 
strong mediators such as thromboxane A.sub.2 and leucotriene. Therefore it 
is considered that compounds having PAF antagonism are useful for remedies 
for varieties of allergic diseases, inflammatory diseases, and 
hyperexcretory diseases, such as asthma, arthritis, and bronchitis. 
Furthermore, recent studies have revealed that PAF is capable of inducing 
the reduction of the blood flow volume of coronary artery. Therefore it is 
also considered that PAF antagonists will be useful as remedies for angina 
pectoris. 
As PAF antagonists, varieties of compounds such as PAF analogues and 
benzodiazepine derivatives has been reported. 
However, a compound having (a) vasodilating activity based on calcium 
antagonism and (b) PAF antagonism have not yet been discovered. 
SUMMARY OF THE INVENTION 
It is therefore a first object of the present invention to provide 
1,4-dihydropyridine derivatives having vasodilating activity based on 
calcium antagonism, and PAF antagonism. 
A second object of the present invention is to provide optically active 
1,4-dihydropyridine derivatives having vasodilating activity based on 
calcium antagonism, and PAF antagonism. 
A third object of the present invention is to provide methods of producing 
the above 1,4-dihydropyridine derivatives and optically active 
1,4-dihydropyridine derivatives. 
The present invention is based on the discovery that 1,4-dihydropyridine 
derivatives in which various amino acid derivatives are amido-bonded to 
either the position 3 or position 5 or both positions of the 
1,4-dihydropyridine ring exhibit antihypertensive action or PAF antagonism 
the same as or greater than that exhibited by the conventional 
1,4-dihydropyridine-3,5-diester derivatives. 
The first object of the present invention is achieved by 
1,4-dihydropyridine derivatives of formula (I): 
##STR2## 
wherein R.sup.1 represents hydrogen, a straight chain, branched chain or 
cyclic alkyl group, an unsubstituted or substituted aromatic hydrocarbon 
group, or an unsubstituted or substituted aromatic heterocyclic group; 
R.sup.2 represents hydrogen, a straight chain, branched chain or cyclic 
alkyl group, and R.sup.1 and R.sup.2 in combination may form a saturated 
or unsaturated hydrocarbon ring; R.sup.4 and R.sup.5 each represent 
hydrogen, an unsubstituted or substituted straight chain, branched chain 
or cyclic alkyl group, an unsubstituted or substituted amino group, an 
unsubstituted or substituted aromatic hydrocarbon group, or an 
unsubstituted or substituted aromatic heterocyclic group; R.sup.6 
represents hydrogen, a straight chain, branched chain or cyclic alkyl 
group, or a trialkylsilyl group; B represents an unsubstituted or 
substituted alkylene group, an unsubstituted or substituted aromatic 
hydrocarbon group, an unsubstituted or substituted aromatic heterocyclic 
group, an unsubstituted or substituted cycloalkylydene group; R.sup.7 
represents an unsubstituted or substituted straight chain, branched chain 
or cyclic alkoxyl group, an unsubstituted or substituted amino group, or 
an unsubstituted or substituted cyclic amino group; R.sup.3 represents 
hydrogen, cyano group, nitro group, --COR.sup.8, an unsubstituted or 
substituted aromatic hydrocarbon group, or an unsubstituted or substituted 
aromatic heterocyclic group, in which R.sup.8 represents an unsubstituted 
or substituted straight chain, branched chain or cyclic alkoxyl group, an 
alkenyloxy group, an alkynyloxy group, or --N(R.sup.61)--B.sup.1 
--COR.sup.71, in which R.sup.61, R.sup.71 and B.sup.1 are respectively the 
same as R.sup.6, R.sup.7, and B. 
The second object of the present invention is achieved by optically active 
1,4-dihydropyridine derivatives of formula (I-a): 
##STR3## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I), and * indicates a chiral 
center. 
The third object of the present invention with respect to the production of 
1,4-dihydropyridine derivatives of formula (I) is achieved by any of the 
following three processes: 
[Process 1] 
A ketone compound of formula (II) is allowed to react with an acrylamide 
compound of formula (III) in the following reaction scheme: 
##STR4## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I). 
[Process 2] 
An amide compound of formula (IV) is allowed to react with an amino 
compound of formula (V) in the following reaction scheme: 
##STR5## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I). 
[Process 3] 
A carboxylic acid derivative of formula (VI) is allowed to react with an 
amine compound of formula (VII) in the following reaction scheme: 
##STR6## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I), and Z represents a hydroxyl 
group, a halogen atom, or an active ester residue. 
In the third object of the present invention, the optically active 
1,4-dihydropyridine derivatives of formula (I-a) are produced by any of 
the following three processes: 
[Process 4] 
A keto-ester derivative of formula (X) is allowed to react with an 
optically active enamine derivative of formula (XI) in the following 
reaction scheme: 
##STR7## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I), R.sup.17 and R.sup.18 are 
different and independently represent an unsubstituted or substituted 
straight chain, branched chain or cyclic alkyl group, an unsubstituted or 
substituted aromatic hydrocarbon group, an unsubstituted or substituted 
aralkyl group, an unsubstituted or substituted straight chain, branched 
chain or cyclic alkoxycarbonyl group, or an unsubstituted or substituted 
straight chain, branched chain or cyclic aminocarbonyl group, and * 
indicates a chiral center. 
[Process 5] 
An N-acylamino acid derivative of formula (XIV) is allowed to react with an 
optically active enamine derivative of formula (XV) in the following 
reaction scheme, followed by allowing the product to react with ammonia or 
an ammonium salt: 
##STR8## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, 
R.sup.17, R.sup.18, and B are respectively the same as previously defined, 
and * indicates a chiral center. 
[Process 6] 
A ketone derivative of formula (XVI) is allowed to react with an optically 
active acrylamide derivative of formula (XVII) in the following reaction 
scheme, followed by allowing the product to react with ammonia or an 
ammonium salt: 
##STR9## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R .sup.5, R.sup.6, R.sup.7, 
R.sup.17, R.sup.18, and B are respectively the same as previously defined, 
and * indicates a chiral center. 
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
In the 1,4-dihydropyridine derivatives of formula (I) and the optically 
active 1,4-dihydropyridine derivatives of formula (I-a), R.sup.1 
represents hydrogen, a straight chain, branched chain or cyclic alkyl 
group having 1 to 6 carbon atoms, such as methyl group, ethyl group, 
propyl group, butyl group, pentyl group, hexyl group, 2-propyl group, 
t-butyl group, cyclopentyl group, and cyclohexyl group; an aromatic 
hydrocarbon group or an aromatic heterocyclic group such as phenyl group, 
pyridyl group, quinolyl group, isoquinolyl group, furyl group, thienyl 
group, benzoxazolyl group, benzthiazolyl group, pyridazinyl group, 
pyrazinyl group, pyrimidyl group, indolyl group, naphthyl group, 
benzoxadiazolyl group, and benzthiadiazolyl group, which may have a 
substituent selected from the group consisting of a halogen atom such as 
fluorine, chlorine, bromine or iodine; hydroxyl group; cyano group; nitro 
group; trifluoromethyl group, trichloromethyl group, azide group; amino 
group; a lower alkyl group having 1 to 6 carbon atoms, such as methyl 
group, ethyl group, propyl group, butyl group, pentyl group or hexyl 
group; a lower alkoxyl group having such as methoxy group, ethoxy group, 
propoxy group, butoxy group, pentyloxy group, or hexyloxy group; benzoyl 
group; a lower alkylthio group such as methythio group, ethylthio group, 
propylthio group, butylthio group, pentylthio group, or hexylthio group; 
phenylthio group; phenoxy group; a lower alkoxycarbonyl group such as 
methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, 
butoxycarbonyl group, or pentyloxycarbonyl group; a lower acyl group such 
as acetyl group, propyonyl group, butylyl group, pentanoyl group, or 
hexanoyl group; benzyloxy group; and cinnamyloxy group. 
R.sup.2 represents hydrogen, the same straight chain, branched chain or 
cyclic alkyl group as represented by R.sup.1. R.sup.2 may be combined with 
R.sup.1 to form a saturated or unsaturated hydrocarbon ring. Examples of 
such a hydrocarbon ring include cyclopentane ring, cyclohexane ring, and 
tetrahydronaphthalene ring. 
R.sup.4 and R.sup.5 each represent hydrogen, the same straight chain, 
branched chain or cyclic alkyl group as represented by R.sup.1 a 
substituted straight chain branched chain or cyclic alkyl group such as 
trifluoromethyl group, or trichloromethyl group, an unsubstituted or 
substituted amino group such as amino group, dimethylamino group, 
diethylamino group, or dipropylamino group, or the same aromatic 
hydrocarbon group or aromatic heterocyclic group as represented by 
R.sup.1. 
R.sup.6 represents hydrogen, the same straight chain, branched chain or 
cyclic alkyl group as represented by R.sup.1, or a trialkylsilyl group. 
B represents an unsubstituted or substituted alkylene group, an 
unsubstituted or substituted aromatic hydrocarbon group, an unsubstituted 
or substituted aromatic heterocyclic group or an unsubstituted or 
substituted cycloalkylydene group. Examples of these groups include 
methylene group, ethylene group, ethylydene group, isopropylydene group, 
2-phenylethylydene group, 3-methylbutylydene group, 
3-(t-butoxycarbonyl)propylydene group, phenylenediyl group, phenylenediyl 
group, cyclohexylydene group, and pyrazinediyl group. 
R.sup.7 represents an unsubstituted or substituted straight chain, branched 
chain or cyclic alkoxyl group, an unsubstituted or substituted amino 
group, or an unsubstituted or substituted cyclic amino group. 
Examples of the unsubstituted or substituted alkoxyl group as follows: 
methoxy group, ethoxy group, n-propyloxy group, n-butoxy group, 
n-pentyloxy group, n-hexyloxy group, n-heptyloxy group, n-octyloxy group, 
n-nonyloxy group, n-decyloxy group, isopropyloxy group, isobutyloxy group, 
cyclopentyloxy group, cyclohexyloxy group, aryloxy group, 2-propyn-1-yloxy 
group, (E)-2-buten-1-yloxy group, (E)-3-buten-1-yloxy group, 
(E)-2-penten-1-yloxy group, (2E,4E)-2,4-hexadienyloxy group, 
2,4-hexadiynyloxy group, (E)-hexa-4-ene-2-yloxy group, 
(E)-3-phenyl-2-propen-1-yloxy group, (Z)-3-phenyl-2-propen-1-yloxy group, 
3-phenyl-2-propyn-1-yloxy group, (2E,4E)-5-phenyl-2,4-pentadien-1-yloxy 
group, 5-phenyl-penta-2,4-diyn-1-yloxy group, (E)-5phenyl 
-penta-2-ene-4-yn-1-yloxy group, (E)-3-[4-(1-imidazolyl 
methyl)phenyl]-2-propen-1-yloxy group, 
(E)-3-[3-1imidazolylmethyl)phenyl]-2-propen-1yloxy group, 
(E)-3-[2-(1-imidazolylmethyl)phenyl]-2-propen-1-yloxy group, 
(E)-3-[4-(1-imidazolyl)phenyl]-2-propen-1-yloxy group, 
(Z)-3-[4-(1-imidazolylmethyl)phenyl]-2-propen-1-yloxy group, (E)-3-[6-( 
1-imidazolylmethyl)pyridin-2-yl]-2-propen-1-yloxy group, 
(E)-3-[5-(1-imidazolylmethyl)furan-2-yl]-2-propen-1-yloxy group, 
(E)-3-[5-(1-imidazolylmethyl)thiophen-2-yl]-2-propen-1-yloxy group, 
(E)-3-phenyl-1-methyl-2-propen-1yloxy group, 
(E)-1-fluoro-3-phenyl-2-propen-1-yloxy group, 2-methoxyethyloxy group, 
3-methoxypropyloxy group, 3-ethoxypropyloxy group, 2-phenoxyethyloxy 
group, 2-phenylthioethyloxy group, 2-(N-methylamino)ethyloxy group, 
2-(N,N-dimethyl-amino)ethyloxy group, 2-(N-methyl-N-phenylamino)ethyloxy 
group, 2-(N,N-diethyl)aminoethyloxy group, 
2-(N-benzyl-N-methyl)aminoethyloxy group 2-(1-piperazinyl)ethyloxy group, 
4-(1-piperazinyl)butyloxy group, 6-(1-piperazinyl)hexyloxy group, 
2-(4-piperidinyl)ethyloxy group, 2-(4-phenylpiperazin-1-yl)ethyloxy group, 
3-(4-phenylpiperazin-1-yl)-propyloxy group, 
4-(4-phenylpiperazin-1-yl)butyloxy group, 
6-(4-phenylpiperazin-1-yl)hexyloxy group, 
2-(4-phenylpiperidin-1-yl)ethyloxy group, 
3-(4-phenylpiperidin-1-yl)-propyloxy group, 
4-(4-phenylpiperidin-1-yl)butyloxy group, 
6-(4-phenylpiperidin-1-yl)hexyloxy group, 
2-[4-(diphenylmethyl)piperazin-1-yl]ethyloxy group, 
3-[4-(diphenylmethyl)piperazin-1-yl]propyloxy group, 
4-[4-(diphenylmethyl)piperazin-1-yl]butyloxy group, 
6-[4-(diphenylmethyl)piperazin-1-yl]hexyloxy group 2-morpholinoethyloxy 
group, N-benzylpyrrolidin-3-yloxy group, N-benzylpiperidin-3-yloxy group, 
2-(1,2,3,4-tetrahydroisoquinolin-2-yl)ethyloxy group, 
2,2,2-trifluoroethyloxy group, 
2-(3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dion-1-yl)ethyloxy group, and 
2-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purin-7-yl)ethyloxy. 
Examples of the unsubstituted or substituted amino group or cyclic amino 
group are as follows: dimethylamino group, diethylamino group, 
dipropylamino group, diisopropylamino group, piperidinyl group, 
piperazinyl group, morpholino group, pyrrolidinyl group, 
4-phenylpiperidinyl group, 4-phenylpiperazinyl group, 
4-diphenylmethylpiperazinyl group, methoxycarbonylmethylamino group, 
ethoxycarbonylmethylamino group, isopropyloxycarbonylmethylamino group, 
t-butoxycarbonylmethylamino group, 
1-(t-butoxycarbonyl)-2-methylpropylamino group, 
1-(t-butoxycarbonyl)ethylamino group, 
1-(t-butoxycarbonyl)-2-phenylethylamino group, 
1-(2-methoxyethoxycarbonyl)-2-methylpropylamino group, 
1-(ethoxycarbonyl)-1-methylethylamino group, 2-(ethoxycarbonyl)ethylamino 
group, and N-methyl-N-ethoxycarbonylmethylamino group. 
R.sup.3 represents hydrogen, cyano group, nitro group, --COR.sup.8, the 
same unsubstituted or substituted aromatic hydrocarbon group, or the same 
unsubstituted or substituted aromatic heterocyclic group as represented by 
R.sup.1. R.sup.8 represents an unsubstituted or substituted straight 
chain, branched chain or cyclic alkoxyl group, an alkenyloxy group, an 
alkynyloxy group, or --N(R.sup.61)--B.sup.1 --COR.sup.71, in which 
R.sup.61, R.sup.71 and B.sup.1 are respectively the same as R.sup.6, 
R.sup.7, and B which are defined previously. Examples of the 
above-mentioned unsubstituted or substituted straight chain, branched 
chain or cyclic alkoxyl group are those of the alkoxyl group defined by 
R.sup.7. 
Specific examples of the 1,4-dihydropyridine derivatives represented by the 
previously mentioned formula (I) are as follows: 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl[-3-methylbutylate, 
(+)-t-butyl 
2-(S)-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl) 
pyridine-3-carbonyl]amino]-3-methylbutylate, 
(+)-t-butyl 2-(S)-[N-[1,4 -dihydro-2,6 -dimethyl-5 
-methoxycarbonyl-4-(R)-(3-nitrophenyl)pyridine-3-carbonyl]amino]-3-methylb 
utylate, 
(-)-t-butyl 2-(R)-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3 
-nitrophenyl)pyridine-3-carbonyl]amino]-3-methylbutylate, 
(-)-t-butyl 2-(R)-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4 
-(R)-(3-nitrophenyl)pyridine-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4(3-nitrophenyl)pyridine- 
3-carbonyl]amino]acetate, 
(+)-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl)pyri 
dine-3-carbonyl]amino]acetate, 
(-)-t-butyl 2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(R)-(3 
-nitrophenyl)pyridine-3-carbonyl]amino]-acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]propionate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4(3-nitrophenyl)pyridine- 
3-carbonyl]amino]-3-phenylpropionate, 
t-butyl 
1-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine-3- 
yl]carbonyl]pyrrolidine-2-carboxylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4(2-chlorophenyl)pyridine 
-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4(2-chlorophenyl)pyridine 
-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4(2-chlorophenyl)pyridine 
-3-carbonyl]amino]propionate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4(2-chlorophenyl)pyridine 
-3-carbonyl]amino]-3-phenylpropionate, 
t-butyl 
1-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-chlorophenyl)pyridine-3 
-carbonyl]amino]pyrrolidine-2-carboxylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-chlorophenyl)pyridin 
e-3-carbonyl]amino]-4-methylpentanoate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-chlorophenyl)pyridin 
e-3-carbonyl]amino]-3-(1-t-butoxycarbonyl)butylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-fluorophenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-trifluoromethylpheny 
l)pyridine-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-methoxyphenyl)pyridi 
ne-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-methylphenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2,4,6-trimethoxyphenyl 
)pyridine-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-chlorophenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-fluorophenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-trifluoromethylpheny 
l)pyridine-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(4-nitrophenyl)pyridine 
-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(4-cyanophenyl)pyridine 
-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-methoxyphenyl)pyridi 
ne-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-phenylpyridine-3-carbon 
yl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-hydroxyphenyl)pyridi 
ne-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-cyclohexylpyridine-3-ca 
rbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-nitrophenyl)pyridine 
-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-nitrophenyl)pyridine 
-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-chlorophenyl)pyridin 
e-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-cyanophenyl)pyridine 
-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-cyanophenyl)pyridine 
-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-ethoxycarbonyl-4-(3-methylphenyl)pyridine 
-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-ethoxycarbonyl-4-(3-nitrophenyl)pyridine- 
3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-isopropyloxycarbonyl-4-(3-nitrophenyl)pyr 
idine-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-(2-methoxyethyloxycarbonyl-4-(3-nitrophen 
yl)pyridine-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-ethoxycarbonyl-4-(3-nitrophenyl)pyridine- 
3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-isopropyloxycarbonyl-4-(3-nitrophenyl)pyr 
idine-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-(2-methoxyethyloxycarbonyl-4-(3-nitrophen 
yl)pyridine-3-carbonyl]amino]-3methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-t-butoxycarbonyl-4-(3-nitrophenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutylate, 
t-butyl 2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxy-carbonyl-4-(3 
-nitrophenyl)pyridine-3 -carbonyl]amino]-3-methylbutylate, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridi 
ne-3-carbonyl]amino]-3-methylbutanoyl]pyrrolidine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridi 
ne-3-carbonyl]amino]-3-methylbutanoyl]-4-phenylpiperidine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3nitrophenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutanoyl]-4-diphenylmethylpiperidine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3nitrophenyl)pyridin 
e-3-carbonyl]amino]acetyl]pyrrolidine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3nitrophenyl)pyridin 
e-3-carbonyl]amino]acetyl]-4-phenylpiperazine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridi 
ne-3-carbonyl]amino]acetyl]-4-diphenylmethylpiperazine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridi 
ne-3-carbonyl]amino]-3-methylbutanoyl]-4-(2-pyridyl)piperazine, 
1-[2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3nitrophenyl)pyridin 
e-3-carbonyl]amino]-3-methylbutanoyl]-4-(2-pyrimidyl)piperazine, 
t-butyl 
2-[N-[5-[N-(t-butoxycarbonyl)methylcarbamoyl]-1,4-dihydro-2,6-dimethyl-4-( 
3-nitrophenyl)pyridine-3-carbonyl]amino]-3-methylbutylate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-3-methylbutylate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]acetate, 
isopropyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]acetate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]propionate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl-N-methylamino]acetate, 
ethyl 
1-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]cyclohexanecarboxylate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]benzoate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]isobutyrate, 
ethyl 
3-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]pyrazine-2-carboxylate, 
t-butyl 
2-[N-[1,4-dihydro-6-methyl-5-methoxycarbonyl-4-(3-nitrophenyl)-2-phenylpyr 
idine-3-carbonyl]amino]-3-methyl butylate, 
t-butyl 
2-[N-[1,4-dihydro-2-methyl-5-methoxycarbonyl-4-(3-nitrophenyl)-6-phenylpyr 
idine-3-carbonyl]amino]acetate, 
2-methoxyethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3carbonyl]amino]-3-methylbutylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-methylphenyl)pyridin 
e-3-carbonyl]amino]acetate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-4-methylpentanoate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-2-cyclopropanecarboxylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-2-cyclopentanecarboxylate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]nicotinate, 
ethyl 
6-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]nicotinate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-2-thiopheneacetate, 
ethyl 
3-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-1,2,4-triazole-5-carboxylate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-2-phenylacetate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]butyrate, 
ethyl 
3-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]butyrate, 
ethyl 
4-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]butyrate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]hexanoate, 
ethyl 
6-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]hexanoate, 
ethyl 
7-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]heptanoate, 
ethyl 
3-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-3-phenylpropionate, 
ethyl 
4-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-2-chlorobenzoate, 
ethyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-4-chlorobenzoate, 
ethyl 
2-[1-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyrid 
ine-3-carbonyl]amino]piperidinecarboxylate, 
ethyl 
2-[1-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyrid 
ine-3-carbonyl]amino]pyrrolecarboxylate, 
t-butyl 
2-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine 
-3-carbonyl]amino]-3-hydroxypropionate 
t-butyl 
2-[N-(1,4-dihydro-5-methoxycarbonyl-6-methyl-4-(3-nitrophenyl)-2-phenylpyr 
idine-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-5-methoxycarbonyl-4,6-dimethyl-2-phenylpyridine-3-carbon 
yl)amino]acetate, 
t-butyl 
2-[N-(2-ethyl-1,4-dihydro-5-methoxycarbonyl-6-methyl-4-(3-nitrophenyl)pyri 
dine-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-5-methoxycarbonyl-6-methyl-2-(2-methoxy-4-methylthiophen 
yl)-4-(3-nitrophenyl)pyridine-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(5-cyano-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3-carbony 
l)amino]acetate, 
(+)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl) 
pyridine-3carbonyl)amino]propionate, 
(-)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(R)-(3-nitrophenyl) 
pyridine-3-carbonyl)amino]propionate, 
(+)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl) 
pyridine-3-carbonyl)amino]-3phenylpropionate, 
(-)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(R)-(3-nitrophenyl) 
pyridine-3-carbonyl)amino]-3-phenylpropionate, 
(+)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl) 
pyridine-3carbonyl)amino]-4-methylpentanoate, 
(-)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(R)-(3-nitrophenyl) 
pyridine-3carbonyl)amino]-4-methylpentanoate, 
(+)-t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl) 
pyridine-3carbonyl)amino]-4-(t-butoxycarbonyl)butylate, 
(-)-t-butyl 
2-(S)-[N-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(R)-(3-nitrophenyl) 
pyridine-3-carbonyl]amino]-4-(t-butoxycarbonyl)butylate, 
(+)-t-butyl 
1-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(S)-(3-nitrophenyl)pyridin 
e-3-carbonyl]pyrrolidine-2-(S)-carboxylate, 
(-)-t-butyl 
1-[1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(R)-(3-nitrophenyl)pyridin 
e-3-carbonyl]pyrrolidine-2-(S)-carboxylate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-fluorophenyl)pyridin 
e-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-phenylpyridine-3-carbon 
yl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2,4,6-trimethoxyphenyl 
)pyridine-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-methoxyphenyl)pyridi 
ne-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-trifluoromethylpheny 
l)pyridine-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(4-cyclohexyl-1,4-dihydro-2,6-dimethyl-5-methoxycarbonylpyridine-3-ca 
rbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-5-methoxycarbonyl-2,4,6-trimethylpyridine-3-carbonyl)ami 
no]acetate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(4-nitrophenyl)pyridine 
-3-carbonyl)amino]acetate, 
t-butyl 
2-[N-(1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-5-pyridylpyridine-3-carbo 
nyl)amino]acetate, 
t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(4-nitrophenyl)pyri 
dine-3-carbonyl)amino]-3-methylbutylate, 
t-butyl 
2-(S)-[N-(4-(2-cyanophenyl)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonylpyri 
dine-3-carbonyl)amino]-3-methylbutylate, 
t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-trifluoromethylp 
henyl)pyridine-3-carbonyl)-amino]-3-methylbutylate, 
t-butyl 
2-(S)-[N-(4-(3-chlorophenyl)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonylpyr 
idine-3-carbonyl)amino]-3-methylbutylate, 
t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(2-methylphenyl)pyr 
idine-3-carbonyl)amino]-3-methylbutylate, 
t-butyl 
2-(S)-[N-(1,4-dihydro-5-methoxycarbonyl-2,4,6-trimethylpyridine-3-carbonyl 
)amino]-3-methylbutylate, and 
t-butyl 
2-(S)-[N-(1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-phenylpyridine-3-ca 
rbonyl)amino]-3-methylbutylate. 
The 1,4-dihydropyridine derivatives of the previously mentioned formula (I) 
can be produced by any of the following three processes: 
[Process 1] 
A ketone compound of formula (II) is allowed to react with an acrylamide 
compound of formula (III) in the following reaction scheme: 
##STR10## 
wherein R.sup.1, R.sup.2 R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I). 
The above reaction can be carried out by mixing the ketone compound of 
formula (II) and the acrylamide compound of formula (III) in an inert 
solvent or without any solvent at 0.degree. C. to 150.degree. C., 
preferably at 80.degree. C. to 120.degree. C. 
Examples of the inert solvent for use in the above reaction include 
aromatic hydrocarbons such as benzene, toluene and xylene; halogenated 
hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; 
alcohols such as methanol, and ethanol; ethers such as diethyl ether, 
tetrahydrofuran, and dioxane; dimethylformamide; and dimethyl sulfoxide. 
It is also preferable that the above reaction be carried out in an 
atmosphere of an inert gas such as nitrogen gas or argon gas, and in the 
dark. 
Furthermore, in order to carry out the above reaction efficiently, it is 
preferable that an equivalent amount of the ketone compound of formula 
(II) be employed with respect to the acrylamide compound of formula (III). 
[Process 2] 
An amide compound of formula (IV) is allowed to react with an amino 
compound of formula (V) in the following reaction scheme under the same 
conditions as in Process 1: 
##STR11## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I). 
[Process 3] 
A carboxylic acid derivative of formula (VI) is allowed to react with an 
amine compound of formula (VII) in the following reaction scheme: 
##STR12## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I), and Z represents a hydroxyl 
group, a halogen atom, or an active ester residue. 
In the carboxylic acid derivative of formula (VI), when Z is a hydroxyl 
group, the reaction can be carried out in the presence of a condensation 
agent. Examples of the condensation agent include carbodiimide agents such 
as N,N-dicyclohexylcarbodiimide and 
1-ethyl-3-(3-diethylaminopropyl)carbodiimide hydrochloride. 
The above reaction can be carried in an inert solvent at 0.degree. C. to 
150.degree. C., preferably at 20.degree. C. to 120.degree. C. 
Examples of the inert solvent for use in the above reaction include 
halogenated hydrocarbons such as dichloromethane, chloroform, and 
1,2-dichloroethane; hydrocarbons such as benzene, toluene and xylene; 
ethers such as ether, tetrahydrofuran, and dioxane; dimethylformamide; and 
dimethyl sulfoxide. 
It is also preferable that the above reaction be carried out in an 
atmosphere of an inert gas such as nitrogen gas or argon gas, and in the 
dark. 
In the above reaction, the carbodiimide agents can be employed in an amount 
of 1 to 1.5 equivalents with respect to the carboxylic acid derivative of 
formula (VI) and the amine compound of formula (VII). 
When Z in formula (VI) is a hydroxyl group, the carboxyl group in the 
carboxylic acid derivative of formula (VI) is converted to a carboxylic 
halide group or an active ester residue to produce a carboxylic acid 
halide or an active ester, and then the compound is allowed to react with 
the amine compound of formula (VII) in an inert solvent, whereby 
1,4-dihydropyridine derivative of formula (I) can be produced. 
The carboxylic acid halide can be produced by a conventional method by 
allowing the carboxylic acid derivative of formula (VI) in which Z is a 
hydroxyl group to react with a phosphorous halide such as phosphorous 
pentachloride, or phosphorous oxychloride; a thionyl halogenide such as 
thionyl chloride, or thionyl bromide. 
The active ester can be produced by a condensation reaction between the 
carboxylic acid of formula (VI) and an alcohol such as 
N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxybenzotriazol, 
cyanomethyl alcohol, 2,4-dinitrophenol, 4-nitrophenol, and 
pentachlorophenol. In this reaction, the previously mentioned 
carbodiimides can be employed in the inert solvent. 
Furthermore, in the above-mentioned Process 3 the 1,4-dihydropyridine 
derivatives of formula (I) can be obtained by converting the compound 
obtained in any of Process 1, 2 or 3 to the following carboxylic acid 
derivative of formula (VIII), followed by allowing the carboxylic acid 
derivative to react with an alcohol compound or an amine compound of 
formula (IX): 
##STR13## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I). 
EQU R.sup.7 --H (IX) 
wherein R.sup.7 is the same as defined previously. 
The above reaction can be carried out under the same conditions by using 
the same solvents as in Process 3 in which the carboxylic acid derivative 
of formula (VI) and the amine derivative of formula (VII) are allowed to 
react. 
The optically active 1,4-dihydropyridine derivatives of formula (I-a) are 
produced by any of the following three processes: 
Process 4] 
##STR14## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I), and * indicates a chiral 
center. 
[Step A] 
The reaction in Step A in the above reaction scheme can be carried out by 
mixing the keto-ester derivative of formula (X) and the optically active 
enamine derivative of formula (XI). The optically active enamine 
derivative of formula (XI) can be easily obtained by allowing a 
commercially available keto-ester compound to react with an optically 
active amine compound. 
It is preferable to use a basic compound to carry out the reaction 
efficiently. Examples of the basic compound are n-butyl lithium, lithium 
diisopropylamide, sodium hydride, isopropyl magnesium halide, and phenyl 
magnesium halide. Such a basic compound is generally employed in an amount 
of 0.5 to 1.5 equivalents to the keto-ester derivative of formula (X). 
Furthermore, it is preferable that the above reaction be carried out in a 
non-protonic solvent. Examples of the non-protonic solvent are ethers such 
as diethyl ether, and tetrahydrofuran, and aromatic hydrocarbons such as 
benzene and toluene. 
The reaction proceeds at temperatures of -120.degree. to 110.degree. C., 
but it is preferable that the reaction be carried out in the temperature 
range of -100.degree. C. to -20.degree. C. to cause the reaction to 
proceed efficiently. 
Furthermore, it is preferable that the reaction be carried out under a 
water-free condition in an atmosphere of an inert gas such as nitrogen gas 
or argon gas in order to obtain the desired product in high yield. 
The product obtained by the above reaction is easily decomposed at room 
temperature and therefore difficult to identify. However the product is 
considered to have the following structure from the identification by use 
of a mass spectrum: 
##STR15## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and 
B are respectively the same as in formula (I), and * indicates a chiral 
center. 
The above reaction product is then allowed to react with ammonia or an 
ammonium salt, whereby the optically active cyanoethylester of formula 
(XII) can be obtained. 
The ammonia and the ammonium salt employed in the above reaction are 
commercially available. Examples of the ammonium salt are ammonium 
acetate, and ammonium chloride. 
It is preferable that the ammonia or the ammonium salt be employed in an 
amount of 1.0 to 20 equivalents, more preferably in an amount of 1.2 to 5 
equivalents, to the keto-ester derivative of formula (X) in order to 
obtain the optically active cyanoethyl ester of formula (XII) in high 
yield. It is also preferable that the reaction with the ammonia or the 
ammonium salt be carried out in a solvent. Examples of the solvent are 
alcohols such as ethanol, methanol and propanol; ethers such as diethyl 
ether and tetrahydrofuran; and hydrocarbons such as hexane, pentane, 
toluene and benzene. 
The reaction proceeds at temperatures of 0.degree. to 60.degree. C., but it 
is preferable that the reaction be carried out at room temperature because 
the operations are simple. 
Furthermore, the reaction in the above Step A can be carried out by 
replacing the keto-ester derivative of formula (X) and the optically 
active enamine derivative of formula (XI) with a keto-ester derivative of 
formula (X') and an enamine derivative of formula (XI') respectively, 
which are shown below: 
##STR16## 
[Step B] 
The reaction in Step B can be carried out by mixing the optically active 
cyanoethyl ester derivative of formula (XII) with a basic compound. 
Examples of the basic compound employed in this reaction are sodium 
methylate, sodium hydroxide, and potassium hydroxide. It is preferable 
that the basic compound be employed in an amount of 1.0 to 3.0 
equivalents, more preferably in an amount of 1.0 to 1.2 equivalents, to 
the optically active cyanoethyl ester derivative of formula (XII), to 
obtain the product of formula (XIII) in high yield. It is also preferable 
that the reaction be carried out in a solvent, such as water, an alcohol 
such as methanol, and ethanol, or a mixed solvent of these solvents, at 
temperatures of -20.degree. C. to 80.degree. C., more preferably at 
temperatures of 0.degree. C. to 25.degree. C. to obtain the product of 
formula (XIII) in high yield. 
[Step C] 
The reaction in Step C can be carried out by subjecting the optically 
active carboxylic acid derivative of formula (XIII) obtained in the above 
Step B and the amine compound of formula (VII) to a condensation reaction. 
This condensation reaction can be carried out in the same reaction 
temperature range, using the same carbodiimide agent and reaction solvent 
as in Process 3. 
The carboxyl group in the optically active carboxylic acid derivative of 
formula (XIII) is converted to a carboxylic halide group or an active 
ester group as in Process 3, and the thus obtained compound is allowed to 
react with the amine compound of formula (VII), whereby a 
1,4-dihydropyridine derivative of formula (I) can be obtained. This 
reaction can be carried out in the same reaction temperature range, using 
the same carbodiimide agent and reaction solvents as in Process 3. 
The optically active 1,4-dihydropyridine derivatives of formula (I-a) can 
be synthesized more efficiently by the following Process 5 and Process 6 
than by the above-mentioned Process 4: 
[Process 5] 
An N-acylamino acid derivative of formula (XIV) is allowed to react with an 
optically active enamine derivative of formula (XV) in the following 
reaction scheme, followed by allowing the product to react with ammonia or 
an ammonium salt: 
##STR17## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, 
R.sup.17, R.sup.18, and B are respectively the same as previously defined, 
and * indicates a chiral center. 
The above reaction can be carried out in the same reaction temperature 
range, using the same reaction solvents as in Step A in Process 4. 
[Process 6] 
A ketone derivative of formula (XVI) is allowed to react with an optically 
active acrylamide derivative of formula (XVII) in the following reaction 
scheme, followed by allowing the product to react with ammonia or an 
ammonium salt: 
##STR18## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, 
R.sup.17, R.sup.18, and B are respectively the same as previously defined, 
and * indicates a chiral center. 
The above reaction can be carried out in the same reaction temperature 
range, using the same reaction solvents as in Step A in Process 4. 
The compounds produced in each of the above processes can be isolated by 
conventional separation methods, extraction, reprecipitation, 
recrystallization, and various types of chromatography. 
When necessary, the 1,4-dihydropyridine derivatives of formula (I) can be 
converted to the corresponding acid-addition salts by the reaction with 
pharmaceutically permissible acids. Examples of such acids are inorganic 
acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, 
sulfuric acid, and nitric acid; and organic acids such as acetic acid, 
propionic acid, lactic acid, and citric acid. 
When the 1,4-dihydropyridine derivatives of formula (I) are used as 
hypotensor, vasodilator, cerebral circulation improvement agent, 
antithrombotic agent, antiasthmatic, antiinflammatory agent, and 
antiallergic agent, the derivatives can be administered perorally, 
intravenously, hypodermically, intramuscularly, or by inhalation. 
Therefore, the derivatives can be used in various administration forms 
including pellet, capsule, liquid, and suppository.