公开(公告)号：US4535158A

公开(公告)日：1985-08-13

申请号：US533538

申请日：1983-09-19

Applicant: Klaus Klessing

Inventor： Klaus Klessing

IPC: A61K31/34 ,  A61K31/52 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D473/00 ,  C07D473/08 ,  C07D493/04 ,  C07D519/00 ,  C07D473/10 ,  C07D473/34

CPC classification number: C07D473/00 ,  C07D473/08 ,  C07D493/04

Abstract: Aminodesoxy-1.4;3.6-dianhydrohexitol derivatives of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2 in each case independently of one another, signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms or wherein R.sup.1 signifies a hydrogen atom and R.sup.2 an adamant(1)yl radical or wherein R.sup.1 , and R.sup.2, together with the nitrogen atom to which they are attached, (a) signify the residue of a cyclic, non-aromatic secondary amine possibly containing a further hetero atom or (b) the aden(9)yl radical possibly mono- or disubstituted on the 6-amino group or (c) the 6-alkylmercaptopurin(9)yl radical or (d) the theophyllin-(7)yl radical or (e) the 6-chloropurin-9-yl radical or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an .omega.-theophyllin(7)ylalkyl radical or an .omega.-theobromin-1-ylalkyl radical or an .omega.-(N,N'-di-lower alkyl-substituted xanthin-N"-yl)alkyl radical, whereby "lower alkyl" signifies an alkyl group with 1 to 5 C-atoms, or an .omega.-adenin-9-ylalkyl radical, whereby the alkyl radical has 2 to 7 C-atoms and can be straight-chained or branched, and wherein R.sup.3 signifies a hydrogen atom, a methanesulphonyl or toluenesulphonyl group, as well as their acid-addition salts.Processes for the preparation of said compounds and use of said compounds as reactive intermediate products for the preparation of the corresponding pharmacologically-effective amino-desoxy-1.4;3.6-dianhydrohexitol nitrates.

Abstract translation: 具有通式I的氨基脱氧-14; 3.6-二羟基己糖醇衍生物，其中R 1和R 2各自独立地表示氢原子或具有1至4个C原子的低级烷基，或其中 R1表示氢原子，R2表示金刚烷基（1）基或其中R1和R2与它们所连接的氮原子一起，（a）表示可能含有 另外的杂原子或（b）可能在6-氨基上单或二取代的腺苷（9）基团，或（c）6-烷基巯基嘌呤（9）基或（d）叶茶素 - （7）基） 或（e）6-氯嘌呤-9-基或其中R1表示氢原子或具有1至4个C原子的低级烷基，R2表示ω-叶茶素（7）基烷基或ω-异丁酰基-1 - 烷基或ω - （N，N'-二 - 低级烷基取代的黄嘌呤-N“ - 基）烷基，其中”低级烷基“表示具有1至5个C原子的烷基，或 ω-腺苷-9-烷基，其中烷基具有2至7个C原子并且可以是直链或支链的，并且其中R3表示氢原子，甲磺酰基或甲苯磺酰基，以及它们的酸 - 加成盐。 用于制备所述化合物的方法和所述化合物作为反应性中间体产物的用途，用于制备相应的药理学有效的氨基脱氧-1,4,3,6-二脱水己醇硝酸盐。

公开(公告)号：US06444662B1

公开(公告)日：2002-09-03

申请号：US09622151

申请日：2000-08-11

Applicant: Shyam Sunder Chatterjee ,  Clemens Erdelmeier ,  Klaus Klessing ,  Dieter Marme ,  Christoph Schächtele

Inventor： Shyam Sunder Chatterjee ,  Clemens Erdelmeier ,  Klaus Klessing ,  Dieter Marme ,  Christoph Schächtele

IPC: C07C5036

CPC classification number: C07C49/743 ,  C07C45/78

Abstract: Described are salts of hyperforin and adhyperforin of formula I [A−]m[B]p+  (I) wherein m is an integer from 1 to 3, p is equal to m and gives the total number of positive charges of the residue [B], [A−] is an anion of formula II with n=0 or 1 and [B]p+ is an ion of an alkali metal or an ammonium ion of a salt-forming nitrogen base of formula III wherein R1 through R4 have a variety of meanings including hydrogen, alkyl, cycloalkyl and similar groups which in turn may be substituted with one or more substituents. The salts serve inter alia for enriching or purifying hyperforin and adhyperforin from St. John's Wort extracts. Pharmaceutical preparations containing the salts are used for treating Alzheimer's Disease.

Abstract translation: 描述了式I的高效蛋白和高血压素的盐，其中m是1至3的整数，p等于m并且给出残基[B]的正电荷的总数，[A-]是式II的阴离子， n = 0或1，[B] p +是式III的形成盐的氮碱的碱金属或铵离子的离子，其中R1至R4具有各种含义，包括氢，烷基，环烷基和类似基团， 可以被一个或多个取代基取代。 这些盐特别用于从圣约翰草提取物中富集或纯化高效蛋白和高血压素。 含有盐的药物制剂用于治疗阿尔茨海默病。

公开(公告)号：US4479951A

公开(公告)日：1984-10-30

申请号：US285406

申请日：1981-07-20

Applicant: Klaus Klessing ,  Shyam S. Chatterjee

Inventor： Klaus Klessing ,  Shyam S. Chatterjee

IPC: A61K31/52 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D493/04 ,  C07D519/00 ,  A61K31/535 ,  C07D473/34

CPC classification number: C07D493/04

Abstract: 1.4;3.6-Dianhydrohexitol nitrates substituted by purine bases, namely, adenyl-desoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula Ia as well as theophyllinyl-desoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula Ib, ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and, independently of one another signify(a) a hydrogen atom,(b) a straight-chained or branched alkyl group with 1 to 7 C-atoms,(c) an .omega.-phenylalkyl group, whereby the alkyl group has 1 to 7 C-atoms and whereby the phenyl ring can be halogen-substituted in the p-position, or wherein(d) R.sup.1 signifies one of the residues given under (a) to (c) and R.sup.2 an acyl radical or an aliphatic, possibly methyl-substituted monocarboxylic acid with 2 to 7 C-atoms, or wherein(e) R.sup.1 and R.sup.2, together with the nitrogen atom to which they are bound, represent the residue of a cyclic, non-aromatic, secondary amine possibly containing a further hetero atom,as well as their physiologically acceptable acid-addition salts.Process for the preparation of said compounds and pharmaceutical compositions containing said compounds.

Abstract translation: 1.4;由嘌呤碱取代的3.6-二氢己糖醇硝酸盐，即通式Ia的茚基脱氧-1,4,3,6-二脱水己醇硝酸盐以及通式Ib的叶酸 - 脱氧-1.4,3.6-二羟基己醇硝酸盐， （Ia）其中R 1和R 2相同或不同，并且彼此独立地表示（a）氢原子，（b）具有1至7个C原子的直链或支链烷基 ，（c）ω-苯基烷基，由此烷基具有1至7个C原子，由此苯环可以在对位被卤素取代，或其中（d）R 1表示下列给出的残基之一： （a）至（c）和R 2为具有2至7个C原子的酰基或脂族，可能为甲基取代的单羧酸，或其中（e）R 1和R 2与它们所键合的氮原子一起， 代表可能含有另外的杂原子的环状，非芳香族仲胺的残基，以及它们的生理学接受 有机酸加成盐。 制备所述化合物和含有所述化合物的药物组合物的方法。

公开(公告)号：US4965283A

公开(公告)日：1990-10-23

申请号：US372640

申请日：1989-06-28

Applicant: Klaus Klessing ,  Shyam S. Chatterjee

Inventor： Klaus Klessing ,  Shyam S. Chatterjee

IPC: C07D307/60 ,  A61K31/365 ,  A61K31/40 ,  A61K31/4025 ,  A61P25/08 ,  C07D405/12 ,  C07D407/12

CPC classification number: C07D307/60

Abstract: Novel esters of amino acids are proposed of which the alcoholic components are formed from threo-4-alkoxy-5-arylhydroxymethyl-2(5H)-furanones. These esters may be present in the form of racemates, pure diastereomers or enantiomers or in the form of diastereomer or enantiomer mixtures. The compounds are anticonvulsive and antiepileptic and due to their good water solubility are easier to administer and more readily absorbable than known anti-convulsives and antiepileptics. A novel process is also disclosed which leads stereoselectively to the diastereomers or the enantiomers or mixtures thereof. The invention further relates to the use of the novel amino acid esters as pharmaceutical preparations and in the production of pharmaceutical preparations.

Abstract translation: PCT No.PCT / DE88 / 00684 Sec。 371日期：1989年6月8日 102（e）日期1989年6月8日PCT公布1988年11月4日PCT Pub。 第WO89 / 04310号公报 日期：1989年5月18日。提出了新型的氨基酸酯，其中的醇组分由苏氨基-4-烷氧基-5-芳基羟甲基-2（5H） - 呋喃酮形成。 这些酯可以以外消旋体，纯非对映异构体或对映异构体的形式或以非对映异构体或对映异构体混合物的形式存在。 这些化合物是抗惊厥和抗癫痫药物，由于其良好的水溶性比已知的抗惊厥药和抗癫痫剂更易于施用并且更容易吸收。 还公开了一种新方法，其立体选择性地引发非对映异构体或其对映异构体或其混合物。 本发明还涉及新型氨基酸酯作为药物制剂和制备药物制剂的用途。

公开(公告)号：US4622324A

公开(公告)日：1986-11-11

申请号：US642140

申请日：1984-08-17

Applicant: Klaus Klessing ,  Shyam S. Chatterjee

Inventor： Klaus Klessing ,  Shyam S. Chatterjee

IPC: A61K31/52 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D493/04 ,  C07D519/00 ,  C07D473/34 ,  A61K31/535

CPC classification number: C07D493/04

Abstract: 1.4;3.6-Dianhydrohexitol nitrates substituted by purine bases, namely, adenyl-desoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula Ia as well as theophyllinyl-desoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula Ib, ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and, independently of one another signify(a) a hydrogen atom,(b) a straight-chained or branched alkyl group with 1 to 7 C-atoms,(c) an .omega.-phenylalkyl group, whereby the alkyl group has 1 to 7 C-atoms and whereby the phenyl ring can be halogen-substituted in the p-position, or wherein(d) R.sup.1 signifies one of the residues given under (a) to (c) and R.sup.2 an acyl radical or an aliphatic, possibly methyl-substituted monocarboxylic acid with 2 to 7 C-atoms, or wherein(e) R.sup.1 and R.sup.2, together with the nitrogen atom to which they are bound, represent the residue of a cyclic, non-aromatic, secondary amine possible containing a further hetero atom,as well as their physiologically acceptable acid-addition salts.Process for the preparation of said compounds and pharmaceutical compositions containing said compounds.

Abstract translation: 1.4;由嘌呤碱取代的3.6-二氢己糖醇硝酸盐，即通式Ia的茚基脱氧-1,4,3,6-二脱水己醇硝酸盐以及通式Ib的叶酸 - 脱氧-1.4,3.6-二羟基己醇硝酸盐， （Ia）其中R 1和R 2相同或不同，并且彼此独立地表示（a）氢原子，（b）具有1至7个C原子的直链或支链烷基 ，（c）ω-苯基烷基，由此烷基具有1至7个C原子，由此苯环可以在对位被卤素取代，或其中（d）R 1表示下列给出的残基之一： （a）至（c）和R 2为具有2至7个C原子的酰基或脂族，可能为甲基取代的单羧酸，或其中（e）R 1和R 2与它们所键合的氮原子一起， 代表可能含有另外的杂原子的环状，非芳香族仲胺的残基，以及它们的生理学接受 有机酸加成盐。 制备所述化合物和含有所述化合物的药物组合物的方法。

公开(公告)号：US4855320A

公开(公告)日：1989-08-08

申请号：US46586

申请日：1987-05-04

Applicant: Shyam S. Chatterjee ,  Klaus Klessing

Inventor： Shyam S. Chatterjee ,  Klaus Klessing

IPC: C07D307/56 ,  A61K31/341 ,  A61K31/365 ,  A61P25/08 ,  B01J23/46 ,  C07C51/353 ,  C07C59/64 ,  C07C67/00 ,  C07C67/30 ,  C07C69/734 ,  C07C201/00 ,  C07C205/56 ,  C07D307/60

CPC classification number: C07C59/64 ,  C07D307/60

Abstract: The present invention provides 5-arylalkyl-4-alkoxy-2(5H)-furanones of the formula: ##STR1## wherein the oxygen atoms on C-5 and C-.alpha., relative to one another, are in the threo-position, with the exclusion of those compounds of the formula (I) wherein R.sup.2 is H or CH.sub.3 when n=0 or 2, R.sup.o =H, R.sup.1 =CH.sub.3, R.sup.3 =H and R.sup.4 =H.The present invention also provides processes for their preparation, as well as new 3-alkoxy-5-(subst.)-phenyl-2(E), 4(E)-pentadienoates as reactive intermediates for the preparation of the new furanone derivatives.The new furanone derivatives of the threo series are active as anticonvulsives/anti-epileptics. Therefore, the present invention also provides medicaments which contain these new furanone derivatives, as well as known furanones, the anticonvulsive/anti-epileptic effectiveness of which has been found for the first time.

Abstract translation: 本发明提供下式的5-芳基烷基-4-烷氧基-2（5H） - 呋喃酮：其中C-5和C-α上的氧原子相对于彼此处于苏打 位置，排除那些当n = 0或2时R 2为H或CH 3的式（I）化合物，Ro = H，R 1 = CH 3，R 3 = H和R 4 = H。 本发明还提供其制备方法，以及作为制备新的呋喃酮衍生物的反应中间体的新的3-烷氧基-5-（低级） - 苯基-2（E），4（E） - 戊二酸二乙酯。 苏氨酸系列的新呋喃酮衍生物作为抗惊厥药/抗癫痫药物是有活性的。 因此，本发明还提供含有这些新的呋喃酮衍生物的药物以及已知的呋喃酮，其首次发现其抗惊厥/抗癫痫效果。

公开(公告)号：US4542137A

公开(公告)日：1985-09-17

申请号：US285425

申请日：1981-07-20

Applicant: Klaus Klessing ,  Shyam S. Chatterjee

Inventor： Klaus Klessing ,  Shyam S. Chatterjee

IPC: A61K31/505 ,  A61K31/52 ,  A61P9/00 ,  A61P9/08 ,  C07D473/06 ,  C07D473/08 ,  C07D473/10 ,  C07D493/04 ,  C07D519/00

CPC classification number: C07D493/04 ,  C07D473/06 ,  C07D473/08 ,  C07D473/10

Abstract: Alkylaminodesoxy-1.4;3.6-dianhydrohexitol nitrates substituted by purine bases of the general formula I, ##STR1## wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms, X a straight-chained or branched alkyl or hydroxyalkyl group with 1 to 7 C-atoms, Y a 1,3-dialkylxanthin-7-yl or a 3,7-dialkylxanthin-1-yl group, each with straight or branched-chained alkyl groups with 1 to 5 C-atoms, or an adenin-9-yl group, as well as their physiologically acceptable acid-addition salts. Process for the preparation of said compounds and pharmaceutical compositions containing said compounds.

Abstract translation: 由通式I的嘌呤碱取代的烷基氨基脱氧-1,4,3,3-二脱水己醇硝酸盐，其中R 1表示氢原子或具有1至4个C原子的低级烷基，X为直链或支链烷基或羟烷基 具有1至7个C原子的基团，Y为1,3-二烷基黄素-7-基或3,7-二烷基黄嘌呤-1-基，每个具有1至5个C原子的直链或支链烷基， 或腺嘌呤-9-基，以及它们的生理上可接受的酸加成盐。 制备所述化合物和含有所述化合物的药物组合物的方法。

公开(公告)号：US4413122A

公开(公告)日：1983-11-01

申请号：US285358

申请日：1981-07-20

Applicant: Klaus Klessing

Inventor： Klaus Klessing

IPC: A61K31/34 ,  A61K31/52 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D473/00 ,  C07D473/08 ,  C07D493/04 ,  C07D519/00

CPC classification number: C07D473/00 ,  C07D473/08 ,  C07D493/04

Abstract: Aminodesoxy-1.4;3.6-dianhydrohexitol derivatives of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2, in each case independently of one another, signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms or wherein R.sup.1 signifies a hydrogen atom and R.sup.2 an adamant(1)yl radical or wherein R.sup.1 and R.sup.2, together with the nitrogen atom to which they are attached, (a) signify the residue of a cyclic, non-aromatic secondary amine possibly containing a further hetero atom or (b) the aden(9)yl radical possibly mono- or disubstituted on the 6-amino group or (c) the 6-alkylmercaptopurin(9)yl radical or (d) the theophyllin(7)yl radical or (e) the 6-chloropurin-9-yl radical or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an .omega.-theophyllin(7)ylalkyl radical or an .omega.-theobromin-1-ylalkyl radical or an .omega.-(N,N'-di-lower alkyl-substituted xanthin-N"-yl)alkyl radical, whereby "lower alkyl" signifies an alkyl group with 1 to 5 C-atoms, or an .omega.-adenin-9-ylalkyl radical, whereby the alkyl radical has 2 to 7 C-atoms and can be straight-chained or branched, and wherein R.sup.3 signifies a hydrogen atom, a methanesulphonyl or toluenesulphonyl group, as well as their acid-addition salts.Processes for the preparation of said compounds and use of said compounds as reactive intermediate products for the preparation of the corresponding pharmacologically-effective amino-desoxy-1.4;3.6-dianhydrohexitol nitrates.

Abstract translation: 氨基脱氧-1,4,3,3-二脱水己醇衍生物，通式Ⅰ，其中R1和R2各自独立地表示氢原子或具有1-4个C原子的低级烷基或 其中R1表示氢原子，R2表示金刚烷基（1）基，或其中R1和R2与它们所连接的氮原子一起，（a）表示可能含有 另外的杂原子或（b）在6-氨基上可能被单取代或二取代的腺嘌呤（9）基团，或（c）6-烷基巯基嘌呤（9）基或（d）叶茶素（7）基或 （e）6-氯嘌呤-9-基或其中R1表示氢原子或具有1至4个C原子的低级烷基，R2表示ω-叶茶素（7）基烷基或ω-鸟嘌呤-1- （N，N'-二低级烷基取代的黄嘌呤-N“ - 基）烷基，其中”低级烷基“表示具有1至5个C原子的烷基，或 nω-腺苷-9-基烷基，其中烷基具有2至7个C原子并且可以是直链或支链的，并且其中R3表示氢原子，甲磺酰基或甲苯磺酰基，以及它们的酸 - 加成盐。 用于制备所述化合物的方法和所述化合物作为反应性中间体产物的用途，用于制备相应的药理学有效的氨基脱氧-1,4,3,6-二脱水己醇硝酸盐。

公开(公告)号：US4364953A

公开(公告)日：1982-12-21

申请号：US285407

申请日：1981-07-20

Applicant: Klaus Klessing ,  Shyam S. Chatterjee

Inventor： Klaus Klessing ,  Shyam S. Chatterjee

IPC: A61K31/34 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D493/04 ,  A61K31/455

CPC classification number: C07D493/04

Abstract: 2-0- and 5-0-substituted 1.4;3.6-dianhydrohexitol mononitrates of the general formula I, ##STR1## wherein R is a halogen-substituted phenyl group, a methanesulphonyl or nicotinoyl group, as well as their physiologically acceptable acid-addition salts, insofar as R signifies the nicotinoyl group.Processes for the preparation of said compounds and pharmaceutical compositions containing said compounds.

Abstract translation: 2-或5-取代的通式Ⅰ，其中R是卤素取代的苯基，甲磺酰基或烟酰基的式（I）的1.4,3.6-二羟基己醇单硝酸盐，以及它们的生理上可接受的 酸加成盐，只要R表示烟酰基。 用于制备所述化合物的方法和含有所述化合物的药物组合物。

公开(公告)号：US4363805A

公开(公告)日：1982-12-14

申请号：US285036

申请日：1981-07-20

Applicant: Klaus Klessing ,  Shyam S. Chatterjee ,  Bernard L. Gabard

Inventor： Klaus Klessing ,  Shyam S. Chatterjee ,  Bernard L. Gabard

IPC: A61K31/34 ,  A61K31/40 ,  A61K31/44 ,  A61K31/445 ,  A61K31/455 ,  A61K31/495 ,  A61K31/535 ,  A61K31/625 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D493/04

CPC classification number: C07D493/04

Abstract: Aminodesoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2 possess the meanings given in claim 1, as well as their pharmacologically acceptable acid-addition salts; processes for the preparation of said compounds, and pharmaceutical compositions containing at least one of said compounds.

Abstract translation: 具有通式I，其中R1和R2具有权利要求1中给出的含义的氨基脱氧-14; 3.6-二羟基己糖醇硝酸盐，及其药理学上可接受的酸加成盐; 所述化合物的制备方法和含有至少一种所述化合物的药物组合物。