US2012053177A1PendingUtilityA1

Compounds and methods for kinase modulation, and indications therefor

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Assignee: IBRAHIM PRABHA NPriority: Jun 22, 2005Filed: Sep 23, 2011Published: Mar 1, 2012
Est. expiryJun 22, 2025(expired)· nominal 20-yr term from priority
Inventors:Prabha N. IbrahimDean R. ArtisRyan BremerGaston HabetsShumeye MamoMarika NespiChao ZhangJiazhong ZhangYong-Liang ZhuRebecca ZuckermanBrian WestYoshisa SuzukiJames TsaiKlaus-Peter HirthGideon BollagWayne SpevakHanna ChoSamuel J. GilletteGuoxian WuHongyao ZhuShenghua Shi
A61P 3/10A61P 37/08A61P 9/00A61P 9/10A61P 7/02A61P 9/04A61P 37/00A61P 3/06A61P 35/02A61P 37/06A61P 37/02A61P 43/00A61P 7/00A61P 31/16A61P 35/00A61P 25/06A61P 25/14A61P 29/00A61P 27/16A61P 3/04A61P 25/16A61P 25/00A61P 3/14A61P 25/28A61P 31/04A61P 27/02A61P 17/06A61P 17/00A61P 13/08A61P 1/04A61P 19/10A61P 15/08A61P 11/06A61P 1/00A61P 1/16A61P 21/04A61P 19/02A61P 17/02A61P 11/00A61P 13/12A61P 1/18C07D 471/04C07D 209/08C07C 45/71C07C 47/565A61K 31/496A61K 31/416C07C 37/62A61K 31/437A61K 31/5377C07C 47/575C07C 45/00C07C 45/673C07C 39/27A61K 31/435
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Claims

Abstract

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

Claims

exact text as granted — not AI-modified
That which is claimed is: 
     
         1 . A method for inhibiting a V600E mutant B-RAF protein kinase comprising contacting the V600E mutant B-RAF protein kinase with an effective amount of a compound (i) having a 3,6-disubstituted-2-fluoro-1-{5-substituted-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}phenyl core structure having the formula set forth below, and (ii) which exhibits an IC 50  of 10 micromolar or less towards the V600E mutant B-RAF protein kinase as revealed by an in vitro assay conducted under Assay Condition B (of the specification) 
       
         
           
           
               
               
           
         
       
     
     
         2 . A method for treating a patient suffering from a disease that is mediated by a V600E mutant B-RAF protein kinase comprising administering to a patient in need thereof an effective amount of a compound (i) having a 3,6-disubstituted-2-fluoro-1-{5-substituted-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}phenyl core structure having the formula set forth below, and (ii) which exhibits an IC 50  of 10 micromolar or less towards the V600E mutant B-RAF protein kinase as revealed by an in vitro assay conducted under Assay Condition B (of the specification) 
       
         
           
           
               
               
           
         
       
     
     
         3 . A method for suppressing undesired proliferation of tumour cells expressing a V600E mutant B-RAF protein kinase comprising contacting tumour cells expressing V600E mutant B-RAF protein kinase with an effective amount of a compound (i) having a 3,6-disubstituted-2-fluoro-1-{5-substituted-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}phenyl core structure having the formula set forth below, and (ii) which exhibits an IC 50  of 10 micromolar or less towards the V600E mutant B-RAF protein kinase as revealed by an in vitro assay conducted under Assay Condition B (of the specification) 
       
         
           
           
               
               
           
         
       
     
     
         4 . A method for treating a B-RAF protein kinase V600E mutation-positive patient suffering from metastatic melanoma comprising administering to a patient in need thereof an effective amount of a compound (i) having a 3,6-disubstituted-2-fluoro-1-{5-substituted-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}phenyl core structure having the formula set forth below, and (ii) which exhibits an IC 50  of 10 micromolar or less towards the V600E mutant B-RAF protein kinase as revealed by an in vitro assay conducted under Assay Condition B (of the specification) 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 4  in which the compound is administered orally. 
     
     
         6 . The method of  claim 5  in which the compound is formulated into a tablet. 
     
     
         7 . The method of  claim 4  in which the compound has a 5-substituent selected from 4-chlorophenyl or chloro. 
     
     
         8 . The method of  claim 4  in which the compound has a 6-substituent selected from fluoro or hydrogen. 
     
     
         9 . The method of  claim 4  in which the 3-substituent is a propane-1-sulfonamido group. 
     
     
         10 . The method of  claim 4  in which the compound is administered at a dose ranging from about 0.01 and 50 mg/kg. 
     
     
         11 . The method of  claim 10  in which the compound is administered at a dose ranging from about 0.1 and 20 mg/kg. 
     
     
         12 . The method of  claim 5  in which the compound is administered in multiple doses.

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