New Salt

Abstract

The present invention relates to a new pharmaceutically acceptable salt, the 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile citrate, a process for its preparation, pharmaceutical formulations containing said salt and to the use of said active salt in therapy, and particularly to GSK3 related conditions and disorders.

1 . A salt, which is 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile citrate.  
   
   
       2 . The salt according to  claim 1  in substantially crystalline form.  
   
   
       3 . The salt according to  claim 1 , which is a Form A characterized by the X-ray powder diffraction d-values and relative intensity 12.7(vs), 6.8(vs), 6.3(s), 4.38(s), 4.23(s) and 3.41(m) Å.  
   
   
       4 . The salt according to  claim 2 , which is a Form A characterized by the X-ray powder diffraction d-values and relative intensity 12.7(vs), 6.8(vs), 6.3(s), 4.38(s), 4.23(s) and 3.41(m) Å.  
   
   
       5 . A process for the preparation of 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile citrate according to  claims 1  to  4  which comprises reacting 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile with citric acid in a solvent.  
   
   
       6 . The process according to  claim 5 , wherein the solvent used is selected from the group comprising ethers, alcohols, ketones, acetates or organic acids, or mixtures thereof, optionally using water as an additive.  
   
   
       7 . A process according to  claim 6  wherein the solvent comprises a mixture of ethanol and water.  
   
   
       8 . A process according to  claim 6  wherein the solvent comprises a mixture of ethanol and acetic acid.  
   
   
       9 . A process according to any one of  claims 5  to  7  wherein said process is carried out at temperature of between −5° C. and +100° C.  
   
   
       10 . A pharmaceutical formulation comprising a therapeutically effective amount of the salt according to any one of claims  1 - 4 , optionally in association with diluents, recipients or inert carriers.  
   
   
       11 . A method of prevention and/or treatment of conditions associated with glycogen synthase kinase-3, comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile citrate.  
   
   
       12 . The method as recited in  claim 11  wherein the salt is substantially crystalline form.  
   
   
       13 . The method as recited in  claim 11  wherein the salt is a Form A characterized by the X-ray powder diffraction d-values and relative intensity 12.7(vs), 6.8(vs), 6.3(s), 4.38(s), 4.23(s) and 3.41(m) Å.  
   
   
       14 . The method as recited in  claim 12  wherein the salt is a Form A characterized by the X-ray powder diffraction d-values and relative intensity 12.7(vs), 6.8(vs), 6.3(s), 4.38(s), 4.23(s) and 3.41(m) Å.  
   
   
       15 . A method of prevention and/or treatment of cognitive disorders, comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]1H-indole-5-carbonitrile citrate.  
   
   
       16 . The method as recited in  claim 15  wherein the salt is substantially crystalline form.  
   
   
       17 . The method as recited in  claim 15  wherein the salt is a Form A characterized by the X-ray powder diffraction d-values and relative intensity 12.7(vs), 6.8(vs), 6.3(s), 4.38(s), 4.23(s) and 3.41(m) Å.  
   
   
       18 . The method as recited in  claim 16  wherein the salt is a Form A characterized by the X-ray powder diffraction d-values and relative intensity 12.7(vs), 6.8(vs), 6.3(s), 4.38(s), 4.23(s) and 3.41(m) Å.  
   
   
       19 . The method as recited in any one of  claims 15  to  18 , wherein the cognitive disorder is dementia, Cognitive Deficit in Schizophrenia (CDS), Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI), Age-Related Cognitive Decline (ARCD) or Cognitive Impairment No Dementia (CIND).  
   
   
       20 . The method according to  claim 19 , wherein the disease is Cognitive Deficit in Schizophrenia.  
   
   
       21 . The method according to  claim 19 , wherein the dementia is associated with neurofibrillar tangle pathologies.  
   
   
       22 . The method according to  claim 19 , wherein the dementia is Frontotemporal dementia (FTD), Frontotemporal dementia Parkinson's Type (FTDP), progressive supranuclear palsy (PSP), Pick's Disease, Niemann-Pick's Disease, corticobasal degeneration, traumatic brain injury (TBI) or dementia pugilistica.  
   
   
       23 . The method according to  claim 19 , wherein the dementia is Alzheimer's Disease (AD), Down syndrome, vascular dementia, Parkinson's Disease (PD), postencephelatic parkinsonism, dementia with Lewy bodies, HIV dementia, Huntington's Disease, amyotrophic lateral sclerosis (ALS), motor neuron diseases (MND), Creuztfeld-Jacob's disease or prion diseases.  
   
   
       24 . The method according to  claim 23 , wherein the disease is Alzheimer's Disease.  
   
   
       25 . The method according to  claim 24 , wherein the treatment is in the delay of the disease progression of Alzheimer's Disease.  
   
   
       26 . A method of prevention and/or treatment of attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD) or affective disorders, comprising administering to a mammal, need of such prevention and/or treatment, a therapeutically effective amount of a salt as defined in any one of  claims 1  to  4 .  
   
   
       27 . The method according to  claim 26 , wherein the affective disorders are Bipolar Disorder including acute mania, bipolar depression, bipolar maintenance, major depressive disorders (MDD) including depression, major depression, mood stabilization, schizoaffective disorders including schizophrenia, or dysthymia.  
   
   
       28 . A method of prevention and/or treatment of Type I diabetes, Type II diabetes, diabetic neuropathy, alopecia or inflammatory diseases, comprising administering to a mammal, including man in need of such prevention and/or treatment, a therapeutically effective amount of a salt as defined in any one of  claims 1  to  4 .  
   
   
       29 . A method of prevention and/or treatment of bone related disorders or conditions comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of a salt as defined in any one of  claims 1  to  4 .  
   
   
       30 . A method of prevention and/or treatment of osteoporosis comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of a compound as described in any one of  claims 1  to  4 .  
   
   
       31 . A method of increasing bone formation comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of a compound as described in any one of  claims 1  to  4 .  
   
   
       32 . A method of increasing cancellous bone formation and/or new bone formation comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of a compound as described in any one of  claims 1  to  4 .  
   
   
       33 . A method of increasing bone mineral density comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of a compound as described in any one of  claims 1  to  4 .  
   
   
       34 . A method of reducing the incidence of fracture comprising administering to a mammal in need of such prevention and/or treatment, a therapeutically effective amount of a compound as described in any one of  claims 1  to  4 .  
   
   
       35 . A method of enhancing fracture healing comprising administering to a mammal, in need of such prevention and/or treatment, a therapeutically effective amount of a compound as described in any one of  claims 1  to  4 .  
   
   
       36 . A method according to  claim 11  wherein said mammal is a human.  
   
   
       37 . A method according to  claim 12  wherein said mammal is a human.  
   
   
       38 . A method according to  claim 13  wherein said mammal is a human.  
   
   
       39 . A method according to  claim 14  wherein said mammal is a human.  
   
   
       40 . A method according to  claim 15  wherein said mammal is a human.  
   
   
       41 . A method according to  claim 16  wherein said mammal is a human.  
   
   
       42 . A method according to  claim 17  wherein said mammal is a human.  
   
   
       43 . A method according to  claim 18  wherein said mammal is a human.  
   
   
       44 . A method according to  claim 19  wherein said mammal is a human.  
   
   
       45 . A method according to  claim 21  wherein said mammal is a human.  
   
   
       46 . A method according to  claim 22  wherein said mammal is a human.  
   
   
       47 . A method according to  claim 23  wherein said mammal is a human.  
   
   
       48 . A method according to  claim 24  wherein said mammal is a human.  
   
   
       49 . A method according to  claim 25  wherein said mammal is a human.  
   
   
       50 . A method according to  claim 26  wherein said mammal is a human.  
   
   
       51 . A method according to  claim 27  wherein said mammal is a human.  
   
   
       52 . A method according to  claim 28  wherein said mammal is a human.  
   
   
       53 . A method according to  claim 29  wherein said mammal is a human.  
   
   
       54 . A method according to  claim 30  wherein said mammal is a human.  
   
   
       55 . A method according to  claim 31  wherein said mammal is a human.  
   
   
       56 . A method according to  claim 32  wherein said mammal is a human.  
   
   
       57 . A method according to  claim 33  wherein said mammal is a human.  
   
   
       58 . A method according to  claim 34  wherein said mammal is a human.  
   
   
       59 . A method according to  claim 35  wherein said mammal is a human.