公开(公告)号：US08653138B2

公开(公告)日：2014-02-18

申请号：US13174899

申请日：2011-07-01

申请人： Aldo Ammendola ,  Julia Diederichs ,  Johann Leban ,  Daniel Vitt

发明人： Aldo Ammendola ,  Julia Diederichs ,  Johann Leban ,  Daniel Vitt

IPC分类号： A61K31/195 ,  A61K31/19 ,  C07C229/00

CPC分类号： C07D333/38 ,  C07C233/59 ,  C07C233/60 ,  C07C255/60 ,  C07C2601/10 ,  C07D307/30 ,  C07D333/58

摘要： The present invention relates to calcium salts of compounds of the general formula (I) wherein X is selected from the group consisting of CH2, S, or O; D is O or S; R8 is hydrogen or alkyl; E is an optionally substituted phenylene group; Y is a monocyclic or bicyclic substituted or unsubstituted 6-9 membered ring system which may contain one or more heteroatoms selected from N or S and which contains at least one aromatic ring; n is 0 or 1, and q is 0 or 1; with the proviso that compounds wherein X═CH2, q=0, Y=unsubstituted phenyl and E=unsubstituted phenylene are excluded; or a hydrate thereof.

摘要翻译： 本发明涉及通式（I）化合物的盐，其中X选自CH 2，S或O; D为O或S; R8是氢或烷基; E是任选取代的亚苯基; Y是单环或双环取代或未取代的6-9元环系，其可含有一个或多个选自N或S的杂原子并且含有至少一个芳环; n为0或1，q为0或1; 条件是其中X = CH 2，q = 0，Y =未取代的苯基和E =未取代的亚苯基的化合物被排除; 或其水合物。

公开(公告)号：US20070219190A1

公开(公告)日：2007-09-20

申请号：US11686263

申请日：2007-03-14

申请人： Johann Leban ,  Daniel Vitt

发明人： Johann Leban ,  Daniel Vitt

IPC分类号： A61K31/538 ,  A61K31/53 ,  A61K31/52 ,  A61K31/496 ,  A61K31/473 ,  A61K31/4545 ,  C07D417/14

CPC分类号： C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D495/04

摘要： The present invention relates to compounds of the general formula(Ig) or pharmaceutically acceptable salts thereof with an acid or a base, or pharmaceutically acceptable prodrugs or a stereoisomer thereof, wherein R1 independently represents H, alkyl, cycloalkyl, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl, or heteroaryl; R2 independently represents NR3R5, R3 independently represents H, COR6, CO2R6, SOR6, SO2R6, SO3R6, alkyl, cycloalkyl, alkoxy, —NH2, alkylamine, —NR7COR6, halogen, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R5 independently represents H, COR6, CO2R6, SOR6, SO2R6, SO3R6, alkyl, cycloalkyl alkoxy, —NH2, alkylamine, —NR7COR6, halogen, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R6 independently represents H, alkyl, cycloalkyl, —NH2, alkylamine, aryl or heteroaryl; R7 independently represents H, alkyl, cycloalkyl, alkoxy, —OH, —SH, alkylthio, hydroxyalkyl, aryl, or heteroaryl; p is 0, or 1; q is 0, or 1; X is CO, CS, or SO2.

摘要翻译： 本发明涉及通式（Ig）的化合物或其药学上可接受的盐与酸或碱或其药学上可接受的前药或立体异构体，其中R 1独立地表示H，烷基， 环烷基，羟基烷基，卤代烷基，卤代烷氧基，芳基或杂芳基; R 2独立地表示NR 3 R 5，R 3独立地表示H，COR 6， SO 2，SO 2，SO 2，SOR 6，SO 2，R 6， ，SO 3 R 6，烷基，环烷基，烷氧基，-NH 2，烷基胺，-NR 7 COR 卤素，-OH，-SH，烷硫基，羟基烷基，卤代烷基，卤代烷氧基，芳基或杂芳基; R 5独立地表示H，COR 6，CO 2，R 6，SOR 6， SO 2 SO 2，SO 3 S 6，烷基，环烷基烷氧基，-NH 2， 2，烷基胺，-NR 7 COR 6，卤素，-OH，-SH，烷硫基，羟基烷基，卤代烷基，卤代烷氧基，芳基或杂芳基; R 6独立地表示H，烷基，环烷基，-NH 2，烷基胺，芳基或杂芳基; R 7独立地表示H，烷基，环烷基，烷氧基，-OH，-SH，烷硫基，羟基烷基，芳基或杂芳基; p为0或1; q为0或1; X是CO，CS或SO 2。

公开(公告)号：US08354433B2

公开(公告)日：2013-01-15

申请号：US12772470

申请日：2010-05-03

申请人： Daniel Vitt ,  Manfred Groeppel ,  Roland Baumgartner ,  Johann Leban

发明人： Daniel Vitt ,  Manfred Groeppel ,  Roland Baumgartner ,  Johann Leban

IPC分类号： A61K31/44

CPC分类号： A61K31/196 ,  A61K31/341 ,  A61K31/381 ,  A61K31/44 ,  C07D213/78 ,  C07D307/68 ,  C07D333/38 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/397 ,  Y02A50/467

摘要： The present invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, for the use as a medicament.

摘要翻译： 本发明涉及用作药物的通式（I）的化合物及其盐和生理功能衍生物。

公开(公告)号：US07247736B2

公开(公告)日：2007-07-24

申请号：US10736739

申请日：2004-11-10

申请人： Johann Leban ,  Bernd Kramer ,  Roland Baumgartner ,  Katharina Aulinger-Fuchs ,  Stefan Tasler

发明人： Johann Leban ,  Bernd Kramer ,  Roland Baumgartner ,  Katharina Aulinger-Fuchs ,  Stefan Tasler

IPC分类号： C07D333/10 ,  C07C235/84

CPC分类号： A61K31/401 ,  A61K31/44 ,  C07C233/60 ,  C07C2601/10 ,  C07D333/24 ,  Y02A50/411

摘要： The present invention provides a compound capable of binding to the ubiquinone binding site of DHODH which contains a non-aromatic ring system as a core structure, a group capable of interacting with structural elements of subsite 2 or 3 of the ubiquinone binding site of DHODH and a group capable of interacting hydrophobically with structural elements of subsite 1 of the ubiquinone binding site of DHODH. Furthermore, the present invention provides a compound capable of binding to the ubiquinone binding site of DHODH which contains an aromatic ring system as a core structure, a group capable of interacting with residues His 56 and/or Tyr 356 of subsite 3 of the ubiquinone binding site of DHODH and a group capable of interacting hydrophobically with structural elements of subsite 1 of the ubiquinone binding site of DHODH.

摘要翻译： 本发明提供能够结合DHODH的泛素结合位点的化合物，其含有非芳香族环系统作为核心结构，能够与DHODH的泛素结合位点的亚位点2或3的结构元件相互作用的基团和 能够与DHODH的泛醌结合位点的亚位点1的结构元件疏水相互作用的基团。 此外，本发明提供能够结合含有芳环系统作为核心结构的DHODH的泛素结合位点的化合物，能够与泛醌结合的亚位点3的残基His 56和/或Tyr 356相互作用的基团 DHODH的位点和能够与DHODH的泛素结合位点的亚位点1的结构元件疏水相互作用的基团。

公开(公告)号：US20070037753A1

公开(公告)日：2007-02-15

申请号：US11501722

申请日：2006-08-10

申请人： Johann Leban ,  Martin Kralik

发明人： Johann Leban ,  Martin Kralik

IPC分类号： A61K38/05 ,  A61K38/04 ,  C07K5/04 ,  C07D403/02

CPC分类号： C07D233/72 ,  A61K38/00 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/14 ,  C07K5/0205 ,  C07K5/06078 ,  C07K5/06191 ,  Y02A50/409

摘要： The invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein Y is —NRaRb, —NRcC═ONRaRb, —NRcC═SNRaRb, —NRcC═NRdNaRb, heterocycle, —C═ONRaRb, heterocycle, or aryl; n is 0 to 8; m is 0, or 1; r is 0 to 3; t is 0 to 3; X is O or N; Z is CH2, C═O, C═S or a single bond; Z1 is CO—R2, CS—R2, (CH2)t—R2 or the side-chain of a naturally occuring amino acid;, Z2 is CO—R2, CS—R2 or (CH2)t—R3 or the side-chain of a naturally occuring amino acid; Z3 is CO—R2, CS—R2 or (CH2)t—R4 or the side-chain of a naturally occuring amino acid; Z4 is H, alkyl, alkoxy, or cycloalkyl; R1, R2, R3, and R4 are independently from each other H, OH, SH, NH2, CN, NO2, alkyl, cycloalkyl, heterocycloalkyl, haloalkyl, alkylthio, haloalkyloxy, hydroxyalkyl, hydroxyalkylamino, alkylamino, alkylaryl, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxyalkyl, alkoxy, aryloxy, heteroaryl, aryl, or halogen.

摘要翻译： 本发明涉及通式（I）的化合物及其盐和生理功能衍生物，其中Y是-NR a，R b， C-ON＆lt; b＆gt; b＆lt;＆lt;＆lt; C＆gt; C-SNR＆lt; b＆gt; b C 1 -C 6卤代烷基，杂环基，C 1 -C 6 - 杂环或芳基;杂环或芳基; n为0〜8; m为0或1; r为0〜3; t为0〜3; X是O或N; Z是CH 2，C-O，C-S或单键; Z 1是CO-R 2，CS-R 2，（CH 2）2， / SUB> -R 2或天然存在的氨基酸的侧链; Z 2是CO-R 2，CS- R 2或（CH 2）2 -TH 3或天然存在的氨基酸的侧链 ; Z 3是CO-R 2，CS-R 2或（CH 2 CH 2） / SUB→4或天然存在的氨基酸的侧链; Z 4是H，烷基，烷氧基或环烷基; R 1，R 2，R 3和R 4彼此独立地为H，OH，SH ，NH 2，CN，NO 2，烷基，环烷基，杂环烷基，卤代烷基，烷硫基，卤代烷氧基，羟烷基，羟烷基氨基，烷基氨基，烷基芳基，烷基亚磺酰基，烷基磺酰基，烷硫基烷基，烷基亚磺酰基烷基 烷基磺酰基烷基，烷氧基烷基，烷氧基，芳氧基，杂芳基，芳基或卤素。

公开(公告)号：US20060069102A1

公开(公告)日：2006-03-30

申请号：US11192009

申请日：2005-07-29

申请人： Johann Leban ,  Harald Schmitt ,  Kristina Wolf ,  Stefano Pegoraro ,  Andreas Wuzik

发明人： Johann Leban ,  Harald Schmitt ,  Kristina Wolf ,  Stefano Pegoraro ,  Andreas Wuzik

IPC分类号： A61K31/496 ,  A61K31/4545 ,  C07D417/14

CPC分类号： C07D401/14 ,  C07D263/48 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D495/04

摘要： The present invention relates to compounds of the general formula (1) and salts and physiologically functional derivatives thereof, wherein R1 is independently hydrogen; alkyl, cycloalkyl, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl or substituted arylalkyl; R2 is independently —NR3R4, R3 is independently alkyl, cycloalkyl, alkoxy, alkylamine, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl, R4 is independently alkyl, cycloalkyl, alkoxy, alkylamine, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R5 is independently H, COR6, CO2R6, SOR6, SO3R6, alkyl, cycloalkyl, alkoxy, —NH2, alkylamine, —NR7COR6, halogen, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R6 is independently H, alkyl, cycloalkyl, —NH2, alkylamine, aryl or heteroaryl; R7 is independently H, alkyl, cycloalkyl, alkoxy, —OH, —SH, alkylthio, hydroxyalkyl, aryl, or heteroaryl; p is 0, or 1; q is 0, or 1; X is CO, or SO2.

摘要翻译： 本发明涉及通式（1）的化合物及其盐和生理功能衍生物，

公开(公告)号：US08592456B2

公开(公告)日：2013-11-26

申请号：US13360050

申请日：2012-01-27

申请人： Johann Leban ,  Stefan Tasler ,  Roland Baumgartner ,  Wael Saeb ,  Carine Chevrier

发明人： Johann Leban ,  Stefan Tasler ,  Roland Baumgartner ,  Wael Saeb ,  Carine Chevrier

IPC分类号： A61K31/454 ,  A61K31/444 ,  A61K31/4439 ,  A61K31/422 ,  C07D401/14 ,  C07D405/14 ,  C07D405/04

CPC分类号： C07D413/04

摘要： The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salt or solvate thereof, as anti-inflammatory and immunomodulatory agents.

公开(公告)号：US07601745B2

公开(公告)日：2009-10-13

申请号：US11375259

申请日：2006-03-15

申请人： Johann Leban ,  Harald Schmitt ,  Kristina Wolf ,  Stefano Pegoraro ,  Andreas Wuzik

发明人： Johann Leban ,  Harald Schmitt ,  Kristina Wolf ,  Stefano Pegoraro ,  Andreas Wuzik

IPC分类号： A01N43/52 ,  A01N43/78 ,  A61K31/415 ,  A61K31/425 ,  C07D235/04 ,  C07D263/58 ,  C07D263/60 ,  C07D277/82 ,  C07D403/02 ,  C07D413/00 ,  C07D498/00

CPC分类号： C07D277/56 ,  C07D263/48 ,  C07D401/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

摘要： The present invention relates to compounds of the general formula (III) or pharmaceutically acceptable salts thereof with an acid or a base, or pharmaceutically acceptable prodrugs or a stereoisomer thereof, wherein R3 is H, —C(O)NRaRb, halogen, alkyl, haloalkyl, aryl, heteroaryl, OH, SH, NR4′OR5′, NH2, amine, alkylamine, alkoxy, cycloalkyl, heterocycloalkyl, hydroxyalkyl, or haloalkyloxy; R4 is H, halogen, alkyl, —C(NR7)NR7R8, —(CH2)paryl, —(CH2)pNR7R8, —C(O)NR7R8, —N═CR7R8, —NR7C(O)R8, cycloalkyl, heterocycloalkyl, haloalkyl, hydroxyalkyl, hyodroxyalkylamino, alkylamino, heteroaryl, or aryl; R5 is halogen, alkyl, —C(NR7)NR7R8, —(CH2)paryl, —(CH2)pNR7R8, —C(O)NR7R8, —N═CR7R8, —NR7C(O)R8, cycloalkyl, heterocycloalkyl, haloalkyl, hydroxyalkyl, hydroxyalkylamino, alkylamino, heteroaryl, or aryl.

摘要翻译： 本发明涉及通式（III）的化合物或其药学上可接受的盐与酸或碱或其药学上可接受的前药或立体异构体，其中R 3是H，-C（O）NR a R b，卤素，烷基， 卤代烷基，芳基，杂芳基，OH，SH，NR4'OR5'，NH2，胺，烷基胺，烷氧基，环烷基，杂环烷基，羟基烷基或卤代烷氧基。 R 4是H，卤素，烷基，-C（NR 7）NR 7 R 8， - （CH 2）paryl， - （CH 2）p NR 17 R 8，-C（O）NR 7 R 8，-N-CR 7 R 8，-NR 7 C（O）R 8，环烷基，杂环烷基， 卤代烷基，羟基烷基，羟基烷基氨基，烷基氨基，杂芳基或芳基; R5是卤素，烷基，-C（NR7）NR7R8， - （CH2）paryl， - （CH2）pNR7R8，-C（O）NR7R8，-N-CR7R8，-NR7C（O）R8，环烷基，杂环烷基，卤代烷基， 羟基烷基，羟基烷基氨基，烷基氨基，杂芳基或芳基。

公开(公告)号：US07531517B2

公开(公告)日：2009-05-12

申请号：US11501722

申请日：2006-08-10

申请人： Johann Leban ,  Martin Kralik

发明人： Johann Leban ,  Martin Kralik

IPC分类号： A61K38/05

CPC分类号： C07D233/72 ,  A61K38/00 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/14 ,  C07K5/0205 ,  C07K5/06078 ,  C07K5/06191 ,  Y02A50/409

摘要： The invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein Y is —NRaRb, —NRcC═ONRaRb, —NRcC═SNRaRb, —NRcC═NRdNaRb, heterocycle, —C═ONRaRb, heterocycle, or aryl; n is 0 to 8; m is 0, or 1; r is 0 to 3; t is 0 to 3; X is O or N; Z is CH2, C═O, C═S or a single bond; Z1 is CO—R2, CS—R2, (CH2)t—R2 or the side-chain of a naturally occuring amino acid;, Z2 is CO—R2, CS—R2 or (CH2)t—R3 or the side-chain of a naturally occuring amino acid; Z3 is CO—R2, CS—R2 or (CH2)t—R4 or the side-chain of a naturally occuring amino acid; Z4 is H, alkyl, alkoxy, or cycloalkyl; R1, R2, R3, and R4 are independently from each other H, OH, SH, NH2, CN, NO2, alkyl, cycloalkyl, heterocycloalkyl, haloalkyl, alkylthio, haloalkyloxy, hydroxyalkyl, hydroxyalkylamino, alkylamino, alkylaryl, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxyalkyl, alkoxy, aryloxy, heteroaryl, aryl, or halogen.

摘要翻译： 本发明涉及通式（I）的化合物及其盐和生理功能衍生物，其中Y为-NR a R b，-NR c C -ONR a R b，-NR c C -R SNR a R b，-NR c C-NR d N a R b，杂环，-C-ONR a R b，杂环， 或芳基; n为0〜8; m为0或1; r为0〜3; t为0〜3; X是O或N; Z是CH 2，C-O，C-S或单键; Z1是CO-R2，CS-R2，（CH2）t-R2或天然存在的氨基酸的侧链; Z2是CO-R2，CS-R2或（CH2）t-R3或侧链 的天然存在的氨基酸; Z3是CO-R2，CS-R2或（CH2）t-R4或天然存在的氨基酸的侧链; Z4是H，烷基，烷氧基或环烷基; R 1，R 2，R 3和R 4彼此独立地是H，OH，SH，NH 2，CN，NO 2，烷基，环烷基，杂环烷基，卤代烷基，烷硫基，卤代烷氧基，羟烷基，羟烷基氨基，烷基氨基，烷基芳基，烷基亚磺酰基，烷基磺酰基， 烷基亚磺酰基烷基，烷基磺酰基烷基，烷氧基烷基，烷氧基，芳氧基，杂芳基，芳基或卤素。

公开(公告)号：US20080261971A1

公开(公告)日：2008-10-23

申请号：US11575647

申请日：2005-07-29

申请人： Johann Leban ,  Harald Schmitt ,  Kristina Wolf ,  Stefano Pegoraro ,  Andreas Wuzik

发明人： Johann Leban ,  Harald Schmitt ,  Kristina Wolf ,  Stefano Pegoraro ,  Andreas Wuzik

IPC分类号： A61K31/5377 ,  A61P35/00 ,  A61P25/00 ,  A61P31/00 ,  A61P19/00 ,  C07D417/14 ,  A61K31/427 ,  A61K31/53 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497

CPC分类号： C07D263/48 ,  C07D277/56 ,  C07D401/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04

摘要： The present invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, (I) wherein R1 is independently hydrogen, alkyl, cycloalkyl, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl or substituted arylalkyl; R2 is independently —NR3R4, (II) or (III) R3 is independently alkyl, cycloalkyl, alkoxy, alkylamine, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl, R4 is independently alkyl, cycloalkyl, alkoxy, alkylamine, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R5 is independently H, COR6, CO2R6, SOR6, SO2R6, SO3R6, alkyl, cycloalkyl, alkoxy, —NH2, alkylamine, —NR7COR6, halogen, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R6 is independently H, alkyl, cycloalkyl, —NH2, alkylamine, aryl or heteroaryl; R7 is independently H, alkyl, cycloalkyl, alkoxy, —OH, —SH, alkylthio, hydroxyalkyl, aryl, or heteroaryl; p is 0, or 1; q is 0, or 1; X is CO, or SO2.

摘要翻译： 本发明涉及通式（I）的化合物及其盐和生理功能衍生物，其中R 1独立地为氢，烷基，环烷基，羟基烷基，卤代烷基，卤代烷氧基，芳基， 取代的芳基，杂芳基，取代的杂芳基，芳基烷基或取代的芳基烷基; R 2独立地是-NR 3 R 4，（II）或（III）R 3独立地是烷基 环烷基，烷氧基，烷基胺，-OH，-SH，烷硫基，羟基烷基，卤代烷基，卤代烷氧基，芳基或杂芳基，R 4独立地为烷基，环烷基，烷氧基，烷基胺，烷硫基，羟基烷基，卤代烷基， 卤代烷氧基，芳基或杂芳基; R 5独立地为H，COR 6，CO 2，R 6，SOR 6， SO 2 SO 2，SO 3 R 6，烷基，环烷基，烷氧基，-NH