公开(公告)号：US4315013A

公开(公告)日：1982-02-09

申请号：US122794

申请日：1980-02-19

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Gerda Mannesmann ,  Wolfgang Losert ,  Jorge Casals

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Gerda Mannesmann ,  Wolfgang Losert ,  Jorge Casals

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/557 ,  A61K31/5585 ,  A61P7/02 ,  A61P9/12 ,  A61P11/08 ,  A61P43/00 ,  C07C405/00 ,  C07D209/52 ,  A61K31/435 ,  C07D401/12 ,  C07D405/12

CPC分类号： C07D209/52 ,  C07C405/00 ,  C07C405/0041

摘要： Prostane derivatives of the formula ##STR1## wherein R.sub.1 is (a) hydrogen, (b) C.sub.1-10 alkyl, (c) C.sub.1-10 alkyl substituted by halogen; C.sub.1-4 alkoxy; C.sub.6-10 aryl; C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; di-C.sub.1-4 -alkylamino; or tri-C.sub.1-4 alkylammonium; (d) C.sub.4-10 cycloalkyl, (e) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (f) C.sub.6-10 aryl, (g) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group, or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S;W is hydroxymethylene or RO-methylene; or ##STR2## wherein OH or OR is in the .alpha.-position and R is an in vivo hydrolyzable and physiologically acceptable ether or acyl group which is conventional for modifying OH groups in prostaglandins;R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are each independently hydrogen or alkyl of 1-5 carbon atoms,R.sub.2 is OH or OR, R being as defined above,or, when R.sub.1 is H, a physiologically compatible salt thereof with a base.

摘要翻译： 其中R 1为（a）氢，（b）C 1-10烷基，（c）被卤素取代的C 1-10烷基; C 1-4烷氧基; C6-10芳基; 被1-3个卤素原子取代的C 6-10芳基，苯基，1-3个C 1-4烷基或氯甲基，氟甲基，三氟甲基，羧基，羟基或C 1-4烷氧基; 二-C 1-4 - 烷基氨基; 或三-C 1-4烷基铵; （d）C 4-10环烷基，（e）被C 1-4烷基取代的C 4-10环烷基，（f）C 6-10芳基，（g）被1-3个卤素原子取代的C 6-10芳基，苯基， -3 C 1-4烷基或氯甲基，氟甲基，三氟甲基，羧基，羟基或C 1-4烷氧基，或（h）5或6个环原子的芳族杂环，其中一个为O，N或S; W是羟基亚甲基或RO-亚甲基; 或其中OH或OR位于α位且R是体内可水解和生理上可接受的醚或酰基，其是常规用于改变前列腺素中的OH基团; R 3，R 4，R 5和R 6各自独立地是氢或1-5个碳原子的烷基，R 2是OH或OR，R如上定义，或者当R 1是H时，其与碱的生理上相容的盐。

公开(公告)号：US5157042A

公开(公告)日：1992-10-20

申请号：US713002

申请日：1991-06-10

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Gerda Mannesmann ,  Michael H. Town

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Gerda Mannesmann ,  Michael H. Town

IPC分类号： C07C69/708 ,  A61K31/225 ,  A61K31/35 ,  A61K31/351 ,  A61K31/557 ,  A61P7/02 ,  A61P9/12 ,  A61P11/08 ,  C07C51/00 ,  C07C51/367 ,  C07C59/125 ,  C07C59/62 ,  C07C67/00 ,  C07C67/31 ,  C07C231/00 ,  C07C231/02 ,  C07C231/12 ,  C07C235/06 ,  C07C235/08 ,  C07C235/88 ,  C07C405/00 ,  C07D309/12 ,  C07D317/72

CPC分类号： C07D317/72 ,  C07C405/0083

摘要： Carbacyclin derivatives of Formula I ##STR1## wherein R.sub.1 is OR.sub.2, wherein R.sub.2 is hydrogen, alkyl, cycloalkyl, aryl, ##STR2## or a heterocyclic residue; or R.sub.1 is NHR.sub.3 wherein R.sub.3 is an acid residue (acyl) or R.sub.2 ;A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH--, or --C.tbd.C--;W is a free or functionally modified hydroxymethylene group or a free or functionally modified ##STR3## wherein the OH-group can be in the .alpha.- or .beta.-position; D is ##STR4## a straight-chain, saturated aliphatic group of 1-10 carbon atoms; or a branched, saturated or straight-chain or branched, unsaturated aliphatic group of 2-10 carbon atoms; all of which are substituted by fluorine atoms;n is 1, 2, or 3;E is a direct bond, --C.tbd.C--, or --CR.sub.6 .dbd.CR.sub.7 --, wherein R.sub.6 is hydrogen or alkyl of 1-5 carbon atoms and R.sub.7 is hydrogen, halogen or alkyl of 1-5 carbon atoms;R.sub.4 is an aliphatic group, cycloalkyl, optionally substituted aryl, or a heterocyclic group; andR.sub.5 is a free or functionally modified hydroxy group; andwhen R.sub.1 is OH, the salts thereof with physiologically compatible bases,are valuable pharmacological agents.

摘要翻译： 式I的卡巴环素衍生物其中R 1是OR 2，其中R 2是氢，烷基，环烷基，芳基，杂芳基或杂环残基; 或R1是NHR3，其中R3是酸残基（酰基）或R2; A是-CH 2 -CH 2 - ，反式-CH = CH-或-C 3位C; W是游离或官能改性的羟基亚甲基或游离或官能改性的“IMAGE”，其中OH基可以是α-或β-位; D是1-10个碳原子的直链饱和脂族基团; 或2-10个碳原子的支链，饱和或直链或支链的不饱和脂族基团; 所有这些都被氟原子取代; n为1,2或3; E是直接键，-C 3 D或-CR 6 = CR 7 - ，其中R 6是氢或1-5个碳原子的烷基，R 7是氢，卤素或1-5个碳原子的烷基; R4是脂族基团，环烷基，任选取代的芳基或杂环基; R5是游离或官能改性的羟基; 当R1是OH时，其与生理上相容的碱的盐是有价值的药剂。

公开(公告)号：US4378370A

公开(公告)日：1983-03-29

申请号：US309967

申请日：1981-10-06

申请人： Helmut Vorbrueggen ,  Bernd Raduechel ,  Werner Skuballa ,  Gerda Mannesmann ,  Jorge Casals-Stenzel ,  Ekkehard Schillinger

发明人： Helmut Vorbrueggen ,  Bernd Raduechel ,  Werner Skuballa ,  Gerda Mannesmann ,  Jorge Casals-Stenzel ,  Ekkehard Schillinger

IPC分类号： C07D307/935 ,  A61K31/34 ,  A61K31/557 ,  A61P43/00 ,  C07D307/93 ,  C07D307/937 ,  C07F7/18

CPC分类号： C07D307/937 ,  C07F7/1856 ,  Y10S514/826

摘要： Prostacyclin derivatives of the formula ##STR1## wherein R.sub.1 is OR.sub.3 wherein R.sub.3 is hydrogen or alkyl of 1-10 carbon atoms, or R.sub.1 is NHR.sub.4 wherein R.sub.4 is alkanoyl or alkanesulfonyl,B is alkylene of 1-5 carbon atoms,A is --CH.sub.2 --CH.sub.2 --, cis--CH.dbd.CH--, or trans--CH.dbd.CH--,W is hydroxymethylene or ##STR2## wherein the OH-group is optionally substituted by alkanoyl of 1-4 carbon atoms and the free or substituted OH-group can be in the .alpha.- or .beta.- position,R.sub.2 is alkyl of 1-6 carbon atoms optionally substituted by phenyl, or R.sub.2 is phenyl,R.sub.5 is hydroxy optionally substituted by alkanoyl of 1-4 carbon atoms,R.sub.6 is hydrogen, fluorine, or alkyl of 1-4 carbon atomsor when R.sub.3 is hydrogen, a salt thereof with a physiologically compatible base,have pharmacological activity e.g., blood pressure-lowering and bronchodilatory effects.

摘要翻译： PCT No.PCT / DE81 / 00031 Sec。 371日期1981年10月6日 102（e）日期1981年10月6日PCT提交1981年2月5日PCT公布。 出版物WO81 / 02296 日本1981年8月20日。其中R 1为OR 3的式（I）其中R 3为氢或1-10个碳原子的烷基，或R 1为NHR 4，其中R 4为烷酰基或链烷磺酰基，B为1- 5个碳原子，A是-CH 2 -CH 2 - ，顺式-CH = CH-或反式-CH = CH-，W是羟基亚甲基或其中OH基任选被1-4个碳原子的烷酰基取代 并且游离或取代的OH基团可以在α或β位，R 2是任选被苯基取代的1-6个碳原子的烷基，或者R 2是苯基，R 5是任选被1-4碳的烷酰基取代的羟基 原子，R6是氢，氟或1-4个碳原子的烷基，或当R3是氢时，其与生理上相容的碱的盐具有药理活性，例如降血压和支气管扩张作用。

公开(公告)号：US4954524A

公开(公告)日：1990-09-04

申请号：US333812

申请日：1989-04-06

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Gerda Mannesmann ,  Ekkehard Schillinger ,  Michael H. Town

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Gerda Mannesmann ,  Ekkehard Schillinger ,  Michael H. Town

IPC分类号： A61K31/16 ,  A61K31/19 ,  A61K31/535 ,  A61K31/5375 ,  A61P7/02 ,  A61P9/12 ,  A61P11/08 ,  C07C67/00 ,  C07C231/00 ,  C07C231/02 ,  C07C231/10 ,  C07C231/12 ,  C07C233/21 ,  C07C235/06 ,  C07C235/08 ,  C07C235/14 ,  C07C235/16 ,  C07C235/30 ,  C07C405/00 ,  C07D295/18 ,  C07H13/04

CPC分类号： C07H13/04 ,  C07C405/0083

摘要： Carbacyclin derivatives of Formula I ##STR1## wherein R.sub.1 is hydrogen or OR.sub.2, wherein R.sub.2 is hydrogen, alkyl, cycloalkyl, aryl, ##STR2## or a heterocyclic residue; or R.sub.1 is NHR.sub.3 wherein R.sub.3 is an acid residue (acyl) or R.sub.2,n is 2, 3, 4, or 5,X is hydrogen or fluorine,A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH--, or --C.tbd.C--,W is a free or functionally modified hydroxymethylene group or a free or functionally modified ##STR3## wherein the OH-group can be in the .alpha.- or .beta.-position, D is ##STR4## a straight-chain, saturated aliphatic group of 1-10 carbon atoms, a branched, saturated or a straight-chain or branched, unsaturated aliphatic group of 2-10 carbon atoms, all of which can optionally be substituted by fluorine atoms,m is 1, 2, or 3,E is a direct bond, --C.tbd.C--, or --CR.sub.6 .dbd.CR.sub.7 -- wherein R.sub.6 and R.sub.7 are different from each other and are hydrogen or alkyl or 1-5 carbon atoms, or are hydrogen or halogen,R.sub.4 is an aliphatic group, cycloalkyl, or optionally substituted aryl, or a heterocyclic group; andR.sub.5 is a free or functionally modified hydroxy group; andwhen R.sub.1 is OH, the salts thereof with physiologically compatible bases, have valuable pharmacological properties.

公开(公告)号：US4497830A

公开(公告)日：1985-02-05

申请号：US381609

申请日：1982-05-24

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Ekkehard Schillinger ,  Gerda Mannesmann ,  Bob Nieuweboer

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Ekkehard Schillinger ,  Gerda Mannesmann ,  Bob Nieuweboer

IPC分类号： A61K31/557 ,  A61P43/00 ,  C07C29/147 ,  C07C33/05 ,  C07C33/12 ,  C07C41/26 ,  C07C43/178 ,  C07C405/00 ,  C07D309/12 ,  C07D317/72 ,  C07F9/40

CPC分类号： C07D317/72 ,  C07C33/12 ,  C07C405/0083 ,  C07C43/178 ,  C07D309/12 ,  C07F9/4015

摘要： Compounds of Formula I ##STR1## wherein X is oxygen or CH.sub.2 ;A is CH.sub.2 --CH.sub.2, trans-CH.dbd.CH or C.tbd.C;W is free or functionally modified hydroxymethylene or free or functionally modified ##STR2## and the OH groups may be in the .alpha.- or the .beta.-position; D is straight chain or branched, saturated or unsaturated hydrocarbon aliphatic of from 1 to 10 carbon atoms, which may be substituted by fluorine;E is C.tbd.C or CR.sub.3 .dbd.CR.sub.4, R.sub.3 and R.sub.4 being different and being hydrogen or alkyl of 1 to 5 carbon atoms;R.sub.1 is free or functionally modified hydroxy; andR.sub.2 is alkyl, cycloalkyl, optionally substituted aryl or heterocyclic,have valuable pharmacological properties, e.g., hypotensive and bronchodilatory characteristics. They can furthermore be used for prophylaxis and therapy of coronary infarct and as a treatment for stroke. They are produced by means of reduction of the corresponding 1-carbonic acid derivatives.

摘要翻译： 式I的化合物其中X是氧或CH 2; A是CH 2 -CH 2，反式-CH = CH或C 3 C; W是游离或官能改性的羟基亚甲基或游离或功能修饰的“IMAGE”，OH基可以是α或β位; D是可以被氟取代的具有1至10个碳原子的直链或支链，饱和或不饱和的烃脂族; E为C 3或C 3或CR 3 = CR 4，R 3和R 4不同，为氢或1至5个碳原子的烷基; R1是游离或官能改性的羟基; 和R2是烷基，环烷基，任选取代的芳基或杂环，具有有价值的药理学性质，例如降血压和支气管扩张特征。 它们还可用于冠状动脉梗塞的预防和治疗以及中风治疗。 它们是通过还原相应的1-碳酸衍生物生产的。

公开(公告)号：US5124343A

公开(公告)日：1992-06-23

申请号：US141233

申请日：1988-01-06

申请人： Helmut Vorbrueggen ,  Hernd Raduechel ,  Werner Skuballa ,  Norbert Schwarz ,  Jorge Casals-Stenzel ,  Gerda Mannesmann ,  Michael H. Town

发明人： Helmut Vorbrueggen ,  Hernd Raduechel ,  Werner Skuballa ,  Norbert Schwarz ,  Jorge Casals-Stenzel ,  Gerda Mannesmann ,  Michael H. Town

IPC分类号： C07C45/59 ,  C07C57/26 ,  C07C57/60 ,  C07C405/00 ,  C07D263/14 ,  C07D317/72 ,  C07F9/40

CPC分类号： C07D317/72 ,  C07C405/0083 ,  C07C45/59 ,  C07C57/26 ,  C07C57/60 ,  C07D263/14 ,  C07F9/4018

摘要： The invention relates to carbacyclins of general Formula I ##STR1## wherein R.sub.1 is the residue CH.sub.2 OH or ##STR2## with R.sub.2 meaning a hydrogen atom, an alkyl, cycloalkyl, aryl residue, a ##STR3## or heterocyclic residue, or R.sub.1 is the residue ##STR4## with R.sub.3 meaning an alkanoyl or alkanesulfonyl residue of respectively 1-10 carbon atoms or the residue R.sub.2, orR.sub.1 is the residue ##STR5## wherein m is the number 1 or 2, X is an oxygen atom or a CH.sub.2 -group,A is a trans--CH.dbd.CH- or --.tbd.C--group,W is a free or functionally modified hydroxymethylene group wherein the OH-group can be in the .alpha.- or .beta.- position,n is the number 1, 2, or 3,D is a straight-chain alkylene group of 1-5 carbon atoms,E is a --C.tbd.C---bond or a --CR.sub.6 =CR.sub.7 --group wherein R.sub.6 and R.sub.7 are different from each other and mean a hydrogen atom or an alkyl group of 1-5 carbon atoms or a hydrogen atom or a halogen atom, preferably chlorine,R.sub.4 is an alkyl, cycloalkyl, or optionally substituted arly group, or a heterocyclic group,R.sub.5 is a free or functionally modified hydroxy group, andif R.sub.2 means a hydrogen atom, the salts thereof with physiologically compatible bases;to processes for the preparation thereof, and to the use thereof as blood-pressure-lowering agents.

摘要翻译： 本发明涉及通式I的碳霉素，其中R 1是残基CH 2 OH或R 2，其中R 2表示氢原子，烷基，环烷基，芳基，芳基或杂环残基，或者R 1是 残基其中R3表示分别为1-10个碳原子的烷酰基或烷磺酰基残基或残基R2，或R1为残基，其中m为数1或2，X为氧原子或CH2- 基团，A是反式-CH = CH-或 - 3BOND C-基团，W是游离或官能改性的羟基亚甲基基团，其中OH-基团可以是α或β位置，n是数1，2 或3，D是1-5个碳原子的直链亚烷基，E是-C3OND C键或-CR6 = CR7-基团，其中R6和R7彼此不同，意指氢 原子或1-5个碳原子的烷基或氢原子或卤素原子，优选氯，R4是烷基，环烷基或任选取代的芳基或杂环基团 p，R5是游离或功能改性的羟基，如果R 2表示氢原子，则其与生理上相容的碱的盐; 其制备方法及其作为降血压剂的用途。

公开(公告)号：US4618626A

公开(公告)日：1986-10-21

申请号：US777535

申请日：1985-09-16

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Gerda Mannesmann ,  Bob Nieuweboer ,  Michael-Harold Town

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Gerda Mannesmann ,  Bob Nieuweboer ,  Michael-Harold Town

IPC分类号： C07C69/708 ,  A61K31/557 ,  A61P1/04 ,  A61P9/08 ,  A61P9/12 ,  A61P11/08 ,  C07C67/10 ,  C07C69/732 ,  C07C405/00 ,  C07C177/00

CPC分类号： C07C405/0083

摘要： Carbacyclin esters of Formula I ##STR1## wherein R.sub.1 is an unsubstituted or substituted aromatic residue,R.sub.2 is a free or functionally modified hydroxy group,R.sub.3 is an alkyl or cycloalkyl group, or an optionally substituted aryl group, or a heterocyclic group,X is an oxygen atom or the group --CH.sub.2 --,A is a --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH--, or --C.tbd.C--group,W is a free or functionally modified hydroxymethylene group or a free or functionally modified ##STR2## wherein the OH-group can be in the .alpha.- or .beta.-position D is the group ##STR3## a straight-chain saturated alkylene group of 1-5 carbon atoms, a branched, saturated or a straight-chain or branched, unsaturated alkylene group of 2-5 carbon atoms, which groups can optionally be substituted by fluorine atoms,E is a direct bond, a --C.tbd.C--group, or a --CR.sub.4 .dbd.CR.sub.5 -- group wherein R.sub.2 and R.sub.5 mean a hydrogen atom or an alkyl group of 1-5 carbon atoms;are useful as blood-pressure-lowering agents, inter alia.

摘要翻译： 式I的卡巴环素酯其中R 1是未取代或取代的芳族残基，R 2是游离或官能改性的羟基，R 3是烷基或环烷基，或任选取代的芳基或杂环基 ，X是氧原子或基团-CH 2 - ，A是-CH 2 -CH 2 - ，反式-CH = CH-或-C 3 C C基，W是游离或官能改性的羟基亚甲基， 功能修饰的“IMAGE”，其中OH基可以在α或β位D是基团，即1-5个碳原子的直链饱和亚烷基，支链，饱和或直链 或2-5个碳原子的支链不饱和亚烷基，该基团可任选被氟原子取代，E是直接键，-C 3 C C基或-CR 4 = CR 5 - 基，其中R 2和R 5表示 氢原子或1-5个碳原子的烷基; 作为降血压剂特别有用。

公开(公告)号：US4552875A

公开(公告)日：1985-11-12

申请号：US510125

申请日：1983-07-01

申请人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Gerda Mannesmann ,  Bob Nieuweboer ,  Michael H. Town

发明人： Werner Skuballa ,  Bernd Raduechel ,  Helmut Vorbrueggen ,  Gerda Mannesmann ,  Bob Nieuweboer ,  Michael H. Town

IPC分类号： A61K31/16 ,  A61K31/19 ,  A61K31/535 ,  A61K31/5375 ,  A61P7/02 ,  A61P9/12 ,  A61P11/08 ,  C07C67/00 ,  C07C231/00 ,  C07C231/02 ,  C07C231/10 ,  C07C231/12 ,  C07C233/21 ,  C07C235/06 ,  C07C235/08 ,  C07C235/14 ,  C07C235/16 ,  C07C235/30 ,  C07C405/00 ,  C07D295/18 ,  C07H13/04 ,  C07C177/00 ,  A61K31/557

CPC分类号： C07H13/04 ,  C07C405/0083

摘要： Carbacyclinamides of Formula I ##STR1## wherein R.sub.1 is NHR.sub.4, wherein R.sub.4 is H, --(CH.sub.2).sub.n --R.sub.8 or straight-chained or branched aliphatic groups of 1-10 carbon atoms, cycloalkyl of 3-10 carbon atoms, aryl, or lower mono- or polyhydroxyalkyl of 2-8 carbon atoms, or R.sub.1 is NR.sub.4 R.sub.5 wherein R.sub.4 and R.sub.5 each are straight-chained or branched, lower, mono- or polyhydroxyalkyl of 2-8 carbon atoms, or R.sub.4 and R.sub.5 together with the adjoining N-atom form a 5- or 6-membered heterocycle which can optionally contain additional hetero atoms and can be substituted; or R.sub.1 is NR.sub.4 R.sub.5 wherein R.sub.4 is an aliphatic group of 1-10 carbon atoms, cycloalkyl of 3-10 carbon atoms, and R.sub.5 is straight-chained or branched aliphatic group of 1-10 carbon atoms, cycloalkyl of 3-10 carbon atoms, aryl, or lower, mono- or polyhydroxyalkyl of 2-8 carbon atoms;n is 1-4;R.sub.8 is --CONH.sub.2 or --N(C.sub.1 -C.sub.4 -alkyl).sub.2 ;R.sub.2 is a free or functionally modified hydroxy group;R.sub.3 is aliphatic, cycloalkyl, optionally substituted aryl, or a heterocyclic group;X is oxygen or --CH.sub.2 --;A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH--, or --CH.tbd.--;W is free or functionally modified hydroxymethylene or free or functionally modified ##STR2## wherein the OH-group can be in the .alpha.- or .beta.-position; D is ##STR3## a straight-chain, saturated aliphatic group of 1-5 carbon atoms, or a branched, saturated or a straight-chain or branched, unsaturated aliphatic group of 2-5 carbon atoms, all of which groups can optionally be substituted by fluorine atoms;m is 1-3;E is a direct bond, --C.tbd.C--, or --CR.sub.6 .dbd.CR.sub.7 --wherein R.sub.6 and R.sub.7 are each a hydrogen atom or an alkyl group of 1-5 carbon atomshave valuable pharmacological properties.

摘要翻译： 式I的卡拉菌素酰胺其中R 1是NHR 4，其中R 4是H， - （CH 2）n -R 8或1-10个碳原子的直链或支链脂族基团，3-10个碳原子的环烷基， 芳基或2-8个碳原子的低级单 - 或多羟基烷基，或R1是NR4R5，其中R4和R5各自是2-8个碳原子的直链或支链，低级，单 - 或多羟基烷基，或R4和R5连同 邻接的N-原子形成5-或6-元杂环，其可以任选地含有另外的杂原子并且可以被取代; 或R1是NR4R5，其中R4是1-10个碳原子的脂族基团，3-10个碳原子的环烷基，R5是1-10个碳原子的直链或支链脂族基团，3-10个碳原子的环烷基， 芳基或更低级的2-8个碳原子的单或多羟基烷基; n为1-4; R8是-CONH2或-N（C1-C4-烷基）2; R2是游离或官能改性的羟基; R3是脂族，环烷基，任选取代的芳基或杂环基; X是氧或-CH 2 - ; A是-CH 2 -CH 2 - ，反式-CH = CH-或-CH 3 OCH 3 - 。 W是游离的或官能改性的羟基亚甲基或游离或功能改性的“IMAGE”，其中OH-基团可以是α-或β-位; D是1-5个碳原子的直链饱和脂族基团，或2-5个碳原子的支链，饱和或直链或支链不饱和脂肪族基团，所有这些基团可任选地为 被氟原子取代; m为1-3; E是直接键，-C 3 D或-CR 6 = CR 7 - 其中R 6和R 7各自为氢原子或1-5个碳原子的烷基具有有价值的药理学性质。

公开(公告)号：US4692464A

公开(公告)日：1987-09-08

申请号：US352411

申请日：1982-02-26

申请人： Werner Skuballa ,  Bernd Raduchel ,  Helmut Vorbruggen ,  Gerda Mannesmann ,  Wolfgang Losert ,  Jorge Casals

发明人： Werner Skuballa ,  Bernd Raduchel ,  Helmut Vorbruggen ,  Gerda Mannesmann ,  Wolfgang Losert ,  Jorge Casals

IPC分类号： C07D309/12 ,  A61K31/557 ,  A61K31/5575 ,  A61K31/5585 ,  A61P7/02 ,  A61P25/02 ,  A61P43/00 ,  C07C45/59 ,  C07C45/67 ,  C07C45/71 ,  C07C51/00 ,  C07C51/353 ,  C07C59/46 ,  C07C62/32 ,  C07C67/00 ,  C07C67/343 ,  C07C69/732 ,  C07C401/00 ,  C07C405/00 ,  C07D317/72 ,  C07D319/12 ,  C07C177/00

CPC分类号： C07D317/72 ,  A61K31/557 ,  C07C405/0083 ,  C07C45/59 ,  C07C45/673 ,  C07C45/71 ,  C07C62/32 ,  C07D319/12

摘要： Compounds of the formula ##STR1## wherein R.sub.1 is (a) hydrogen, (b) C.sub.1-10 alkyl, (c) C.sub.1-10 alkyl substituted by halogen; C.sub.1-4 alkoxy; C.sub.6-10 aryl; C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; di-C.sub.1-4 -alkylamino; or tri-C.sub.1-4 -alkylammonium, (d) C.sub.4-10 cycloalkyl, (e) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (f) C.sub.6-10 aryl, (g) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group, or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S;A is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH-- or --C.tbd.C--;W is hydroxymethylene, RO-methylene, CH.sub.3 or CH.sub.3, ##STR2## wherein OH or OR is in the .alpha.- or .beta.-position and R is an in vivo hydrolyzable and physiologically acceptable ether or acyl group which is conventional for modifying OH groups in prostaglandins;D and E together are a direct bond, orD is C.sub.1-10 alkylene, C.sub.1-10 alkenylene or C.sub.1-10 alkynylene or one of these groups substituted by fluorine, andE is oxygen, --C.tbd.C-- or a direct bond;R.sub.2 is (a) a C.sub.1-10 hydrocarbon aliphatic radical, (b) a C.sub.6-10 hydrocarbon aliphatic radical substituted by C.sub.6-10 aryl or by C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; (c) C.sub.4-10 cycloalkyl, (d) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (e) C.sub.6-10 aryl, (f) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S; andR.sub.3 is OH or OR; and, when R.sub.1 is hydrogen, the salts thereof with physiologically compatible bases, are effective as antihypertensive, bronchiodilators, thrombocyte aggregation inhibitors, inter alia.

公开(公告)号：US4191694A

公开(公告)日：1980-03-04

申请号：US928126

申请日：1978-07-26

申请人： Werner Skuballa ,  Bernd Raduchel ,  Norbert Schwarz ,  Helmut Vorbruggen ,  Bernd Muller ,  Gerda Mannesmann ,  Olaf Loge ,  Ekkehardt Schillinger ,  Jorge Casals-Stenzel

发明人： Werner Skuballa ,  Bernd Raduchel ,  Norbert Schwarz ,  Helmut Vorbruggen ,  Bernd Muller ,  Gerda Mannesmann ,  Olaf Loge ,  Ekkehardt Schillinger ,  Jorge Casals-Stenzel

IPC分类号： A61K31/557 ,  A61K31/34 ,  A61K31/343 ,  A61K31/5575 ,  A61P7/02 ,  A61P7/10 ,  A61P9/06 ,  A61P9/12 ,  A61P43/00 ,  C07C405/00 ,  C07D307/935 ,  C07D307/937 ,  C07D307/93

CPC分类号： C07D307/937 ,  C07C405/00 ,  Y10S514/821 ,  Y10S514/822 ,  Y10S514/869

摘要： Prostane derivatives of the formula ##STR1## wherein R.sub.1 is OR.sub.2 or NHR.sub.3 ;R.sub.2 is hydrogen, C.sub.1-10 alkyl, C.sub.4-10 cycloalkyl, C.sub.6-10 aryl, or a 5 or 6 membered heterocyclic ring having 1-3 hetero atoms selected from O, N and S;R.sub.3 is the residue of a hydrocarbon carboxylic or sulfonic acid of 1-15 carbon atoms;W is (a) an OH-substituted methylene group, (b) a ##STR2## wherein the OH-groups in (a) or (b) can be in the .alpha.- or .beta.-position, or (c) such a group wherein the H atom of the OH group is replaced by the residue of a hydrocarbon carboxylic or sulfonic acid of 1-15 carbon atoms or by a conventional etherifying OH-blocking group;R.sub.4 is OH or hydroxy whose H atom is replaced as defined for W; andR.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 each independently is hydrogen or alkyl of 1-5 carbon atoms; or R.sub.9 and R.sub.10 together represent a direct bond; and, when R.sub.11 is alkyl, R.sub.10 can also be chlorine;and, for a derivative wherein R.sub.2 is hydrogen, the salts thereof with physiologically compatible bases,have improved prostaglandin activity.

摘要翻译： 其中R1为OR2或NHR3的式（Ⅰ）所示的前驱体衍生物; R2是氢，C1-10烷基，C4-10环烷基，C6-10芳基或具有1-3个选自O，N和S的杂原子的5或6元杂环; R3是1-15个碳原子的烃羧酸或磺酸的残基; W是（a）OH-取代的亚甲基，（b）其中（a）或（b）中的OH基可以是α或β-位，或（c）这样的基团 其中OH基团的H原子被1-15个碳原子的烃羧酸或磺酸的残基或通过常规的醚化OH-封闭基团取代; R4是OH或羟基，其H原子被替换为W定义; R 5，R 6，R 7，R 8，R 9，R 10和R 11各自独立地为氢或1-5个碳原子的烷基; 或R 9和R 10一起代表直接键; 当R 11为烷基时，R 10也可为氯; 并且对于其中R 2是氢的衍生物，其与生理上相容的碱的盐具有改善的前列腺素活性。