公开(公告)号：US07459470B2

公开(公告)日：2008-12-02

申请号：US10476755

申请日：2002-05-03

申请人： Alexander Ernst ,  Andreas Huth ,  Martin Krueger ,  Karl-Heniz Thierauch ,  Andreas Menrad ,  Martin Haberey

发明人： Alexander Ernst ,  Andreas Huth ,  Martin Krueger ,  Karl-Heniz Thierauch ,  Andreas Menrad ,  Martin Haberey

IPC分类号： A61K31/47 ,  C07D213/89

CPC分类号： C07D213/89 ,  C07D401/12 ,  C07D405/12

摘要： Substituted N-oxidanthranilamide derivatives, their production and use as pharmaceutical agents for treating diseases that are triggered by persistent angiogenesis are described. The compounds according to the invention can be used as or in the case of psoriasis, Kaposi's sarcoma, restenosis, endometriosis, Crohn's disease, Hodgkin's disease, leukemia; arthritis, such as rheumatoid arthritis, hemangioma, angiofibroma; eye diseases, such as diabetic retinopathy, neovascular glaucoma; renal diseases, such as glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic syndrome, transplant rejections and glomerulopathy; fibrotic diseases, such as cirrhosis of the liver, mesangial cell proliferative diseases, arteriosclerosis, injuries to nerve tissue, and inhibition of the reocclusion of vessels after balloon catheter treatment, in vascular prosthetics or after mechanical devices are used to keep vessels open, such as, e.g., stents, as immunosuppressive agents, as a support in scar-free healing, senile keratosis and contact dermatitis. The compounds according to the invention can also be used as VEGFR-3 inhibitors in the case of lymphangiogenesis.

摘要翻译： 描述了取代的N-氧化邻氨基苯甲酰胺衍生物，其作为用于治疗由持续性血管生成触发的疾病的药剂的生产和用途被描述。 根据本发明的化合物可以用作银屑病，卡波西肉瘤，再狭窄，子宫内膜异位症，克罗恩病，霍奇金病，白血病，牛皮癣， 关节炎，如类风湿关节炎，血管瘤，血管纤维瘤; 眼睛疾病如糖尿病性视网膜病变，新生血管性青光眼; 肾脏疾病如肾小球性肾炎，糖尿病肾病，恶性肾硬化，血栓性微血管病综合征，移植排斥反应和肾小球病; 纤维化疾病，如肝硬化，肾小球膜细胞增生性疾病，动脉硬化，神经组织损伤，以及球囊导管治疗后血管再狭窄的抑制，血管修复术或机械装置用于保持血管开放的诸如 例如作为免疫抑制剂的支架，作为无疤痕愈合的支持，老年角化病和接触性皮炎。 在淋巴管生成的情况下，根据本发明的化合物也可以用作VEGFR-3抑制剂。

公开(公告)号：US20060116380A1

公开(公告)日：2006-06-01

申请号：US11265517

申请日：2005-11-03

申请人： Rolf Bohlmann ,  Martin Haberey ,  Andreas Huth ,  Stuart Ince ,  Martin Krueger ,  Karl-Heinz Thierauch ,  Holger Hess-Stumpp ,  Andreas Reichel

发明人： Rolf Bohlmann ,  Martin Haberey ,  Andreas Huth ,  Stuart Ince ,  Martin Krueger ,  Karl-Heinz Thierauch ,  Holger Hess-Stumpp ,  Andreas Reichel

IPC分类号： A61K31/506 ,  A61K31/501 ,  A61K31/4709 ,  A61K31/497 ,  A61K31/444 ,  C07D403/14 ,  C07D401/14

CPC分类号： C07D401/12

摘要： The invention relates to novel anthranilamide pyridinureas as VEGF receptor kinase inhibitors, their production and use as pharmaceutical agents for preventing or treating diseases that are triggered by persistent angiogenesis.

公开(公告)号：US07012081B2

公开(公告)日：2006-03-14

申请号：US10275479

申请日：2001-05-07

申请人： Martin Krueger ,  Andreas Huth ,  Orlin Petrov ,  Dieter Seidelmann ,  Karl-Heinz Thierauch ,  Martin Haberey ,  Andreas Menrad ,  Alexander Ernst

发明人： Martin Krueger ,  Andreas Huth ,  Orlin Petrov ,  Dieter Seidelmann ,  Karl-Heinz Thierauch ,  Martin Haberey ,  Andreas Menrad ,  Alexander Ernst

IPC分类号： A61K31/47 ,  C07D215/00 ,  C07D217/00

CPC分类号： C07D213/80 ,  C07C237/40 ,  C07D211/26 ,  C07D211/32 ,  C07D211/62 ,  C07D217/22 ,  C07D265/26 ,  C07D309/04 ,  C07D309/06 ,  C07D317/72 ,  C07D401/12 ,  C07D405/12

摘要： Substituted anthranilamides and use thereof as pharmaceutical agents for treating diseases that are triggered by persistent angiogenesis as well as their intermediate products for the production of anthranilamides are described.

摘要翻译： 描述了取代的邻氨基苯甲酰胺及其用作治疗由持续血管发生引起的疾病的药物及其用于制备邻氨基苯甲酰胺的中间产物。

公开(公告)号：US06878720B2

公开(公告)日：2005-04-12

申请号：US10180289

申请日：2002-06-26

申请人： Karl-Heinz Altmann ,  Guido Bold ,  Pascal Furet ,  Paul William Manley ,  Jeanette Marjorie Wood ,  Stefano Ferrari ,  Francesco Hofmann ,  Jürgen Mestan ,  Andreas Huth ,  Martin Krüger ,  Dieter Seidelmann ,  Andreas Menrad ,  Martin Haberey ,  Karl-Heinz Thierauch

发明人： Karl-Heinz Altmann ,  Guido Bold ,  Pascal Furet ,  Paul William Manley ,  Jeanette Marjorie Wood ,  Stefano Ferrari ,  Francesco Hofmann ,  Jürgen Mestan ,  Andreas Huth ,  Martin Krüger ,  Dieter Seidelmann ,  Andreas Menrad ,  Martin Haberey ,  Karl-Heinz Thierauch

IPC分类号： C07D233/64 ,  A61K20060101 ,  A61K31/00 ,  A61K31/166 ,  A61K31/167 ,  A61K31/415 ,  A61K31/417 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/443 ,  A61K31/444 ,  A61K31/47 ,  A61K31/4745 ,  A61K31/497 ,  A61K31/505 ,  A61P20060101 ,  A61P17/00 ,  A61P27/02 ,  A61P35/00 ,  A61P43/00 ,  C07C20060101 ,  C07C223/02 ,  C07C237/30 ,  C07C317/26 ,  C07D20060101 ,  C07D211/22 ,  C07D213/04 ,  C07D213/38 ,  C07D213/40 ,  C07D213/61 ,  C07D213/64 ,  C07D213/89 ,  C07D215/12 ,  C07D215/14 ,  C07D215/36 ,  C07D215/58 ,  C07D233/54 ,  C07D265/26 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/02

CPC分类号： A61K31/415 ,  A61K31/44 ,  A61K31/47 ,  C07D213/38 ,  C07D213/56 ,  C07D213/64 ,  C07D213/89 ,  C07D215/12 ,  C07D233/54 ,  C07D405/12

摘要： Described are compunds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10—(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO2; R1 is aryl; R2 is a bicyclic heteroaryl group comprising one ring nitrogen atom with the exception that R2 cannot represent 2-phthalimidyl; any of R3, R4, R5 and R6, independently of the other, is H or a substituent other than hydrogen; and R7 and R8, independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

摘要翻译： 描述的是式（I）的化合物，其中W是O或S; X为NR8; Y为CR 9 R 10 - （CH 2）n，其中R 9和R 10彼此独立地为氢或低级烷基，n为0〜3的整数。 或Y为SO2; R1是芳基; R2是包含一个环氮原子的二环杂芳基，不同的是R 2不能代表2-邻苯二酰亚氨基; R 3，R 4，R 5和R 6中的任何一个独立地为H或氢以外的取代基; 且R 7和R 8彼此独立地为H或低级烷基; 或N-氧化物或其药学上可接受的盐在制备用于治疗对VEGF受体酪氨酸激酶活性的抑制作出反应的肿瘤疾病的药物产品中的用途。 式（I）化合物可用于治疗，例如， 的肿瘤疾病，如肿瘤疾病，视网膜病变和年龄相关性黄斑变性。

公开(公告)号：US20050054654A1

公开(公告)日：2005-03-10

申请号：US10870491

申请日：2004-06-18

申请人： Andreas Huth ,  Ludwig Zorn ,  Martin Krueger ,  Stuart Ince ,  Karl Thierauch ,  Andreas Menrad ,  Martin Haberey ,  Holger Hess-Stumpp

发明人： Andreas Huth ,  Ludwig Zorn ,  Martin Krueger ,  Stuart Ince ,  Karl Thierauch ,  Andreas Menrad ,  Martin Haberey ,  Holger Hess-Stumpp

IPC分类号： C07D213/61 ,  C07D213/73 ,  C07D213/74 ,  C07D213/75 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D43/02 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  C07D41/02

CPC分类号： C07D213/61 ,  C07D213/73 ,  C07D213/74 ,  C07D213/75 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04

摘要： VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridinamides, their production and use as pharmaceutical agents for treating diseases that are triggered by persistent angiogenesis, as well as intermediate products for the production of the compounds are described. The compounds according to the invention can be used as or in the case of tumor or metastasis growth, psoriasis, Kaposi's sarcoma, restenosis, such as, e.g., stent-induced restenosis, endometriosis, Crohn's disease, Hodgkin's disease, leukemia; arthritis, such as rheumatoid arthritis, hemangioma, angiofibroma; eye diseases, such as diabetic retinopathy, neovascular glaucoma; renal diseases, such as glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic syndrome, transplant rejections and glomerulopathy; fibrotic diseases, such as cirrhosis of the liver; mesangial cell proliferative diseases, arteriosclerosis, injuries to nerve tissue, and inhibition of the reocclusion of vessels after balloon catheter treatment, in vascular prosthetics or after mechanical devices are used to keep vessels open, such as, e.g., stents, as immunosuppressive agents, as a support in scar-free healing, senile keratosis and contact dermatitis. The compounds according to the invention can also be used as VEGFR-3 inhibitors in the case of lymphangiogenesis.

摘要翻译： 描述了VEGFR-2和VEGFR-3抑制性邻氨基苯酰胺吡啶酰胺，其作为用于治疗由持续血管发生引起的疾病的药物的制备和用途，以及用于制备化合物的中间产物。 根据本发明的化合物可用于或在肿瘤或转移生长的情况下，牛皮癣，卡波西肉瘤，再狭窄，例如支架诱导的再狭窄，子宫内膜异位，克罗恩病，霍奇金病，白血病; 关节炎，如类风湿关节炎，血管瘤，血管纤维瘤; 眼睛疾病如糖尿病性视网膜病变，新生血管性青光眼; 肾脏疾病如肾小球性肾炎，糖尿病肾病，恶性肾硬化，血栓性微血管病综合征，移植排斥反应和肾小球病; 纤维化疾病，如肝硬化; 肾小球膜细胞增生性疾病，动脉硬化，神经组织损伤，以及球囊导管治疗后血管假体中或使用机械装置用于保持血管开放（例如，支架）作为免疫抑制剂的抑制，作为免疫抑制剂 无疤痕愈合，老年角化病和接触性皮炎的支持。 在淋巴管生成的情况下，根据本发明的化合物也可以用作VEGFR-3抑制剂。

公开(公告)号：US06376480B1

公开(公告)日：2002-04-23

申请号：US09738286

申请日：2000-12-18

申请人： Gerald Kirsch ,  Andreas Steinmeyer ,  Günter Neef ,  Katica Schwarz ,  Ruth Thieroff-Ekerdt ,  Herbert Wiesinger ,  Andreas Menrad ,  Martin Haberey

发明人： Gerald Kirsch ,  Andreas Steinmeyer ,  Günter Neef ,  Katica Schwarz ,  Ruth Thieroff-Ekerdt ,  Herbert Wiesinger ,  Andreas Menrad ,  Martin Haberey

IPC分类号： A61K3159

CPC分类号： C07C401/00

摘要： A method of preparing a pharmaceutical composition, comprising combining a pharmaceutically compatible vehicle with a compound according to formula (I)

摘要翻译： 一种制备药物组合物的方法，包括将药学上相容的载体与式（I）化合物

公开(公告)号：US4532236A

公开(公告)日：1985-07-30

申请号：US531898

申请日：1983-07-27

申请人： Robert Nickolson ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Martin Haberey

发明人： Robert Nickolson ,  Helmut Vorbrueggen ,  Jorge Casals-Stenzel ,  Martin Haberey

IPC分类号： A61K31/34 ,  A61K31/557 ,  A61P43/00 ,  C07C51/09 ,  C07C51/38 ,  C07C55/32 ,  C07C57/52 ,  C07C69/533 ,  C07C69/593 ,  C07C69/65 ,  C07C405/00 ,  C07D307/935 ,  C07D307/937 ,  C07D407/00 ,  C07D407/12 ,  C07F7/18 ,  C07F9/40

CPC分类号： C07D307/935 ,  C07C405/00 ,  C07C405/0033 ,  C07C51/09 ,  C07C51/38 ,  C07C55/32 ,  C07C57/52 ,  C07D307/937 ,  C07D407/12 ,  C07F7/1856 ,  C07F9/4015

摘要： Prostacyclin derivatives of general Formula I ##STR1## wherein R.sub.1 is the residue OR.sub.3 wherein R.sub.3 means hydrogen or alkyl of 1-10 carbon atoms substituted, if desired, by halogen, aryl, C.sub.1 -C.sub.4 -alkoxy, or C.sub.1 -C.sub.4 -dialkylamino; cycloalkyl, aryl, or a heterocyclic residue; or is the residue NHR.sub.4 wherein R.sub.4 means hydrogen, an alkanoyl residue, or an alkanesulfonyl residue of respectively 1-10 carbon atoms,A is a --CH.sub.2 --CH.sub.2 -- or trans--CH.dbd.CH--group,W is a ##STR2## wherein the OH-group can be respectively esterified with a benzoyl or alkanoic acid residue of 1-4 carbon atoms, or can be etherified with a tetrahydropyranyl, tetrahydrofuranyl, C.sub.1 -C.sub.4 -alkoxyalkyl, or tri(C.sub.1 -C.sub.4 -alkyl)-silyl residue, wherein the free or esterified OH-group can be in the .alpha.- or .beta.-position,D and E jointly mean a direct bond orD is a straight-chain or branched alkylene group of 1-5 carbon atoms,E is an oxygen atom or a direct bond,R.sub.2 is a straight-chain or branched-chain alkyl group of 1-6 carbon atoms, a straight-chain or branched-chain alkenyl group of 2-6 carbon atoms which can be substituted by phenyl, halogen, or C.sub.1 -C.sub.4 -alkyl and, if D and E jointly represent a direct bond, is an alkynyl residue of 2-6 carbon atoms optionally substituted in the 1-position by halogen or C.sub.1 -C.sub.4 -alkyl,R.sub.5 is a hydroxy group which can be esterified with an alkanoic acid residue of 1-4 carbon atoms or which can be etherified with a tetrahydropyranyl, tetrahydrofuranyl, alkoxyalkyl, or trialkylsilyl residue and, if R.sub.3 is hydrogen, the salts thereof with physiologically compatible bases, and a process for the preparation thereof.The compounds exhibit blood-pressure-lowering and thrombocyte-aggregation-inhibiting activity.

公开(公告)号：US07071344B1

公开(公告)日：2006-07-04

申请号：US09509934

申请日：1998-09-29

申请人： Andreas Steinmeyer ,  Gunter Neef ,  Gerald Kirsch ,  Katica Schwarz ,  Herbert Wiesinger ,  Martin Haberey ,  Marianne Fahnrich ,  Gernot Langer

发明人： Andreas Steinmeyer ,  Gunter Neef ,  Gerald Kirsch ,  Katica Schwarz ,  Herbert Wiesinger ,  Martin Haberey ,  Marianne Fahnrich ,  Gernot Langer

IPC分类号： C07J41/00 ,  A61K31/59

CPC分类号： C07C401/00 ,  A61K31/59 ,  A61K38/13 ,  A61K39/395 ,  A61K31/445 ,  A61K31/435 ,  A61K2300/00

摘要： The invention relates to novel vitamin D derivatives of general formula (I), a method for the production thereof, intermediate products of the method and the utilization of vitamin D derivatives for producing medicaments.

摘要翻译： 本发明涉及通式（I）的新型维生素D衍生物，其制备方法，该方法的中间产物和用于生产药物的维生素D衍生物的利用。

公开(公告)号：US20060074112A1

公开(公告)日：2006-04-06

申请号：US11254897

申请日：2005-10-20

申请人： Karl-Heinz Altmann ,  Guido Bold ,  Pascal Furet ,  Paul Manley ,  Jeanette Wood ,  Stefano Ferrari ,  Francesco Hofmann ,  Jurgen Mestan ,  Andreas Huth ,  Martin Kruger ,  Dieter Seidelmann ,  Andreas Menrad ,  Martin Haberey ,  Karl-Heinz Thierauch

发明人： Karl-Heinz Altmann ,  Guido Bold ,  Pascal Furet ,  Paul Manley ,  Jeanette Wood ,  Stefano Ferrari ,  Francesco Hofmann ,  Jurgen Mestan ,  Andreas Huth ,  Martin Kruger ,  Dieter Seidelmann ,  Andreas Menrad ,  Martin Haberey ,  Karl-Heinz Thierauch

IPC分类号： C07D213/56 ,  A61K31/44 ,  C07D233/54

CPC分类号： A61K31/415 ,  A61K31/44 ,  A61K31/47 ,  C07D213/38 ,  C07D213/56 ,  C07D213/64 ,  C07D213/89 ,  C07D215/12 ,  C07D233/54 ,  C07D405/12

摘要： Described are compunds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10—(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO2; R1 is aryl; R2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R2 cannot represent 2-phthalimidyl, and in case of Y═SO2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R3, R4, R5 and R6, independently of the other, is H or a substituent other than hydrogen; and R7 and R8, independently of each, other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

摘要翻译： 描述的是式（I）的化合物，其中W是O或S; X是NR 8; Y是CR 9 R 10其中R 9是（CH 2）n - 和R 10彼此独立地为氢或低级烷基，n为0〜3的整数。 或Y为SO 2; R 1是芳基; R 2是包含一个或多个环氮原子的单环或双环杂芳基，除了R 2不能表示2-邻苯二甲酰亚氨基，并且在Y-SO的情况下 2不能表示2,1,3-苯并噻二唑-4-基; R 3，R 4，R 5和R 6中的任何一个独立地是H或 除氢以外的取代基; R 7和R 8分别独立地为H或低级烷基; 或N-氧化物或其药学上可接受的盐在制备用于治疗对VEGF受体酪氨酸激酶活性的抑制作出反应的肿瘤疾病的药物产品中的用途。 式（I）化合物可用于治疗，例如， 的肿瘤疾病，如肿瘤疾病，视网膜病变和年龄相关性黄斑变性。

公开(公告)号：US20050080058A1

公开(公告)日：2005-04-14

申请号：US10658326

申请日：2003-09-10

申请人： Andreas Steinmeyer ,  Gerald Kirsch ,  Gunter Neef ,  Katica Schwarz ,  Ruth Thieroff-Ekerdt ,  Herbert Wiesinger ,  Martin Haberey ,  Marianne Fahnrich

发明人： Andreas Steinmeyer ,  Gerald Kirsch ,  Gunter Neef ,  Katica Schwarz ,  Ruth Thieroff-Ekerdt ,  Herbert Wiesinger ,  Martin Haberey ,  Marianne Fahnrich

IPC分类号： A61K31/00 ,  A61K31/045 ,  A61K31/047 ,  A61K31/41 ,  A61K31/42 ,  A61K31/421 ,  A61K31/4245 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/59 ,  A61K31/593 ,  A61P17/00 ,  A61P19/00 ,  A61P19/10 ,  A61P25/04 ,  A61P29/00 ,  A61P35/00 ,  C07C35/32 ,  C07C401/00 ,  C07D207/32 ,  C07D207/333 ,  C07D213/30 ,  C07D233/54 ,  C07D233/64 ,  C07D263/06 ,  C07D263/32 ,  C07D271/06 ,  C07D271/10 ,  C07D277/06 ,  C07D277/12 ,  C07D277/24 ,  C07D307/42 ,  C07D333/16

CPC分类号： C07D207/333 ,  C07C35/32 ,  C07C401/00 ,  C07D233/64 ,  C07D263/32 ,  C07D271/06 ,  C07D271/10 ,  C07D277/24 ,  C07D307/42 ,  C07D333/16

摘要： Compounds of Formula I, wherein Y1, Y2, R1-R6, Q and Z are as defined herein, are vitamin D derivatives. These compounds are useful for, e.g., the treatment hyperprolifierative diseases of the skin, tumor diseases and precancerous stages, auto-immune diseases, rejection reactions in the case of autologous, allogenic or xenogenic transplants, AIDS, atopic skin conditions, secondary hyperparathyroidism, renal osteodystrophia, senile and postmenopausal osteoporosis, diabetes mellitus type II, degenerative diseases of the peripheral and central nervous system, hypercalcemias, granulomatous diseases, paraneoplastic hypercalcemias, hypercalcemias in hyperparathyroidism, hirsutism, ateriosclerosis, and/or inflammatory diseases.

摘要翻译： 其中Y1，Y2，R1-R6，Q和Z如本文所定义的式I化合物是维生素D衍生物。 这些化合物可用于例如治疗皮肤过度增压疾病，肿瘤疾病和癌前期，自身免疫疾病，自体，同种异体移植或异种移植中的排斥反应，艾滋病，特应性皮肤病，继发性甲状旁腺功能亢进，肾脏 骨质疏松症，老年人和绝经后骨质疏松症，II型糖尿病，外周和中枢神经系统的退行性疾病，高钙血症，肉芽肿性疾病，副肿瘤性高钙血症，甲状旁腺功能亢进的高钙血症，多毛症，动脉硬化和/或炎症性疾病。