公开(公告)号：US4618626A

公开(公告)日：1986-10-21

申请号：US777535

申请日：1985-09-16

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

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

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

CPC classification number: C07C405/0083

Abstract: 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.

Abstract translation: 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：US4219479A

公开(公告)日：1980-08-26

申请号：US963240

申请日：1978-11-24

Applicant: Helmut Vorbruggen ,  Werner Skuballa ,  Bernd Raduchel ,  Wolfgang Losert ,  Olaf Loge ,  Bernd Muller ,  Gerda Mannesmann

Inventor： Helmut Vorbruggen ,  Werner Skuballa ,  Bernd Raduchel ,  Wolfgang Losert ,  Olaf Loge ,  Bernd Muller ,  Gerda Mannesmann

IPC: A61K31/557 ,  A61K31/34 ,  A61K31/343 ,  A61K31/5575 ,  A61P1/04 ,  A61P7/02 ,  A61P9/12 ,  A61P11/00 ,  C07C405/00 ,  C07D307/935 ,  C07D307/937 ,  A61K31/335 ,  C07D307/93

CPC classification number: C07D307/937

Abstract: Stabilized prostacyclins having a wide range of pharmacological activity and long duration of such activity, have the formula ##STR1## wherein R.sub.1 is (a) OR.sub.3, wherein R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl or a heterocyclic residue; or (b) NHR.sub.4 wherein R.sub.4 is an acid residue;B is straight-chain or branched alkylene of 2-10 carbon atoms;A is --CH.sub.2 --CH.sub.2 --, cis--CH.dbd.CH--, trans--CH.dbd.CH-- or --C.tbd.C--,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 and E together are a direct bond; orD is straight-chain or branched alkylene of 1-5 carbon atoms; andE is oxygen or sulfur or a direct bond,R.sub.2 is alkyl, cycloalkyl, optionally substituted aryl or a heterocyclic group; andR.sub.5 is free or functionally modified hydroxy; and when R.sub.3 is hydrogen, the salts thereof with physiologically compatible bases.

Abstract translation: 具有广泛的药理活性和长时间的这种活性的稳定的前列环素具有下式（IMAGE），其中R1是（a）OR3，其中R3是氢，烷基，环烷基，芳基或杂环残基; 或（b）NHR 4，其中R 4是酸残基; B是2-10个碳原子的直链或支链亚烷基; A是-CH 2 -CH 2 - ，顺式-CH = CH-，反式-CH = CH-或-C 3BOND 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，其中OH-基团可以是 在alpha或beta位置; D和E一起是直接的债券; 或D是1-5个碳原子的直链或支链亚烷基; 并且E是氧或硫或直接键，R 2是烷基，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; 并且当R3是氢时，其盐与生理上相容的碱基。

公开(公告)号：US4191694A

公开(公告)日：1980-03-04

申请号：US928126

申请日：1978-07-26

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

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

IPC: 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 classification number: C07D307/937 ,  C07C405/00 ,  Y10S514/821 ,  Y10S514/822 ,  Y10S514/869

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5124343A

公开(公告)日：1992-06-23

申请号：US141233

申请日：1988-01-06

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

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

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

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

Abstract: 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.

Abstract translation: 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：US4378370A

公开(公告)日：1983-03-29

申请号：US309967

申请日：1981-10-06

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

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

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

CPC classification number: C07D307/937 ,  C07F7/1856 ,  Y10S514/826

Abstract: 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.

Abstract translation: 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

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

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

IPC: 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 classification number: C07H13/04 ,  C07C405/0083

Abstract: 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：US4692464A

公开(公告)日：1987-09-08

申请号：US352411

申请日：1982-02-26

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

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

IPC: 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 classification number: C07D317/72 ,  A61K31/557 ,  C07C405/0083 ,  C07C45/59 ,  C07C45/673 ,  C07C45/71 ,  C07C62/32 ,  C07D319/12

Abstract: 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：US4497830A

公开(公告)日：1985-02-05

申请号：US381609

申请日：1982-05-24

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

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

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

CPC classification number: C07D317/72 ,  C07C33/12 ,  C07C405/0083 ,  C07C43/178 ,  C07D309/12 ,  C07F9/4015

Abstract: 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.

Abstract translation: 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：US4466969A

公开(公告)日：1984-08-21

申请号：US385414

申请日：1982-05-17

Applicant: Robert C. Nikolson ,  Helmut Vorbruggen ,  Jorge Casals-Stenzel ,  Gerda Mannesmann

Inventor： Robert C. Nikolson ,  Helmut Vorbruggen ,  Jorge Casals-Stenzel ,  Gerda Mannesmann

IPC: A61K31/34 ,  A61K31/557 ,  A61P43/00 ,  C07C17/08 ,  C07C21/14 ,  C07C57/03 ,  C07C57/13 ,  C07C57/52 ,  C07C69/593 ,  C07C69/606 ,  C07D307/935 ,  C07D307/937 ,  C07D407/12 ,  C07F9/40 ,  C07F9/48 ,  C07F9/535 ,  C07F9/54

CPC classification number: C07D307/935 ,  C07C17/08 ,  C07C57/03 ,  C07C57/13 ,  C07C57/52 ,  C07D307/937 ,  C07F9/4015 ,  C07F9/5352

Abstract: Prostacyclin, although having a useful dilating effect on blood vessels, is not sufficiently stable to ensure successful use as a hypotensive agent.A 7-oxo prostacyclin derivative of the general formula ##STR1## in which R.sub.1 represents the radical OR.sub.3 whereinR.sub.3 represents hydrogen, a straight-chain or branched optionally substituted, (C.sub.1 -C.sub.10)alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocyclic,orR.sub.1 represents the radical NHR.sub.4 whereinR.sub.4 represents hydrogen, or a group derived from an unsaturated or saturated, unsubstituted or substituted, (C.sub.1 -C.sub.15)organic carboxylic or sulphonic acid,A represents --CH.sub.2 --CH.sub.2 --, cis--CH.dbd.CH-- or trans--CH.dbd.CH--,W represents ##STR2## either having a free or functionally modified hydroxy group which may be in the .alpha.- or .beta.-position,D and E together represent a direct bond, orD represents a straight-chain or branched, unsaturated or saturated, optionally substituted (C.sub.1 -C.sub.10)alkylene, andE represents oxygen or a direct bond,R.sub.2 represents a straight-chain or branched optionally substituted, (C.sub.1 -C.sub.10)alkyl, a straight-chain or branched optionally substituted, (C.sub.2 -C.sub.10)alkenyl, or, where D and E together represent a direct bond, a straight-chain or branched optionally substituted (C.sub.2 -C.sub.6)alkynyl,andR.sub.5 represents a free or functionally modified hydroxy group,has proved to have not only a hypotensive and bronchodilative action, for example, but also an increased stability over prostacyclin. Advantages in medicinal use over other prostaglandins have also been found.

Abstract translation: PCT No.PCT / EP81 / 00148 Sec。 371日期1982年5月17日 102（e）日期1982年5月17日PCT提交1981年9月17日PCT公布。 出版物WO82 / 01002 日期：1982年4月1日。前列环素尽管对血管具有有用的扩张作用，但不能保证成功地用作血压降低剂。 （I）的7-氧代前列环素衍生物，其中R 1表示基团OR 3，其中R 3表示氢，直链或支链任选取代的（C 1 -C 10）烷基，任选取代的芳基，任选取代的 环烷基，任选取代的杂环基，或R 1表示基团NHR 4，其中R 4表示氢，或衍生自不饱和或饱和，未取代或取代的（C1-C15）有机羧酸或磺酸的基团，A表示-CH2-CH2-， 顺式-CH = CH-或反式-CH = CH-，W表示具有游离或功能改性的羟基，其可以是α或β位，D和E一起代表直接键，或 D表示直链或支链，不饱和或饱和的任选取代的（C 1 -C 10）亚烷基，E表示氧或直接键，R 2表示直链或支链任选取代的（C 1 -C 10）烷基， 直链或支链 取代的（C 2 -C 10）烯基，或其中D和E一起代表直接键，直链或支链任选取代的（C 2 -C 6）炔基，R 5表示游离或官能改性的羟基， 不仅具有低血压和支气管扩张作用，而且比前列环素具有更高的稳定性。 也发现药物使用优于其他前列腺素的优点。

公开(公告)号：US4315013A

公开(公告)日：1982-02-09

申请号：US122794

申请日：1980-02-19

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

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

IPC: 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 classification number: C07D209/52 ,  C07C405/00 ,  C07C405/0041

Abstract: 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.

Abstract translation: 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。