Patent
Methods and compositions for stimulating neurogenesis and inhibiting neuronal degeneration
| العنوان: | Methods and compositions for stimulating neurogenesis and inhibiting neuronal degeneration |
|---|---|
| Patent Number: | 8,999,972 |
| تاريخ النشر: | April 07, 2015 |
| Appl. No: | 13/231584 |
| Application Filed: | September 13, 2011 |
| مستخلص: | The present invention provides methods and compositions comprising compounds useful for stimulating neurogenesis. The methods and compositions comprising compounds are also useful for inhibiting neuronal degeneration. Thus, the present invention can be used in the treatment of diseases and conditions characterized by neuronal loss and reduced neurogenesis including Alzheimer's disease, stroke, traumatic brain injury, and depression. This invention could also be used for research products including single agents or mixtures of agents to promote, proliferate, differentiate, or maintain neurons from stem or progenitor cells. |
| Inventors: | Kelleher-Andersson, Judith (Clarksville, MD, US) |
| Assignees: | Neuronascent, Inc. (Clarksville, MD, US) |
| Claim: | 1. A method for stimulating neurogenesis and inhibiting neuronal degeneration in a mammal, comprising administering a pharmaceutical composition in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration in the mammal, said pharmaceutical composition comprising a compound selected from the group consisting of: [chemical expression included] [chemical expression included] and a pharmaceutically-acceptable carrier. |
| Claim: | 2. The method of claim 1 , wherein said mammal is a human. |
| Claim: | 3. The method of claim 2 , wherein said human is a patient suffering from a condition selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder and chronic depression. |
| Claim: | 4. A method for stimulating neurogenesis and inhibiting neuronal degeneration in a mammal, comprising administering a pharmaceutical composition comprising a compound of the formula: [chemical expression included] wherein: each R 1 is independently selected from the group consisting of H, F, Cl, Br, R 7 , and —O—R 7 , wherein R 7 is a substituted 1-6 carbon alkyl or a 6-14 carbon aryl or aralkyl group; R 2 is selected from O or S; R 3 is (CH 2) m , wherein m is 1, 2 or 3; R 4 is selected from the group consisting of an N and (CH n), wherein n equals 1 or 2, with the proviso that when R 4 is nitrogen then m in R 3 should not be equal to 1; R 6 is H; each R 8 is independently —X, —R 9 , —OR 9 , —SR 9 , —N(R 9) 2 , —CN, —NO 2 , —NC(O)R 9 , —C(O)R 9 , —C(O)N(R 9) 2 , —S(O) 2 R 9 , —S(O) 2 NR 9 , —S(O)R 9 , —C(O)R 9 , —C(O)OR 9 , or —C(O)N(R 9) 2 ; wherein each X is independently a halogen; each R 9 is independently —H, alkyl, alkenyl, alkynyl, aryl, heterocycle, protecting group or prodrug moiety; and a pharmaceutically acceptable carrier in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration in the mammal. |
| Claim: | 5. The method of claim 4 , wherein said mammal is a human. |
| Claim: | 6. The method of claim 5 , wherein said human is a patient suffering from a condition selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder and chronic depression. |
| Current U.S. Class: | 514/218 |
| Patent References Cited: | 3773919 November 1973 Boswell et al. 4089809 May 1978 Farrior, Jr. 4233871 November 1980 Alessi 4438052 March 1984 Weder et al. 4438253 March 1984 Casey et al. 4485054 November 1984 Mezei et al. 4532089 July 1985 MacDonald 4540786 September 1985 Wright 4652441 March 1987 Okada et al. 4686228 August 1987 Campbell et al. 4897269 January 1990 Mezei 5100669 March 1992 Hyon et al. 5665428 September 1997 Cha et al. 5770222 June 1998 Unger et al. 5820880 October 1998 Alving et al. 5888533 March 1999 Dunn 6287588 September 2001 Shih et al. 6747002 June 2004 Cheung et al. 6974818 December 2005 Kyle et al. 2004/0006091 January 2004 Kyle et al. 2004/0072818 April 2004 Dunning et al. 59-33264 February 1984 2005-525365 August 2005 WO-0216360 February 2002 WO-2004/083235 September 2004 |
| Other References: | Swanson et al, “Identification and Biological Evaluation of 4-(3-Trifluoromethylpyridin-2-yl)piperazine-1-carboxylic Acid (5-Trifluoromethylpyridin-2-yl)amide, a High Affinity TRPV1 (VR1) Vanilloid Receptor Antagonist”, J. Med. Chem., vol. 48, 2005, pp. 1857-1872. cited by applicant Griswold et al, “Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis”, Blood, vol. 104, 2004, pp. 2912-2918. cited by applicant Kim et al, “Transient Receptor Potential Vanilloid Subtype 1 Mediates Cell Death of Mesencephalic Dopaminergic Neurons In Vivo and In Vitro”, The Journal of Neuroscience, vol. 25, No. 3, Jan. 19, 2005, pp. 662-671. cited by applicant Kim, S.R. et al. “Transient Receptor Potential Vanilloid Subtype 1 Mediates Cell Death of Mesencephalic Dopaminergic Neurons In Vivo and In Vitro,” The Journal of Neuroscience, Jan. 19, 2005, 25(3)662-671. cited by applicant Notice of Reasons for Rejection mailed Jun. 4, 2012 for corresponding Japanese Patent Application No. 2008-531431 with English translation (10 pages). cited by applicant Swanson, D.M. et al. “Identification and Biological Evaluation of 4-(3-Trifluoromethylpyridin-2-yl)piperazine-1-carboxylic Acid (5-Trifluoromethylpyridin-2-yl)amide, a High Affinity TRPV (VR1) Vanilloid Receptor Antagonist,” J. Med. Chem. 2005, 48, 1857-1872. cited by applicant EP 06803851 Supplementary European Search Report (search completed Jun. 21, 2010) (2 pages). cited by applicant Examiner's First Report on corresponding Australian Patent Application No. 2006292256 dated Sep. 23, 2011 (4 pages). cited by applicant Giswold, et al. “Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis.” Blood, 104(9):2912-2918 (Nov. 1, 2004) (7 pages). cited by applicant Kanai et al. “Involvement of an increased spinal TRPV1 sensitization through its up-regulation in mechanical allodynia of CCI rates.” Neuropharmacology, 49:977-984 (2005) (8 pages). cited by applicant PCT International Search Report for Application No. PCT/US06/36463 dated Oct. 16, 2007 (4 pages). cited by applicant Srivastava, et al. “Thiophene-fused quinoline analogues: Facile synthesis of 3-amino-2-cyanothieno [2, 3-b] quinolines from 2-chloro-3-cyanoquinolines.” Indian Journal of Chemistry, 44B:2077-2081 (Oct. 2005) (5 pages). cited by applicant Sun, Q. et al., “4-(2-Pyridyl)piperazine-1-carboxamides: Potent Vanilloid Receptor 1 Antagonists,” Bioorganic & Medicinal Chemistry Letters 13 (2003) 3611-3616. cited by applicant Swanson et al. “Identification and biological evaluation of 4-(3-Trifluoromethylpyridin-2-yl) piperazine-1-carboxylic acid (5-Trifluoromethypyridin-2-yl) amide, a high affinity TRPV1 (VR1) vanilloid.” J. Med. Chem., 48:1857-1872 (2005) (16 pages). cited by applicant Tafesse et al. “Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists,” Bioorganic & Medicinal Chemistry Letters, 2004, vol. 14, No. 22, pp. 5513-5519. cited by applicant Weil, A. et al., “Conservation of Functional and Pharmacological Properties in the Distantly Related Temperature Sensors TRPV1 and TRPM8,” Molecular Pharmacology, May 2005, vol. 68, No. 2, pp. 518-527. cited by applicant Patent Examination Report No. 2, AU Patent Application No. 2006292256, Oct. 12, 2012, 4 pages. cited by applicant |
| Assistant Examiner: | Sackey, Ebenezer O |
| Primary Examiner: | Wilson, James O |
| Attorney, Agent or Firm: | Pickering, Wilmer Cutler Hale and Dorr LLP |
| رقم الانضمام: | edspgr.08999972 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |