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 disulfate and crystalline forms of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide monosulfate. Furthermore, the present invention provides compositions comprising the crystalline forms and therapeutic use of the crystalline forms. In one embodiment, the crystal-line compound is (2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide.

1 . A crystalline form of a sulfate salt of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide. 
     
     
         2 . The crystalline form of  claim 1 , wherein said sulfate salt is 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide disulfate. 
     
     
         3 . The crystalline form of  claim 2 , which exhibits an X-ray powder diffraction pattern comprising peaks at about 8.01±0.3; 21.30±0.3; and 21.99±0.3 degrees two-theta. 
     
     
         4 . The crystalline form of  claim 3 , wherein the X-ray powder diffraction pattern further comprising peaks at about 9.85±0.3 and 18.88±0.3 degrees two-theta. 
     
     
         5 . The crystalline form of  claim 3 , which exhibits an IR spectrum comprising peaks at about 2968±10; 1696±10; and 1175±10 cm −1 . 
     
     
         6 . The crystalline form of  claim 5 , wherein the IR spectrum further comprising peaks at about 3322±10, 1023±10 and 855±10 cm −1 . 
     
     
         7 . The crystalline form of  claim 3 , which exhibits a Raman spectrum comprising peaks at about 1032.73±10; 976.30±10; and 851.86±10 cm −1 . 
     
     
         8 . The crystalline form of  claim 7 , wherein the Raman spectrum further comprising peaks at about 1448.50±10, 1308.93±10 and 773.04±10 cm −1 . 
     
     
         9 . The crystalline form of  claim 3 , which exhibits a Differential Scanning calorimetry (DSC) thermogram comprising an endotherm at about 216±2.0° C. 
     
     
         10 . The crystalline form of  claim 1 , which is a crystalline form of 2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide monosulfate. 
     
     
         11 . The crystalline form of  claim 10 , which exhibits an X-ray powder diffraction pattern comprising peaks at about 23.307±0.3; 15.874±0.3; and 7.896±0.3 degrees two-theta. 
     
     
         12 . The crystalline form of  claim 11 , wherein the X-ray powder diffraction pattern further comprising peaks at about 21.018±0.3 and 9.818±0.3 degrees two-theta. 
     
     
         13 . The crystalline form of  claim 11 , which exhibits an IR spectrum comprising peaks at about 2948±10; 1638±10; and 1097±10 cm −1 . 
     
     
         14 . The crystalline form of  claim 13 , wherein the IR spectrum further comprising peaks at about 2589±10, 1079±10 and 613±10 cm −1 . 
     
     
         15 . The crystalline form of  claim 11 , which exhibits an Raman spectrum comprising peaks at about 1451.20±10; 969.34±10; and 780.09±10 cm −1 . 
     
     
         16 . The crystalline form of  claim 15 , wherein the Raman spectrum further comprising peaks at about 1308.71±10, 1021.17±10 and 493.04±10 cm −1 . 
     
     
         17 . The crystalline form of  claim 11 , which exhibits a Differential Scanning calorimetry (DSC) thermogram comprising an endotherm having an onset at about 245±2.0° C. 
     
     
         18 . The crystalline form of  claim 10 , which exhibits an X-ray powder diffraction pattern comprising peaks at about 7.92±0.3; 17.97±0.3; and 23.49±0.3 degrees two-theta. 
     
     
         19 . The crystalline form of  claim 18 , wherein the X-ray powder diffraction pattern further comprising peaks at about 9.83±0.3 and 15.92±0.3 degrees two-theta. 
     
     
         20 . The crystalline form of  claim 18 , which exhibits an IR spectrum comprising peaks at about 2947±10; 1638±10; and 1097±10 cm −1 . 
     
     
         21 . The crystalline form of  claim 20 , wherein the IR spectrum further comprising peaks at about 3037±10, 1538±10 and 1064±10 cm −1 . 
     
     
         22 . The crystalline form of  claim 18 , which exhibits a Differential Scanning calorimetry (DSC) thermogram having an endotherm having an onset at about 40±2.0° C. and an exotherm having an onset at about 99±2.0° C. 
     
     
         23 . The crystalline form of  claim 1 , which is (2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide. 
     
     
         24 . A composition comprising a crystalline form of  claim 1 . 
     
     
         25 . 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 of  claim 1 . 
     
     
         26 . The method of  claim 25 , wherein the disorder is a neurodegenerative disorder. 
     
     
         27 . The method of  claim 26 , wherein the disorder is selected from the group consisting of Alzheimer's disease, Huntington's disease, Pick's disease, frontotemporal dementia, amyotrophic lateral sclerosis and other motor neuron disorders, epilepsy, Parkinson's disease, spinal cord injury, stroke, hypoxia, ischemia, brain injury, traumatic brain injury, diabetic neuropathy, peripheral neuropathy, chemotherapy-induced neuropathy, genetic neuropathy, myopathies, genetic, acquired or traumatic hearing loss, nerve transplantation, multiple sclerosis, peripheral nerve injury, dementia, HIV related dementia, hair loss, chemotherapy-induced hair loss, age-related hair loss, glaucoma, retinal degeneration, retinal degeneration associated with glaucoma, cognitive impairment, anesthesia-induced cognitive impairment, disorders related to stem cell degeneration and disorders related to stem cell death, and Alzheimer's dementia associated with Down's Syndrome.