Showing posts with label WO 2012044577. Show all posts
Showing posts with label WO 2012044577. Show all posts

Tuesday 23 December 2014

WO 2012044577 A1.......Dual inhibitors of met and vegf for the treatment of castration resistant prostate cancer and osteoblastic bone metastases

Figure imgf000020_0002



 Figure imgf000020_0003
  Foretinib (Exelixis, GlaxoSmithKline) (aka XL-880)

 Figure imgf000028_0001



 Foretinib (Exelixis, GlaxoSmithKline) (aka XL-880)




 WO 2012044577 A1.......Dual inhibitors of met and vegf for the treatment of castration resistant prostate cancer and osteoblastic bone metastases
 http://www.google.com/patents/WO2012044577A1?cl=en



In another embodiment, the compound of Formula I is Compound 1 :
Figure imgf000005_0001
Compound 1
or a pharmaceutically acceptable salt thereof. Compound I is known as N-(4-{[6,7- bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-l, l- dicarboxamide. WO 2005/030140 describes the synthesis of N-(4-{[6,7- bis(methyloxy)quinolin-4-yl]oxy }phenyl)-N'-(4-fluorophenyl)cyclopropane-l, l- dicarboxamide (Example 12, 37, 38, and 48) and also discloses the therapeutic activity of this molecule to inhibit, regulate and/or modulate the signal transduction of kinases, (Assays, Table 4, entry 289). Example 48 is on paragraph [0353] in WO 2005/030140.
[0013] In another embodiment, the compound of Formula I is Compound 2:
Figure imgf000005_0002
Compound 2
  Foretinib (Exelixis, GlaxoSmithKline) (aka XL-880)


or a pharmaceutically acceptable salt thereof. Compound 2 is known as is N-[3-fluoro-4- ({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4- fluorophenyl)cyc!opropane- 1,1 -dicarboxamide. WO 2005-030140 describes the synthesis of Compound (I) (Examples 25, 30, 36, 42, 43 and 44) and also discloses the therapeutic activity of this molecule to inhibit, regulate and/or modulate the signal transduction of kinases, (Assays, Table 4, entry 312). Compound 2 has been measured to have a c-Met IC50 value of about 0.6 nanomolar (nM). PC1YUS09/064341, which claims priority to U.S. provisional application 61/199,088, filed November 13, 2008, describes a scaled-up synthesis of Compound I.