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    Thiosuccinic Acid Derivatives and the Use Thereof
    3.
    发明申请
    Thiosuccinic Acid Derivatives and the Use Thereof 有权
    硫代琥珀酸衍生物及其用途

    公开(公告)号：US20090011986A1

    公开(公告)日：2009-01-08

    申请号：US11914426

    申请日：2006-05-03

    Applicant: Rajendra Kumar Joshi ,  Hans-Peter Strebel ,  Jitka Ulrichova ,  Thomas J. Schmidt

    Inventor： Rajendra Kumar Joshi ,  Hans-Peter Strebel ,  Jitka Ulrichova ,  Thomas J. Schmidt

    IPC: A61K38/00 ,  A61P37/00 ,  A61P25/00 ,  A61P31/12 ,  A61P35/00 ,  A61K31/198 ,  A61P17/00 ,  A61P9/00 ,  C07K14/00 ,  C07C323/58

    CPC classification number: C07K14/001 ,  C07C323/58 ,  C07K5/0215

    Abstract: The present invention relates to compounds of the Formula (I), wherein X1 and X2 independently represent O, NH or S; R1 and R2 are independently selected from the group consisting of a C1-C30 hydrocarbyl group, an amino acid bonded via an amide bond or a peptide bonded via an amide bond each having up to 200 amino acids, the conjugated residue X1 or X2 in this case being NH, and hydrogen, both radicals R1 and R2 preferably not being H; and R3 is a residue selected from group consisting of —S—R6, wherein R6 is a C1-C30 hydrocarbyl group, at least one of R1 and R2 not being H when X1 and X2 are oxygen, —S—CH2—CH(NH2)(COOH) (cysteine-S-yl), a homologue or derivative (e.g. N-acetyl cysteine-S-yl) thereof, a peptide having up to 200 amino acids which contains at least one amino acid radical with a thiol group, preferably a cysteine radical, and is bonded via the thio sulfur, preferably via the cysteine sulfur (peptide-S-yl), coenzyme A which is bonded via a thiol group or fragments thereof, acyl carrier protein bonded via a thiol group, and dihydrolipoic acid bonded via a thiol group; and pharmaceutically acceptable salts thereof. The present invention also relates to the use of these compounds for preparing a drug, drugs containing the same and their use for the therapy of diseases such as autoimmune disease, NF-kappaB mediated diseases, psoriasis, psoriatic arthritis, neurodermitis, enteris regionalis Crohn, cardiac insufficiency, chronic obstructive pulmonary diseases and asthma and in transplantation medicine.

    Abstract translation: 本发明涉及式（I）的化合物，其中X 1和X 2独立地表示O，NH或S; R1和R2独立地选自C1-C330烃基，通过酰胺键键合的氨基酸或通过酰胺键键合的多肽，其中每个氨基酸具有多达200个氨基酸，该共轭残基X1或X2在此 情况是NH和氢，基团R 1和R 2优选不是H; 并且R 3是选自-S-R 6，其中R 6是C 1 -C 30烃基的残基，当X 1和X 2是氧时，R 1和R 2中的至少一个不是H，-S-CH 2 -CH（NH 2） ）（COOH）（半胱氨酸-S-基），其同系物或衍生物（例如N-乙酰半胱氨酸-S-基），具有至多200个氨基酸的肽，其含有至少一个具有硫醇基的氨基酸基团， 优选通过硫代硫，优选经由半胱氨酸硫（肽-S-基），通过硫醇基或其片段键合的辅酶A，通过硫醇基键合的酰基载体蛋白和二氢硫辛酸 通过硫醇基键合; 和其药学上可接受的盐。 本发明还涉及这些化合物在制备药物中的用途，含有该药物的药物及其用于治疗疾病如自身免疫性疾病，NF-κB介导的疾病，牛皮癣，牛皮癣关节炎，神经性皮炎，局部肠炎克罗恩病， 心功能不全，慢性阻塞性肺疾病和哮喘和移植医学。

    Fumaric acid amides
    4.
    发明授权
    Fumaric acid amides 有权
    富马酸酰胺

    公开(公告)号：US07157423B2

    公开(公告)日：2007-01-02

    申请号：US10433295

    申请日：2002-01-08

    Applicant: Rajendra Kumar Joshi ,  Hans-Peter Strebel

    Inventor： Rajendra Kumar Joshi ,  Hans-Peter Strebel

    IPC: A61K38/11 ,  A61K38/08 ,  C07K7/64 ,  C07K7/04 ,  A61K38/00 ,  A61K38/02 ,  C07K2/00 ,  C07K1/107

    CPC classification number: A61K31/198 ,  A61K31/194 ,  A61K31/225

    Abstract: Fumaric acid amides of the general formula (I) wherein R1 represents OR3 or a D- or L-amino acid radical —NH—CHR4—COOH bonded via an amide bond, wherein R3 is hydrogen, a straight-chained or branched, optionally substituted C1-24 alkyl radical, a phenyl radical or C6-10 aralkyl radical and R4 is a side chain of a natural or synthetic amino acid and R2 represents a D- or L-amino acid radical —NH—CHR5—COOH bonded via an amide bond or a peptide radical comprising 2 to 100 amino acids bonded via an amide bond, wherein R5 is a side chain of a natural or synthetic amino acid, are used for preparing a drug (1) for the therapy of an autoimmune disease; (2) for use in transplantation medicine; (3) for the therapy of mitochondrial diseases; or (4) for the therapy of NF-kappaB mediated diseases.

    Abstract translation: 通式（I）的富马酸酰胺，其中R 1表示OR 3或D或L-氨基酸基-NH-CHR 4， 其中R 3是氢，直链或支链的任选取代的C 1-24烷基，苯基或 C 6-10芳烷基和R 4是天然或合成氨基酸的侧链，R 2表示D-或L 通过酰胺键或包含通过酰胺键键合的2至100个氨基酸的肽基键合的氨基酸基-NH-CHR 5 -COOH，其中R 5为 天然或合成氨基酸的侧链用于制备用于治疗自身免疫性疾病的药物（1）; （2）用于移植药物; （3）治疗线粒体疾病; 或（4）用于治疗NF-kappaB介导的疾病。

    Use of fumaric acid derivatives in transplant medicine
    5.
    发明授权
    Use of fumaric acid derivatives in transplant medicine 有权
    在移植药物中使用富马酸衍生物

    公开(公告)号：US06359003B1

    公开(公告)日：2002-03-19

    申请号：US09719189

    申请日：2000-12-08

    Applicant: Rajendra Kumar Joshi ,  Hans-Peter Strebel

    Inventor： Rajendra Kumar Joshi ,  Hans-Peter Strebel

    IPC: A61K31225

    CPC classification number: A61K31/225 ,  A61K2300/00

    Abstract: The invention relates to the use of certain fumaric acid monoalkyl esters as salts or a free acid either alone or in combination with a dialkyl fumarate for producing pharmaceutical preparations for use in transplantation medicine, especially for treating, alleviating or suppressing host-versus-graft reactions. For this purpose, the fumaric acid monoalkyl esters may be used in combination with preparations conventionally used in transplantation medicine and immuno suppressives, especially such as cyclosporines.

    Abstract translation: 本发明涉及某些富马酸单烷基酯作为盐或游离酸单独使用或与富马酸二烷基酯组合用于制备用于移植药物的药物制剂，特别是用于治疗，减轻或抑制宿主对移植物反应 。 为此，富马酸单烷基酯可以与常规用于移植医学和免疫抑制剂，特别是环孢菌素的制剂组合使用。

    Fumaric acid micro tablets
    6.
    发明授权
    Fumaric acid micro tablets 有权
    富马酸微片

    公开(公告)号：US06355676B1

    公开(公告)日：2002-03-12

    申请号：US09743978

    申请日：2001-01-17

    Applicant: Rajendra Kumar Joshi ,  Hans-Peter Strebel

    Inventor： Rajendra Kumar Joshi ,  Hans-Peter Strebel

    IPC: A61K31315

    CPC classification number: A61K31/22 ,  A61K9/2054 ,  A61K9/2059 ,  A61K9/2866 ,  A61K9/4858 ,  A61K2300/00

    Abstract: The present invention relates to the use of one or more salts of fumaric acid monoalkyl esters of the general formula optionally in admixture with dialkyl fumarate of the formula wherein A is a bivalent cation from the series consisting of Ca, Mg, Zn or Fe or a monovalent cation from the series Li, Na or K, respectively, and n denotes the numeral 1 or 2 depending on the type of cation, and, optionally, commonly used pharmaceutical excipients and vehicles for preparing a pharmaceutical composition in the form of micro-tablets or micro-pellets for the treatment of psoriatic arthritis, neurodermatitis, psoriasis and enteritis regionalis Crohn.

    Abstract translation: 本发明涉及通式1的富马酸单烷基酯的一种或多种盐与马来酰亚胺的富马酸二烷基酯的混合物的使用A是由Ca，Mg，Zn或Fe组成的一系列的二价阳离子或一价阳离子 分别为Li，Na或K系列，n为取决于阳离子类型的数字1或2，以及任选的通常使用的药物赋形剂和载体，用于制备微片或微型形式的药物组合物 用于治疗牛皮癣关节炎，神经性皮炎，牛皮癣和肠炎的小肠 - 克罗恩病。

    USE OF FUMARIC ACID DERIVATIVES FOR TREATING CARDIAC INSUFFICIENCY, AND ASTHMA
    7.
    发明申请
    USE OF FUMARIC ACID DERIVATIVES FOR TREATING CARDIAC INSUFFICIENCY, AND ASTHMA 有权
    用于治疗心脏缺血症的乳酸衍生物的使用和ASTHMA

    公开(公告)号：US20110124615A1

    公开(公告)日：2011-05-26

    申请号：US12884573

    申请日：2010-09-17

    Applicant: Rajendra Kumar Joshi ,  Hans-Peter Strebel ,  Christian Zaugg ,  Michael Tamm

    Inventor： Rajendra Kumar Joshi ,  Hans-Peter Strebel ,  Christian Zaugg ,  Michael Tamm

    IPC: A61K31/225 ,  A61K31/315 ,  A61K31/573 ,  A61K31/197 ,  A61K31/215 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  C12N5/071

    CPC classification number: A61K31/225 ,  A61K31/197 ,  A61K31/231 ,  A61K31/573 ,  A61K2300/00

    Abstract: According to a first aspect the invention relates to the use of fumaric acid derivatives selected from the group consisting of dialkyl fumarates, monoalkyl hydrogen fumarates, fumaric acid monoalkyl ester salts, fumaric acid monoamides, monoamido fumaric acid salts, fumaric acid diamides, monoalkyl monoamido fumarates, carbocyclic and oxacarbocyclic oligomers of these compounds and mixtures thereof for preparing a drug for the treatment or prevention of cardiac insufficiency, in particular left ventricular insufficiency, myocardial infarction and angina pectoris.According to a second aspect the invention relates to the use of fumaric acid derivatives, selected from the group consisting of dialkyl fumarates, monoalkyl hydrogen fumarates, fumaric acid monoalkyl ester salts, fumaric acid monoamides, monoamido fumaric acid salts, fumaric acid diamides, monoalkyl monoamido fumarates, carbocyclic and oxacarbocyclic oligomers of these compounds and mixtures thereof for preparing a drug for the treatment of asthma and chronic obstructive pulmonary diseases, especially asthma caused by allergies, infections, analgesics, job conditions or physical effort, mixed forms of asthma, or asthma cardiale.

    Abstract translation: 根据第一方面，本发明涉及富马酸衍生物的用途，所述富马酸衍生物选自富马酸二烷基酯，富马酸单烷基酯，富马酸单烷基酯盐，富马酸单酰胺，单酰氨基富马酸盐，富马酸二酰胺，单烷基单酰氨基富马酸盐 这些化合物的碳环和氧杂环低聚物及其混合物，用于制备用于治疗或预防心功能不全，特别是左心室功能不全，心肌梗死和心绞痛的药物。 根据第二方面，本发明涉及富马酸衍生物的用途，所述富马酸衍生物选自富马酸二烷基酯，富马酸单烷基酯，富马酸单烷基酯盐，富马酸单酰胺，单酰基富马酸盐，富马酸二酰胺，单烷基单酰胺基 这些化合物的富马酸盐，碳环和氧杂环低聚物及其混合物，用于制备用于治疗哮喘和慢性阻塞性肺疾病的药物，特别是由过敏，感染，止痛剂，工作条件或体力，哮喘或哮喘混合形式引起的哮喘 心脏病

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