公开(公告)号：US4029692A

公开(公告)日：1977-06-14

申请号：US671381

申请日：1976-03-29

申请人： Leo Alig ,  Robert Nickolson ,  Rudolf Wiechert ,  Andor Furst ,  Klaus Kieslich ,  Marcel Muller ,  Ulrich Kerb

发明人： Leo Alig ,  Robert Nickolson ,  Rudolf Wiechert ,  Andor Furst ,  Klaus Kieslich ,  Marcel Muller ,  Ulrich Kerb

IPC分类号： A61K31/185 ,  A61K31/19 ,  A61K31/21 ,  A61K31/215 ,  A61K31/22 ,  A61K31/56 ,  A61P5/38 ,  A61P29/00 ,  C07J63/00 ,  C12P33/02 ,  C07C69/74 ,  C07C61/36 ,  C07C69/16 ,  C07C69/28

CPC分类号： C07J63/008 ,  C07J63/00 ,  Y10S514/87 ,  Y10S514/93

摘要： The present disclosure relates to steroid carboxylic acids and derivatives thereof. More particularly, the disclosure is concerned with D-homosteroid carboxylic acids and their derivatives, a process for the preparation thereof and pharmaceutical compositions containing same. The instant compounds are active endocrinal agents, especially as antiinflammatory agents.

摘要翻译： 本公开涉及类固醇羧酸及其衍生物。 更具体地，本公开涉及D-类固醇类羧酸及其衍生物，其制备方法和含有它们的药物组合物。 本发明化合物是活性内分泌剂，特别是作为抗炎剂。

公开(公告)号：US4348327A

公开(公告)日：1982-09-07

申请号：US276563

申请日：1981-06-23

申请人： Robert Nickolson ,  Ulrich Kerb ,  Rudolf Wiechert ,  Leo Alig ,  Andor Furst ,  Marcel Muller

发明人： Robert Nickolson ,  Ulrich Kerb ,  Rudolf Wiechert ,  Leo Alig ,  Andor Furst ,  Marcel Muller

IPC分类号： C07J3/00 ,  C07J41/00 ,  C07J63/00 ,  C07J9/00

CPC分类号： C07J63/008 ,  C07J3/005 ,  C07J41/0066 ,  C07J41/0094

摘要： 17.alpha.-hyroxy- and 17a.alpha.-hydroxy-D-homoetiocarboxylic acids of the formula ##STR1## wherein n is 1 or 2,A is ##STR2## and R.sub.1 is H or CH.sub.3are prepared by hydrating the corresponding 17-nitriles with a mixture of a lower carboxylic acid and its anhydride in the presence of perchloric acid. The resultant 17.beta.-N-acylcarboxamide is then treated with an alkali metal hydroxide in a polyhydric alcohol at an elevated temperature. The product acids are intermediates, e.g., for the production of steroids having antiinflammatory activity.

摘要翻译： 其中n为1或2的17α-羟基 - 和17α-羟基-D-高聚羧酸，其中n为1或2，A为H，并且R 1为H或CH 3是通过用相应的17-腈水解 在高氯酸存在下，低级羧酸及其酸酐的混合物。 然后在升高的温度下，用多元醇中的碱金属氢氧化物处理所得的17β-酰基羧酰胺。 产物酸是中间体，例如用于生产具有抗炎活性的类固醇。

公开(公告)号：US4472310A

公开(公告)日：1984-09-18

申请号：US359713

申请日：1982-03-11

申请人： Dieter Bittler ,  Henry Laurent ,  Klaus Nickisch ,  Robert Nickolson ,  Rudolf Wiechert

发明人： Dieter Bittler ,  Henry Laurent ,  Klaus Nickisch ,  Robert Nickolson ,  Rudolf Wiechert

IPC分类号： C07J1/00 ,  C07J21/00 ,  C07J53/00 ,  C07J71/00

CPC分类号： C07J21/003 ,  C07J1/0025 ,  C07J53/008 ,  C07J71/001

摘要： The disclosure concerns 5.beta.-hydroxy-.DELTA..sup.6 -steroids of the general formula ##STR1## wherein R.sup.1 is hydrogen, acyl, lower alkyl, or the tetrahydropyranyl residue andR.sup.2, R.sup.3 individually are respectively hydrogen or jointly are methylene andX stands for oxygen, the groupings ##STR2## (wherein R.sup.4 means hydrogen or acyl) and ##STR3## (wherein R.sup.5 means hydrogen or lower alkyl) and a process for the preparation thereof by reacting corresponding 7.alpha.-chloro-5.beta.,6.beta.-epoxy steroids in an inert solvent with metallic zinc in a lower aliphatic carboxylic acid or dilute mineral acid at temperatures of between room temperature and 100.degree. C., preferably at 40.degree.-70.degree. C.The compounds producible by this method are intermediates for the preparation of 3-keto-.DELTA..sup.4 -6.beta.,7.beta.-methylene steroids constituting pharmacologically valuable compounds, for example aldosterone antagonists.

摘要翻译： PCT No.PCT / DE81 / 00111 Sec。 371日期1982年3月11日 102（e）1982年3月11日PCT PCT。 公开号WO82 / 00294 日本1982年2月4日。该公开内容涉及通式为“IMAGE”的5ββ-羟基-DTATA-类固醇，其中R 1为氢，酰基，低级烷基或四氢吡喃基，R2，R3分别为氢或共同 （其中R 4表示氢或酰基）和（其中R 5表示氢或低级烷基）及其制备方法，通过使相应的7α- 氯代-5β，6β-环氧类固醇在惰性溶剂中与金​​属锌在低级脂族羧酸或稀无机酸中在室温至100℃之间，优选40℃-70℃的温度下进行。化合物 通过该方法可生产的是制备构成药理学上有价值的化合物的3-酮-TATA4-6β，7β-亚甲基甾族化合物的中间体，例如醛固酮拮抗剂。

公开(公告)号：US4721729A

公开(公告)日：1988-01-26

申请号：US702092

申请日：1985-02-08

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Robert Nickolson ,  Martin Haberey ,  Olaf Loge ,  Claus-Steffen Stuerzebecher

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Robert Nickolson ,  Martin Haberey ,  Olaf Loge ,  Claus-Steffen Stuerzebecher

IPC分类号： C07C43/14 ,  A61K31/557 ,  A61P43/00 ,  C07C27/00 ,  C07C35/31 ,  C07C35/52 ,  C07C41/00 ,  C07C45/00 ,  C07C49/24 ,  C07C49/255 ,  C07C49/76 ,  C07C67/00 ,  C07C405/00 ,  C07C177/00

CPC分类号： C07C405/0083 ,  Y10S514/829

摘要： Carbacyclins of Formula I ##STR1## wherein R.sub.1 is an alkyl, cycloalkyl, aryl, aralkyl, or heterocyclic group,Y is a keto group or a hydroxymethylene group,X is a --CH.sub.2 -- group or an oxygen atom,A is a --CH.sub.2 --CH.sub.2 --, a trans--CH.dbd.CH-- or a --C.tbd.C-- group,W is a hydroxymethylene group or a ##STR2## D is the group ##STR3## a straight-chain or branched, saturated alkylene group or unsaturated alkylene group of up to 5 carbon atoms which can optionally be substituted by 1-2 fluorine atoms,n is 1, 2 or 3,E is a direct bond, a --C.tbd.C-- group or a --CR.sub.4 .dbd.CR.sub.5 -- group wherein R.sub.4 is hydrogen or an alkyl group and R.sub.5 is hydrogen, halogen or an alkyl group,R.sub.2 is an alkyl, cycloalkyl, aryl, or heterocyclic group, andR.sub.3 is a hydroxy group,are valuable, e.g., as cytoprotective agents.

摘要翻译： 式I的卡巴菌素其中R 1是烷基，环烷基，芳基，芳烷基或杂环基，Y是酮基或羟亚甲基，X是-CH 2 - 基或氧原子，A是 -CH 2 -CH 2 - ，反式-CH = CH-或-C 3 C C基团，W是羟基亚甲基基团，或者D是基团，即直链或支链饱和亚烷基 或至多5个碳原子的不饱和亚烷基，其可任选被1-2个氟原子取代，n为1,2或3，E为直接键，-C 3位C基团或-CR 4 = CR 5 - 基团，其中R 4是氢或烷基，R 5是氢，卤素或烷基，R 2是烷基，环烷基，芳基或杂环基，并且R 3是羟基，是有价值的，例如作为细胞保护剂。

公开(公告)号：US5190973A

公开(公告)日：1993-03-02

申请号：US599916

申请日：1990-10-19

申请人： Robert Nickolson ,  Helmut Vorbrueggen ,  Claus S. Stuerzebecher ,  Martin Haberey

发明人： Robert Nickolson ,  Helmut Vorbrueggen ,  Claus S. Stuerzebecher ,  Martin Haberey

IPC分类号： C07C405/00 ,  C07D307/935 ,  C07D307/937

CPC分类号： C07D307/935 ,  C07C405/00 ,  C07D307/937

摘要： The invention concerns 20-alkyl-7-oxoprostacyclin derivatives of general Formula I ##STR1## wherein R.sub.1 is the residue OR.sub.3 where R.sub.3 means hydrogen or alkyl of 1-10 carbon atoms optionally substituted by halogen, phenyl, C.sub.1 -C.sub.4 -alkoxy or C.sub.1 -C.sub.4 -dialkylamino; cycloalkyl, aryl or a heterocyclic residue, or the residue NHR.sub.4 where R.sub.4 means hydrogen or an alkanoyl or alkanesulfonyl residue of respectively 1-10 carbon atoms,n is 1 or 2,A is a CH.sub.2 --CH.sub.2 --, cis--CH.dbd.CH-- or trans--CH.dbd.CH--group,W is a ##STR2## or a ##STR3## wherein the OH-group can respectively be esterified with a benzoyl or alkanoic acid residue of 1-4 carbon atoms, or etherified with a tetrahydropyranol, tetrahydrofuranyl, alkoxyalkyl or trialkylsilyl residue, wherein the free or esterified OH-group can be in the .alpha.- or .beta.-position,R.sub.2 is a straight-chain or branched-chain alkyl group of 1-6 carbon atoms,R.sub.5 is a hydroxy group which can be esterified with an alkanoic acid residue of 1-4 carbon atoms or etherified with a tetrahydropyranyl, tetrahydrofuranyl, alkoxyalkyl or trialkylsilyl residue,R.sub.6 and R.sub.7 are hydrogen or a straight-chain or branched-chain alkyl group of 1-4 carbon atoms, or R.sub.6 and R.sub.7 jointly represent a trimethylene group,R.sub.8 and R.sub.9 jointly represent a linkage or hydrogen or a straight-chain or branched-chain alkyl group of 1-4 carbon atoms,and, if R.sub.3 is hydrogen, the salts thereof with physiologically compatible bases; their production; and their use as medicinal agents.

摘要翻译： 本发明涉及通式I（I）的20-烷基-7-氧代前列环素衍生物，其中R 1是残基OR 3，其中R 3表示氢或1-10个碳原子的任选被卤素，苯基，C 1 -C 4 - 烷氧基或C 1 -C 4 - 二烷基氨基; 环烷基，芳基或杂环残基，或残基NHR4，其中R4表示氢或分别为1-10个碳原子的烷酰基或烷磺酰基，n为1或2，A为CH2-CH2-，顺式-CH = CH- 或反式-CH = CH-基团，W为“IMAGE”或“IMAGE”，其中OH基团可分别用1-4个碳原子的苯甲酰基或链烷酸残基酯化，或用四氢吡喃醇醚化，四氢呋喃基 ，烷氧基烷基或三烷基甲硅烷基残基，其中游离或酯化的OH基可以是α或β-位，R2是1-6个碳原子的直链或支链烷基，R5是羟基， 可以用1-4个碳原子的链烷酸残基酯化，或与四氢吡喃基，四氢呋喃基，烷氧基烷基或三烷基甲硅烷基残基醚化，R6和R7是氢或1-4个碳原子的直链或支链烷基， 或R6和R7共同表示三亚甲基，R8和R9共同表示键或 氢或1-4个碳原子的直链或支链烷基，如果R 3是氢，则其与生理上相容的碱的盐; 他们的生产; 并将其用作药剂。

公开(公告)号：US4532236A

公开(公告)日：1985-07-30

申请号：US531898

申请日：1983-07-27

申请人： Robert Nickolson ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Martin Haberey

发明人： Robert Nickolson ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Martin Haberey

IPC分类号： A61K31/34 ,  A61K31/557 ,  A61P43/00 ,  C07C51/09 ,  C07C51/38 ,  C07C55/32 ,  C07C57/52 ,  C07C69/533 ,  C07C69/593 ,  C07C69/65 ,  C07C405/00 ,  C07D307/935 ,  C07D307/937 ,  C07D407/00 ,  C07D407/12 ,  C07F7/18 ,  C07F9/40

CPC分类号： C07D307/935 ,  C07C405/00 ,  C07C405/0033 ,  C07C51/09 ,  C07C51/38 ,  C07C55/32 ,  C07C57/52 ,  C07D307/937 ,  C07D407/12 ,  C07F7/1856 ,  C07F9/4015

摘要： Prostacyclin derivatives of general Formula I ##STR1## wherein R.sub.1 is the residue OR.sub.3 wherein R.sub.3 means hydrogen or alkyl of 1-10 carbon atoms substituted, if desired, by halogen, aryl, C.sub.1 -C.sub.4 -alkoxy, or C.sub.1 -C.sub.4 -dialkylamino; cycloalkyl, aryl, or a heterocyclic residue; or is the residue NHR.sub.4 wherein R.sub.4 means hydrogen, an alkanoyl residue, or an alkanesulfonyl residue of respectively 1-10 carbon atoms,A is a --CH.sub.2 --CH.sub.2 -- or trans--CH.dbd.CH--group,W is a ##STR2## wherein the OH-group can be respectively esterified with a benzoyl or alkanoic acid residue of 1-4 carbon atoms, or can be etherified with a tetrahydropyranyl, tetrahydrofuranyl, C.sub.1 -C.sub.4 -alkoxyalkyl, or tri(C.sub.1 -C.sub.4 -alkyl)-silyl residue, wherein the free or esterified OH-group can be in the .alpha.- or .beta.-position,D and E jointly mean a direct bond orD is a straight-chain or branched alkylene group of 1-5 carbon atoms,E is an oxygen atom or a direct bond,R.sub.2 is a straight-chain or branched-chain alkyl group of 1-6 carbon atoms, a straight-chain or branched-chain alkenyl group of 2-6 carbon atoms which can be substituted by phenyl, halogen, or C.sub.1 -C.sub.4 -alkyl and, if D and E jointly represent a direct bond, is an alkynyl residue of 2-6 carbon atoms optionally substituted in the 1-position by halogen or C.sub.1 -C.sub.4 -alkyl,R.sub.5 is a hydroxy group which can be esterified with an alkanoic acid residue of 1-4 carbon atoms or which can be etherified with a tetrahydropyranyl, tetrahydrofuranyl, alkoxyalkyl, or trialkylsilyl residue and, if R.sub.3 is hydrogen, the salts thereof with physiologically compatible bases, and a process for the preparation thereof.The compounds exhibit blood-pressure-lowering and thrombocyte-aggregation-inhibiting activity.

公开(公告)号：US4089852A

公开(公告)日：1978-05-16

申请号：US682967

申请日：1976-05-04

申请人： Robert Nickolson

发明人： Robert Nickolson

IPC分类号： C07J1/00 ,  C07J13/00 ,  C07J17/00

CPC分类号： C07J13/005 ,  C07J1/0033 ,  C07J17/00

摘要： .DELTA..sup.16 -21-HYDROXY-20-KETO STEROIDS OF THE PREGNANE SERIES HAVING AN OTHERWISE UNSUBSTITUTED D-ring and a 13-methyl or -ethyl group, and 21-ethers and -esters thereof, are produced by reaction of a corresponding D-ring saturated 17-keto steroid with a lithium compound of the formula ##STR1## thereby converting the 17-keto group to a 17.beta.-hydroxy-20.alpha.-enol ether in which the 17.alpha.-side chain has the formula ##STR2## wherein R.sub.3 and R.sub.4 have the values given above, and, in any desired sequence, splitting off R.sub.3 and/or R.sub.4 enol ether by hydrolysis; eliminating 17.beta.-hydroxy group, preferably after acylation, with formation of a .DELTA..sup.16 -double bond; and, if desired, splitting off any blocking group.

摘要翻译： 具有其他不分离的D-环和13-甲基或乙基的PREGNANE系列的DELTA 16-21-羟基-20-酮酸类固醇及其21-醚和 - 酯通过相应的D- 环状饱和的17-酮类固醇与式“IMAGE”的锂化合物反应，从而将17-酮基转化为17β-羟基-20α-烯醇醚，其中17α-侧链具有式，其中 R3和R4具有上述给出的值，并且以任何所需的顺序通过水解分离R3和/或R4烯醇醚; 消除17个β-羟基，优选在酰化后，形成DELTA16-双键; 并且如果需要，分解任何封闭基团。