公开(公告)号：US06589972B2

公开(公告)日：2003-07-08

申请号：US09867835

申请日：2001-05-30

Applicant: Andreas Schoop ,  Gerhard Mueller ,  Ulf Brueggemeier ,  Delf Schmidt ,  Beatrix Stelte-Ludwig ,  Joerg Keldenich

Inventor： Andreas Schoop ,  Gerhard Mueller ,  Ulf Brueggemeier ,  Delf Schmidt ,  Beatrix Stelte-Ludwig ,  Joerg Keldenich

IPC: A01N4350

CPC classification number: C07C311/19 ,  C07C311/47

Abstract: The present invention relates to compounds of the general formula (1) wherein R4 is —SO2R4′, —COOR4″, —COR4′, —CONR4′2 or —CSNR4′2; R4′ is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; R4″ is a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; L is a sulphonamide, amide, ether, ester, keto, urea, thioether, sulphoxide or sulphone unit optionally extended by one or two methylene groups; and X is N, O or S; and their physiologically acceptable salts and stereoisomers. The present invention furthermore relates to a process for the preparation of the compounds of the formula (1), a pharmaceutical composition containing at least one of these compounds, and the use of compounds of the formula (1) for the production of a pharmaceutical composition having integrin-antagonistic action and in particular for the therapy and prophylaxis of cancer, osteolytic diseases such as osteoporosis, arteriosclerosis, restenosis and ophthalmic disorders.

Abstract translation: 本发明涉及通式（1）的化合物，其中R 4是-SO 2 R 4'，-COOR 4“，-COR 4'， - CONR 4'2或-CSNR 4'2; R 4'是氢，取代或未取代的烷基或环烷基残基，取代或未取代的芳基残基或饱和或不饱和的任选取代的杂环残基; R 4“是取代或未取代的烷基或环烷基残基，取代或未取代的芳基残基或饱和或不饱和的任选取代的杂环残基; L是任选被一个或两个亚甲基延伸的磺酰胺，酰胺，醚，酯，酮，脲，硫醚，亚砜或砜单元; X为N，O或S; 及其生理上可接受的盐和立体异构体。 本发明还涉及制备式（1）化合物的方法，含有这些化合物中的至少一种的药物组合物，以及式（1）化合物在制备药物组合物中的用途 具有整合素拮抗作用，特别是用于治疗和预防癌症，溶骨性疾病如骨质疏松症，动脉硬化，再狭窄和眼科疾病。

公开(公告)号：US06339083B1

公开(公告)日：2002-01-15

申请号：US09211274

申请日：1998-12-14

Applicant: Klaus Urbahns ,  Delf Schmidt ,  Ulf Brueggemeier ,  Christoph Gerdes ,  Beatrix Stelte-Ludwig ,  Jörg Keldenich ,  Elke Stahl

Inventor： Klaus Urbahns ,  Delf Schmidt ,  Ulf Brueggemeier ,  Christoph Gerdes ,  Beatrix Stelte-Ludwig ,  Jörg Keldenich ,  Elke Stahl

IPC: A61K315513

CPC classification number: C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds of the general formula (I): and their preparation and use for the production of pharmaceuticals, and pharmaceuticals comprising these compounds.

Abstract translation: 本发明涉及通式（I）的化合物及其药物制备和用途以及包含这些化合物的药物。

公开(公告)号：US06291503B1

公开(公告)日：2001-09-18

申请号：US09232738

申请日：1999-01-15

Applicant: Andreas Schoop ,  Gerhard Mueller ,  Ulf Brueggemeier ,  Delf Schmidt ,  Beatrix Stelte-Ludwig ,  Joerg Keldenich

Inventor： Andreas Schoop ,  Gerhard Mueller ,  Ulf Brueggemeier ,  Delf Schmidt ,  Beatrix Stelte-Ludwig ,  Joerg Keldenich

IPC: A01N4356

CPC classification number: C07C311/19 ,  C07C311/47

Abstract: The present invention relates to compounds of the general formula (1) wherein R4 is —SO2R4, —COOR4′, —COR4′, —CONR4′2 or —CSNR4′2; R4′ is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; R4″ is a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; L is a sulphonamide, amide, ether, ester, keto, urea, thioether, sulphoxide or sulphone unit optionally extended by one or two methylene groups; and X is N, O or S; and their physiologically acceptable salts and stereoisomers. The present invention furthermore relates to a process for the preparation of the compounds of the formula (1), a pharmaceutical composition containing at least one of these compounds, and the use of compounds of the formula (1) for the production of a pharmaceutical composition having integrin-antagonistic action and in particular for the therapy and prophylaxis of cancer, osteolytic diseases such as osteoporosis, arteriosclerosis, restenosis and ophthalmic disorders.

Abstract translation: 本发明涉及通式（1）的化合物，其中R4是-SO2R4，-COOR4'，-COR4'，-CONR4'2或-CSNR4'2; R 4'是氢，取代或未取代的烷基或环烷基残基，取代或未取代的芳基残基或饱和或不饱和的任选取代的杂环残基; R 4“是取代或未取代的烷基或环烷基残基，取代或未取代的芳基残基或饱和或不饱和的任选取代的杂环残基; L是任选被一个或两个亚甲基延伸的磺酰胺，酰胺，醚，酯，酮，脲，硫醚，亚砜或砜单元; X为N，O或S; 及其生理上可接受的盐和立体异构体。 本发明还涉及制备式（1）化合物的方法，含有这些化合物中的至少一种的药物组合物，以及式（1）化合物在制备药物组合物中的用途 具有整合素拮抗作用，特别是用于治疗和预防癌症，溶骨性疾病如骨质疏松症，动脉硬化，再狭窄和眼科疾病。

公开(公告)号：US5932587A

公开(公告)日：1999-08-03

申请号：US883673

申请日：1997-06-27

Applicant: Carsten Schmeck ,  Matthias Muller-Gliemann ,  Gunter Schmidt ,  Arndt Brandes ,  Rolf Angerbauer ,  Michael Logers ,  Klaus-Dieter Bremm ,  Hilmar Bischoff ,  Delf Schmidt ,  Joachim Schuhmacher

Inventor： Carsten Schmeck ,  Matthias Muller-Gliemann ,  Gunter Schmidt ,  Arndt Brandes ,  Rolf Angerbauer ,  Michael Logers ,  Klaus-Dieter Bremm ,  Hilmar Bischoff ,  Delf Schmidt ,  Joachim Schuhmacher

IPC: C07D491/044 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/445 ,  A61K31/451 ,  A61K31/55 ,  A61P3/06 ,  A61P9/10 ,  C07C229/14 ,  C07D211/86 ,  C07D211/90 ,  C07D213/80 ,  C07D401/04 ,  C07D471/04 ,  C07D491/04 ,  C07D491/20 ,  C07D493/14 ,  C07D495/04 ,  C07F7/18

CPC classification number: C07D213/80 ,  C07C229/14 ,  C07D211/86 ,  C07D211/90 ,  C07D471/04 ,  C07D491/04 ,  C07D495/04 ,  C07F7/1856

Abstract: The heterocyclic-fused pyridines are prepared by reaction of the corresponding heterocyclic-fused pyridine aldehydes with appropriately substituted Grignard or Wittig reagents. The heterocyclic-fused pyridines are suitable as active compounds in medicaments, in particular in medicaments for the treatment of dislipidaemia and arteriosclerosis.

Abstract translation: 杂环稠合的吡啶通过相应的杂环稠合吡啶醛与适当取代的格利雅或维蒂希试剂的反应来制备。 杂环稠合的吡啶适合作为药物中的活性化合物，特别是用于治疗血脂异常和动脉硬化的药物。

公开(公告)号：US5849749A

公开(公告)日：1998-12-15

申请号：US883695

申请日：1997-06-27

Applicant: Peter Fey ,  Rolf Angerbauer ,  Delf Schmidt ,  Hilmar Bischoff ,  Wolfgang Kanhai ,  Martin Radtke ,  Wolfgang Karl

Inventor： Peter Fey ,  Rolf Angerbauer ,  Delf Schmidt ,  Hilmar Bischoff ,  Wolfgang Kanhai ,  Martin Radtke ,  Wolfgang Karl

IPC: C07D213/30 ,  A61K31/44 ,  A61K31/4418 ,  A61P3/06 ,  A61P9/10 ,  C07D213/55 ,  C07F7/02

CPC classification number: C07D213/55 ,  Y02P20/55

Abstract: The 6-(hydroxymethyl-ethyl)pyridines are prepared by a process in which the 3-hydroxymethylpyridines which are hydroxyl-protected in the 6-position are oxidized to the 3-aldehyde, this is then converted into the corresponding oxoheptenoic acid derivative using a Wittig-Homer reaction, after this the oxo group is reduced to the hydroxyl group and then the isomers are separated by chromatography. The 6-(hydroxymethyl-ethyl)pyridines are suitable as active compounds in medicaments, in particular in medicaments having antiarteriosclerotic activity.

Abstract translation: 6-（羟甲基 - 乙基）吡啶通过其中6-位被羟基保护的3-羟甲基吡啶氧化为3-醛的方法制备，然后将其转化为相应的氧代庚烯酸衍生物，使用 维ig - 荷马克反应后，将氧代基还原成羟基，然后通过色谱分离异构体。 6-（羟甲基 - 乙基）吡啶适合作为药物中的活性化合物，特别是具有抗动脉硬化活性的药物。

公开(公告)号：US5470982A

公开(公告)日：1995-11-28

申请号：US950623

申请日：1992-09-24

Applicant: Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

Inventor： Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

IPC: C07D213/55 ,  C07D405/04 ,  C07D409/04 ,  C07D405/14

CPC classification number: C07D213/55 ,  C07D405/04 ,  C07D409/04

Abstract: For the treatment of lipoproteinaemia and arteriosclerosis, the new disubstituted pyridines of the formula ##STR1## in which R.sup.1 is optionally substituted aryl or heteroaryl,R.sup.2 is cycloalkyl or optionally substituted alkyl,R.sup.3 is hydrogen, cycloalkyl, or optionally substituted alkyl, aryl or heteroaryl,X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--,A is ##STR2## R.sup.6 is hydrogen or alkyl, and R.sup.7 is hydrogen, alkyl, aralkyl or a cation.

Abstract translation: 对于脂蛋白血症和动脉硬化的治疗，式（I）的新二取代吡啶其中R 1为任选取代的芳基或杂芳基，R 2为环烷基或任选取代的烷基，R 3为氢，环烷基或任选取代的烷基， 芳基或杂芳基，X是-CH 2 -CH 2 - 或-CH = CH-，A是R 6或R 6是氢或烷基，R 7是氢，烷​​基，芳烷基或阳离子。

公开(公告)号：US5177080A

公开(公告)日：1993-01-05

申请号：US798675

申请日：1991-11-26

Applicant: Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

Inventor： Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

IPC: A61K31/44 ,  A61K31/4418 ,  A61P3/06 ,  A61P9/10 ,  C07D213/26 ,  C07D213/30 ,  C07D213/55 ,  C07D213/56

CPC classification number: C07D213/30 ,  C07D213/26 ,  C07D213/55 ,  C07D213/56

Abstract: Substituted pyridyl-dihydroxy-heptenoic acid of the formula ##STR1## and its salts, if desired in an isomeric form, have a superior inhibitory action on HMG-CoA reductase and thus bring about a surprisingly good lowering of the cholesterol content in the blood.

Abstract translation: 如果需要，取代的式（I）的吡啶基 - 二羟基 - 庚烯酸及其盐，如果需要，以异构形式，对HMG-CoA还原酶具有优异的抑制作用，因此导致令人惊奇的降低胆固醇含量 血液。

公开(公告)号：US5173495A

公开(公告)日：1992-12-22

申请号：US564502

申请日：1990-08-08

Applicant: Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

Inventor： Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

IPC: C07D213/55 ,  C07D405/04 ,  C07D409/04

CPC classification number: C07D405/04 ,  C07D213/55 ,  C07D409/04

Abstract: For the treatment of lipoproteinaemia and arteriosclerosis, the polysubstituted pridines of the formula ##STR1## in which R.sup.1 is optionally substituted furyl or thienyl,R.sup.2 is cycloalkyl or optionally substituted alkyl,R.sup.3 is hydrogen, cycloalkyl, or optionally substituted alkyl, aryl or heteroaryl,X is --CH.dbd.CH--,A is ##STR2## R.sup.6 is hydrogen or alkyl, and R.sup.7 is hydrogen, alkyl, aralkyl or a cation.

Abstract translation: 为了治疗脂蛋白血症和动脉硬化，式（I）的多取代脯氨酸其中R 1是任选被取代的呋喃基或噻吩基，R2是环烷基或任选取代的烷基，R 3是氢，环烷基或任选取代的烷基，芳基 或杂芳基，X是-CH = CH-，A是R6是氢或烷基，R7是氢，烷​​基，芳烷基或阳离子。

公开(公告)号：US5169857A

公开(公告)日：1992-12-08

申请号：US627086

申请日：1990-12-13

Applicant: Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

Inventor： Rolf Angerbauer ,  Peter Fey ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

IPC: C07D213/55 ,  C07D213/80 ,  C07D213/82 ,  C07D213/85 ,  C07D213/89 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D409/06 ,  C07F7/08 ,  C07F7/18

CPC classification number: C07D213/80 ,  C07D213/55 ,  C07D213/82 ,  C07D213/85 ,  C07D213/89 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D409/06 ,  C07F7/0812 ,  C07F7/0818 ,  C07F7/1856

Abstract: Novel compounds for treating hyperproteinaemia, lipoproteinaemia or arteriosclerosis of the formula ##STR1## in which A, B, D and E can have varied meanings,X is --CH.sub.2 --CH.sub.2 or --CH.dbd.CH--, andR is ##STR2## wherein R.sup.21 denotes hydrogen or alkyl andR.sup.22denotes hydrogen,deontes alkyl, aryl or aralkyl, ordenotes a cation,and their oxidation products.

Abstract translation: 用于治疗高蛋白血症，脂蛋白血症或动脉硬化的新型化合物，其中A，B，D和E可以具有不同含义，X是-CH 2 -CH 2或-CH = CH-，R是

公开(公告)号：US5164506A

公开(公告)日：1992-11-17

申请号：US673697

申请日：1991-04-19

Applicant: Peter Fey ,  Rolf Angerbauer ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

Inventor： Peter Fey ,  Rolf Angerbauer ,  Walter Hubsch ,  Thomas Philipps ,  Hilmar Bischoff ,  Dieter Petzinna ,  Delf Schmidt ,  Gunter Thomas

IPC: C07D211/90 ,  C07D213/64 ,  C07D213/70 ,  C07F7/18

CPC classification number: C07D213/64 ,  C07D211/90 ,  C07D213/70 ,  C07F7/1856

Abstract: For inhibiting HMG-CoA reductase and cholesterol synthesis, the novel 2-pyridones and pyrid-2-thiones of the formula ##STR1## in which A is optionally substituted aryl or heterocyclic,B is optionally substituted alkyl, cycloalkyl or aryl,D and E independently are optionally substituted aryl or heterocyclic, H, nitro, cyano, optionally substituted alkyl, alkenyl or imino, amino, alkoxy or acyl, or forms a ring with B,G is O or S,X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, andR represents a group of the formula ##STR2## and salts thereof.

Abstract translation: 为了抑制HMG-CoA还原酶和胆固醇合成，式（IMAGE）中的新的2-吡啶酮和吡啶-2-硫酮，其中A是任选取代的芳基或杂环，B是任选取代的烷基，环烷基或芳基，D和E 独立地是任选取代的芳基或杂环，H，硝基，氰基，任选取代的烷基，烯基或亚氨基，氨基，烷氧基或酰基，或与B形成环，G是O或S，X是-CH 2 -CH 2 - CH = CH-，R代表下式的基团及其盐。