公开(公告)号：US06369086B1

公开(公告)日：2002-04-09

申请号：US09262351

申请日：1999-03-04

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K314439

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： The present invention relates generally to novel substituted oxindole compounds and compositions. Such compounds and compositions have utility as pharmacological agents in treating diseases or conditions alleviated by the inhibition or antagonism of protein kinase activated signalling pathways. In particular, the present invention relates to a series of substituted oxindole compounds, which exhibit protein tyrosine kinase and protein serine/threonine kinase inhibition, and which are useful in inhibiting tumor growth via inhibition of such kinases as well as protecting a patient undergoing chemotherapy from chemotherapy induced alopecia.

摘要翻译： 本发明一般涉及新型取代的羟基吲哚化合物和组合物。 这样的化合物和组合物可用作治疗通过抑制或拮抗蛋白激酶激活的信号通路而减轻的疾病或病症的药理学作用。 特别地，本发明涉及一系列取代的羟吲哚化合物，其表现出蛋白质酪氨酸激酶和蛋白质丝氨酸/苏氨酸激酶抑制，并且其可用于通过抑制这种激酶抑制肿瘤生长以及保护接受化疗的患者 化疗引起秃发。

公开(公告)号：US07105529B2

公开(公告)日：2006-09-12

申请号：US09999331

申请日：2001-11-30

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K31/505 ,  A61K31/44 ,  A61K31/425

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

公开(公告)号：US06541503B2

公开(公告)日：2003-04-01

申请号：US09924431

申请日：2001-08-08

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Stephen Vernon Frye ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K31429

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

公开(公告)号：US06387919B1

公开(公告)日：2002-05-14

申请号：US09486960

申请日：2000-06-06

申请人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

发明人： Stephen Thomas Davis ,  Scott Howard Dickerson ,  Philip Anthony Harris ,  Robert Neil Hunter, III ,  Lee Frederick Kuyper ,  Michael Joseph Luzzio ,  James Marvin Veal ,  Duncan Herrick Walker

IPC分类号： A61K314045

CPC分类号： C07D231/12 ,  C07D209/34 ,  C07D209/40 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

摘要： Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7 sulfonyl-C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

摘要翻译： 式（I）化合物：其中X为N，CH，CCF 3或C（C 1-12脂族基）; R 4是磺酸，C 1-12脂族磺酰基，磺酰基-C 1-12脂族基，C 1-12脂族磺酰基-C 1-6脂族基，C 1-6脂族氨基，R 7磺酰基，R 7磺酰基-C 1-12脂族基， R7-氨基磺酰基，R7-氨基磺酰基-C1-12脂族，R7-磺酰氨基，R7-磺酰氨基-C12-12脂族，氨基磺酰基氨基，二-C1-12脂族氨基，二-C1-12脂族氨基羰基，二-C1-12脂族 氨基磺酰基，二-C 1-12脂族氨基，二-C1-12脂族氨基羰基，二C1-12脂族氨基磺酰基-C1-12脂族基，（R8）1-3 - 芳基氨基，（R8）1-3 - 芳基磺酰基，（ R8）1-3-芳基 - 氨基磺酰基，（R8）1-3-芳基 - 磺酰基氨基，Het-氨基，Het-磺酰基，Het-氨基磺酰基，氨基亚氨基氨基或氨基亚氨基磺酰基，R5是氢; 并且其中R 4和R 5任选地连接以形成稠环，包含它们的药物制剂及其在治疗中的用途，特别是用于治疗由CDK2活性介导的疾病，例如由癌症化学疗法或放射治疗引起的脱发。

公开(公告)号：US6100273A

公开(公告)日：2000-08-08

申请号：US977217

申请日：1997-11-24

申请人： Jeffrey Mark Besterman ,  Michael Glenn Evans ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  Michael Robert Peel ,  Daniel David Sternbach

发明人： Jeffrey Mark Besterman ,  Michael Glenn Evans ,  Karen Elizabeth Lackey ,  Michael Joseph Luzzio ,  Michael Robert Peel ,  Daniel David Sternbach

IPC分类号： A61K31/47 ,  A61K31/675 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07F9/6561 ,  A61K31/4745

CPC分类号： C07D317/66 ,  C07D319/18

摘要： The present invention relates to water soluble, camptothecin derivatives of formula (I). ##STR1## wherein A represents a moiety of the formula (IIA), (IIB) or (IIC): ##STR2## X is selected from the group consisting of alkyl, aryl, (CH.sub.2).sub.m OR.sup.1, (CH.sub.2).sub.m SR.sup.1 and (CH.sub.2).sub.m NR.sup.1 R.sup.2 wherein m is an integer of 0 to 6, and R.sup.1 and R.sup.2 are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.

摘要翻译： 本发明涉及式（I）的水溶性喜树碱衍生物。 其中A表示式（IIA），（IIB）或（IIC）的部分：X选自烷基，芳基，（CH2）mOR1，（CH2）mSR1和（CH2）mNR1R2，其中m为 0〜6的整数，R 1和R 2为氢，低级烷基，芳基或与氮一起形成5-7元环; q为0〜2的整数; n表示整数1或2; p为1〜6的整数。 Y和W选自烷基，芳基，烷氧基，芳氧基和氨基，Q是氧或硫; 磷是磷; J表示完成5或6元芳环所必需的原子; 及其药学上可接受的盐; 它们用作拓扑异构酶抑制剂，它们的制备; 并用于治疗癌症。

公开(公告)号：US06172064B2

公开(公告)日：2001-01-09

申请号：US09382333

申请日：1999-08-25

申请人： Robert Carl Andrews ,  Marc Werner Andersen ,  David John Cowan ,  David Norman Deaton ,  Scott Howard Dickerson ,  David Harold Drewry ,  Michael David Gaul ,  Michael Joseph Luzzio ,  Brian Edward Marron ,  Michael Howard Rabinowitz

发明人： Robert Carl Andrews ,  Marc Werner Andersen ,  David John Cowan ,  David Norman Deaton ,  Scott Howard Dickerson ,  David Harold Drewry ,  Michael David Gaul ,  Michael Joseph Luzzio ,  Brian Edward Marron ,  Michael Howard Rabinowitz

IPC分类号： C07D21170

CPC分类号： C07D213/40 ,  C07C259/06 ,  C07D295/13 ,  C07D333/24

摘要： A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof. Also described are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine.

摘要翻译： 具有通式结构式W的化合物族是反向异羟肟酸基团，R 1，R 2，R 3，R 4，R 5和R 6如说明书中所述，或其药学上可接受的盐，溶剂化物，生物可水解的酯，可生物水解的酰胺， 亲和试剂或其前药。 还描述了它们的制备方法，包括这些化合物的药物组合物及其在药物中的用途。

公开(公告)号：US07741336B2

公开(公告)日：2010-06-22

申请号：US12181991

申请日：2008-07-29

申请人： John Charles Kath ,  Michael Joseph Luzzio

发明人： John Charles Kath ,  Michael Joseph Luzzio

IPC分类号： C07D403/12 ,  C07D403/14 ,  A61K31/506 ,  A61P35/00

CPC分类号： C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D513/04

摘要： The present invention relates to a compound of the formula 1 wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

摘要翻译： 本发明涉及式1的化合物，其中R 1 -R 4如本文所定义。 这种新型嘧啶衍生物可用于治疗哺乳动物中异常细胞生长，如癌症。 本发明还涉及使用这些化合物治疗哺乳动物，特别是人类异常细胞生长的方法以及含有这些化合物的药物组合物。

公开(公告)号：US20080182840A1

公开(公告)日：2008-07-31

申请号：US12059889

申请日：2008-03-31

申请人： JOHN CHARLES KATH ,  Michael Joseph Luzzio

发明人： JOHN CHARLES KATH ,  Michael Joseph Luzzio

IPC分类号： A61K31/506 ,  C07D403/00 ,  A61K31/5377 ,  A61P35/00 ,  A61K31/397 ,  C07D413/14

CPC分类号： C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D513/04

摘要： The present invention relates to a compound of the formula 1 wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

摘要翻译： 本发明涉及式1化合物，其中R 1至R 4如本文所定义。 这种新型嘧啶衍生物可用于治疗哺乳动物中异常细胞生长，如癌症。 本发明还涉及使用这些化合物治疗哺乳动物，特别是人类异常细胞生长的方法以及含有这些化合物的药物组合物。

公开(公告)号：US07109337B2

公开(公告)日：2006-09-19

申请号：US11127809

申请日：2005-05-12

申请人： John Charles Kath ,  Michael Joseph Luzzio

发明人： John Charles Kath ,  Michael Joseph Luzzio

IPC分类号： C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  A61K31/506 ,  A61P35/00

CPC分类号： C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention relates to a compound of the formula 1 wherein R1–R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

摘要翻译： 本发明涉及式1化合物，其中R 1至R 4如本文所定义。 这种新型嘧啶衍生物可用于治疗哺乳动物中异常细胞生长，如癌症。 本发明还涉及使用这些化合物治疗哺乳动物，特别是人类异常细胞生长的方法以及含有这些化合物的药物组合物。

公开(公告)号：US07109335B2

公开(公告)日：2006-09-19

申请号：US10733215

申请日：2003-12-11

申请人： John Charles Kath ,  Michael Joseph Luzzio

发明人： John Charles Kath ,  Michael Joseph Luzzio

IPC分类号： C07D401/14 ,  C07D401/12 ,  C07D403/14 ,  C07D403/12 ,  A61K31/506 ,  A61P35/00

CPC分类号： C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D513/04

摘要： The present invention relates to a compound of the formula 1 wherein R1–R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.