公开(公告)号：US07385059B2

公开(公告)日：2008-06-10

申请号：US11336599

申请日：2006-01-20

申请人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

发明人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

IPC分类号： C07D211/00 ,  A01N43/40

CPC分类号： C07D231/38 ,  A61K31/415 ,  A61K31/4152 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04

摘要： The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

公开(公告)号：US20070105900A1

公开(公告)日：2007-05-10

申请号：US10563350

申请日：2004-07-04

申请人： Valerio Berdini ,  Andrew Woodhead ,  Paul Wyatt ,  Michael O'Brien ,  Eva Navarro

发明人： Valerio Berdini ,  Andrew Woodhead ,  Paul Wyatt ,  Michael O'Brien ,  Eva Navarro

IPC分类号： A61K31/4709 ,  A61K31/4745 ,  A61K31/422 ,  A61K31/42 ,  A61K31/4439 ,  A61K31/4178 ,  A61K31/416 ,  C07D403/14 ,  C07D471/02

CPC分类号： C07D401/14 ,  A61K31/00 ,  A61K31/4184 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

摘要： The invention provides compounds of the formula (I): The compounds have activity against cyclin dependent kinases, glycogen synthase kinase and Auroa kinases and are therefore useful to treat cancer and viral diseases.

摘要翻译： 本发明提供式（I）化合物：该化合物具有抗细胞周期蛋白依赖性激酶，糖原合成酶激酶和Auroa激酶的活性，因此可用于治疗癌症和病毒性疾病。

公开(公告)号：US20050080067A1

公开(公告)日：2005-04-14

申请号：US10469094

申请日：2002-02-25

申请人： Marcello Allegretti ,  Riccardo Bertini ,  Valerio Berdini ,  Cinzia Bizzarri ,  Maria Cesta ,  Vito Di Cioccio ,  Gianfranco Caselli ,  Francesco Colotta

发明人： Marcello Allegretti ,  Riccardo Bertini ,  Valerio Berdini ,  Cinzia Bizzarri ,  Maria Cesta ,  Vito Di Cioccio ,  Gianfranco Caselli ,  Francesco Colotta

IPC分类号： C07D295/12 ,  A61K31/165 ,  A61K31/198 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4453 ,  A61K31/5375 ,  A61K31/5377 ,  A61P1/04 ,  A61P9/10 ,  A61P11/00 ,  A61P13/12 ,  A61P17/02 ,  A61P17/06 ,  A61P19/02 ,  A61P19/04 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07C231/02 ,  C07C231/16 ,  C07C233/40 ,  C07C233/44 ,  C07C233/51 ,  C07C235/34 ,  C07C235/70 ,  C07C237/22 ,  C07C279/12 ,  C07C281/16 ,  C07D211/58 ,  C07D233/24 ,  C07D233/46 ,  C07D295/13 ,  C07D295/14 ,  C07D451/04 ,  A61K31/397 ,  A61K31/195 ,  A61K31/40 ,  A61K31/55

CPC分类号： C07C233/51 ,  A61K31/165 ,  A61K31/198 ,  A61K31/445 ,  A61K31/4453 ,  A61K31/5375 ,  C07B2200/07 ,  C07C231/02 ,  C07C231/16 ,  C07C233/40 ,  C07C233/44 ,  C07C235/34 ,  C07C235/70 ,  C07C235/78 ,  C07C237/20 ,  C07C237/22 ,  C07C279/12 ,  C07C281/16 ,  C07D211/04 ,  C07D211/58 ,  C07D233/24 ,  C07D233/46 ,  C07D295/13 ,  C07D451/04

摘要： (R)-2-Arylpropionamide compounds of formula (I) are described. The process for their preparation and pharmaceutical preparations thereof are also described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbate recruitment of polymorphonuclear leukocytes (leukocytes PMN) and of monocytes at the inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use in the inhibition of the chemotaxis of neutrophils and monocytes induced by the C5a fraction of the complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor. Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of PMN leukocytes. The compounds of the invention are used in the treatment of psoriasis, ulcerative cholitis, glomerular nephritis, acute respiratory insufficiency, idiopathic fibrosis, rheumatoid arthritis and in the prevention and the treatment of injury caused by ischemia and reperfusion.

摘要翻译： 描述了式（I）的（R）-2-芳基丙酰胺化合物。 还描述了其制备方法及其制备药物。 本发明的2-芳基丙酰胺可用于预防和治疗由于多发性白细胞（白细胞PMN）和单核细胞在炎症部位的加剧性募集引起的组织损伤。 特别地，本发明涉及式（I）的2-芳基丙酸的ω-氨基烷基酰胺的R对映异构体，其用于抑制由补体的C5a部分诱导的嗜中性粒细胞和单核细胞的趋化性和其它 其生物活性与7-TD受体激活相关的趋化蛋白。 选择的式（I）化合物是C5a诱导的嗜中性粒细胞和单核细胞的趋化性和IL-8诱导的PMN白细胞趋化性的双重抑制剂。 本发明的化合物用于治疗牛皮癣，溃疡性胆囊炎，肾小球肾炎，急性呼吸功能不全，特发性纤维化，类风湿性关节炎，以及预防和治疗由缺血和再灌注引起的损伤。