公开(公告)号：US4882329A

公开(公告)日：1989-11-21

申请号：US303996

申请日：1989-01-30

申请人： Ulrich Lerch ,  Rainer Henning ,  Joachim Kaiser

发明人： Ulrich Lerch ,  Rainer Henning ,  Joachim Kaiser

IPC分类号： C07D401/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/4427 ,  A61K31/445 ,  A61K31/495 ,  A61P3/00 ,  A61P3/14 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D209/34 ,  C07D401/12

CPC分类号： C07D401/12 ,  C07D209/34

摘要： Calcium antagonists of the formula ##STR1## with R(1), R(2), R(3) and R(4) being, inter alia, H, alkyl, alkoxy, halogen, in some cases phenyl; m being 1-4; n being 0-3; X being CH.sub.2, O, S, CO, CHOH or CR.sub.2, and R(5) being various groups containing nitrogen atoms, are described.They are obtained by reaction of compounds II which are likewise new and which contain in place of R(5) a leaving group Y (Cl, Br, I) with the appropriate (cyclic) amino compound.Another synthesis comprises reaction of the appropriate indolinone derivative IV which has a non-etherified hydroxyl group with a side chain which contains a terminal leaving group Z (Cl, Br, I) in the presence of a base.Furthermore, indolinone derivatives VI with an ether side chain with a terminal epoxide group can be reacted with (cyclic) amines to give compounds I.

摘要翻译： 具有R（1），R（2），R（3）和R（4）的式（I）的化合物拮抗剂尤其是H，烷基，烷氧基，卤素，在一些情况下为苯基; m为1-4; n为0-3; X是CH 2，O，S，CO，CHOH或CR 2，R（5）是含有氮原子的各种基团。 它们通过同样新的且含有代替R（5）离去基团Y（Cl，Br，I）的化合物II与适当的（环状）氨基化合物反应而获得。 另一种合成方法包括在碱存在下，具有非醚化羟基的合适的吲哚啉酮衍生物IV与含有末端离去基团Z（Cl，Br，I）的侧链的反应。 此外，具有末端环氧基团的醚侧链的二氢吲哚衍生物VI可以与（环状）胺反应，得到化合物I.

公开(公告)号：US4659838A

公开(公告)日：1987-04-21

申请号：US681329

申请日：1984-12-13

申请人： Ulrich Lerch

发明人： Ulrich Lerch

IPC分类号： C07B57/00 ,  C07B31/00 ,  C07C67/00 ,  C07D209/02 ,  C07D209/42 ,  C07D209/44 ,  C07D209/52 ,  C07D209/12

CPC分类号： C07D209/52

摘要： The invention relates to a process for resolving racemic mixtures of bicyclic imino-.alpha.-carboxylic acid esters into the components of the formula Ia and Ib ##STR1## in which R.sup.1 stands for an aliphatic, cycloaliphatic, aromatic or araliphatic radical,A denotes hydrogen and B and C together form a carbon chain or C denotes hydrogen and A and B together form a carbon chain, by crystallizing diastereoisomeric salts, which comprises preparing the salts of the racemic esters with optically active O,O-diacyltartaric acids in a suitable solvent in which only one of the two diastereoisomeric salts crystallizes in optically pure form, if desired purifying the diastereoisomeric salt by recrystallization, reprecipitation or trituration, and finally adding basec to the salt to cleave it into the pure enantiomer of the formula Ia or Ib.The invention also relates to diastereoisomeric salts of an ester of the formula Ia or Ib and a diacyltartaric acid.

摘要翻译： 本发明涉及一种将双环亚氨基-α-羧酸酯的外消旋混合物分解成式Ia和Ib的组分的方法，其中R1代表脂族，脂环族，芳族或芳脂族基团，A表示氢和 B和C一起形成碳链或C表示氢，A和B一起形成碳链，通过结晶非对映异构体盐，其包括在合适的溶剂中制备外消旋酯与光学活性O，O-二酰基酒石酸的盐 如果需要，通过重结晶，再沉淀或研磨纯化非对映异构体盐，最后加入碱以将其切割成式Ia或Ib的纯对映体，两种非对映异构体盐中只有一种以光学纯的形式结晶。 本发明还涉及式Ia或Ib的酯和二酰基酒石酸的非对映异构体盐。

公开(公告)号：US4595685A

公开(公告)日：1986-06-17

申请号：US684711

申请日：1984-12-21

申请人： Rainer Henning ,  Ulrich Lerch ,  Joachim Kaiser

发明人： Rainer Henning ,  Ulrich Lerch ,  Joachim Kaiser

IPC分类号： A61K31/54 ,  A61K31/5415 ,  A61P3/00 ,  A61P9/00 ,  C07D279/16 ,  C07D317/00 ,  C07D417/04 ,  C07D417/12 ,  C07D279/10

CPC分类号： C07D417/04 ,  C07D279/16 ,  C07D417/12

摘要： Benzothiazine derivatives of the formula I ##STR1## with (R(1), R(1)', R(1)", R(4) and R(4)' equal to hydrogen, alkyl, alkoxy, halogen, nitro, hydroxyl, acetamido or amino; R(2) equal to hydrogen, alkyl, alkenyl, phenyl; R(3) equal to hydrogen, alkyl, alkenyl, phenyl; R(5) equal to hydrogen or (C.sub.1 -C.sub.3)-alkyl; R(6) equal to one of the following groups, ##STR2## with R(7) and R(8) equal to hydrogen, alkyl, cycloalkyl, phenyl; R(9) equal to hydrogen, alkyl, phenyl, pyridyl, pyrimidinyl or benzoyl; R(10) equal to hydrogen, alkyl, phenyl; R(11) equal to hydrogen, hydroxyl, alkoxy or, together with R(12), a bond; and R(12) equal to hydrogen or, together with R(11), a bond; m equal to 1, 2, 3 or 4; n equal to 0 or 1; p equal to 0, 1, 2, 3 or 4, and X equal to oxygen or two hydrogen atoms, and salts of the compounds of the formula I with physiologically tolerated acids and a process for the preparation of compounds I, likewise a method of treatment of disturbances of the calcium balance of a human body are described.

摘要翻译： 式（I）与（R（1），R（1）'，R（1）“，R（4）和R（4）'等于氢，烷基，烷氧基， 卤素，硝基，羟基，乙酰氨基或氨基; R（2）等于氢，烷基，烯基，苯基; R（3）等于氢，烷基，链烯基，苯基; R（5）等于氢或（C1-C3 ） - 烷基; R（6）等于以下基团之一，其中R（7）和R（8）等于氢，烷基，环烷基，苯基; R（9）等于氢， 烷基，苯基，吡啶基，嘧啶基或苯甲酰基; R（10）等于氢，烷基，苯基; R（11）等于氢，羟基，烷氧基或与R（12） 等于氢或与R（11）一起键; m等于1,2,3或4; n等于0或1; p等于0,1,2,3或4，X等于 氧或两个氢原子，以及式I化合物与生理学上可耐受的酸的盐以及制备化合物I的方法，同样是治疗钙粘蛋白紊乱的方法 描述一个人的身体。

公开(公告)号：US5688672A

公开(公告)日：1997-11-18

申请号：US460873

申请日：1995-06-05

申请人： Gerhard Kretzschmar ,  Johannes Meiwes ,  Manfred Schudok ,  Peter Hammann ,  Ulrich Lerch ,  Susanne Grabley

发明人： Gerhard Kretzschmar ,  Johannes Meiwes ,  Manfred Schudok ,  Peter Hammann ,  Ulrich Lerch ,  Susanne Grabley

IPC分类号： C07D233/64 ,  C07D333/24 ,  C07D333/28 ,  C07D333/42 ,  C07D409/06 ,  C07K1/00 ,  C12P13/04 ,  C12P13/06 ,  C12P17/00 ,  C12R1/01 ,  C12R1/19 ,  C12N9/10

CPC分类号： C07D409/06 ,  C07D333/24 ,  C07D333/28 ,  C07D333/42 ,  C12P13/04 ,  C12P17/00 ,  Y10S435/829 ,  Y10S435/849 ,  Y10S435/875 ,  Y10S435/88 ,  Y10S435/886 ,  Y10S435/898

摘要： Process for the biotechnological preparation of L-thienylalanines in enantiomerically pure form from 2-hydroxy-3-thienylacrylic acids L-Thienylalanines are prepared via the hydantoin or the azlactone route. The starting substances used for the biotransformation are 2-hydroxy-3-thienylacrylic acids. The innovative step consists in the transamination of the enol form of the 2-hydroxy-3-thienylacrylic acids to give L-thienylalanines with the aid of biotransformation. The transaminiation is carried out in the presence of L-aspartic acid or L-glutamic acid as amino donor.

摘要翻译： 通过2-羟基-3-噻吩基丙烯酸以对映体纯的形式生物技术制备L-噻吩丙氨酸的方法L-噻吩丙氨酸通过乙内酰脲或吖内酯途径制备。 用于生物转化的起始物质是2-羟基-3-噻吩基丙烯酸。 创新的步骤在于2-羟基-3-噻吩基丙烯酸的烯醇形式的转氨基化，借助于生物转化得到L-噻吩基丙氨酸。 转氨酶在L-天冬氨酸或L-谷氨酸作氨基供体存在下进行。

公开(公告)号：US5231084A

公开(公告)日：1993-07-27

申请号：US711719

申请日：1991-06-07

申请人： Franz Hock ,  Josef Scholtholt ,  Hansjorg Urbach ,  Rainer Henning ,  Ulrich Lerch ,  Wolf-Ulrich Nickel ,  Wolfgang Ruger

发明人： Franz Hock ,  Josef Scholtholt ,  Hansjorg Urbach ,  Rainer Henning ,  Ulrich Lerch ,  Wolf-Ulrich Nickel ,  Wolfgang Ruger

IPC分类号： A61K38/00 ,  C07K5/02

CPC分类号： C07K5/0222 ,  A61K38/00

摘要： The invention relates to new comoounds having a cognition adjuvant action, to the use of ACE inhibitors as medicaments having a cognition adjuvant action, to agents containing them, and to the use thereof for the treatment and prophylaxis of cognitive dysfunctions.

摘要翻译： 本发明涉及具有认知辅助作用的新物质，ACE抑制剂用作具有认知辅助作用的药物，含有它们的药剂，以及其用于治疗和预防认知功能障碍的用途。

公开(公告)号：US5015642A

公开(公告)日：1991-05-14

申请号：US230407

申请日：1988-08-10

申请人： Ulrich Lerch ,  Rainer Henning ,  Hansjorg Urbach ,  Joachim Kaiser

发明人： Ulrich Lerch ,  Rainer Henning ,  Hansjorg Urbach ,  Joachim Kaiser

IPC分类号： A61K31/54 ,  A61K31/5415 ,  A61P3/00 ,  A61P3/14 ,  A61P9/00 ,  C07D279/16 ,  C07D417/12

CPC分类号： C07D417/12 ,  C07D279/16

摘要： Compounds I ##STR1## in which R(1) and R(4) equal H, alkyl, alkoxy, Hal, CF.sub.3, NO.sub.2, OH, acetamido or amino;R(2) equals H, alk(en)yl or phenylalkyl (optionally substituted);R(3) equals H, (cyclo)alk(en)yl-(alkyl), phenyl or phenylalkyl (optionally substituted);A equal CHOH, CO, CH.dbd.CH, C.tbd.C, CH.sub.2, O or S;m equals 1 or 2;n equals 1 to 3;p equals 0 to 4;R(5) equals some amino groups, and their salts, exhibit excellent calcium-antagonistic activity.Processes for their preparation are described.

摘要翻译： 其中R（1）和R（4）等于H，烷基，烷氧基，Hal，CF 3，NO 2，OH，乙酰氨基或氨基的化合物I（I） R（2）等于H，alk（en）或苯基烷基（任选取代的）; R（3）等于H，（环）烷基（en） - （烷基），苯基或苯基烷基（任选取代的）; 相同的CHOH，CO，CH = CH，C 3BOND C，CH 2，O或S; m等于1或2; n等于1到3; p等于0到4; R（5）等于一些氨基，它们的盐表现出优异的钙拮抗作用。 描述其制备方法。

公开(公告)号：US3961062A

公开(公告)日：1976-06-01

申请号：US562048

申请日：1975-03-26

申请人： Ulrich Lerch ,  Ernold Granzer

发明人： Ulrich Lerch ,  Ernold Granzer

IPC分类号： C07D521/00 ,  A61K31/47

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08

摘要： This application discloses pharmaceutical compositions containing, and a method of treatment with, 1-(1-imidazolyl)-isoquinolines of the general formula I and their physiologically tolerated salts, ##SPC1##In which R.sub.1, R.sub.2 and R.sub.3 represent hydrogen, alkyl of 1 to 4 carbon atoms or phenyl, R.sub.1, R.sub.2 and R.sub.3 may be identical or different, R.sub.4 represents hydrogen, alkyl of 1 to 4 carbon atoms, phenyl or chlorine, and R.sub.5 represents hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl or chlorine.

摘要翻译： 本申请公开了含有通式I的1-（1-咪唑基） - 异喹啉及其生理耐受盐的药物组合物，其中R 1，R 2和R 3表示氢，1至4个碳原子的烷基 原子或苯基，R 1，R 2和R 3可以相同或不同，R 4表示氢，1-4个碳原子的烷基，苯基或氯，R 5表示氢，1至6个碳原子的烷基，5至8个碳原子的环烷基 原子，苯基或氯。

公开(公告)号：US5252738A

公开(公告)日：1993-10-12

申请号：US822930

申请日：1992-01-21

申请人： Bernhard Kammermeier ,  Ulrich Lerch

发明人： Bernhard Kammermeier ,  Ulrich Lerch

IPC分类号： C07D217/26

CPC分类号： C07D217/26

摘要： A process for the preparation of racemic and optically active 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is described, in which dihalo-o-xylylenes are cyclized to dicarboxylic acid esters in basic medium using dialkyl N-acylamidomalonates of the formula (CO.sub.2 R.sup.1).sub.2 CHNHCOR.sup.2, in which R.sup.1 is (C.sub.1 -C.sub.4)-alkyl and R.sup.2 is H, (C.sub.1 -C.sub.4)-alkyl or (C.sub.6 -C.sub.12)-aryl, decarboxylated by basic hydrolysis and subsequent acid work-up and then reacted in acid medium to give (D,L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, or dihalo-o-xylylenes are cyclized in basic medium to give the dicarboxylic acid esters and these are reacted directly without isolation in a one-pot process to give (D,L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, if desired the racemic 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted with (-)menthol and p-toluenesulfonic acid to give (-)menthyl (D)- or (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate, then the diastereomers are separated by column chromatography and subjected to basic hydrolysis to give (D)- or (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, or (D,L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is esterified by means of benzyl alcohol and p-toluenesulfonic acid, reacted with D(-)mandelic acid to give benzyl (D)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (D)-mandelate and benzyl (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (D)-mandelate or with L(+)mandelic acid to give benzyl (D)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (L)-mandelate and benzyl (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (L)-mandelate and then the compounds obtained are separated into the optical antipodes by fractional crystallization in an inert solvent and the enantiomers (D)- or (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid are liberated by basic hydrolysis, the chiral auxiliary reagent being recovered.

公开(公告)号：US5091427A

公开(公告)日：1992-02-25

申请号：US401842

申请日：1989-09-01

申请人： Wolf-Ulrich Nickel ,  Rainer Henning ,  Wolfgang Ruger ,  Ulrich Lerch ,  Hansjorg Urbach ,  Franz Hock ,  Gabriele Wiemer

发明人： Wolf-Ulrich Nickel ,  Rainer Henning ,  Wolfgang Ruger ,  Ulrich Lerch ,  Hansjorg Urbach ,  Franz Hock ,  Gabriele Wiemer

IPC分类号： A61K31/495 ,  A61P25/00 ,  A61P25/28 ,  C07D241/08 ,  C07D403/04 ,  C07D405/04 ,  C07D455/04 ,  C07D471/04 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D513/04 ,  C07K1/113 ,  C07K5/06

CPC分类号： C07D487/04 ,  C07D241/08

摘要： The invention relates to compounds of the formula I ##STR1## in which R.sup.1, R.sup.2 and R.sup.4 represent optionally substituted aliphatic, alicyclic, alicyclic-aliphatic, aromatic, araliphatic, heteroaromatic or heteroaromatic-aliphatic radicals, with R.sup.2, if not already covered by the above-mentioned definitions, denoting the side-chain, which is protected if necessary, of a naturally occurring .alpha.-amino acid, R.sup.4 can additionally represent ##STR2## R.sup.3 denotes an optionally substituted aliphatic, alicyclic, aromatic or araliphatic radical, or R.sup.3 and R.sup.4 form, together with the atoms carrying them, a mono-, bi- or tricyclic heterocyclic ring system,agents containing these, and the use thereof as pharmaceuticals having a psychotropic action for the prophylaxis of disorders of the central nervous system, especially having a nootropic action for the treatment of cognitive dysfunctions.

摘要翻译： 本发明涉及式I（I）的化合物，其中R 1，R 2和R 4表示任选取代的脂族，脂环族，脂环族 - 脂族，芳族，芳脂族，杂芳族或杂芳族 - 脂族基团，其中R2，如果不是 由上述定义所涵盖，表示如果必要的话保护的侧链，天然存在的α-氨基酸，R4可以另外表示任选取代的脂族，脂环族，芳族或芳脂族基团， 或R3和R4与携带它们的原子一起形成单环，双环或三环杂环体系，含有它们的试剂，以及作为具有用于预防中枢神经系统疾病的精神作用的药物的用途， 特别是具有用于治疗认知功能障碍的向推动作用。

公开(公告)号：US5043346A

公开(公告)日：1991-08-27

申请号：US340656

申请日：1989-04-20

申请人： Franz Hock ,  Josef Scholtholt ,  Hansjorg Urbach ,  Rainer Henning ,  Ulrich Lerch ,  Wolf-Ulrich Nickel ,  Wolfgang Ruger

发明人： Franz Hock ,  Josef Scholtholt ,  Hansjorg Urbach ,  Rainer Henning ,  Ulrich Lerch ,  Wolf-Ulrich Nickel ,  Wolfgang Ruger

IPC分类号： C07C219/02 ,  A61K38/00 ,  A61P25/28 ,  C07K1/02 ,  C07K1/06 ,  C07K1/113 ,  C07K5/02 ,  C07K5/06

CPC分类号： C07K5/0222 ,  A61K38/005

摘要： The invention relates to amino acid esters of the formula I ##STR1## in which n is 2 and R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meaning indicated in the description, to a process and intermediates for the preparation thereof, to agents containing them, and the use thereof.

摘要翻译： 本发明涉及式I（I）的氨基酸酯，其中n为2，R 1，R 2，R 3，R 4和R 5具有说明书所示的含义，涉及制备方法和中间体 含有它们的试剂及其用途。