公开(公告)号：US4002762A

公开(公告)日：1977-01-11

申请号：US544934

申请日：1975-01-28

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： C07D211/90 ,  A61K31/455

CPC分类号： C07D211/90 ,  Y10S514/929

摘要： 3-Substituted 2-amino-3,4-dihydropyridine-3-carboxylic acid esters are produced by reacting 2-amino-1,4-dihydropyridine-3-carboxylic acid esters with an alkylating agent in the presence of an inert organic solvent at a temperature of from 20.degree. C to 200.degree. C. The compounds, of which 2-amino-3,6-dimethyl-4-phenyl-3,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is a typical embodiment, possess antihypertensive and coronary dilating properties.

摘要翻译： 3-取代的2-氨基-3,4-二氢吡啶-3-羧酸酯是通过2-氨基-1,4-二氢吡啶-3-羧酸酯与烷基化剂在惰性有机溶剂的存在下反应来制备的 温度为20℃至200℃。其中2-氨基-3,6-二甲基-4-苯基-3,4-二氢吡啶-3,5-二羧酸二乙酯是其典型的实例， 具有抗高血压和冠状动脉扩张性能。

公开(公告)号：US4001235A

公开(公告)日：1977-01-04

申请号：US503345

申请日：1974-09-05

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： C07D211/90 ,  C07D215/54 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04 ,  C07D239/26

CPC分类号： C07D401/04 ,  C07D211/90 ,  C07D215/54 ,  C07D405/04 ,  C07D409/04

摘要： 2-Amino-1,4-dihydropyridines bearing a carbonyl function in the 5-position and being optionally substituted by lower alkyl or phenyl in the 6-position, and the corresponding 2-amino-1,4,5,6,7,8-hexahydro-5-oxoquinolines, which derivatives are further substituted by a carbonyl group in the 3-position and optionally substituted in the 4-position by lower alkyl, phenyl, substituted phenyl or a heterocyclic group are antihypertensive agents and coronary vessel dilators. The compounds, of which 2-amino-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3,5-diethyl ester is a representative embodiment, are prepared through condensation of an ylideneacetoacetic acid ester and an amidine.

公开(公告)号：US3981893A

公开(公告)日：1976-09-21

申请号：US578465

申请日：1975-05-19

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： A61K31/35 ,  C07D309/22 ,  C07D409/04

CPC分类号： C07D309/22 ,  A61K31/35 ,  C07D409/04

摘要： 2-Amino-4 H-pyrane derivatives of the formula ##SPC1##WhereinR.sup.1 and R.sup.2 are the same or different and each is hydrogen or straight- or branched-chain alkyl;R.sup.3 is straight- or branched-chain alkyl, phenyl or --COOR' wherein R' is a straight, branched or cyclic saturated or unsaturated aliphatic hydrocarbon;R.sup.4 is straight, branched or cyclic alkyl or alkenyl, aryl unsubstituted or substituted by 1, 2 or 3 of the same or different substituents selected from the group consisting of alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl, carbalkoxy, and --SO.sub.n alkyl wherein n is 0, 1 or 2, orR.sup.4 is naphthyl, quinolyl, pyridyl, thienyl or furyl unsubstituted or substituted by alkyl, alkoxy or halogen;R.sup.5 is straight, branched or cyclic alkyl or --OR" wherein R" is a straight, branched or cyclic hydrocarbon or said hydrocarbon interrupted by 1 or 2 oxygen atoms; andR.sup.6 is hydrogen or alkyl;Are useful for their strong coronary action and as antihypertensive agents.

摘要翻译： 式WHEREIN R1和R2的2-氨基-4H-吡喃衍生物相同或不同，各自为氢或直链或支链烷基; R3是直链或支链烷基，苯基或-COOR'，其中R'是直链，支链或环状的饱和或不饱和脂族烃; R4是直链，支链或环状的烷基或链烯基，未被取代或被1,2或3个相同或不同的选自烷基，烷氧基，卤素，硝基，氰基，三氟甲基，烷氧羰基和-SOn 烷基，其中n为0,1或2，或R4为萘基，喹啉基，吡啶基，噻吩基或呋喃基，未取代或被烷基，烷氧基或卤素取代; R5是直链，支链或环状烷基或-OR“，其中R”是直链，支链或环状烃或被1或2个氧原子间断的所述烃; R6为氢或烷基; 有用于其强大的冠状动脉和抗精神病药。

公开(公告)号：US3951994A

公开(公告)日：1976-04-20

申请号：US468458

申请日：1974-05-09

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： A61K31/395 ,  A61K31/44 ,  C07D455/02 ,  C07D471/04 ,  C07D213/57

CPC分类号： C07D471/04 ,  A61K31/395 ,  A61K31/44 ,  C07D455/02 ,  Y10S514/929

摘要： 1,4-Dihydropyridines bearing carbonyl functions in the 3- and 5-positions, being optionally substituted by lower alkyl in the 6-position, being substituted in the 4-position by lower alkyl, phenyl, substituted phenyl or a heterocyclic group, and being fused through the 1- and 2-positions to a five, six or seven membered cycloalkyl ring, one methylene group of which can be replaced by sulfur, oxygen imino or alkylimino, are antihypertensive agents and coronary vessel dilators. The compounds, of which 6-methyl-4-(3-nitrophenyl)-1,2-pentamethylene-1,4-dihydropyridine-3,5-dicarboxylic acid 3,5-diethyl ester is a representative embodiment, are prepared through condensation of an ylideneacetoacetic acid ester and a cyclic enamino carbonyl derivative.

摘要翻译： 在3-位和5-位具有羰基官能团的1,4-二氢吡啶，任选被6位的低级烷基取代，在4-位被低级烷基，苯基，取代的苯基或杂环基取代，和 通过1-和2-位融合成五，六或七元环烷基环，其中一个亚甲基可以被硫，氧亚氨基或烷基亚氨基取代，是抗高血压剂和冠状血管扩张剂。 其中6-甲基-4-（3-硝基苯基）-1,2-戊烯-1,4-二氢吡啶-3,5-二羧酸3,5-二乙酯的代表性实施例是通过缩合 的亚乙酰乙酸酯和环状氨基羰基衍生物。

公开(公告)号：US3932646A

公开(公告)日：1976-01-13

申请号：US399387

申请日：1973-09-21

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： A61K31/455

CPC分类号： A61K31/455 ,  Y10S514/929

摘要： Pharmaceutical compositions containing unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylate as the active ingredient and methods of using same. The said ingredients are unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylic acid which are substituted at position-4 of the dihydropyridine ring by phenyl or a substituted phenyl moiety. The compositions have cardiovascular activity which makes them useful for effecting coronary vascular dilation and in the treatment of hypertension.

摘要翻译： 含有1,4-二氢吡啶3,5-二羧酸不对称酯作为活性成分的药物组合物及其使用方法。 所述成分是1,4-二氢吡啶3,5-二羧酸的不对称酯，它们在二氢吡啶环的4位被苯基或取代的苯基部分取代。 该组合物具有心血管活性，使其可用于实现冠状动脉血管扩张和治疗高血压。

公开(公告)号：US4136187A

公开(公告)日：1979-01-23

申请号：US518283

申请日：1974-10-29

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： C07D211/90 ,  A61K31/455

CPC分类号： C07D211/90 ,  Y10S514/929

摘要： 4,5-Dihydropyridines bearing an N,N-disubstituted amino group in the 2-position, carbonyl functions in the 3- and 5-positions and being optionally substituted in the 6-position by lower alkyl or phenyl and, in the 4-position by lower alkyl, phenyl, substituted phenyl or a heterocyclic group, are antihypertensive agents and coronary vessel dilators. The compounds, of which 2-pyrrolidino-6-methyl-4-(3-nitrophenyl)-4,5-dihydropyridine-3,5-dicarboxylic acid 3,5-diethyl ester is a representative embodiment, are prepared through condensation of an ylideneacetoacetic acid ester and a substituted 3,3-diaminoacrylate.

公开(公告)号：US3989708A

公开(公告)日：1976-11-02

申请号：US526510

申请日：1974-11-25

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： C07D239/20 ,  C07D211/90 ,  C07D213/55 ,  C07D215/14

CPC分类号： C07D211/90 ,  Y10S514/929

摘要： 2-Amino-1,4-dihydropyridines bearing an ester carbonyl function in the 3-position, being optionally substituted by lower alkyl in the 5-position, and being substituted in the 4- and 6-positions by lower alkyl, phenyl, substituted phenyl or a heterocyclic group are antihypertensive agents and coronary vessel dilators. The compounds, of which 2-amino-6-methyl-4-(3-chlorophenyl)-1,4-dihydropyridine-3 carboxylic acid ethyl ester is a representative embodiment, are prepared through condensation of an .alpha.-B-unsaturated ketone and an amidine.

摘要翻译： 3-位上具有酯羰基官能团的2-氨基-1,4-二氢吡啶，任选被5-位的低级烷基取代，并在4-和6-位被低级烷基，苯基，取代的 苯基或杂环基是抗高血压剂和冠状血管扩张剂。 其中2-氨基-6-甲基-4-（3-氯苯基）-1,4-二氢吡啶-3-羧酸乙酯的代表性实施方案是通过α-β-不饱和酮和 脒

公开(公告)号：US3957998A

公开(公告)日：1976-05-18

申请号：US455258

申请日：1974-03-27

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： A61K31/455 ,  C07D211/90 ,  C07D401/04 ,  C07D405/04

CPC分类号： C07D401/04 ,  A61K31/455 ,  C07D211/90 ,  C07D405/04 ,  Y10S514/929

摘要： 2,6-Diamino-1,4-dihydropyridines bearing carbonyl functions in the 3- and 5-positions and being substituted in the 4-position by lower alkyl, phenyl, substituted phenyl or a heterocyclic group are antihypertensive agents and coronary vessel dilators. The compounds, of which 2,6-diamino-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3,5-diethyl ester is a representative embodiment, are prepared through condensation of an amidine with either an aldehyde or an ylidenecyanoacetoacetic acid ester.

摘要翻译： 在3-和5-位上具有羰基官能团的2,6-二氨基-1,4-二氢吡啶是低级烷基，苯基，取代的苯基或杂环基在4-位上被取代的是抗高血压剂和冠状血管扩张剂。 其中2,6-二氨基-4-（3-硝基苯基）-1,4-二氢吡啶-3,5-二羧酸3,5-二乙酯是一个代表性的实施方案，通过脒与 醛或亚基甲酰乙酰乙酸酯。

公开(公告)号：US3951993A

公开(公告)日：1976-04-20

申请号：US453863

申请日：1974-03-22

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： C07D211/90 ,  C07D405/04 ,  C07D213/32

CPC分类号： C07D405/04 ,  C07D211/90

摘要： 2-Amino-4,5-dihydropyridines-3,5-dicarboxylates substituted by lower alkoxy or lower alkylthio in the 6-position and optionally substituted in the 4-position by lower alkyl, phenyl, substituted phenyl or a heterocyclic group are antihypertensive agents and coronary vessel dilators. The compounds, of which 2-amino-4-(3-nitrophenyl)-6-ethoxy-4,5-dihydropyridine-3,5-dicarboxylic acid diethyl ester is a representative embodiment, are prepared through condensation of an aldehyde and a 3-aminoacrylate bearing an alkoxy or alkylthio group in the 3-position.

公开(公告)号：US3951991A

公开(公告)日：1976-04-20

申请号：US531599

申请日：1974-12-11

申请人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

发明人： Horst Meyer ,  Friedrich Bossert ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： A61K31/455 ,  C07D401/04 ,  C07D409/04 ,  C07D213/71

CPC分类号： C07D401/04 ,  A61K31/455 ,  C07D409/04 ,  Y10S514/929

摘要： 3,4-Dihydropyridones of the formula ##SPC1##Wherein R.sup.1 is hydrogen, straight or branched chain alkyl, or --COOR' wherein R' is a straight, branched or cyclic, saturated or unsaturated hydrocarbon or said hydrocarbon interrupted by 1 or 2 oxygen atoms; R.sup.2 is a straight, branched or cyclic, saturated or unsaturated hydrocarbon, aryl unsubstituted or substituted by 1 to 3 of the same or different substitutents selected from the group consisting of alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl, carbalkoxy and SO.sub.n --alkyl wherein n is 0, 1 or 2, or naphthyl, quinolyl, isoquinolyl, pyridyl, pyrimidyl, thenyl, furyl or pyrryl unsubstituted or substituted by 1 or more substituents selected from the group consisting of alkyl, alkoxy and halogen; and R.sup.3 is a straight or branched chain hydrocarbon or said hydrocarbon interrupted by 1 or 2 oxygen atoms, are produced by reacting an .alpha.,.beta.-unsaturated carboxylic acid ester of the formula ##EQU1## wherein R is alkyl, alkenyl or alkynyl, and R.sup.1 and R.sup.2 are as above defined, with an amidine of the formula ##EQU2## wherein R.sup.3 is as above defined. These compounds are useful as coronary agents and as anti-hypertensive agents.

摘要翻译： 式WHEREIN R 1是氢，直链或支链烷基或-COOR'的3,4-二氢吡啶酮，其中R'是直链，支链或环状，饱和或不饱和烃或被1或2个氧原子间断的烃; R2是直链，支链或环状的饱和或不饱和的烃，未取代或被1至3个选自烷基，烷氧基，卤素，硝基，氰基，三氟甲基，碳烷氧基和SO n- 烷基，其中n为0,1或2，或萘基，喹啉基，异喹啉基，吡啶基，嘧啶基，噻吩基，呋喃基或吡啶基，未取代或被一个或多个选自烷基，烷氧基和卤素的取代基取代; 并且R3是直链或支链烃或被1或2个氧原子间断的所述烃通过使式R 1 R 2 -CH = C ANGLE COOR的α，β-不饱和羧酸酯反应制备，其中R是烷基，烯基 或炔基，并且R 1和R 2如上所定义，与式H 2 N AN CLE C-CH 2 COOR 3 HN的脒反应，其中R 3如上所定义。 这些化合物可用作冠状动脉剂和抗高血压剂。