公开(公告)号：US4081596A

公开(公告)日：1978-03-28

申请号：US633396

申请日：1975-11-19

申请人： Eike Moller ,  Karl Meng ,  Egbert Wehinger ,  Harald Horstmann

发明人： Eike Moller ,  Karl Meng ,  Egbert Wehinger ,  Harald Horstmann

IPC分类号： C07D231/20 ,  C07D231/24 ,  C07D231/52 ,  A61K31/415

CPC分类号： C07D231/52 ,  C07D231/20 ,  C07D231/24 ,  Y10S514/869

摘要： 1-Substituted pyrazol-5-ones of the formula ##STR1## and pharmaceutically acceptable, nontoxic salts thereof, wherein R is hydrogen, amino, alkyl, alkenyl, phenyl or trifluoromethyl;R.sup.1 is hydrogen, alkyl, alkenyl, unsubstituted or substituted aryl or unsubstituted or substituted aralkyl;R.sup.2 is alkyl; andR.sup.3 is pyridyl, aryl or substituted by:A. 1 or 2 of the same or different substitutents selected from the group consisting of halogen, trifluoromethyl, lower alkyl, lower alkenyl and lower alkoxy;B. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms;C. mono(lower alkyl)amino, di(lower alkyl)amino, trifluoromethoxy, nitro, cyano, carbamoyl, lower alkylcarbamoyl, di(lower alkyl)carbamoyl, sulphamyl, lower alkylsulphamyl, di(lower alkyl)sulphamyl, or --SO.sub.n lower alkyl wherein n is 0, 1 or 2;D. a member selected from the group consisting of mono(lower alkyl)amino, di(lower alkyl)amino, trifluoromethyl, nitro, cyano, carbamoyl, lower alkylcarbamoyl, di(lower alkyl)carbamoyl, sulphamyl, lower alkylsulphamyl, di(lower alkyl) sulphamyl, and --SO.sub.n lower alkyl wherein n is 0, 1 or 2, and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkoxy, halogen, and trifluoromethyl; orE. a fused, saturated or unsaturated 5-, 6-, or 7-membered ring or said ring containing 1 or 2 oxygen or sulphur atoms;ARE USEFUL FOR THEIR DIURETIC, SALURETIC, ANTIHYPERTENSIVE AND ANTITHROMBOTIC EFFECTS.

公开(公告)号：US4069334A

公开(公告)日：1978-01-17

申请号：US672500

申请日：1976-03-31

申请人： Eike Moller ,  Karl Meng ,  Egbert Wehinger ,  Harald Horstmann

发明人： Eike Moller ,  Karl Meng ,  Egbert Wehinger ,  Harald Horstmann

IPC分类号： C07D231/20 ,  A61K31/415

CPC分类号： C07D231/20 ,  Y10S514/869

摘要： Pyrazole derivatives of the formula: ##STR1## and pharmaceutically acceptable nontoxic salts thereof WHEREINR is hydrogen, trifluoromethyl or alkyl;R.sup.1 is hydrogen or alkyl;R.sup.2 is alkyl;R.sup.3 is aryl substituted by:A. one or two of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl, alkenyl and alkoxy;B. one substituent selected from the group consisting of alkylamino, dialkylamino wherein the alkyl moieties may form a heterocyclic ring with the nitrogen atom to which they are attached, cycloalkyl, cycloalkenyl, trifluoromethoxy, nitro, cyano, carbonamido unsubstituted or substituted by 1 or 2 alkyl moieties, sulphonamido unsubstituted or substituted by 1 or 2 alkyl moieties, and SO.sub.n -alkyl wherein n is 0, 1 or 2;C. one substituent selected from the group consisting of alkylamino, dialkylamino wherein the alkyl moieties may form a heterocyclic ring with the nitrogen atom to which they are attached, cycloalkyl, cycloalkenyl, trifluoromethoxy, nitro, cyano, carbonamido unsubstituted or substituted by 1 or 2 alkyl moieties, sulphonamido unsubstituted or substituted by 1 or 2 alkyl moieties, and SO.sub.n -alkyl wherein n is 0, 1 or 2, and by one or two substituents selected from the group consisting of alkyl, alkenyl, alkoxy, halogen and trifluoromethyl; orD. two substituents on the aryl moiety form a branched or unbranched saturated or unsaturated 5- to 7-membered isocyclic or heterocyclic ring, which ring can also have 1 or 2 oxygen atoms or sulfur atoms; or SO.sub.n -alkyl wherein n is 0, 1 or 2; orR.sup.3 is naphthyl or pyridyl; andR.sup.4 is R.sup.5 CO wherein R.sup.5 is alkyl unsubstituted or substituted by 1, 2 or 3 halogen moieties, by alkoxy, or by mono- or dialkylamino; lower alkoxy; dialkylamino; thiophene; phenyl unsubstituted or substituted by 1 or 2 alkyl, trifluoromethyl, alkoxy, nitro or halogen moieties; or a 5- to 7-membered heterocycle unsubstituted or substituted by 1 or 2 halogen, alkyl or nitro moieties; orR.sup.4 is Z-SO.sub.2 wherein Z is alkyl, phenyl or phenyl substituted by 1 or 2 alkyl, halogen, nitro, trifluoromethyl or trifluoromethylsulphonyl moieties; or dichloroquinoxalinyl.The pyrazole derivatives and their salts are useful as diuretics, saluretics and antihypertensives.

摘要翻译： 下式的吡唑衍生物：其中R为氢，三氟甲基或烷基; R1是氢或烷基; R2是al

公开(公告)号：US4061653A

公开(公告)日：1977-12-06

申请号：US637861

申请日：1975-12-04

申请人： Harald Horstmann ,  Karl Meng ,  Egbert Wehinger

发明人： Harald Horstmann ,  Karl Meng ,  Egbert Wehinger

IPC分类号： C07D231/52 ,  C07D231/38 ,  A61K31/415

CPC分类号： C07D231/52 ,  Y10S514/822 ,  Y10S514/869

摘要： 1-Substituted-3-amino-pyrazol-5-ones of the formula ##STR1## or a pharmaceutically acceptable non-toxic salt thereof wherein R is A. PHENYL SUBSTITUTED BY ONE OR TWO IDENTICAL OR DIFFERENT SUBSTITUENTS SELECTED FROM THE GROUP CONSISTING OF ALKYL, PHENYL, TRIFLUOROMETHYL, TRIFLUOROMETHOXY, NITRO, CYANO, FLUORO, BROMO, IODO, LOWER ALKYLAMINO, A CARBONAMIDO MOIETY OF THE FORMULA ##STR2## and a sulphonamido moiety of the formula ##STR3## wherein R.sub.1 and R.sub.2 are each hydrogen or straight or branched chain alkyl of 1 to 4 carbon atoms, or R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached may be linked together to form a 5-, 6- or 7-membered heterocyclic ring wherein the nitrogen atom is the only heteroatom or wherein oxygen is also present as a ring member;B. phenyl having an annellated branched or un-branched, saturated or unsaturated, 5-, 6- or 7-membered isocyclic or heterocyclic ring wherein the heterocyclic ring has one or more oxygen heteroatoms and/or one or more sulphur heteroatoms, said phenyl ring being otherwise unsubstituted or chlorosubstituted;C. phenyl substituted by SO.sub.n -alkyl wherein n is zero, 1 or 2, straight or branched chain alkoxy or - O -(CH.sub.2).sub.n',-N(alkyl).sub.2 wherein n' is 2 or 3;D. phenyl substituted by 2 identical substituents selected from the group consisting of alkoxy of 1 to 4 carbon atoms and trifluoromethyl;E. phenyl having 2 different substituents selected from the group consisting of alkyl, phenyl, halogen, alkoxy, trifluoromethyl, trifluoromethoxy, lower alkylamino, nitro, cyano, --SO.sub.n --alkyl wherein n is zero, 1 or 2, a carbonamido moiety of the formula ##STR4## and a sulphonamido of the formula ##STR5## wherein R.sub.3 and R.sub.4 are each hydrogen or alkyl; F. TRICHLOROPHENYL;G. naphthyl having 1 or 2 identical or different substituents selected from the group consisting of halogen and alkyl; orh. unsubstituted .beta.-naphthyl, anthyryl or phenanthryl, are produced by reacting a hydrazine of the formula R--CH.sub.2 --NH--NH.sub.2 wherein R is as above defined with an acetic acid derivative of the formula ##STR6## wherein X is hydroxy, alkoxy, aralkoxy, amino or alkylamino; and either a. Y' is hydrogen and Y" is cyano;b. Y' and Y" together form the moiety ##STR7## wherein Y is alkoxy, aryloxy, aralkoxy, alkylmercapto, aralkylmercapto or amino.The 1-Substituted-3-amino-pyrazol-5-ones and their salts exhibit strong diuretic, saluretic and anti-hypertensive effects.

公开(公告)号：US4045571A

公开(公告)日：1977-08-30

申请号：US633601

申请日：1975-11-20

申请人： Eike Moller ,  Karl Meng ,  Egbert Wehinger ,  Harald Horstmann

发明人： Eike Moller ,  Karl Meng ,  Egbert Wehinger ,  Harald Horstmann

IPC分类号： C07D231/20 ,  C07D231/52 ,  A61K31/415

CPC分类号： C07D231/20 ,  C07D231/52

摘要： Pharmaceutical compositions useful for effecting diuresis and saluresis and for treating hypertension in humans and animals are produced by combining a pyrazol-5-one of the formula: ##STR1## or a pharmaceutically acceptable nontoxic salt thereof wherein R is hydrogen, lower alkyl or amino;X is methylene, ethylene, methylene wherein 1 hydrogen atom is substituted by lower alkyl, or ethylene wherein 1 hydrogen atom is substituted by lower alkyl or 1 hydrogen atom on each of the two carbon atoms is substituted by lower alkyl;Y is a direct bond, oxygen or sulphur, provided that when X is methylene wherein 1 hydrogen atom is substituted by alkyl of 1 to 4 carbon atoms, Y is a direct bond; Z is aryl of 6 to 10 carbon atoms unsubstituted or substituted by:A. 1 to 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, and alkenoxy of 2 to 4 carbon atoms; cycloalkenyl of 5, 6 or 7 carbon atoms;C. lower alkylamino, dilower alkylamino, trifluoromethoxy, nitro, cyano, carbamoyl, lower alkylcarbamoyl, dilower alkylcarbamoyl, sulphamyl, lower alkylsulphamyl, dilower alkylsulphamyl, --SO.sub.n --lower alkyl wherein n is 0, 1 or 2, or said dialkylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulphamyl, alkylsulphamyl, or dialkylsulphamyl, the nitrogen atom of which is a member of a 5-, 6- or 7-membered ring or said ring which additionally contains an oxygen atom;D. lower alkylamino, dilower alkylamino, trifluoromethoxy, nitro, cyano, carbamoyl, lower alkylcarbamoyl, dilower alkylcarbamoyl, sulphamyl, lower alkylsulphamyl, dilower alkylsulphamyl, or --SO.sub.n --lower alkyl wherein n is 0, 1 or 2, and 1 or 2 substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkenoxy of 2 to 4 carbon atoms, halogen and trifluoromethyl; orE. a fused, saturated or unsaturated 5-, 6- or 7-membered ring or said ring additionally containing 1 or 2 oxygen or sulphur atoms, in combination with a pharmaceutically acceptable nontoxic inert diluent or carrier.The compositions are preferably administered orally or parenterally and in the latter case, sterile or isotonic aqueous solutions are preferred.

摘要翻译： 通过将以下结构式的吡唑-5-酮或其药学上可接受的无毒盐（其中R为氢，低级烷基或氨基）组合而制备用于实现利尿和黄疸以及用于治疗人和动物高血压的药物组合物。 X是亚甲基，亚乙基，亚甲基，其中1个氢原子

公开(公告)号：US4044141A

公开(公告)日：1977-08-23

申请号：US654278

申请日：1976-02-02

申请人： Friedrich Bossert ,  Egbert Wehinger ,  Kurt Stoepel ,  Wulf Vater ,  Stanislav Kazda

发明人： Friedrich Bossert ,  Egbert Wehinger ,  Kurt Stoepel ,  Wulf Vater ,  Stanislav Kazda

IPC分类号： C07D211/02 ,  A61K31/4427 ,  A61K31/455 ,  A61P9/08 ,  A61P9/12 ,  C07D211/90 ,  C07D401/04 ,  C07D213/55

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

摘要： 1,4-Dihydropyridines characterized by a carbo(arylalkoxy) group in the 5-position, an aryl group in the 4-position and a alkanoyl or carbalkoxy group in the 3-position and further optionally substituted in the 1,2 and 6-positions are coronary dilating, spasmolytic and hypotensive agents. The compounds, of which 2,6-dimethyl-3-carbomethoxy-4-(2-nitrophenyl)-5-carbobenzoxy-1,4-dihydropyridine is a representative embodiment, are prepared through the reaction of an ylidene-.beta.-dicarbonyl compound, which may be generated in situ from the corresponding .beta.-dicarbonyl compound and an aldehyde, and an enaminocarboxylic acid ester, which may also be generated in situ from a .beta.-dicarbonyl compound and an amine.

摘要翻译： 其特征在于5-位上的碳（芳基烷氧基）基团，4-位上的芳基和3-位的烷酰基或烷氧基，并且进一步任选被1,2和6-位取代的1,4-二氢吡啶， 位置是冠状动脉扩张，解痉和降血压药。 其中2,6-二甲基-3-甲酯基-4-（2-硝基苯基）-5-苄氧羰基-1,4-二氢吡啶的代表性实例是通过亚基-β-二羰基 化合物，其可以由相应的β-二羰基化合物和醛和烯氨基羧酸酯原位产生，其也可以由β-二羰基化合物和胺原位产生。

公开(公告)号：US4020178A

公开(公告)日：1977-04-26

申请号：US585963

申请日：1975-06-11

申请人： Friedrich Bossert ,  Egbert Wehinger ,  Wulf Vater ,  Kurt Stoepel

发明人： Friedrich Bossert ,  Egbert Wehinger ,  Wulf Vater ,  Kurt Stoepel

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

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

摘要： A new class of 1,4-dihydropyridines which are characterized by the presence of ester substitutes at positions 3 and 5 of the nucleus and by the presence of an alkoxyalkyl have particular application as coronary dilators, antifibrillators, anti-hypertensives, and as muscular and vascular spasmolytics.

摘要翻译： 特征在于在核的位置3和5处存在酯取代基和存在烷氧基烷基的新类型的1,4-二氢吡啶具有特别的用途作为冠状动脉扩张剂，抗纤维化剂，抗高血压药，以及肌肉和 血管解痉药。

公开(公告)号：US3974278A

公开(公告)日：1976-08-10

申请号：US576724

申请日：1975-05-12

申请人： Friedrich Bossert ,  Egbert Wehinger ,  Wulf Vater ,  Kurt Stoepel

发明人： Friedrich Bossert ,  Egbert Wehinger ,  Wulf Vater ,  Kurt Stoepel

IPC分类号： C07D401/04 ,  C07D213/55 ,  A01N9/22

CPC分类号： C07D401/04

摘要： A new class of 1,4-dihydropyridines which are characterized by the presence of ester substitutes at positions 3 and 5 of the nucleus and by the presence of an alkoxyalkyl at position 2. The products exhibit coronary activity and have particular application as coronary dilators, anti-fibrillators, anti-hypertensives, and as muscular and vascular spasmolytics.

摘要翻译： 一类新的1,4-二氢吡啶，其特征在于在核的位置3和5处存在酯取代基，并且在位置2处存在烷氧基烷基。产物表现出冠状动力，并且具有特定用途作为冠状动脉扩张器， 抗纤维化器，抗高血压药，以及肌肉和血管解痉药。