公开(公告)号：US5935976A

公开(公告)日：1999-08-10

申请号：US138076

申请日：1998-08-21

申请人： Guido Bold ,  Hans-Georg Capraro ,  Alexander Fassler ,  Marc Lang ,  Shripad Subray Bhagwat ,  Satish Chandra Khanna ,  Janis Karlis Lazdins ,  Jurgen Mestan

发明人： Guido Bold ,  Hans-Georg Capraro ,  Alexander Fassler ,  Marc Lang ,  Shripad Subray Bhagwat ,  Satish Chandra Khanna ,  Janis Karlis Lazdins ,  Jurgen Mestan

IPC分类号： C07D295/12 ,  A61K31/075 ,  A61K31/16 ,  A61K31/165 ,  A61K31/275 ,  A61K31/325 ,  A61K31/35 ,  A61K31/351 ,  A61K31/352 ,  A61K31/395 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/445 ,  A61K31/47 ,  A61K31/495 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/695 ,  A61K38/05 ,  A61P31/12 ,  A61P31/18 ,  C07C237/22 ,  C07C255/60 ,  C07C271/22 ,  C07C311/19 ,  C07C311/42 ,  C07C317/50 ,  C07D207/12 ,  C07D207/16 ,  C07D207/26 ,  C07D207/28 ,  C07D209/18 ,  C07D209/42 ,  C07D211/40 ,  C07D211/46 ,  C07D211/48 ,  C07D211/60 ,  C07D211/62 ,  C07D213/30 ,  C07D213/65 ,  C07D213/81 ,  C07D213/82 ,  C07D277/06 ,  C07D277/20 ,  C07D277/40 ,  C07D277/56 ,  C07D295/155 ,  C07D295/215 ,  C07D307/20 ,  C07D307/33 ,  C07D309/04 ,  C07D309/12 ,  C07D311/24 ,  C07D317/60 ,  C07D401/04 ,  C07K5/00

CPC分类号： C07D207/26 ,  A61K31/47 ,  A61K31/495 ,  C07C255/60 ,  C07C271/22 ,  C07C311/19 ,  C07C311/42 ,  C07C317/50 ,  C07D207/28 ,  C07D209/42 ,  C07D211/46 ,  C07D211/62 ,  C07D213/30 ,  C07D213/82 ,  C07D277/06 ,  C07D277/40 ,  C07D295/155 ,  C07D307/20 ,  C07D309/04 ,  C07D309/12 ,  C07D311/24 ,  C07D317/60 ,  C07C2101/14 ,  C07C2102/10

摘要： Antiretroviral compounds (which are effective, for example, against HIV) of the formula I ##STR1## in which R.sub.1 is an acyl radical lower-alkoxy-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amino, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl;or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals);R.sub.2 and R.sub.3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen;R.sub.4 is lower alkyl, cyclohexyl or phenyl; and R.sub.5 is lower alkyl; and n is 1 or 2,or salts thereof, are novel.

摘要翻译： 其中R1是其低级烷氧基未被取代或被卤素，苯基，低级烷氧基或杂环取代的酰基低级烷氧基 - 低级 - 烷酰基的抗逆转录酶病毒化合物（其例如抗HIV） 选自哌啶基，吡咯烷基，四氢吡喃基，四氢呋喃基，噻唑烷基，噻唑基，吲哚基或4H-1-苯并吡喃基，其未被取代或被氧代，羟基，氨基，低级烷基，低级烷氧基羰基和/或苯基 - 低级 - 烷氧基羰基取代。 低级烷酰基，其未被取代或被所述未取代或取代的杂环基之一取代; 被杂环基或杂环基 - 低级烷基取代的芳基羰基或杂环基羰基; 被羟基和低级烷基取代的苯基 - 低级 - 烷酰基; 或芳基磺酰基; 或根据描述定义的氨基酸的残基（并且可以通过上述酰基之一在氨基氮上酰化）; 苯基，氰基苯基，苯基 - 低级 - 烷基，卤素，卤代低级烷基，氰基，羟基，低级烷氧基，低级烷氧基，低级烷氧基，低级烷氧基， 低级烷氧基，低级烷氧基 - 低级烷氧基，低级烷氧基 - 低级 - 烷氧基，低级烷氧基 - 低级 - 烷氧基，羧基 - 低级 - 烷氧基，羟基 - 低级 - 烷氧基，氨基甲酰基 - 低级烷氧基， 烷氧基和未被卤素取代的苯基 - 低级烷基磺酰基; R4是低级烷基，环己基或苯基; R5为低级烷基; n为1或2，或其盐为新颖的。

公开(公告)号：US5663200A

公开(公告)日：1997-09-02

申请号：US545170

申请日：1995-10-19

申请人： Guido Bold ,  Hans-Georg Capraro ,  Alexander Fassler ,  Marc Lang ,  Shripad Subray Bhagwat ,  Satish Chandra Khanna ,  Janis Karlis Lazdins ,  Jurgen Mestan

发明人： Guido Bold ,  Hans-Georg Capraro ,  Alexander Fassler ,  Marc Lang ,  Shripad Subray Bhagwat ,  Satish Chandra Khanna ,  Janis Karlis Lazdins ,  Jurgen Mestan

IPC分类号： C07D295/12 ,  A61K31/075 ,  A61K31/16 ,  A61K31/165 ,  A61K31/275 ,  A61K31/325 ,  A61K31/35 ,  A61K31/351 ,  A61K31/352 ,  A61K31/395 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/445 ,  A61K31/47 ,  A61K31/495 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/695 ,  A61K38/05 ,  A61P31/12 ,  A61P31/18 ,  C07C237/22 ,  C07C255/60 ,  C07C271/22 ,  C07C311/19 ,  C07C311/42 ,  C07C317/50 ,  C07D207/12 ,  C07D207/16 ,  C07D207/26 ,  C07D207/28 ,  C07D209/18 ,  C07D209/42 ,  C07D211/40 ,  C07D211/46 ,  C07D211/48 ,  C07D211/60 ,  C07D211/62 ,  C07D213/30 ,  C07D213/65 ,  C07D213/81 ,  C07D213/82 ,  C07D277/06 ,  C07D277/20 ,  C07D277/40 ,  C07D277/56 ,  C07D295/155 ,  C07D295/215 ,  C07D307/20 ,  C07D307/33 ,  C07D309/04 ,  C07D309/12 ,  C07D311/24 ,  C07D317/60 ,  C07D401/04 ,  C07K5/00 ,  A61K31/215 ,  C07C271/20

CPC分类号： C07D207/26 ,  A61K31/47 ,  A61K31/495 ,  C07C255/60 ,  C07C271/22 ,  C07C311/19 ,  C07C311/42 ,  C07C317/50 ,  C07D207/28 ,  C07D209/42 ,  C07D211/46 ,  C07D211/62 ,  C07D213/30 ,  C07D213/82 ,  C07D277/06 ,  C07D277/40 ,  C07D295/155 ,  C07D307/20 ,  C07D309/04 ,  C07D309/12 ,  C07D311/24 ,  C07D317/60 ,  C07C2101/14 ,  C07C2102/10

摘要： Antiretroviral compounds (which are effective, for example, against HIV) of the formula I ##STR1## in which R.sub.1 is an acyl radical lower-alkoxyl-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amine, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl;or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals);R.sub.2 and R.sub.3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen;R.sub.4 is lower alkyl, cyclohexyl or phenyl; and R.sub.5 is lower alkyl; and n is 1 or 2, or salts thereof, are novel.

摘要翻译： 抗逆转录病毒化合物（其有效的，例如针对HIV）具有式I的低级烷酰基，其低级烷酰基未被取代或被卤素，苯基，低级烷氧基或选自哌啶基，吡咯烷基 四氢呋喃基，噻唑烷基，噻唑基，吲哚基或4H-1-苯并吡喃基，其未被取代或被氧代，羟基，胺，低级烷基，低级烷氧基羰基和/或苯基 - 低级 - 烷氧基羰基取代; 低级烷酰基，其未被取代或被所述未取代或取代的杂环基之一取代; 被杂环基或杂环基 - 低级烷基取代的芳基羰基或杂环基羰基; 被羟基和低级烷基取代的苯基 - 低级 - 烷酰基; 或芳基磺酰基; 或根据描述定义的氨基酸的残基（并且可以通过上述酰基之一在氨基氮上酰化）; 苯基，氰基苯基，苯基 - 低级 - 烷基，卤素，卤代低级烷基，氰基，羟基，低级烷氧基，低级烷氧基，低级烷氧基，低级烷氧基， 低级烷氧基，低级烷氧基 - 低级烷氧基，低级烷氧基 - 低级 - 烷氧基，低级烷氧基 - 低级 - 烷氧基，羧基 - 低级 - 烷氧基，羟基 - 低级 - 烷氧基，氨基甲酰基 - 低级烷氧基， 烷氧基和未被卤素取代的苯基 - 低级烷基磺酰基; R4是低级烷基，环己基或苯基; R5为低级烷基; n为1或2，或其盐为新颖的。

公开(公告)号：US5807891A

公开(公告)日：1998-09-15

申请号：US838347

申请日：1997-04-08

申请人： Guido Bold ,  Hans-Georg Capraro ,  Alexander Fassler ,  Marc Lang ,  Shripad Subray Bhagwat ,  Satish Chandra Khanna ,  Janis Karlis Lazdins ,  Jurgen Mestan

发明人： Guido Bold ,  Hans-Georg Capraro ,  Alexander Fassler ,  Marc Lang ,  Shripad Subray Bhagwat ,  Satish Chandra Khanna ,  Janis Karlis Lazdins ,  Jurgen Mestan

IPC分类号： C07D295/12 ,  A61K31/075 ,  A61K31/16 ,  A61K31/165 ,  A61K31/275 ,  A61K31/325 ,  A61K31/35 ,  A61K31/351 ,  A61K31/352 ,  A61K31/395 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/445 ,  A61K31/47 ,  A61K31/495 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/695 ,  A61K38/05 ,  A61P31/12 ,  A61P31/18 ,  C07C237/22 ,  C07C255/60 ,  C07C271/22 ,  C07C311/19 ,  C07C311/42 ,  C07C317/50 ,  C07D207/12 ,  C07D207/16 ,  C07D207/26 ,  C07D207/28 ,  C07D209/18 ,  C07D209/42 ,  C07D211/40 ,  C07D211/46 ,  C07D211/48 ,  C07D211/60 ,  C07D211/62 ,  C07D213/30 ,  C07D213/65 ,  C07D213/81 ,  C07D213/82 ,  C07D277/06 ,  C07D277/20 ,  C07D277/40 ,  C07D277/56 ,  C07D295/155 ,  C07D295/215 ,  C07D307/20 ,  C07D307/33 ,  C07D309/04 ,  C07D309/12 ,  C07D311/24 ,  C07D317/60 ,  C07D401/04 ,  C07K5/00 ,  A61K31/215 ,  C07C271/20

CPC分类号： C07D207/26 ,  A61K31/47 ,  A61K31/495 ,  C07C255/60 ,  C07C271/22 ,  C07C311/19 ,  C07C311/42 ,  C07C317/50 ,  C07D207/28 ,  C07D209/42 ,  C07D211/46 ,  C07D211/62 ,  C07D213/30 ,  C07D213/82 ,  C07D277/06 ,  C07D277/40 ,  C07D295/155 ,  C07D307/20 ,  C07D309/04 ,  C07D309/12 ,  C07D311/24 ,  C07D317/60 ,  C07C2101/14 ,  C07C2102/10

摘要： Antiretroviral compounds (which are effective, for example, against HIV) of the formula I ##STR1## in which R.sub.1 is an acyl radical lower-alkoxy-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amino, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl; or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals); R.sub.2 and R.sub.3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen; R.sub.4 is lower alkyl, cyclohexyl or phenyl; and R.sub.5 is lower alkyl; and n is 1 or 2, or salts thereof, are novel.

摘要翻译： 式（I）的抗逆转录病毒化合物（其有效的，例如抗HIV），其中R1是其低级烷氧基未被取代或被卤素取代的酰基低级烷氧基 - 低级 - 烷酰基，苯基 低级烷氧基或选自哌啶基，吡咯烷基，四氢吡喃基，四氢呋喃基，噻唑烷基，噻唑基，吲哚基或4H-1-苯并吡喃基的杂环基，其未被取代或被氧代，羟基，氨基，低级烷基，低级烷氧基羰基和/或苯基 低级烷氧基羰基 低级烷酰基，其未被取代或被所述未取代或取代的杂环基之一取代; 被杂环基或杂环基 - 低级烷基取代的芳基羰基或杂环基羰基; 被羟基和低级烷基取代的苯基 - 低级 - 烷酰基; 或芳基磺酰基; 或根据描述定义的氨基酸的残基（并且可以通过上述酰基之一在氨基氮上酰化）; 苯基，氰基苯基，苯基 - 低级 - 烷基，卤素，卤代低级烷基，氰基，羟基，低级烷氧基，低级烷氧基，低级烷氧基，低级烷氧基， 低级烷氧基，低级烷氧基 - 低级烷氧基，低级烷氧基 - 低级 - 烷氧基，低级烷氧基 - 低级 - 烷氧基，羧基 - 低级 - 烷氧基，羟基 - 低级 - 烷氧基，氨基甲酰基 - 低级烷氧基， 烷氧基和未被卤素取代的苯基 - 低级烷基磺酰基; R4是低级烷基，环己基或苯基; R5为低级烷基; n为1或2，或其盐为新颖的。

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：US08268837B2

公开(公告)日：2012-09-18

申请号：US11285664

申请日：2005-11-22

申请人： Nicholas J Donato ,  Doriano Fabbro ,  Paul W Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

发明人： Nicholas J Donato ,  Doriano Fabbro ,  Paul W Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

IPC分类号： A61K31/519

CPC分类号： A61K35/02 ,  A61K31/506 ,  A61K31/519

摘要： The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Btk kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine.

摘要翻译： 本发明涉及一种组合，其包含（a）至少一种降低c-Src活性的化合物和（b）N- {5- [4-（4-甲基 - 哌嗪基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺或其单甲磺酸盐; 包含所述组合的药物组合物; 以及治疗具有白血病，特别是慢性骨髓性白血病的温血动物的方法，包括向所述动物施用至少一种抑制Src激酶家族成员，Btk激酶家族，Tec激酶家族的活性的化合物或 Raf激酶抑制剂，特别是抑制c-Src蛋白酪氨酸激酶活性或同时抑制c-Src蛋白酪氨酸激酶活性和Bcr-Abl酪氨酸激酶活性，单独或与Bcr-Abl抑制剂组合，特别是N - {5- [4-（4-甲基 - 哌嗪子基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺。

公开(公告)号：US20080176879A1

公开(公告)日：2008-07-24

申请号：US11911575

申请日：2006-05-01

申请人： Leila Alland ,  Doriano Fabbro ,  Jurgen Mestan ,  Paul W. Manley

发明人： Leila Alland ,  Doriano Fabbro ,  Jurgen Mestan ,  Paul W. Manley

IPC分类号： A61K31/506 ,  A61P35/04

CPC分类号： A61K31/506

摘要： The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of systemic mastocytosis.

摘要翻译： 本发明涉及嘧啶氨基苯甲酰胺衍生物在制备用于治疗系统性肥大细胞增多症的药物中的应用。

公开(公告)号：US20070149539A1

公开(公告)日：2007-06-28

申请号：US11679901

申请日：2007-02-28

申请人： Nicholas Donato ,  Doriano Fabbro ,  Paul Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

发明人： Nicholas Donato ,  Doriano Fabbro ,  Paul Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

IPC分类号： A61K31/506 ,  A61K31/497 ,  A61K31/519

CPC分类号： A61K35/02 ,  A61K31/506 ,  A61K31/519

摘要： The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamdio]-2-methylphenyl }-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N- {5- [4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl }-4-(3-pyridyl)-2-pyrimidine-amine.

摘要翻译： 本发明涉及一种组合，其包含（a）至少一种降低c-Src活性的化合物和（b）N- {5- [4-（4-甲基 - 哌嗪基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺或其单甲磺酸盐; 包含所述组合的药物组合物; 以及治疗具有白血病，特别是慢性骨髓性白血病的温血动物的方法，包括向动物施用至少一种抑制Src激酶家族成员，Tec激酶家族或Raf激酶抑制剂的活性的化合物， 特别是抑制c-Src蛋白酪氨酸激酶活性或同时抑制c-Src蛋白酪氨酸激酶活性和Bcr-Abl酪氨酸激酶活性，单独或与Bcr-Abl抑制剂组合，特别是N- {5- [ 4-（4-甲基 - 哌嗪子基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺。

公开(公告)号：US20070027167A1

公开(公告)日：2007-02-01

申请号：US11515981

申请日：2006-09-05

申请人： Nicholas Donato ,  Doriano Fabbro ,  Paul Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

发明人： Nicholas Donato ,  Doriano Fabbro ,  Paul Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

IPC分类号： A61K31/519

CPC分类号： A61K35/02 ,  A61K31/506 ,  A61K31/519

摘要： The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamdio]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine.

摘要翻译： 本发明涉及一种组合，其包含（a）至少一种降低c-Src活性的化合物和（b）N- {5- [4-（4-甲基 - 哌嗪基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺或其单甲磺酸盐; 包含所述组合的药物组合物; 以及治疗具有白血病，特别是慢性骨髓性白血病的温血动物的方法，包括向所述动物施用至少一种抑制Src激酶家族成员，Tec激酶家族或Raf激酶抑制剂的活性的化合物， 特别是抑制c-Src蛋白酪氨酸激酶活性或同时抑制c-Src蛋白酪氨酸激酶活性和Bcr-Abl酪氨酸激酶活性，单独或与Bcr-Abl抑制剂组合，特别是N- {5- [ 4-（4-甲基 - 哌嗪子基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺。

公开(公告)号：US20060074094A1

公开(公告)日：2006-04-06

申请号：US11285664

申请日：2005-11-22

申请人： Nicholas Donato ,  Doriano Fabbro ,  Paul Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

发明人： Nicholas Donato ,  Doriano Fabbro ,  Paul Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

IPC分类号： A61K31/519

CPC分类号： A61K35/02 ,  A61K31/506 ,  A61K31/519

摘要： The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Btk kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine.

摘要翻译： 本发明涉及一种组合，其包含（a）至少一种降低c-Src活性的化合物和（b）N- {5- [4-（4-甲基 - 哌嗪基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺或其单甲磺酸盐; 包含所述组合的药物组合物; 以及治疗具有白血病，特别是慢性骨髓性白血病的温血动物的方法，包括向所述动物施用至少一种抑制Src激酶家族成员，Btk激酶家族，Tec激酶家族的活性的化合物或 Raf激酶抑制剂，特别是抑制c-Src蛋白酪氨酸激酶活性或同时抑制c-Src蛋白酪氨酸激酶活性和Bcr-Abl酪氨酸激酶活性，单独或与Bcr-Abl抑制剂组合，特别是N - {5- [4-（4-甲基 - 哌嗪子基 - 甲基） - 苯甲酰氨基] -2-甲基苯基} -4-（3-吡啶基）-2-嘧啶胺。

公开(公告)号：US08119649B2

公开(公告)日：2012-02-21

申请号：US12466186

申请日：2009-05-14

申请人： Nicholas J Donato ,  Doriano Fabbro ,  Paul W Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

发明人： Nicholas J Donato ,  Doriano Fabbro ,  Paul W Manley ,  Jurgen Mestan ,  Markus Warmuth ,  Michael Hallek ,  Moshe Talpaz ,  Ji Wu

IPC分类号： A61K31/519

CPC分类号： A61K35/02 ,  A61K31/506 ,  A61K31/519

摘要： The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Btk kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine.