公开(公告)号：US5302582A

公开(公告)日：1994-04-12

申请号：US727388

申请日：1991-07-05

申请人： Laszlo Vertesy ,  Peter Schindler ,  Herbert Kogler ,  Hans-Wolfram Fehlhaber ,  Francoise Delevallee

发明人： Laszlo Vertesy ,  Peter Schindler ,  Herbert Kogler ,  Hans-Wolfram Fehlhaber ,  Francoise Delevallee

IPC分类号： C12P21/02 ,  A61K31/70 ,  A61K31/7028 ,  A61K38/00 ,  A61K38/55 ,  A61P25/04 ,  C07H7/02 ,  C07H15/12 ,  C07K1/113 ,  C07K5/06 ,  C07K9/00 ,  C07K14/195 ,  C07K14/41 ,  C07K14/81 ,  C07K17/00 ,  C12N1/14 ,  C12N1/20 ,  C12N9/99 ,  C12P19/26 ,  C12P19/28 ,  C12R1/47

CPC分类号： C12R1/47 ,  C07K9/001 ,  C07K9/003 ,  C12N1/14 ,  A61K38/00

摘要： The invention relates to new biologically active glycopeptides of the general formulaSacch--A--B--Rin which Sacch represents a monosaccharide residue with, where appropriate, the OH groups being partially or completely substituted,A represents the residue of a neutral L- or D-amino acid or --if B is absent--represents the residue of a neutral D-amino acid,B is absent or represents the residue of a neutral L- or D-amino acid or of an optionally .omega.-substituted bi-functional acidic or basic L- or D-amino acid, and R represents hydroxyl, (C.sub.1 -C.sub.8)-alkoxy, an amino radical which is optionally substituted by one or two identical or different radicals from the series comprising (C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.8)-cycloalkyl, (C.sub.5 -C.sub.8)-heteroalkyl or (C.sub.5 -C.sub.8)-heteroaryl, or another acid derivative. These compounds have enkephalinase-inhibiting properties and can thus be used, for example, as analgesics in human and veterinary medicine. The isolation of these compounds from Streptomyces albus ATCC 21838, and further processes for their preparation, are also described.

摘要翻译： 本发明涉及通式为Sacch-ABR的新的生物活性糖肽，其中Sacch代表单糖残基，在适当的情况下OH基部分或完全被取代，A代表中性L-或D-氨基酸的残基 或 - 如果B不存在 - 表示中性D-氨基酸的残基，B不存在或表示中性L-或D-氨基酸或任选（ω） - 取代的双官能酸性或碱性的残基 L-或D-氨基酸，R代表羟基，（C1-C8） - 烷氧基，任选被一个或两个相同或不同的基团取代的氨基，所述基团包括（C 1 -C 8） - 烷基， -C 8） - 环烷基，（C 5 -C 8） - 杂烷基或（C 5 -C 8） - 杂芳基或其它酸衍生物。 这些化合物具有脑啡肽酶抑制性质，因此可用于例如人和兽医学中的镇痛药。 这些化合物从Streptomyces albus ATCC 21838的分离以及其制备方法也被描述。

公开(公告)号：US4877796A

公开(公告)日：1989-10-31

申请号：US084456

申请日：1987-08-12

申请人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee ,  Michel Fortin

发明人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee ,  Michel Fortin

IPC分类号： A61K31/47 ,  A61P7/06 ,  A61P7/10 ,  A61P9/06 ,  A61P9/12 ,  A61P25/04 ,  C07D215/40 ,  C07D401/12 ,  C07D409/12

CPC分类号： C07D215/40

摘要： A compound selected from the group consisting of all enantiomeric and diastereoisomeric forms of a decahydroquinoline of the formula ##STR1## wherein R.sub.1 is alkyl of 1 to 5 carbon atoms, R.sub.2 is selected from the group consisting of hydrogen and akyl of 1 to 5 carbon atoms, A is selected from the group consisting of --(CH.sub.2).sub.n --, --CH.sub.2 O-- and alkylene substituted with alkyl having a total of 2 to 8 carbon atoms, n is an integer from 0 to 5, Z is selected from the group consisting of optionally substituted phenyl, optionally substituted naphthyl, optionally substituted indenyl, optionally substituted heteromonocycle of 5 to 6 members and optionally substituted heterobicycle with the proviso that when Z is o-alkoxy-phenyl, A is not --(CH.sub.2).sub.n -- in which n is O, and their non-toxic, pharmaceutically acceptable acid addition salts and their quaternary ammonium salts and intermediates having analgesic, diuretic, hypotensive, anti-arrithmic and anti-cerebral-ischaemic properties.

摘要翻译： 选自下式的化合物：其中R 1为1至5个碳原子的烷基，R 2选自氢和1至5个碳原子的烷基的所有对映异构体和非对映异构体形式的十氢喹啉的化合物 原子，A选自 - （CH 2）n - ， - CH 2 O-和被具有总共2至8个碳原子的烷基取代的亚烷基，n是0至5的整数，Z选自 由任选取代的苯基，任选取代的萘基，任选取代的茚基，任选取代的5至6个成员的异单环和任选取代的杂双环，条件是当Z是邻 - 烷氧基 - 苯基时，A不是 - （CH2）n-，其中 n是O，它们的无毒的药学上可接受的酸加成盐及其季铵盐和具有止痛，利尿，降压，抗对数和抗脑缺血性质的中间体。

公开(公告)号：US4839358A

公开(公告)日：1989-06-13

申请号：US159265

申请日：1988-02-23

申请人： Jean-Paul Vevert ,  Francoise Delevallee ,  Jean-Claude Gasc ,  Francis Petit

发明人： Jean-Paul Vevert ,  Francoise Delevallee ,  Jean-Claude Gasc ,  Francis Petit

IPC分类号： C07D295/22 ,  A61K31/40 ,  A61K31/445 ,  A61K31/4468 ,  A61K31/495 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/54 ,  A61K31/55 ,  A61P3/00 ,  A61P25/04 ,  A61P25/24 ,  A61P25/26 ,  C07D211/56 ,  C07D265/30 ,  C07D277/04 ,  C07D295/32

CPC分类号： C07D295/32

摘要： Novel .alpha.-mercaptomethyl-benzene propanamides of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen and ##STR2## R.sub.1 ' is selected from the group consisting of alkyl of 1 to 5 carbon atoms and aryl optionally substituted with at least one member of the group consisting of --OH, --NO.sub.2, halogen and alkyl and alkoxy of 1 to 5 carbon atoms, X and X' are individually selected from the group consisting of hydrogen, alkyl and alkoxy of 1 to 5 carbon atoms, --OH, halogen and --CF.sub.3, R.sub.2 is selected from the group consisting of pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl, tetrahydrothiazinyl and hexahydroazepinyl, all optionally substituted with at least one member of the group consisting of alkyl and alkoxy of 1 to 5 carbon atoms, --OH, --NO.sub.2, --CF.sub.3, halogen and acyl of an organic carboxylic acid of 1 to 7 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity, antidepression and anxiolytic properties.

摘要翻译： 式Ⅰ的新型α-巯基甲基 - 苯丙酰胺，其中R 1选自氢和R 1'选自1至5个碳原子的烷基和任选被 由-OH，-NO 2，卤素和1至5个碳原子的烷基和烷氧基组成的组中的至少一个成员，X和X'分别选自氢，烷基和1至5个碳原子的烷氧基， -OH，卤素和-CF 3，R 2选自吡咯烷基，吗啉基，哌啶基，哌嗪基，四氢噻嗪基和六氢氮杂卟啉，全部任选被至少一个由1至5个碳原子的烷基和烷氧基组成的组取代 具有1至7个碳原子的有机羧酸的-OH，-NO 2，-CF 3，卤素和酰基及其具有止痛活性，抗抑郁和抗焦虑性质的无毒的药学上可接受的酸加成盐。

公开(公告)号：US5278180A

公开(公告)日：1994-01-11

申请号：US863801

申请日：1992-05-04

申请人： Francois Clemence ,  Claudine Maushart ,  Philippe Mackiewicz ,  Francoise Delevallee

发明人： Francois Clemence ,  Claudine Maushart ,  Philippe Mackiewicz ,  Francoise Delevallee

IPC分类号： C07D249/08 ,  A61K31/41

CPC分类号： C07D249/08

摘要： A novel process for the preparation of 4H-1,2,4-triazoles in their racemic or optically active forms of the formula ##STR1## wherein the compounds have analgesic activity.

摘要翻译： 一种用于制备其式（*化学结构*）I的外消旋或光学活性形式的4H-1,2,4-三唑的新方法，其中化合物具有止痛活性。

公开(公告)号：US5098934A

公开(公告)日：1992-03-24

申请号：US542731

申请日：1990-06-22

申请人： Jean-Paul Vevert ,  Francoise Delevallee ,  Rogert Deraedt

发明人： Jean-Paul Vevert ,  Francoise Delevallee ,  Rogert Deraedt

IPC分类号： C07D257/06 ,  A61K31/16 ,  A61K31/265 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/42 ,  A61K31/421 ,  A61K31/423 ,  A61K31/425 ,  A61K31/426 ,  A61K31/428 ,  A61K31/44 ,  A61K31/4409 ,  A61P25/04 ,  A61P43/00 ,  C07C67/00 ,  C07C323/60 ,  C07C325/00 ,  C07C327/32 ,  C07D213/75 ,  C07D235/12 ,  C07D235/14 ,  C07D235/30 ,  C07D257/04 ,  C07D261/14 ,  C07D263/48 ,  C07D263/58 ,  C07D277/00 ,  C07D277/18 ,  C07D277/20 ,  C07D277/46 ,  C07D277/82

CPC分类号： C07D213/75 ,  C07D235/30 ,  C07D277/18 ,  C07D277/46 ,  C07D277/82

摘要： Novel .omega.-mercaptopropanamides and their homologs of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen and ##STR2## R.sub.1 ' is selected from the group consisting of alkyl of 1 to 5 carbon atoms and aryl optionally substituted with at least one member of the group consisting of --OH, alkyl and alkoxy of 1 to 5 carbon atoms, --NO.sub.2 and halogen, n is an integer from 1 to 5, R.sub.2 is selected from the group consisting of hydrogen alkyl of 1 to 5 carbon atoms and aryl and aralkyl of 6 to 15 carbon atoms optionally substituted with at least one member of the group consisting of alkyl and alkoxy of 1 to 5 carbon atoms, --OH, halogen and --CF.sub.3, R.sub.3 is selected from the group consisting of a) hydrogen, b) phenyl optionally substituted with at least one member of the group consisting of alkyl and alkoxy of 1 to 5 carbon atoms, --OH, --NO.sub.2, halogen, --CF.sub.3, carboxymethyl, alkoxycarbonylmethyl with 1 to 5 alkoxy carbon atoms, aralkoxy of 7 to 15 carbon atoms and ##STR3## and c) a heterocycle selected from the group consisting of thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, benzimidazolyl, benzothiazolyl and benzoxazolyl, all optionally substituted with alkyl of 1 to 5 carbon atoms, X and X' are individually selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms and their salts with non-taxic, pharmaceutically acceptable acids and bases with the proviso that when R.sub.2 is hydrogen and n is 1, R.sub.3 is not phenyl optionally substituted with at least one member of the group consisting of halogen and alkyl and alkoxy of 1 to 5 carbon atoms and when R.sub.2 is methyl and n is 1, R.sub.3 is not phenyl substituted with carboxymethyl having very good analgesic activity and enkephalinase inhibiting activity.

摘要翻译： 新型ω-巯基丙酰胺及其同系物式（Ⅰ）其中R 1选自氢和R 1'选自1至5个碳原子的烷基和任选被 由1至5个碳原子的-OH，烷基和烷氧基组成的组中的至少一个，-NO 2和卤素，n是1至5的整数，R 2选自1至5个碳的烷基 6至15个碳原子的芳基和芳烷基，任选被至少一个由1至5个碳原子的烷基和烷氧基取代的基团，-OH，卤素和-CF 3，R 3选自 ）氢，b）任选被至少一个由1-5个碳原子的烷基和烷氧基取代的苯基，-OH，-NO 2，卤素，-CF 3，羧甲基，具有1至5个烷氧基碳原子的烷氧羰基甲基， 7至15个碳原子的芳烷氧基和c）a 选自噻唑基，4,5-二氢 - 噻唑基，吡啶基，恶唑基，异恶唑基，咪唑基，嘧啶基，四唑基，苯并咪唑基，苯并噻唑基和苯并恶唑基的杂环，全部任选被1至5个碳原子的烷基取代，X和X “独立地选自氢和1至5个碳原子的烷基，并且它们与非税，药学上可接受的酸和碱的盐，条件是当R 2是氢且n是1时，R 3不是任选被取代的苯基 与卤素和1至5个碳原子的烷基和烷氧基中的至少一个成员，当R 2是甲基且n是1时，R 3不是具有非常好的镇痛活性和脑啡肽酶抑制活性的羧甲基取代的苯基。

公开(公告)号：US4963567A

公开(公告)日：1990-10-16

申请号：US371995

申请日：1989-06-27

申请人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee ,  Michel Fortin

发明人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee ,  Michel Fortin

IPC分类号： A61K31/47 ,  A61P7/06 ,  A61P7/10 ,  A61P9/06 ,  A61P9/12 ,  A61P25/04 ,  C07D215/40 ,  C07D401/12 ,  C07D409/12

CPC分类号： C07D215/40

摘要： A compound selected from the group consisting of all enantiomeric and diastereoisomeric forms of a decahydroquinoline of the formula ##STR1## wherein R.sub.1 is alkyl of 1 to 5 carbon atoms, R.sub.2 is selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms, A is selected from the group consisting of --(CH.sub.2).sub.n --, --CH.sub.2 O-- and alkylene substituted with alkyl having a total of 2 to 8 carbon atoms, n is an integer from 0 to 5, Z is selected from the group consisting of optionally substituted phenyl, optionally substituted naphthyl, optionally substituted indenyl, optionally substituted heteromonocycle of 5 to 6 members and optionally substituted hetero-bicycle with the proviso that when Z is o-alkoxy-phenyl, A is not --(CH.sub.2).sub.n -- in which n is O, and their non-toxic, pharmaceutically acceptable acid addition salts and their quaternary ammonium salts and intermediates having analgesic, diuretic, hypotensive, anti-arrithmic and anti-cerebral-ischaemic properties.

公开(公告)号：US4880803A

公开(公告)日：1989-11-14

申请号：US103919

申请日：1987-10-01

申请人： Francoise Delevallee ,  Roger Deraedt ,  Josette Benzoni

发明人： Francoise Delevallee ,  Roger Deraedt ,  Josette Benzoni

IPC分类号： C07D209/58 ,  A61K31/40 ,  A61K31/403 ,  A61K31/445 ,  A61K31/495 ,  A61K31/535 ,  A61K31/55 ,  A61P5/38 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P35/00 ,  A61P37/00

CPC分类号： A61K31/40

摘要： A method of inducing immunostimulating activity in warm-blooded animals comprising administering to warm-blooded animals an immunostimulating amount of at least one maleo-pimaric acid compound of the formula ##STR1## wherein R.sub.1 and R.sub.2 together with the nitrogen to which they are attached form an optionally substituted saturated heterocycle optionally containing at least one other heteroatom, Y is selected from the group consisting of hydrogen, amino, alkyl of 1 to 5 carbon atoms optionally substituted with at least one hydroxy, dialkylamino with alkyl of 1 to 5 carbon atoms, alkoxy carbonyl of 2 to 5 carbon atoms, acyl of an organic carboxylic acid of 1 to 5 carbon atoms and ##STR2## X is an alkylene of 1 to 5 carbon atoms and R.sub.1 and R.sub.2 have the above definition.

摘要翻译： 一种在温血动物中诱导免疫刺激活性的方法，包括向温血动物施用免疫刺激量的至少一种下式的马来酸 - 海松酸化合物，其中R1和R2与它们所连接的氮一起 形成任选地含有至少一个其它杂原子的任选取代的饱和杂环，Y选自氢，氨基，任选被至少一个羟基，二烷基氨基与1至5个碳原子的烷基取代的1至5个碳原子的烷基 2至5个碳原子的烷氧基羰基，1至5个碳原子的有机羧酸的酰基，X是1至5个碳原子的亚烷基，R 1和R 2具有上述定义。

公开(公告)号：US4614736A

公开(公告)日：1986-09-30

申请号：US718175

申请日：1985-04-01

申请人： Francoise Delevallee ,  Roger Deraedt ,  Simone Jouquey

发明人： Francoise Delevallee ,  Roger Deraedt ,  Simone Jouquey

IPC分类号： A61K9/02 ,  A61K31/57 ,  A61P5/38 ,  C07J5/00

CPC分类号： A61K31/57

摘要： A novel method of treating inflammation of the colon and rectum of warm-blooded animals comprising administering to the colon and rectum of warm-blooded animals an anti-inflammatorily effective amount of 9.alpha.,11.beta.-dichloro-16.alpha.-methyl-21-oxycarbonyldicyclohexylmethoxy-.DELTA..sup.1,4 -pregnadiene-3,20-dione.

摘要翻译： 一种治疗温血动物结肠和直肠炎症的新方法，包括向结肠和直肠的温血动物施用抗炎剂有效量的9α，11β-二氯-16α-甲基-21- 氧羰基二环己基甲氧基-TATA1,4-孕烯二烯-3,20-二酮。

公开(公告)号：US5234944A

公开(公告)日：1993-08-10

申请号：US970776

申请日：1992-11-03

申请人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee ,  Michel Fortin

发明人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee ,  Michel Fortin

IPC分类号： C07D295/135 ,  C07D311/96

CPC分类号： C07D295/135 ,  C07D311/96

摘要： A compound selected from the group consisting of enantiomers and diastereoisomer forms and mixtures thereof of the formula ##STR1## wherein R.sub.6 is selected from the group consisting of hydrogen, halogen and alkyl and alkoxy of 1 to 5 carbon atoms, R.sub.1 and R.sub.2 are individually hydrogen or alkyl of 1 to 5 carbon atoms or taken together with the carbon atoms to which they are attached form a cycloalkyl of 3 to 6 carbon atoms optionally containing a heteroatom selected from the group consisting of --S--, --O-- and --N--, one of A and B has the formula ##STR2## and the other has the formula ##STR3## R is selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms, Z is selected from the group consisting of --(CH.sub.2).sub.n --, branched alkylene of 2 to 8 carbon atoms and --CH.sub.2 O--, n is an integer of 0 to 5, X, X' and X" are individually selected from the group consisting of hydrogen, alkyl and alkoxy of 1 to 4 carbon atoms, halogen, --OH, --CF.sub.3, --NO.sub.2, --NH.sub.2, mono and dialkylamino of 1 to 4 alkyl carbon atoms and sulfamino, R.sub.3 and R.sub.4 are individually selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms or taken together with the nitrogen atom to which they are attached form a 5 to 6 member heterocycle optionally containing a member of the group consisting of --O--, --S-- and ##STR4## R.sub.1 ' is hydrogen or alkyl of 1 to 4 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having a strong affinity for optical receptors, central analgesic, diuretic, anti-arrythmic, hypotensive and cerebral anti-ischemic activity.

摘要翻译： 选自下组的对映异构体和非对映异构体形式的化合物及其混合物，其中R 6选自氢，卤素和1至5个碳原子的烷基和烷氧基，R 1和R 2分别为 氢或1至5个碳原子的烷基或与它们所连接的碳原子一起形成3至6个碳原子的环烷基，任选地含有选自-S - ， - O-和-N - ，A和B中的一个具有式，另一个具有式（Ia）的化合物，其选自氢和1至5个碳原子的烷基，Z选自 - （ CH 2）n支链亚烷基，-CH 2 O-，n为0〜5的整数，X，X'和X“分别选自氢，烷基和烷氧基的1 至4个碳原子，卤素，-OH，-CF 3，-NO 2，-NH 2，1至4个烷基的单和二烷基氨基 碳原子和磺氨基，R3和R4分别选自氢和1至5个碳原子的烷基，或与它们所连接的氮原子一起形成5至6个成员杂环，任选地含有 由-O-，-S-和R IMA'组成的基团是氢或1至4个碳原子的烷基，它们对光学受体具有强亲和力的无毒的药学上可接受的酸加成盐，中枢性镇痛药，利尿剂， 抗焦虑，降压和脑抗缺血活性。

公开(公告)号：US4925859A

公开(公告)日：1990-05-15

申请号：US167375

申请日：1988-03-31

申请人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee

发明人： Francois Clemence ,  Odile Le Martret ,  Francoise Delevallee

IPC分类号： C07D213/75 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/505 ,  A61P29/00 ,  C07D213/82 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14

CPC分类号： C07D213/82 ,  C07D417/12

摘要： Novel pyridines of the formula ##STR1## wherein R is selected from the group consisting of (a) phenyl optionally substituted with at least one member of the group consisting of hydroxy, alkyl and alkoxy of 1 to 5 carbon atoms, halogen, --CF.sub.3 and --NO.sub.2 and (b) a 5 to 6 member hetercyclic optionally substituted with alkyl of 1 to 5 carbon atoms, R.sub.1 and R.sub.2 are individually selected from the group consisting of (a) alkyl of 1 to 5 carbon atoms, (b) 5 to 6 member heterocyclic optionally substituted with alkyl of 1 to 5 carbon atoms and (c) phenyl and naphthyl optionally substituted with at least one member of the group consisting of hydroxy, alkyl and alkoxy of 1 to 5 carbon atoms, halogen, --NO.sub.3 and --CF.sub.3, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, --(CF.sub.2).sub.n --CF.sub.3 and ##STR2## n is an integer from 0 to 4 and Alk is alkyl of 1 to 5 carbon atoms and their non-toxic, pharmaceutically acceptable salts with acids and bases having anti-inflammatory and anti-rheumatic properties.

摘要翻译： 式（I）的新吡啶，其中R选自（a）任选被至少一个由1-5个碳原子的羟基，烷基和烷氧基组成的组中的一个取代基取代的苯基，卤素，-CF 3 和（b）任选被1至5个碳原子的烷基取代的5至6元杂环，R 1和R 2分别选自（a）1至5个碳原子的烷基，（b）5 至（C）任选被1至5个碳原子的烷基取代的6元杂环，和（c）任选被至少一个选自1至5个碳原子的烷基和烷氧基的基团取代的苯基和萘基，卤素，-NO 3和 -CF 3，R 3选自氢，1〜5个碳原子的烷基， - （CF 2）n -CF 3，n为0〜4的整数，Alk为1〜5个碳原子的烷基 和它们的无毒，药学上可接受的盐与酸和碱具有抗炎和抗风湿性 matic属性。