Crystalline forms of neurotrophin mimetic compounds and their salts

Abstract

The present invention includes crystalline forms of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide and crystalline forms of salts and/or solvates of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide. Furthermore, the present invention provides compositions comprising the crystalline forms and therapeutic use of the crystalline forms.

1 .- 11 . (canceled) 
     
     
         12 . A crystalline form of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide, or a sulfate salt, solvate, or a combination thereof, which exhibits an X-ray powder diffraction pattern comprising peaks at about 25.3±0.3 and 27.0±0.3 degrees two-theta. 
     
     
         13 . The crystalline form of  claim 12 , wherein the X-ray powder diffraction pattern further comprising peaks at about 17.45±0.3 degrees two-theta. 
     
     
         14 . The crystalline form of  claim 12 , which exhibits an Raman spectrum comprising peaks at about 2964±10; 2880±10; and 972±10 cm −1 . 
     
     
         15 . The crystalline form of  claim 14 , wherein the Raman spectrum further comprising peaks at about 1448±10 and 1310±10 cm −1 . 
     
     
         16 . The crystalline form of  claim 12 , which exhibits a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 176.5±2.0. 
     
     
         17 . (canceled) 
     
     
         18 . A crystalline form of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide, or a sulfate salt, solvate, or a combination thereof, which exhibits an X-ray powder diffraction pattern comprising peaks at about 21.8±0.3; 22.5±0.3; and 19.3±0.3 degrees two-theta. 
     
     
         19 . The crystalline form of  claim 18 , wherein the X-ray powder diffraction pattern further comprising peaks at about 24.6±0.3 and 15.5±0.3 degrees two-theta. 
     
     
         20 . The crystalline form of  claim 18 , which exhibits an Raman spectrum comprising peaks at about 2980±10; 2943±10; 2889±10; and 1033±10 cm −1 . 
     
     
         21 . The crystalline form of  claim 20 , wherein the Raman spectrum further comprising peaks at about 975±10 and 851±10 cm −1 . 
     
     
         22 . The crystalline form of  claim 18 , which exhibits a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 228.0±2.0. 
     
     
         23 .- 61 . (canceled) 
     
     
         62 . The crystalline form of  claim 12 , which comprises (2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide. 
     
     
         63 . A composition comprising a crystalline form  claim 12 . 
     
     
         64 . A method for treating a disorder involving degeneration or dysfunction of cells expressing p75 comprising administering to a patient in need of such treatment a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form  claim 12 . 
     
     
         65 . The method of  claim 64 , wherein the disorder is a neurodegenerative disorder. 
     
     
         66 . The method of  claim 64 , wherein the disorder is selected from the group consisting of Alzheimer's disease, Huntington's disease, Pick's disease, amyotrophic lateral sclerosis, epilepsy, Parkinson's disease, spinal cord injury, stroke, hypoxia, ischemia, brain injury, diabetic neuropathy, peripheral neuropathy, nerve transplantation, multiple sclerosis, peripheral nerve injury, and hair loss. 
     
     
         67 . The crystalline form of  claim 18 , which comprises (2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide. 
     
     
         68 . A composition comprising a crystalline form  claim 18 . 
     
     
         69 . A crystalline form of  claim 12  further comprising bishydrogen sulfate. 
     
     
         70 . A crystalline form of  claim 18  further comprising bishydrogen sulfate. 
     
     
         71 . A method for treating a disorder involving degeneration or dysfunction of cells expressing p75 comprising administering to a patient in need of such treatment a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form  claim 18 . 
     
     
         72 . The method of  claim 70 , wherein the disorder is a neurodegenerative disorder. 
     
     
         73 . The method of  claim 70 , wherein the disorder is selected from the group consisting of Alzheimer's disease, Huntington's disease, Pick's disease, amyotrophic lateral sclerosis, epilepsy, Parkinson's disease, spinal cord injury, stroke, hypoxia, ischemia, brain injury, diabetic neuropathy, peripheral neuropathy, nerve transplantation, multiple sclerosis, peripheral nerve injury, and hair loss.