PYRIDINE DERIVATIVES AND PRODUCTION THEREOF

Abstract: 1,4-Dihydropyridine-3-carboxylates having the general formula and the pharmacologically acceptable salts thereof are found to exhibit marked coronary vasodilating, hypotensive and other vasodilating actions with very little toxicity, so that they can be widely applied as remedies for circulatory diseases.

Description: The present invention relates to 1,4-dihydropyridine-3-carboxylates and salts thereof as well as methods for manufacturing them. Compounds of the present invention are represented by the following general formula (I) in which R¹ to R⁶ are substituents given hereunder: R¹ is a group represented by the general formula (II) where A representes in which n is an integer of 0 to 2 and R¹¹ and R¹² are same or different and are selected from a group consisting of hydrogen, alkyl, alkoxycarbonyl, phenyl, alkoxy, alkoxyalkyl, phenoxy and aralkyloxy or R¹¹ and R¹² form an alkylene group with 3 to 7 carbon atoms when n is 1; or, when n is 2, both R¹¹ and R¹² are hydrogens or two R¹¹ form a double bond while R¹² means hydrogen; and R⁷, R⁸, R⁹ and R¹⁰ are same or different and are hydrogen or alkyl; R² represents lower alkyl; R³ represents a substituent selected from a group consisting of: hydrogen; hydrocarbon with 1 to 10 carbon atoms which is branched or nonbranched; in chain , ring or a combination of them; containing 0 to 4 unsaturated bonds, and is with or without one or more of substituent(s) selected from a group consisting of alkoxy, aryloxy, aralkyloxy, amino, alkyl-substituted amino, alkylthio, pyridyl, furfuryl and tetrahydrofurfuryl; a group of a formula in which X is nitrogen or oxygen; R¹³ is lover alkyl or lower alkenyl when X is nitrogen and, when X is oxygen, R¹³ does not exist; R¹⁴ is hydrogen, alkyl or phenyl with or without alkyl substituent(s); ℓ is an integer of 0 to 2; and m is an integer of 1 to 4; a group of a formula in which q is an integer of 0 to 2 and r is an integer of 0 to 2; and a group of a formula in which t is an integer of 1 to 2 and Y is oxygen, R⁴ is lower alkyl; R⁵ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl, and alkylsulfonyl; and R⁶ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl and alkylsulfonyl. The present invention includes compounds having the general formula (I) and methods of manufacturing them, in which compounds R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or more lower alkyl substituents R² is lower alkyl of 1 to 4 carbon atoms R³ is lower alkyl with 1 to 5 carbon atoms or 2-(N-benzyl-N-lower alkylamino)-alkyl R⁴ is lower alkyl of 1 to 4 carbon atoms R⁵ is nitro, halogen, trihalomethyl or dihaloalkoxy R⁶ is hydrogen or halogen; or R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or two lower alkyl substituents of 1 to 3 carbon atoms R² is methyl, ethyl, propyl or isopropyl R³ is lower alkyl of 1 to 4 carbon atoms or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl, ethyl, propyl or isopropyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy R⁶ is hydrogen or chlorine; or R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl, ethyl or isopropyl substituent at 5-position R² is methyl R³ is methyl, ethyl or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy at 2- or 3-position R⁶ is hydrogen, or chlorine at 2-position; or R¹ is 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl substituent at 5-position R² is methyl R³ is methyl or ethyl R⁴ is methyl R⁵ is nitro or trifluoromethyl at 2- or 3-position R⁶ is hydrogen. Compounds belonging to the present invention will be further illustrated as hereunder. Examples of cyclic phosphonate groups represented by the general formula (II) included in R¹ are as follows: 2-oxo-1,3,2-dioxaphosphorinan-2-yl; 4-methyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 5-methyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 5-ethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 2-oxo-5-n-propyl-1,3,2-dioxaphosphorinan-2-yl; 5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 5-isobutyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 2-oxo-5-phenyl-1,3,2-dioxaphosphorinan-2-yl; 5-methoxy-2-oxo-1,3,2-dioxaphosphorian-2-yl; 5-ethoxy-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 5-benzyloxy-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 2-oxo-5-phenoxy-1,3,2-dioxaphosphorinan-2-yl; 5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 2-oxo-5,5-di-n-propyl-1,3,2-dioxaphosphorinan-2-yl; 5,5-dimethoxycarbonyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 5,5-diethoxycarbonyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 4(R),6(R)-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 4,4,6-trimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 4,4,6,6-tetramethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl; 2-oxo-1,3,2-dioxaphospholan-2-yl; 4,5-dimethyl-2-oxo-1,3,2-dioxaphospholan-2-yl; 2-oxo-4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-2-yl; 2-oxo-1,3,2-dioxaphosphepan-2-yl; 4,7-dimethyl-2-oxo-1,3,2-dioxaphosphepan-2-yl; 2-oxo-4,7-dihydro-1,3,2-dioxaphosphepin-2-yl; 7-oxo-6,8-dioxa-7-phosphaspiro(3,5)nonan-7-yl; 8-oxo-7,9-dioxa-8-phosphaspiro(4,5)decan-8-yl; and 3-oxo-2,4-dioxa-3-phosphaspiro(5,5)undecan-3-yl. Examples of R² in the compounds of the present invention are lower alkyls such as, for example, methyl, ethyl and propyl. Aliphatic hydrocarbons included in R³ in the compounds of the present invention are , for example, as follows: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, tert-pentyl, 1,2-dimethylpropyl, n-hexyl, and isohexyl. Examples of unsaturated hydrocarbons for R³ are those with 3 to 5 carbon atoms such as, for example, allyl, crotyl, betamethallyl, 1-ethyl-2-propenyl, propargyl, 1-methyl-2-butenyl, 3-butenyl, 3-methyl-3-butenyl, 3-butynyl and prenyl. Examples of cyclic hydrocarbons for R³ are those with 3 to 7 membered ring such as, for example, cycloalkyl inclucing cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc. and cycloalkylaklyl including cyclopropylmethyl, cyclobutylmethyl and cyclopentylmethyl. Examples of alkoxyalkyl groups are beta-methoxyethyl, beta-ethoxyethyl, beta-n-propoxyethyl, beta-isopropoxyethyl, 3-methyl-3-methoxybutyl, 1,3-dimethoxy-2-propyl and the like. Examples of phenylalkyl groups are benzyl, phenethyl and the like. Examples of phenylalkenyl groups are cinnamyl and the like. R³ may also include 2-dimethylaminoethyl, 2-diethylaminoethyl, 2-methylthioethyl, 2-ethylthioethyl, 2-propylthioethyl, tetrahydrofurfuryl, pyridylalkyls (such as, for example, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-(2-pyridyl)-ethyl, 3-(3-pyridyl)-propyl and the like which are particularly preferred), and the like. Further examples of R³ are 2-(N-benzyl-N-methylamino)-ethyl, 2-(N-phenethyl-N-methylamino)-ethyl, 3-(N-benzyl-N-methylamino)-propyl, 4-(N-benzyl-N-methylamino)-butyl, 5-(N-benzyl-N-methylamino)-pentyl, 2-(N-benzyl-N-methylamino)-1-phenylethyl, and the like. Examples of aralkyloxyalkyl groups are beta-benzyloxyethyl, beta-phenethyloxyethyl and the like and examples of aryloxyalkyl groups include substituted or unsubstituted beta-phenoxyethyl. Still further examples of R³ are N-benzyl-4-piperidinyl, N-benzyl-3-piperidinyl, N-benzyl-2-piperidinyl, N-phenyl-4-piperidinyl, N-phenethyl-4-piperidinyl and the like. Additionally further examples of R³ are 2,2-ethylenedioxypropyl, 2,2-trimethylenedioxypropyl, 3,3-ethylenedioxybutyl, 2-oxopropyl, 3-oxobutyl and the like. Examples of R⁴ in the compounds of the present invention are lower alkyls such as, for example, methyl, ethyl and propyl. As hereinabove, R¹, R², R³ and R⁴ in the present invention compounds are exemplified but the present invention is not limited to such examplified ones only. In addition to the compounds which will be exemplified later, the following compounds are also included in and covered by the present invention. It is, again, to be understood that those compounds are given only for the purpose of exemplification and the present invention is never restricted and limited to the following exemplified compounds. Methyl 4-(2-chlorophenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 4-(3-chlorophenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)- 1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-n-propyl-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 5-(5-isobutyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5,5-di-n-propyl-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(8-oxo-7,9-dioxa-8-phosphaspiro[4,5]decan-8-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-phenyl-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(4-methyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(4,4,6-trimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(4,4,6,6-tetramethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-5-(5-methoxy-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-5-(5-ethoxy-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; methyl 5-(5-benzyloxy-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-phenoxy-1,3,2-dioxaphosphorinan-2-yl)- 1,4-dihydropyridine-3-carboxylate; methyl 5-(5,5-dimethoxycarbonyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-5-(4,5-dimethyl-2-oxo-1,3,2-dioxaphospholan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphospholan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphepan-2-yl)-1,4-dihydropyridine-3-carboxylate; methyl 2,6-dimethyl-5-(4,7-dimethyl-2-oxo-1,3,2-dioxaphosphepan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate and the like. The present invention compounds have asymmetric carbon atom(s) and all optical isomers and mixtures thereof are included in and covered by the scope of the present invention. In case the racemic compound is a base, it is, if desired, treated with an optically active acid to carry out optical resolution and, from the resoluted salt, optically active base of the present invention compound is obtained. In case it is an acid, then it is, if desired, treated with optically active base and desired optically active acid can be obtained by similar way. Now, among various 1,4-dihydropyridine derivatives, it has been known that dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (generic name: nifedipine) is a compound exhibiting coronary vasodilating action and hypotensive action. From EP-A-0 121 117 1,4-dihydropyridine-3-carboxylate derivatives are known which have been found to exhibit vasodilating, peripheral blood vessel dilating and blood pressure decreasing action and are useful as remedies for angina pectoris, hypertension, brain circulatory disorder and other circular diseases. The linear homologs described in this publication are, however, not fully sufficient with respect to their activity. The present inventors have studied to find novel compounds exhibiting vasodilating and hypotensive actions, found that new 1,4-dihydropyridine-3-carboxylates and salts thereof represented by a general formula (I) exhibit excellent vasodilating and hypotensive actions with high safety, and achieved the present invention. In the field of derivatives of the compounds represented by a general formula (I), dihydropyridine compounds having the following structure have been known (cf. von K. Issleib, R. Wolff and M. Lengies: J. prakt. Chem. 318, 207-20 (1976)). However, in the report by Issleib, et al, manufacture of only the following two compounds was described and, as illustrated later, those two compounds do not exhibit hypotensive action at all. An object of the present invention is to offer novel derivatives exhibiting excellent vasodilating and hypotensive action by introducing various electronegative groups into a phenyl group placed at 1,4-dihydropyridine and further by converting one of carboxylate groups in nifedipine to a cyclic phosphonate group. Main manufacture methods for the present invention compound (I) are given as hereunder. Method 1. in which R¹, R², R³, R⁴, R⁵ and R⁶ are the same as those already defined. Starting materials (V), (III) and (IV-N) are mixed within a molar ratio of 1:0.8:0.8 to 1:4:4 and, more preferably, in a ratio of 1:0.9:0.9 to 1:1.5:1.5. The reaction is carried out at room temperature to 150°C and, more preferably, at 40 to 100°C, in the presence or absence of alcohol (such as methanol, ethanol, isopropanol and the like), aromatic hydrocarbon (such as benzene, toluene and the like), halogenated hydrocarbon (such as chloroform, carbon tetrachloride and the like), nonprotonic solvent (such as acetonitrile, N,N-dimethylformamide and the like), ether (such as tetrahydrofuran, dioxane and the like), water, etc. Separation of the desired product from the reaction mixture is conducted by conventional methods such as, for example, concentration, extraction, column chromatography, recrystallization and the like. Other methods for the manufacture of the present invention compounds are given hereunder by tray of reaction formulas. In such methods, the reaction can be conducted using the same molar ratio, reaction solvents, reaction temperature and separation technique as in the Method 1. Method 2. in which R¹, R², R³, R⁴, R⁵ and R⁶ are the same as those already defined. The starting material (VI) is easily obtained by a dehydration-condensation of (V) and (III) used in the Method 1 in organic solvent. Method 3. Method 4. in which R¹, R², R³, R⁴, R⁵ and R⁶ are the same as those already defined. Method 5. Method 6. The ammonium salt given hereinabove includes ammonium acetate, ammonium carbonate, ammonium bicarbonate and the like. Phosphonates represented by the general formula (III) used as starting materials are known in literatures or can be manufactured by known methods. For example, refer to: A. N. Pudovik and V. P. Aver'yanoua: Zhur. Obshch. Doklady Akad. Nauk. S.S.S.R. 101, 889-92(1955). beta-Ketocarboxylates of the general formula (IV) used as starting materials are known in literatures or can be manufactured by known methods. For example, refer to D. Borrmann: "Umsetzung von Diketen mit Alkoholen, Phenolen und Mercaptanen" in Houben-Weyl, Methoden der organischen Chemie, Volume VII 4, 230 (1968); Y. Oikawa, K. Sugano and O. Yonemitsu: J. Org. Chem. 43, 2087(1978). Enamino esters of the formula (IV-N) used as starting materials are known in literatures or can be manufactured by known methods. Refer, for example, to: A. C. Cope, et al: J. Am. Chem. Soc. 67, 1017(1945). Enamino esters of the general formula (III-N) used as starting materials can be manufactured by the same way as in the manufacture of (IV-N). Aromatic aldehydes of the general formula (V) used as starting materials are known in literatures or can be manufactured by conventional methods. Refer, for example, to E. Mosettig: Organic Reactions. VII, page 218 and succeedings (1954). Benzylidene derivatives of the general formula (VI) used as starting materials can be manufactured by methods known in literatures such as, for example, A. N. Pudoruk, G. E. Yastrebova and V. I. Nikitina: Zh. Obshch. Khim. 37, 510-11(1967) and R. Wolff und M. Lengies: J. prakt. Chem. 318, 207-20 (1976). In the reference examples given later, manufacture thereof will be exemplified. Benzylidene derivatives of the general formula (VII) used as starting materials are known in literatures or can be manufactured by known methods. Refer, for example, to: G. Jones: "The Knoevenagel Condensation" in Organic Reactions. Vol. XV. page 204 and succeedings (1967). All of the compounds according to the present invention including pharmacologically-acceptable salts thereof, of course, are with very little toxicity and exhibit marked coronary vasodilating, hypotensive and other vasodilating actions and, accordingly, they can be widely applied as remedies for circulatory diseases such as hypertension, cardiac insufficiency, arrhythmia, angina pectoris, myocardial infarction, cerebral vessel disturbance, peripheral circulatory insufficiency and the like. When compared with nifedipine and diltiazem which are known compounds for the similar diseases, the present invention compounds exhibit weaker action on heart muscle, more characteristic action on coronary vessel, and hypotensive action with slower onset and longer duration of action. Representative compounds of the present invention were tested for coronary vasodilating and hypotensive action comparing with diltiazem. The result is given below. 1. Test Method and Result thereof. (a) Coronary vasodilating action. Constant pressure perfusion samples of guinea pig heart isolated by a method according to Langendorff were treated with the present invention compounds by administration via coronary artery and the effect was examined (Table 1). With reference to coronary vasodilating action of diltiazem measured by the same method, the increasing rates in perfusion by administration of 10⁻⁷, 10⁻⁶ and 10⁻⁵ gram/heart were 4, 16 and 55%, respectively. It is, therefore, apparent that the present invention compounds exhibit more excellent coronary vasodilating action. (b) Hypotensive action. Blood pressure of femoral artery of rats (with normal blood pressure) under unanesthetized condition was measured directly using a pressure tranducer. The present invention compounds were given orally at doses of 1, 3 and 10 mg/kg, and changes in blood pressure were continuously recorded. Percent decrease of mean blood pressure at the peak effect was calculated. The maximum changes in mean blood pressure (%) were shown as "hypotensive action" (Table 2). Hypotensive action of diltiazem(which is a known hypotensive drug) measured by the same method at the doses of 3, 10 and 30 mg/kg were 0, 11.2 and 33.0%, respectively. Hypotensive action of the compound of Example 4 which is one of the most representative compounds of this invention was tested using spontaneously hypertensive rats and was compared with those of Nifedipine and Diltiazem hydrochloride. The method applied was that the drugs were orally given to the rats of which systolic arterial blood pressure were higher than 180 mmHg when it was measured plethysmographically using tail arteries. The result is shown in Table 3. Example Number Perfusion Increasing Rate Example Number Perfusion Increasing Rate 10⁻⁷ 10⁻⁶ gram/heart 10⁻⁷ 10⁻⁶ gram/heart 3 10% 18% 39 12% 31% 6 10 52 40 29 82 8 11 33 43 12 56 10 12 22 45 10 29 11 11 53 46 12 19 12 14 67 48 13 35 17 10 23 49 14 34 20 10 32 50 15 46 22 21 31 52 10 62 24 12 41 53 16 25 29 34 59 56 55 75 30 13 26 57 11 17 32 24 77 59 24 33 34 13 38 62 19 70 37 22 26 Example Number Hypotensive Action (%) (% Decreases in Mean Blood Pressure [at peak effect]) 10 3 1 mg/kg 2 50.1 39.2 18.4 3 20.9 11.1 8.2 4 41.9 39.0 42.6 5 46.2 43.3 39.7 7 31.4 18.4 12.7 8 37.1 15.5 8.1 9 40.4 12.9 12.7 17 47.0 36.8 24.8 18 45.5 42.7 15.7 22 18.4 10.4 7.3 26 43.8 37.1 28.7 28 33.9 26.6 16.5 32 30.5 21.2 7.8 50 47.2 44.3 42.3 51 45.4 43.0 21.1 52 42.8 37.2 18.4 53 49.7 45.4 24.5 59 35.1 29.1 7.1 62 48.3 37.4 10.6 64 41.5 16.5 6.9 68 45.8 41.7 13.0 76 40.2 35.0 10.5 It is, therefore, apparent that the present invention compounds exhibit very excellent hypotensive action. Incidentally, two compounds represented by the general formula (VIII) (R = hydrogen or methoxy) were subjected to the same test and found to exhibit no hypotensive action at all. (c) Acute Toxicity. Toxicity of the present invention compounds are very weak. All LD₅₀ values measured were not less than 400 mg/kg by oral administration to rats. When the present invention compounds are given as pharmaceuticals, they are administered to animals including human being as they are or in a form of pharmaceutical preparation containing 0.1 to 99.5%, more preferably 0.5 to 90%, of them in pharmaceutically acceptable non-toxic and inert carriers. Examples of the carriers applicable are one or more of solid, semi-solid or liquid diluents, fillers and other pharmaceutical auxiliary agents. It is desired that the pharmaceutical preparations are administered as a unit dosage form. The present invention pharmaceutical preparations may be administered per os, into tissue, locally (such as via skin) or rectally. Of course the administration is conducted by a form suitable for each route. For instance, oral administration is especially preferred. It is desired that the dose is regulated after considering the state of the patients such as age, body weight, etc., administration route, and the nature and degree of the disease but, usually, the grange of 1 to 1000 mg, preferably 2 to 100mg, of the present invention compound per day is common. Of course, in some cases, it is sufficient even below the above range and, in other cases, even more dosage may be necessary. When large dose is given, it is desired that the compound is administered dividedly - i.e. several times a day. Oral administration is carried out by a solid or liquid dose unit form such as, for example, pure powder, diluted powder, tablets, sugar coated tablets, capsules, granules, suspensions, liquid, syrups, drops, sublingual tablets and other forms. Pure powder is manufactured by making active substance into suitable fine size. Diluted powder is manufactured by making the active substance into suitable fine size and the mixed with similarly fine carriers such as starch, mannitol and other edible hydrocarbons and others. If necessary, seasoning agents, preservatives, dispersion agents, colouring agents, perfumes, and others may be mixed therewith. Capsules are manufactured as follows. Thus, the pure powder or diluted powder in powdery form as above or the granules as illustrated in the entry of tablets are filled in outer capsules such as, for example, gelatine capsule. It is of course possible to mix the powdery substances with lubricants or fluidizing agents such as, for example, colloidal silica, talc, magnesium stearate, calcium stearate, solid polyethylene glycol and the like followed by conducting the filling operation. Addition of disintegrating agents or solubilizing agents such as, for example, carboxy methyl cellulose, carboxy methyl cellulose calcium, hydroxypropyl cellulose with low degree of substitution, calcium carbonate, sodium carbonate and the like is effective in improving the effectiveness of the pharmaceuticals when capsules are taken. Finely powdered compound of the present invention may also be suspended and dispersed in vegetable oil, polyethylene glycol, glycerine, surface active agents, and the like and packed with gelatine sheets to afford soft capsules. Tablets are manufactured by first preparing powdery mixture, then made into granules or slugs, mixed with disintegrating agents or lubricants, and then made into tablets. Powdery mixtures are prepared by mixing a suitably pulverized substance with the above-given diluents or bases followed, if necessary, by mixing with combining agents (such as sodium carboxy methyl cellulose, alginates, gelatine, polyvinyl pyrrolidone, polyvinyl alcohol and the like), solubilization retarding agents (such as paraffine), reabsorbing agents (such as quaternary salts) and/or adsorbing agents (such as bentonite, kaolin, dicalcium phosphate and the like). Powdery mixtures may be made into granules by first wetting with combining agents such as syrup, starch paste, gum arabicum, cellulose solution or polymer solution followed by a compulsory passing through a sieve. Instead of granulating the powder as such, the powder may be first treated with a tablet machine and then pulverizing the obtained slugs of various forms to give granules. Granules thus prepared are mixed with lubricants such as stearates, stearic acid, talc, mineral oil and others whereupon it is possible to prevent adherence each other. Such a lubricated mixture is then compressed to make tablets. Alternatively, the active substances are, without granulation and making into slugs, directly compressed into tablets after mixing with fluidizing inert carriers. Transparent or semitransparent protective coatings comprising closed shellac membrane, coatings, of sugar or polymers, and brushing up coatings comprising waxes may also be used. Other preparation forms for oral administration such as solutions, syrups, elixiers, and the like may also be in a dosage unit form in which its definite amount contains definite amount of the pharmaceutically active substance. Syrups are manufactured by dissolving a compound in a suitable aqueous solution of sweetening agent and perfumes. Elixiers are prepared by the use of non-toxic alcoholic carriers. Suspensions are prepared by dispersing the compound in non-toxic carriers. If necessary, solubilizing agents and emulsifying agents (such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters, etc), preservatives, seasoning agents (such as peppermint oil, saccharine, etc.) and others may also be added. If necessary, dose unit forms for oral administration may be made into microcapsules. Said form may also be coated and embedded in polymers or wax so that prolongation of acting time or sustained released effect can be resulted. Parenteral administration can be done by the use of liquidal dosage unit forms (such as solution or suspension) suitable for subcutaneous, intramuscular or intravenous injections. They are manufactured first by suspending or dissolving a definite amount of the compound in non-toxic liquid carriers suitable for each injection purpose such as aqueous or oily medium and then by sterilizing said suspension or solution. Alternatively, a definite amount of the compound is taken into vials and then the vial together with the content therein are sterilized and sealed. In order to make the substance dissolved or mixed immediately before administration, preliminary or auxiliary vials or carriers may be prepared in addition to pulverized or lyophilized effective constituent. In order to make the injection solution isotonic, non-toxic salt or a solution thereof nay be added thereto. Further, stabilizers, preservatives, emulsifiers, and the like may be simultaneously applied. Rectal administration can be conducted by the use of suppositories in which the compound is mixed with a lower melting solid (which is soluble or insoluble in water) such as, for example, polyethylene glycol, cacao butter, higher esters (such as myristyl palmitate) or a mixture thereof. Pharmaceutical preparations of the present invention compounds may be combined with other pharmaceuticals such as, for example, nitrites, beta-blockers, diuretic hypotensive drugs, and the like and may be used jointly with them. Manufacture methods of the starting materials for the present invention compounds are given as follows under Reference Example. Then several examples concerning the manufacture of the present invention compounds follow. Of course, the present invention is not limited or restricted thereto. Reference Example 1. A mixture of 10.0 grams of 2-acetonyl-2-oxo-1,3,2-dioxaphosphorinane and 8.48 grams of m -nitrobenzaldehyde was dissolved in 120 ml of toluene, 1.0 gram of piperidine and 2.0 grams of acetic acid were added as catalysts and the mixture was heated to reflux for 15 hours with a water-remover. After cooled, the crystals separated out were removed by filtration, the filtrate was washed with water, then with aqueous solution of sodium hydroxide, further with 20% sodium acid sulfite solution and finally with water, and the organic solvent layer was dried. The solvent was removed by evaporation in vacuo, the residue was purified by silica gel column chromatography, and 4.5 grams of 2-(1-(3-nitrobenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane was obtained as an EZ mixture. Recrystallized from ethyl acetate. M.p. 144-145.5°C. IR (cm⁻¹): 1695, 1610, 1525, 1350, 1270, 1055. Elementary analysis calculated for C₁₃H₁₄NO₆P: C 50.17, H 4.53, N 4.50; Found: 50.26, H 4.66, N 4.54%. Similarly prepared were the following compounds: 2-(1-(2-Nitrobenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane: m.p. 134-143°C (recrystallized from ethyl acetate). 2-(1-(2-Trifluoromethylbenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane: pale brown oil. IR (film, cm⁻¹): 1700, 1320, 1280, 1170, 1120, 1055, 965, 815, 770. 2-(1-(2-Difluoromethoxybenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane: m.p. 85-87°C (recrystallized from ether-ethyl acetate). 2-(1-(2,3-Dichlorobenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane: m.p. 93-95°C (recrystallized from ether-ethyl acetate). Example 1. (a) Into 80 ml of isopropanol were dissolved 5.5 grams of 2-(1-(3-nitrobenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane and 2.1 grams of methyl 3-aminocrotonate and the mixture was heated to reflux for 10 hours. After the reaction, the reaction solution was concentrated in vacuo, the residue was made crystallized by addition of ethyl acetate, and crystals separated out were collected by filtration. The crude crystals were recrystallized from ethyl acetate to give 3.6 grams of methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate, m. p. 221-3°C. IR (KBr, cm⁻¹): 3290, 3230, 3110, 1710, 1650, 1535, 1505, 1350, 1250, 1220, 1100, 930, 850, 810. NMR (CDCl₃, δ): 1.72-1.82 (1H, m), 2.04-2.16 (1H, m), 2.33 (3H, s), 2.35 (3H, d, J = 2.5 Hz), 3.67 (3H, s), 3.93-4.28 (2H, m), 4.40-4.60 (2H, m), 4.86 (1H, d, J = 10.5 Hz), 6.21 (1H, d, J = 5Hz), 7.38 (1H, t, J = 8 Hz), 7.63 (1H, d, J = 8Hz), 8.01 (1H, m), 8.10 (1H, t, J = 2 Hz). Elementary analysis calculated for C₁₈H₂₁N₂O₇P: C 52.95, H 5.18, N 6.86; Found: C 52.83, H 5.14, N 6.68%. (b) 2-Acetonyl-2-oxo-1,3,2-dioxaphosphorinane (1.78 grams) was dissolved in 10 ml of methanol and ammonia gas was bubbled thereinto with ice cooling and stirring for ten minutes. The reaction solution was stirred at room temperature for 2 hours and methanol was removed by evaporation in vacuo. The residue was dissolved in 10 ml of anhydrous ethanol, 100 mg of sodium hydride (50% mineral oil) was added, the mixture was stirred for 10 minutes, then a mixture of 2.41 grams of methyl 2-(3-nitrobenzylidene)-acetoacetate and 1 gram of ammonium carbonate was added, and the mixture was heated to reflux for eight hours with stirring. The reaction solution was concentrated in vacuo, the residue was dissolved in ethyl acetate, the solution was washed with 5% aqueous solution of sodium hydroxide, then with water, the organic solvent layer was dried with magnesium sulfate, and concentrated in vacuo. The concentrate was purified by subjecting to a silica gel column chromatography to give 0.41 gram of methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. (c) 2-Acetonyl-2-oxo-1,3,2-dioxaphosphorinane (1.78 grams) was dissolved in 10 ml of methanol and ammonia gas was bubbled thereinto for ten minutes with stirring and ice cooling. The reaction solution was stirred at room temperature for two hours and methanol was removed therefrom by evaporation in vacuo. The residue was dissolved in 15 ml of anhydrous ethanol, 200 mg of sodium hydride (50% mineral oil) was added thereto, stirred for ten minutes, then 1.51 grams of 3-nitrobenzaldehyde, 1.16 grams of methyl acetoacetate, and 1 gram of ammonium carbonate were added thereto, and the mixture was heated to reflux for eight hours. Then the reaction solution was subjected to an after-treatment as same as in (b) to give 0.32 gram of methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. Example 2. A mixture of 3.11 grams of 2-(1-(3-nitrobenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphosphorinane and 2.48 grams of 2-(N-benzyl-N-methylamino)ethyl 3-aminocrotonate was dissolved in 30 ml of isopropanol and the mixture was heated to reflux for eight hours. The reaction solution was concentrated in vacuo and the residue was purified by subjecting to a column chromatography (silica gel, n-hexane-ethyl acetate). The resulting pale yellow oil (3.8 grams) was crystallized with ether and recrystallized from a mixture of ethyl acetate and ether to give 3.2 grams of 2-(N-benzyl-N-methylamino)ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate, pale yellow crystals, m.p. 139-40°C. IR (KBr, cm⁻¹): 3290, 3220, 3100, 1695, 1645, 1530, 1505, 1350, 1250, 1230, 1050. NMR (CDCl₃, δ): 1.68-1.80 (1H, m), 1.95-2.15 (1H, m), 2.21 (3H,s),2.32(3H,s) 2.34 (3H, d, J = 2.5Hz), 2.66 (2H, t, J = 6.0 Hz), 3.51 (2H, s), 3.9-4.1 (2H, m), 4.20 (2H, t, J = 6.0 Hz), 4.35-4.60 (2H, m), 4.89 (1H, d, J = 10.5 Hz), 6.37 (1H, d, J = 5Hz), 7.26 (5H, s), 7.3 -7.4 (1H, m), 7.66 (1H, d, J = 8Hz), 7.98 (1H, d, J = 8Hz), 8.10 (1H, t, J = 2 Hz). Elementary analysis calculated for C₂₇H₃₂N₃O₇P: C 59.88, H 5.96, N 7.76; Found: C 59.80, H 6.10, N 7.68%. Example 3. N-Benzyl-4-piperidinyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. The same reaction and after-treatment as in Example 2 were conducted and purification with column chromatography (silica gel, n-hexane-ethyl acetate) gave pale yellow oily product. MS (m/e): M⁺ 567. IR (film, cm⁻¹): 3300, 3220, 3100, 1690, 1645, 1530, 1500, 1350, 1235, 1090, 1055. Example 4. Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. A mixture of 4.04 grams of 2-(1-(2-nitrobenzylidene)-acetonyl)-2-oxo-1,3,2-dioxaphorinane and 1.61 grams of methyl 3-aminocrotonate in 80 ml of ethanol was heated to reflux for twenty hours. The reaction solution was concentrated in vacuo, to the residue was added 40 ml of ethyl acetate, the mixture was heated with stirring for 10 minutes, allowed to cool until room temperature, crystals separated out were collected by filtration, washed with ethyl acetate, and the resulting crude crystals were recrystallized from ethanol to give 3.6 grams of the title product, yellow crystals, m.p. 249-51°C. IR (KBr, cm⁻¹): 3280, 3200, 3080, 1690, 1650, 1630, 1530, 1505, 1350, 1250, 1230, 1060, 930, 820, 805. NMR (CDCl₃, δ): 1.64-1.74 (2H, m), 2.27 (3H, s), 2.45 (3H, d, J = 2.6 Hz), 3.57 (3H, s), 3.85-4.05 (2H, m), 4.20-4.70 (2H, m), 5.60 (1H, d, J = 10.5Hz), 6.22 (1H, d, J =6Hz), 7.20-7.29 (1H, m), 7.40-7.56 (2H, m), 7.70 (1H, d, J = 8.0 Hz). Elementary analysis calculated for C₁₈H₂₁N₂O₇P: C 52.95, H 5.18, N 6.86; Found: C 52.81, H 5.24, N 6.81%. Example 5. Ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. The same reaction and after-treatment as in Example 4 were carried out to give the title product, yellow crystals, m.p. 173-5° (recrystallized from ethyl acetate). IR (KBr, cm⁻¹): 3280, 3210, 3100, 1700, 1640, 1535, 1500, 1355, 1310, 1235, 1110, 1060. NMR (CDCl₃, δ): 1.19 (3H, t, J = 7Hz), 1.67-1.76 (2H, m), 2.26 (3H, s), 2.41 (3H, d, J = 2Hz), 3.86-4.35 (6H, m), 5.68 (1H, d, J = 10.5 Hz), 6.48 (1H, d, J = 5Hz), 7.20-7.28 (1H, m), 7.40-7.56 (2H, m), 7.75 (1H, d-d, J = 1.8 Hz). Elementary analysis calculated for C₁₉H₂₃N₂O₇P: C 54.03, H 5.49, N 6.63; Found: C 53.83, H 5.57, N 6.68%. Similarly prepared were the compounds given in the following Examples 6 to 74 by the same way as in Examples 1 to 5. Example 6. Isopropyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 159-61°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.77, N 6.42; Found: C 55.06, H 5.90, N 6.40%. Example 7. Methyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 208-9°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.77, N 6.42; Found: C 55.08, H 5.76, N 6.33%. Example 8. Ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 154-6°C. Elementary analysis calculated for C₂₁H₂₇N₂O₇P: C 56.00, H 6.04, N 6.22; Found: C 56.33, H 6.06, N 5.91%. Example 9. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 125-6°C. Elementary analysis calculated for C₂₉H₃₆N₃O₇P.¹/₂ H₂O: C 60.20, H 6.45, N 7.26; Found: C 60.21, H 6.64, N 7.07%. Example 10. 2-(N,N-Dimethylamino)ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 96-8°C. Elementary analysis calculated for C₂₃H₃₂N₃O₇P: C 55.98, H 6.54, N 8.52; Found: C 55.66, H 6.78, N 8.38%. Example 11. 2-n-Propoxyethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 163-4°C. Elementary analysis calculated for C₂₄H₃₃N₂O₈P: C 56.69, H 6.54, N 5.51; Found: C 56.60, H 6.78, N 5.52%. Example 12. 2-Benzyloxyethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 166-7°C. Elementary analysis calculated for C₂₈H₃₃N₂O₈P: C 60.43, H 5.98, N 5.03; Found: C 60.10, H 5.98, N 5.03%. Example 13. 2-Methoxy-1-methoxymethylethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 174-5°C. Elementary analysis calculated for C₂₄H₃₃N₂O₉P: C 54.96, H 6.34, N 5.34; Found: C 54.61, H 6.55, N 5.17%. Example 14. 2-Pyridylmethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxyalte. M.p. 195-6°C. Elementary analysis calculated for C₂₅H₂₈N₃O₇P.¹/₂ H₂O: C 57.47, H 5.59, N 8.04; Found: C 57.65, H 5.53, N 8.10%. Example 15. Methyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 249-51°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.77, N 6.42; Found: C 54.83, H 5.88, N 6.38%. Example 16. Methyl 2,6-dimethyl-5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 198-200°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.77, N 6.42; Found: C 54.81, H 5.72, N 6.19%. Example 17. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. Oily substance. MS (m/e): M⁺ 569. Example 18. Methyl 2,6-dimethyl-5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 125-35°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.77, N 6.42; Found: C 54.83, H 5.88, N 6.38. Example 19. Methyl 2,6-dimethyl-5-[4(R),6(R)-dimethyl2-oxo-1,3,2-dioxaphosphorinan-2-yl]-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 225-6°C. [α] 23 / D= -24.67 (c = 0.762, ethanol). Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.77, N 6.42; Found: C 54.98, H 5.80, N 6.43%. Example 20. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-[4(R),6(R)-dimethy]-2-oxo-1,3,2-dioxaphosphorinan-2-yl]-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. Pale yellow oily substance. MS (m/e): M⁺ 569. [α] D = 9.40 (c = 1.340, ethanol). Example 21. Methyl 5-(5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 223-4°C. Elementary analysis calculated for C₂₂H₂₉N₂O₇P: C 56.89, H 6.29, N 6.03; Found: C 56.77, H 6.46, N 5.99%. Example 22. 2-(N-Benzyl-N-methylamino)-ethyl 5-(5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 171-2°C. Elementary analysis calculated for C₃₁H₄₀N₃O₇P: C 62.30, H 6.75, N 7.03; Found: C 62.30, H 6.95, N 6.99%. Example 23. Ethyl 5-(5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 151-2°C. Elementary analysis calculated for C₂₃H₃₁N₂O₇P: C 57.74, H 6.53, N 5.85; Found: C 57.90, H 6.85, N 5.80%. Example 24. Methyl 5-(5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 234-5°C. Elementary analysis calculated for C₂₂H₂₉N₂O₇P: C 56.89, H 6.29, N 6.03; Found: C 56.70, H 6.39, N 6.04%. Example 25. Ethyl 5-(5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 201-3°C. Elementary analysis calculated for C₂₃H₃₁N₂O₇P: C 57.74, H 6.53, N 5.85; Found: C 57.67, H 6.64, N 5.83%. Example 26. Methyl 5-(5-methyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 177-9°C. Elementary analysis calculated for C₁₉H₂₃N₂O₇P: C 54.03, H 5.49, N 6.63; Found: C 53.72, H 5.63, N 6.45%. Example 27. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-(5-methyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 156-8°C. Elementary analysis calculated for C₂₈H₃₄N₃O₇P: C 60.54, H 6.17, N 7.56; Found: C 60.24, H 6.41, N 7.39%. Example 28. Methyl 5-(5-ethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 122-3°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P: C 55.05, H 5.78, N 6.42; Found: C 54.66, H 5.83, N 6.43%. Example 29. 2-(N-Benzyl-N-methylamino)-ethyl 5-(5-ethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 145-6°C. Elementary analysis calculated for C₂₉H₃₆N₃O₇P: C 61.15, H 6.37, N 7.38; Found: C 60.95, H 6.48, N 7.28%. Example 30. Methyl 5-(5-ethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 163-4°C. Elementary analysis calculated for C₂₀H₂₅N₂O₇P.¹/₄ H₂O: C 54.48, H 5.83, N 6.35; Found: C 54.61, H 5.91, N 6.38%. Example 31. Methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 94-6°C. Elementary analysis calculated for C₂₁H₂₇N₂O₇P.¹/₄ H₂O: C 55.44, H 6.09, N 6.16; Found: C 55.55, H 6.18, N 6.15%. Example 32. Ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 127-30°C. Elementary analysis calculated for C₂₂H₂₉N₂O₇P: C 56.89, H 6.29, N 6.03; Found: C 56.84, H 6.31, N 6.03%. Example 33. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-(5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 161-2°C. Elementary analysis calculated for C₃₀H₃₈N₃O₇P: C 61.74, H 6.56, N 7.20; Found: C 61.54, H 6.75, N 7.08%. Example 34. Methyl 2,6-dimethyl-5-(5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 182-4°C. Elementary analysis calculated for C₂₁H₂₇N₂O₇P.¹/₂ H₂O: C 54.90, H 6.14, N 6.10; Found: C 54.75, H 6.24, N 6.11%. Example 35. Ethyl 2,6-dimethyl-5-(5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 156-8°C. Elementary analysis calculated for C₂₂H₂₉N₂O₇P: C 56.89, H 6.29, N 6.03; Found: C 56.88, H 6.45, N 5.87%. Example 36. Methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(7-oxo-6,8-dioxa-7-phosphaspiro(3,5)nonan-7-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 217-19°C. Elementary analysis calculated for C₂₁H₂₅N₂O₇P: C 56.25, H 5.62, N 6.25; Found: C 56.02, H 5.81, N 6.11%. Example 37. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(7-oxo-6,8-dioxa-7-phosphaspiro(3,5)nonan-7-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 188-9°C. Elementary analysis calculated for C₃₀H₃₆N₃O₇P: C 61.95, H 6.24, N 7.22; Found: C 61.83, H 6.39, N 7.22%. Example 38. Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(7-oxo-6,8-dioxa-7-phosphoaspiro(3,5)nonan-7-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 174-7°C. Elementary analysis calculated for C₂₁H₂₅N₂O₇P.¹/₄ H₂O: C 55.69, H 5.68, N 6.19; Found: C 55.73, H 5.75, N 6.11%. Example 39. Ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(7-oxo-6,8-dioxa-7-phosphaspiro(3,5)nonan-7-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 125-8°C. Elementary analysis calculated for C₂₂H₂₇N₂O₇P.¹/₄ iso-Pr₂O: C 57.84, H 6.30, N 5.74; Found: C 57.77, H 6.54, N 5.53%. Example 40. Methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(3-oxo-2,4-dioxa-3-phosphaspiro (5,5)undecan-3-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 199-200°C. Elementary analysis calculated for C₂₃H₂₉N₂O₇P: C 57.98, H 6.13, N 5.88; Found: C 57.80, H 6.23, N 5.81%. Example 41. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(3-oxo-2,4-dioxa-3-phosphaspiro(5,5)undecan-3-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 198-200°C. Elamentary analysis calculated for C₃₂H₄₀N₃O₇P: C 63.04, H 6.61, N 6.89; Found: C 63.06, H 6.79, N 6.77%. Example 42. Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(3-oxo-2,4-dioxa-3-phosphaspiro(5,5)undecan-3-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 136-7°C. Elementary analysis calculated for C₂₃H₂₉N₂O₇P: C 57.98, H 6.13, N 5.88; Found: C 57.70, H 6.41, N 5.53%. Example 43. Ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(3-oxo-2,4-dioxa-3-phosphaspiro(5,5)undecan-3-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 138-40°C. Elementary analysis calculated for C₂₄H₃₁N₂O₇P: C 58.77, H 6.37, N 5.71; Found: C 58.74, H 6.50, N 5.67%. Example 44. Methyl 5-(5,5-diethoxycarbonyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 216-17°C. Elementary analysis calculated for C₂₄H₂₉N₂O₁₁P: C 52.18, H 5.29, N 5.07; Found: C 52.05, H 5.46, N 5.06%. Example 45. 2-(N-Benzyl-N-methylamino)-ethyl 5-(5,5-diethoxycarbonyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 142-3°C. Elementary analysis calculated for C₃₃H₄₀N₃O₁₁P: C 57.81, H 5.88, N 6.13; Found: C 57.67, H 6.12, N 6.06%. Example 46. Methyl 5-(5,5-diethoxycarbonyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 198-9°C. Elementary analysis calculated for C₂₄H₂₉N₂O₁₁P: C 52.18, H 5.29, N 5.07; Found: C 52.12, H 5.36, N 5.09%. Example 47. Methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 236-7°C. Elementary analysis calculated for C₂₁H₂₇N₂O₇P: C 56.00, H 6.04, N 6.22; Found: C 56.04, H 6.24, N 6.22%. Example 48. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 186-8°C. Elementary analysis calculated for C₃₀H₃₈N₃O₇P: C 61.74, H 6.56, N 7.20; Found: C 61.71, H 6.69, N 7.12%. Example 49. 2-n-Propoxyethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 169-70°C. Elementary analysis calculated for C₂₅H₃₅N₂O₈P: C 57.47, H 6.75, N 5.36; Found: C 57.37, H 6.95, N 5.37%. Example 50. Methyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 209-11°C. Elementary analysis calculated for C₁₉H₂₁F₃NO₅P: C 52.91, H 4.91, N 3.25; Found: C 52.94, H 5.15, N 3.16%. Example 51. Ethyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 175-7°C. Elementary analysis calculated for C₂₀H₂₃F₃NO₅P: C 53.94, H 5.21, N 3.14; Found: C 53.77, H 5.30, N 3.27%. Example 52. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. Pale yellow oil. MS (m/e) M⁺ 564. Example 53. Methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 192-3°C. Elementary analysis calculated for C₁₉H₂₂F₂NO₆P: C 53.15, H 5.16, N 3.26; Found: C 53.15, H 5.28, N 3.25. Example 54. Ethyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 191-2°C. Elementary analysis calculated for C₂₀H₂₄F₂NO₆P: C 54.18, H 5.46, N 3.16; Found: C 54.12, H 5.65, N 3.14%. Example 55. 2-(N-Benzyl-N-methylamino)-ethyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. Pale brown oil. MS (m/e): M⁺ 562. Example 56. Methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 275-7°C. Elementary analysis calculated for C₁₈H₂₀Cl₂NO₅P: C 50.02, H 4.66, N 3.24; Found: C 50.00, H 4.74, N 3.18%. Example 57. Ethyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 265-7°C. Elementary analysis calculated for C₁₉H₂₂Cl₂NO₅P: C 51.14, H 4.97, N 3.14; Found: C 51.01, H 4.95, N 3.11%. Example 58. Methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 167-8°C. Elementary analysis calculated for C₂₀H₂₄Cl₂NO₅P: C 52.19, H 5.26, N 3.04; Found: C 52.21, H 5.31, N 3.12%. Example 59. 2-(N-Benzyl-N-methylamino)-ethyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 197-8°C. Elementary analysis calculated for C₂₉H₃₅Cl₂N₂O₅P: C 58.69, H 5.94, N 4.72; Found: C 58.53, H 6.04, N 4.61%. Example 60. Methyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 210-12°C. Elementary analysis calculated for C₂₁H₂₅F₃NO₅P: C 54.90, H 5.49, N 3.09; Found: C 54.91, H 5.58, N 3.08%. Example 61. Ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 223-5°C. Elementary analysis calculated for C₂₂H₂₇F₃NO₅P: C 55.82, H 5.75, N 2.96; Found: C 55.94, H 5.89, N 2.97%. Example 62. 2-(N-Benzyl-N-methylamino)-ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. Pale brown oil. MS (m/e): M⁺ 592. Example 63. Methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 217-18°C. Elementary analysis calculated for C₂₁H₂₆F₂NO₆P: C 55.14, H 5.73, N 3.06; Found: C 55.31, H 5.91, N 3.02%. Example 64. 2-(N-Benzyl-N-methylamino)-ethyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. Pale yellow oil. MS (m/e): M⁺ 590. Example 65. Ethyl 2,6-dimethyl-5-(4,6-dimethyl-2-oxo-1,3,2 dioxaphosphorinan-2-yl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 228-30°C. Elementary analysis calculated for C₂₁H₂₇N₂O₇P: C 56.00, H 6.04, N 6.22; Found: C 56.05, H 6.08, N 6.17%. Example 66. Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-4,7-dihydro-1,3,2-dioxaphosphepin -2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 221-2.5°C. Elementary analysis calculated for C₁₉H₂₁N₂O₇P: C 54.29, H 5.04, N 6.66; Found: C 54.33, H 5.04, N 6.59%. Example 67. tert-Butyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 120-4°C. Elementary analysis calcualted for C₂₁H₂₇N₂O₇P: C 56.00, H 6.04, N 6.22; Found: C 55.93, H 6.13, N 6.21%. Example 68. Cyclopropylmethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 206-8°C. Elementary analysis calculated for C₂₁H₂₅N₂O₇P: C 56.25, H 5.62, N 6.25; Found: C 56.31, H 5.56, N 6.32%. Example 69. Cyclopropylmethyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 225-5.5°C. Elementary analysis calculated for C₂₂H₂₅F₃NO₅P: C 56.05, H 5.35, N 2.97; Found: C 56.02, H 5.51, N 2.98%. Example 70. 2,2-Ethylenedioxypropyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. M.p. 126-7.5°C. Elementary analysis calculated for C₂₂H₂₇N₂O₉P: C 53.44, H 5.50, N 5.67; Found: C 53.06, H 5.37, N 5.67%. Example 71. 2,2-Ethylenedioxypropyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 188-9.5°C. Elementary analysis calculated for C₂₃H₂₇F₃NO₇P: C 53.39, H 5.26, N 2.71; Found: C 53.57, H 5.28, N 2.70%. Example 72. Benzyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 197-8°C. Elementary analysis calculated for C₂₅H₂₅F₃NO₅P: C 59.17, H 4.97, N 2.76; Found: C 59.24, H 5.05, N 2.67%. Example 73. Cyclopentyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 236-8°C. Elementary analysis calculated for C₂₃H₂₇F₃NO₅P: C 56.91, H 5.61, N 2.89; Found: C 56.72, H 5.70, N 2.79%. Example 74. Allyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. M.p. 192-3°C. Elementary analysis calculated for C₂₁H₂₃F₃NO₅P: C 55.15, H 5.07, N 3.06; Found: C 55.55, H 5.17, N 3.04%. Example 75. 2-Oxopropyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate. 2,2-Ethylenedioxypropyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-cabroxylate (2.3 grams) was heated to reflux for 6 hours in 20 ml of ethanol containing 2.5 ml of 10% hydrochloric acid. The solvent was evaporated therefrom in vacuo, the residue was dissolved in methylene chloride, the solution was dried with magensium sulphate, and the solvent was evaporated therefrom. The residue was subjected to silica gel column chromatography to purify whereupon 1.6 grams of the title compound, pale yellow noncrystalline powder. IR (KBr, cm⁻¹): 3300, 3225, 3100, 1735, 1705, 1650, 1535, 1505, 1360, 1240, 1110, 1055, 930. Elementary analysis calculated for C₂₀H₂₃N₂O₈P: C 53.34, H 5.15, N 6.22; Found: C 53.34, H 5.43, N 5.97%. Example 76. 2-Oxopropyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate. 2,2-Ethylenedioxypropyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate (2.5 grams) was subjected to the same reaction and after-treatment as in Example 75 to give 1.88 grams of the title compound, colourless non-crystalline powder. IR (KBr, cm⁻¹): 3280, 3220, 3100, 1735, 1700, 1640, 1500, 1310, 1230, 1150, 1100, 1050. Elementary analysis calculated for C₂₁H₂₃F₃NO₆P: C 53.28, H 4.90, N 2.96; Found: C 53.47, H 5.24, N 2.84%.

Claims: Claims for the following Contracting States : CH, DE, LI 1,4-Dihydropyridine-3-carboxylate represented by the following general formula (I) and salts thereof. in which R¹ is a group represented by the general formula (II) where A represents in which n is an integer of 0 to 2 and R¹¹ and R¹² are same or different and are selected from a group consisting of hydrogen, alkyl, alkoxycarbonyl, phenyl, alkoxy, alkoxyalkyl, phenoxy and aralkyloxy or R¹¹ and R¹² form an alkylene group with 3 to 7 carbon atoms when n is 1; or, when n is 2, both R¹¹ and R¹² are hydrogens or two R¹¹ form a double bond while R¹² means hydrogen; and R⁷, R⁸, R⁹ and R¹⁰ are same or different and are hydrogen or alkyl; R² represents lower alkyl; R³ represents a substituent selected from a group consisting of: hydrogen; hydrocarbon with 1 to 10 carbon atoms which is branched or nonbranched; in chain , ring or a combination of them; containing 0 to 4 unsaturated bonds, and is with or without one or more of substituent(s) selected from a group consisting of alkoxy, aryloxy, aralkyloxy, amino, alkyl-substituted amino, alkylthio, pyridyl, furfuryl and tetrahydrofurfuryl; a group of a formula in which X is nitrogen or oxygen; R¹³ is lower alkyl or lower alkenyl when X is nitrogen and, when X is oxygen, R¹³ does not exist; R¹⁴ is hydrogen, alkyl or phenyl with or without alkyl substituent(s); ℓ is an integer of 0 to 2; and m is an integer of 1 to 4; a group of a formula in which q is an integer of 0 to 2 and r is an integer of 0 to 2; and a group of a formula in which t is an integer of 1 to 2 and Y is oxygen, R⁴ is lower alkyl; R⁵ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl, and alkylsulfonyl; and R⁶ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl and alkylsulfonyl. The compound (I) and its salt of Claim 1 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or more lower alkyl substituents R² is lover alkyl of 1 to 4 carbon atoms R³ is lower alkyl with 1 to 5 carbon atoms or 2-(N-benzyl-N-lower alkylamino)-alkyl R⁴ is lover alkyl of 1 to 4 carbon atoms R⁵ is nitro, halogen, trihalomethyl or dihaloalkoxy R⁶ is hydrogen or halogen. The compound (I) and its salt of Claim 2 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or two lower alkyl substituents of 1 to 3 carbon atoms R² is methyl, ethyl, propyl or isopropyl R³ is lower alkyl of 1 to 4 carbon atoms or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl, ethyl, propyl or isopropyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy R⁶ is hydrogen or chlorine. The compound (I) ad its salt of Claim 3 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl, ethyl or isopropyl substituent at 5-position R² is methyl R³ is methyl, ethyl or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy at 2- or 3-position R⁶ is hydrogen, or chlorine at 2-position. The compound (I) and its salt of Claim 4 in which R¹ is 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl substituent at 5-position R² is methyl R³ is methyl or ethyl R⁴ is methyl R⁵ is nitro or trifluoromethyl at 2- or 3-position R⁶ is hydrogen. Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate and salts thereof. Ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate and salts thereof. Methyl 5-(5-methyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate and salts thereof. Methyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate and salts thereof. 2-(N-Benzyl-N-methylamino)ethyl 5-(5-ethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate and salts thereof. Ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(5-isopropyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridene-3-carboxylate and salts thereof. Ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(3-oxo-2,4-dioxa-3-phosphaspiro(5,5)undecan-3-yl)-1,4-dihydropyridine-3-carboxylate and salts thereof. 2-(N-Benzyl-N-methylamino)ethyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate and salts thereof. Methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate and salts thereof. 2-(N-Benzyl-N-methylamino)ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine-3-carboxylate and salts thereof. 2-(N-Benzyl-N-methylamino)ethyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate and salts thereof. A method of manufacturing 1,4-dihydropyridine-3-carboxylate represented by the following general formula (I) and salts thereof according to Claim 1, characterized in that, a benzaldehyde compound of a formula (V) is made to react with a compound of a formula (III) in organic solvent to cause dehydration-condensation giving a compound of a formula (VI) and said (VI) is made to react with a compound of a formula (IV) or enamino ester thereof in an organic solvent or, without isolating (VI), all of (V), (III) and (IV) (or enamino ester of (IV) ) are made present in an organic solvent and the reaction is conducted in the presence of ammonia or ammonium salt in case (IV) is used and, in case enamino ester of (IV) is used, in the absence of ammonia or ammonium salt to afford (I), wherein in the above formulas, R¹ to R⁶ are as follows: R¹ is a group represented by the general formula (II) where A representes in which n is an integer of 0 to 2 and R¹¹ and R¹² are same or different and are selected from a group consisting of hydrogen, alkyl, alkoxycarbonyl, phenyl, alkoxy, alkoxyalkyl, phenoxy and aralkyloxy or R¹¹ and R¹² form an alkylene group with 3 to 7 carbon atoms when n is 1; or, when n is 2, both R¹¹ and R¹² are hydrogens or two R¹¹ form a double bond while R¹² means hydrogen; and R⁷, R⁸, R⁹ and R¹⁰ are same or different and are hydrogen or alkyl; R² represents lower alkyl; R³ represents a substituent selected from a group consisting of: hydrogen; hydrocarbon with 1 to 10 carbon atoms which is branched or nonbranched; in chain , ring or a combination of them; containing 0 to 4 unsaturated bonds, and is with or without one or more of substituent(s) selected from a group consisting of alkoxy, aryloxy, aralkyloxy, amino, alkyl-substituted amino, alkylthio, pyridyl, furfuryl and tetrahydrofurfuryl; a group of a formula in which X is nitrogen or oxygen; R¹³ is lower alkyl or lower alkenyl when X is nitrogen and, when X is oxygen, R¹³ does not exist; R¹⁴ is hydrogen, alkyl or phenyl with or without alkyl substituent(s); ℓ is an integer of 0 to 2; and m is an integer of 1 to 4; a group of a formula in which q is an integer of 0 to 2 and r is an integer of 0 to 2; and a group of a formula in which t is an integer of 1 to 2 and Y is oxygen, R⁴ is lower alkyl; R⁵ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl, and alkylsulfonyl; and R⁶ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl and alkylsulfonyl. A method of Claim 17 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or more lower alkyl substituents R² is lower alkyl of 1 to 4 carbon atoms R³ is lower alkyl with 1 to 5 carbon atoms or 2-(N-benzyl-N-lower alkylamino)-alkyl R⁴ is lower alkyl of 1 to 4 carbon atoms R⁵ is nitro, halogen, trihalomethyl or dihaloalkoxy R⁶ is hydrogen or halogen. A method of Claim 18 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or two lower alkyl substituents of 1 to 3 carbon atoms R² is methyl, ethyl, propyl or isopropyl R³ is lower alkyl of 1 to 4 carbon atoms or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl, ethyl, propyl or isopropyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy R⁶ is hydrogen or chlorine. A method of Claim 19 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl, ethyl or isopropyl substituent at 5-position R² is methyl R³ is methyl, ethyl or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy at 2- or 3-position R⁶ is hydrogen or chlorine at 2-position. A method of Claim 20 in which R¹ is 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl substituent at 5-position R² is methyl R³ is methyl or ethyl R⁴ is methyl R⁵ is nitro or trifluoromethyl at 2- or 3-position R⁶ is hydrogen. A method of manufacturing 1,4-dihydropyridine-3-carboxylate of the following general formula (I) or salts thereof according to Claim 1, characterized in that, a benzaldehyde compound of a general formula (V) is subjected to a dehydration-condensation in an organic solvent with a compound represented by a formula (IV) to give a compound represented by a formula (VII) and then the compound (VII) is made to react with a compound of a formula (III) or enamino ester of (III) in an organic solvent or, without isolation of the compound (VII), all of (V), (IV) and (III) or enamino ester thereof are at the same time made present in an organic solvent and made to react in the presence of ammonia or ammonium salt when (III) is used and, when enamino ester of (III) is used, in the absence of ammonia or ammonium salt to give (I), wherein in the above formulas, R¹ to R⁶ are as follows: R¹ is a group represented by the general formula (II) where A representes in which n is an integer of 0 to 2 and R¹¹ and R¹² are same or different and are selected from a group consisting of hydrogen, alkyl, alkoxycarbonyl, phenyl, alkoxy, alkoxyalkyl, phenoxy and aralkyloxy or R¹¹ and R¹² form an alkylene group with 3 to 7 carbon atoms when n is 1; or, when n is 2, both R¹¹ and R¹² are hydrogens or two R¹¹ form a double bond while R¹² means hydrogen; and R⁷, R⁸, R⁹ and R¹⁰ are same or different and are hydrogen or alkyl; R² represents lower alkyl; R³ represents a substituent selected from a group consisting of: hydrogen; hydrocarbon with 1 to 10 carbon atoms which is branched or nonbranched; in chain , ring or a combination of them; containing 0 to 4 unsaturated bonds, and is with or without one or more of substituent(s) selected from a group consisting of alkoxy, aryloxy, aralkyloxy, amino, alkyl-substituted amino, alkylthio, pyridyl, furfuryl and tetrahydrofurfuryl; a group of a formula in which X is nitrogen or oxygen; R¹³ is lower alkyl or lower alkenyl when X is nitrogen and, when X is oxygen, R¹³ does not exist; R¹⁴ is hydrogen, alkyl or phenyl with or without alkyl substituent(s); ℓ is an integer of 0 to 2; and m is an integer of 1 to 4; a group of a formula in which q is an integer of 0 to 2 and r is an integer of 0 to 2; and a group of a formula in which t is an integer of 1 to 2 and Y is oxygen, R⁴ is lower alkyl; R⁵ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl, and alkylsulfonyl; and R⁶ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl and alkylsulfonyl. A method of Claim 22 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or more lower alkyl substituents R² is lower alkyl of 1 to 4 carbon atoms R³ is lower alkyl with 1 to 5 carbon atoms or 2-(N-benzyl-N-lower alkylamino)-alkyl R⁴ is lover alkyl of 1 to 4 carbon atoms R⁵ is nitro, halogen, trihalomethyl or dihaloalkoxy R⁶ is hydrogen or halogen. A method of Claim 23 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or two lover alkyl substituents of 1 to 3 carbon atoms R² is methyl, ethyl, propyl or isopropyl R³ is lower alkyl of 1 to 4 carbon atoms or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl, ethyl, propyl or isopropyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy R⁶ is hydrogen or chlorine. A method of Claim 24 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl, ethyl or isopropyl substituent at 5-position R² is methyl R³ is methyl, ethyl or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy at 2- or 3-position R⁶ is hydrogen or chlorine at 2-position. A method of Claim 25 in which R¹ is 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl substituent at 5-position R² is methyl R³ is methyl or ethyl R⁴ is methyl R⁵ is nitro or trifluoromethyl at 2- or 3-position R⁶ is hydrogen. Claims for the following Contracting State : AT A method of manufacturing 1,4-dihydropyridine-3-carboxylate represented by the following general formula (I) and salts thereof, characterized in that, a benzaldehyde compound of a formula (V) is made to react with a compound of a formula (III) in organic solvent to cause dehydration-condensation giving a compound of a formula (VI) and said (VI) is made to react with a compound of a formula (IV) or enamino ester thereof in an organic solvent or, without isolating (VI), all of (V), (III) and (IV) (or enamino ester of (IV) ) are made present in an organic solvent and the reaction is conducted in the presence of ammonia or ammonium salt in case (IV) is used and, in case enamino ester of (IV) is used, in the absence of ammonia or ammonium salt to afford (I), wherein in the above formulas, R¹ to R⁶ are as follows: R¹ is a group represented by the general formula (II) where A representes in which n is an integer of 0 to 2 and R¹¹ and R¹² are same or different and are selected from a group consisting of hydrogen, alkyl, alkoxycarbonyl, phenyl, alkoxy, alkoxyalkyl, phenoxy and aralkyloxy or R¹¹ and R¹² form an alkylene group with 3 to 7 carbon atoms when n is 1; or, when n is 2, both R¹¹ and R¹² are hydrogens or two R¹¹ form a double bond while R¹² means hydrogen; and R⁷, R⁸, R⁹ and R¹⁰ are same or different and are hydrogen or alkyl; R² represents lower alkyl; R³ represents a substituent selected from a group consisting of: hydrogen; hydrocarbon with 1 to 10 carbon atoms which is branched or nonbranched; in chain , ring or a combination of them; containing 0 to 4 unsaturated bonds, and is with or without one or more of substituent(s) selected from a group consisting of alkoxy, aryloxy, aralkyloxy, amino, alkyl-substituted amino, alkylthio, pyridyl, furfuryl and tetrahydrofurfuryl; a group of a formula in which X is nitrogen or oxygen; R¹³ is lower alkyl or lower alkenyl when X is nitrogen and, when X is oxygen, R¹³ does not exist; R¹⁴ is hydrogen, alkyl or phenyl with or without alkyl substituent(s); ℓ is an integer of 0 to 2; and m is an integer of 1 to 4; a group of a formula in which q is an integer of 0 to 2 and r is an integer of 0 to 2; and a group of a formula in which t is an integer of 1 to 2 and Y is oxygen, R⁴ is lower alkyl; R⁵ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl, and alkylsulfonyl; and R⁶ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl and alkylsulfonyl. A method of Claim 1 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or more lower alkyl substituents R² is lower alkyl of 1 to 4 carbon atoms R³ is lower alkyl with 1 to 5 carbon atoms or 2-(N-benzyl-N-lower-alkylamino)-alkyl R⁴ is lower alkyl of 1 to 4 carbon atoms R⁵ is nitro, halogen, trihalomethyl or dihaloalkoxy R⁶ is hydrogen or halogen, A method of Claim 2 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or two lower alkyl substituents of 1 to 3 carbon atoms R² is methyl, ethyl, propyl or isopropyl R³ is lower alkyl of 1 to 4 carbon atoms or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl, ethyl, propyl or isopropyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy R⁶ is hydrogen or chlorine. A method of Claim 3 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl, ethyl or isopropyl substituent at 5-position R² is methyl R³ is methyl, ethyl or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy at 2- or 3-position R⁶ is hydrogen or chlorine at 2-position, A method of Claim 4 in which R¹ is 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl substituent at 5-position R² is methyl R³ is methyl or ethyl R⁴ is methyl R⁵ is nitro or trifluoromethyl at 2- or 3-position R⁶ is hydrogen. A method of manufacturing 1,4-dihydropyridine-3-carboxylate of the following general formula (I) or salts thereof, characterized in that, a benzaldehyde compound of a general formula (V) is subjected to a dehydration-condensation in an organic solvent with a compound represented by a formula (IV) to give a compound represented by a formula (VII) and then the compound (VII) is made to react with a compound of a formula (III) or enamino ester of (III) in an organic solvent or, without isolation of the compound (VII), all of (V), (IV) and (III) or enamino ester thereof are at the same time made present in an organic solvent and made to react in the presence of ammonia or ammonium salt when (III) is used and, when enamino ester of (III) is used, in the absence of ammonia or ammonium salt to give (I), wherein in the above formulas, R¹ to R⁶ are as follows: R¹ is a group represented by the general formula (II) where A representes in which n is an integer of 0 to 2 and R¹¹ and R¹² are same or different and are selected from a group consisting of hydrogen, alkyl, alkoxycarbonyl, phenyl, alkoxy, alkoxyalkyl, phenoxy and aralkyloxy or R¹¹ and R¹² form an alkylene group with 3 to 7 carbon atoms when n is 1; or, when n is 2, both R¹¹ and R¹² are hydrogens or two R¹¹ form a double bond while R¹² means hydrogen; and R⁷, R⁸, R⁹ and R¹⁰ are same or different and are hydrogen or alkyl; R² represents lower alkyl; R³ represents a substituent selected from a group consisting of: hydrogen; hydrocarbon with 1 to 10 carbon atoms which is branched or nonbranched; in chain , ring or a combination of them; containing 0 to 4 unsaturated bonds, and is with or without one or more of substituent(s) selected from a group consisting of alkoxy, aryloxy, aralkyloxy, amino, alkyl-substituted amino, alkylthio, pyridyl, furfuryl and tetrahydrofurfuryl; a group of a formula in which X is nitrogen or oxygen; R¹³ is lower alkyl or lower alkenyl when X is nitrogen and, when X is oxygen, R¹³ does not exist; R¹⁴ is hydrogen, alkyl or phenyl with or without alkyl substituent(s); ℓ is an integer of 0 to 2; and m is an integer of 1 to 4; a group of a formula in which q is an integer of 0 to 2 and r is an integer of 0 to 2; and a group of a formula in which t is an integer of 1 to 2 and Y is oxygen, R⁴ is lower alkyl; R⁵ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl, and alkylsulfonyl; and R⁶ is a group selected from a group consisting of hydrogen, nitro, cyano, trifluoromethyl, difluoromethoxy, halogen, azide, alkoxycarbonyl, aminocarbonyl, sulfamyl and alkylsulfonyl. A method of Claim 6 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or more lower alkyl substituents R² is lower alkyl of 1 to 4 carbon atoms R³ is lower alkyl with 1 to 5 carbon atoms or 2-(N-benzyl-N-lower alkylamino)-alkyl R⁴ is lower alkyl of 1 to 4 carbon atoms R⁵ is nitro, halogen, trihalomethyl or dihaloalkoxy R⁶ is hydrogen or halogen. A method of Claim 7 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without one or two lower alkyl substituents of 1 to 3 carbon atoms R² is methyl, ethyl, propyl or isopropyl R³ is lower alkyl of 1 to 4 carbon atoms or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl, ethyl, propyl or isopropyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy R⁶ is hydrogen or chlorine. A method of Claim 8 in which R¹ is 3-oxo-2,4-dioxa-3-phosphaspiro[5.5]undecan-3-yl or 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl, ethyl or isopropyl substituent at 5-position R² is methyl R³ is methyl, ethyl or 2-(N-benzyl-N-methylamino)ethyl R⁴ is methyl R⁵ is nitro, chlorine, trifluoromethyl or difluoromethoxy at 2- or 3-position R⁶ is hydrogen or chlorine at 2-position. A method of Claim 9 in which R¹ is 2-oxo-1,3,2-dioxaphosphorinan-2-yl with or without methyl substituent at 5-position R² is methyl R³ is methyl or ethyl R⁴ is methyl R⁵ is nitro or trifluoromethyl at 2- or 3-position R⁶ is hydrogen.

Inventors: KIMURA, KIYOSHI, MORITA, IWAO
Applicants: NIPPON SHINYAKU COMPANY, LIMITED
Application year: 1985
Main classification: C07F9
IPC codes: A61P9, A61K31, C07F9