Novel Polymorph Forms Of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine

Abstract

Polymorph forms of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine p-hydroxybenzoate, and methods for their preparation, pharmaceutical composition containing said polymorph(s) and use, are disclosed. The polymorphs can be administered to patients susceptible to or suffering from conditions and disorders, such as central nervous system disorders, to treat and/or prevent such disorders.

1 - 6 . (canceled) 
   
   
       7 . A method for treatment of central nervous system disorder, comprising administering to a mammal, in need of such treatment, a therapeutically effective amount of:
 a crystalline polymorph A of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine p-hydroxybenzoate, exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees (2-θ°) at around 7.6, 15.2 and 19.7;   a crystalline polymorph B of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine p-hydroxybenzoate, exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees (2-θ°) at around 8.0, 9.6 and 16.1; or   a mixture of polymorphs comprising polymorph A of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine p-hydroxybenzoate, exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees (2-θ°) at around 7.6, 15.2, and 19.7; and polymorph B of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine p-hydroxybenzoate, exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees (2-θ°) at around 8.0, 9.6 and 16.1, in ratios of 5:95 to 95:5.   
   
   
       8 . The method of  claim 7 , wherein the disorder is selected from the group consisting of age-associated memory impairment, mild cognitive impairment, presenile dementia (early onset Alzheimer's disease), senile dementia (dementia of the Alzheimer's type), Lewy body dementia, vascular dementia, Alzheimer's disease, stroke, AIDS dementia complex, attention deficit disorder, attention deficit hyperactivity disorder, dyslexia, schizophrenia, schizophreniform disorder and schizoaffective disorder. 
   
   
       9 . The method of  claim 7 , wherein the disorder is selected from the group consisting of mild to moderate dementia of the Alzheimer's type, attention deficit disorder, mild cognitive impairment and age associated memory impairment. 
   
   
       10 . (canceled) 
   
   
       11 . A method for treatment of a central nervous system disorder, comprising administering to a mammal, in need of such treatment, a therapeutically effective amount of a polymorph of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine p-hydroxybenzoate, wherein the polymorph is isolated by recrystallization from ethanol, methanol, isopropyl alcohol, acetone, ethyl acetate and/or acetonitrile. 
   
   
       12 . The method of  claim 7  wherein the crystalline polymorph A comprises an X-ray powder diffraction pattern substantially the same as that shown in table 1. 
   
   
       13 . The method of  claim 7  wherein the crystalline polymorph B comprises an X-ray powder diffraction pattern substantially the same as that shown in table 2. 
   
   
       14 . The method of  claim 11  wherein the crystalline polymorph A comprises an X-ray powder diffraction pattern substantially the same as that shown in table 1. 
   
   
       15 . The method of  claim 11  wherein the crystalline polymorph B comprises an X-ray powder diffraction pattern substantially the same as that shown in table 2.