Claims
- 1. A compound of the formula:
- 2. The compound according to claim 1, wherein Q is selected from a 5 to 6 membered partially unsaturated or fully saturated heterocyclic ring containing a single nitrogen ring atom and four to five carbon ring atoms, wherein said ring is optionally fused to a three-membered ring.
- 3. The compound according to claim 2, wherein Q is selected from piperidyl or pyrrolidyl optionally substituted at one of the ring carbons with phenyl, methyl or hydroxy; or 3-Azabicyclo[3.1.0]hexyl.
- 4. The compound according to claim 1, wherein R1 is selected from (C1-C6)-straight alkyl, (C1-C6)-straight alkyl-Ar, (C1-C6)-straight alkyl-cycloalkyl, (C3-C6)-straight or branched alkenyl, or (C3-C6)-straight or branched alkenyl-Ar.
- 5. The compound according to claim 4, wherein R1 is selected from methyl, ethyl, —CH2-phenyl, —CH2-methylphenyl, —CH2-methoxyphenyl, —CH2-fluorophenyl, —CH2-difluorophenyl, —CH2—CH2-phenyl, —CH2-cyclopropyl, —CH2—CH═C(CH3)2, —CH2—CH═CH2, or —CH2—CH═CH-phenyl.
- 6. The compound according to claim 1, wherein:
p is 0 or 1; and X is C or N.
- 7. The compound according to claim 1, wherein Y is a bond, —O—, —CH<, or ═CH<.
- 8. The compound according to claim 1, wherein one of A or B is selected from optionally substituted phenyl or optionally substituted pyridyl and the other of A or B is selected from hydrogen, optionally substituted phenyl, optionally substituted pyridyl, or is absent.
- 9. The compound according to claim 8, wherein one of A or B is absent or is selected from hydrogen, phenyl, chlorophenyl, dichlorophenyl, fluorophenyl, or difluorophenyl and the other of A or B is selected from phenyl, chlorophenyl, dichlorophenyl, fluorophenyl, or difluorophenyl.
- 10. The compound according to claim 1, wherein said compound is selected from any one of compounds 1, 7, 15, 20, 21, 26, 28, 30, 39, 41, 42, 44, 47, 48, 49, 52, 58, 60, 65, 69, 84, 85, 86, 90, 100, 101, 102, 103, 205, 206, 221, 223, 225, 238, 240, 242, 246, 255, 260, 261, 262, 263, 265, 267, 268, 271, 273, 275, 276, 277, 278, or 279.
- 11. A composition comprising a compound according to any one of claims 1 to 10 in an amount sufficient to stimulate nerve growth or prevent neurodegeneration; and a pharmaceutically acceptable carrier.
- 12. The composition according to claim 11, additionally comprising a neurotrophic factor.
- 13. The composition according to claim 12, wherein said neurotrophic factor is selected from nerve growth factor (NGF), insulin-like growth factor (IGF-1) and its active truncated derivatives such as gIGF-l and Des(1-3)IGF-I, acidic and basic fibroblast growth factor (aFGF and bFGF, respectively), platelet-derived growth factors (PDGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factors (CNTF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3)and neurotrophin 4/5 (NT-4/5).
- 14. The composition according to claim 11, wherein said composition is formulated for oral or parenteral administration to a patient.
- 15. The composition according to claim 12, wherein said composition is formulated for oral or parenteral administration to a patient.
- 16. A method for promoting neuronal repair or preventing neuronal damage in a patient or in an ex vivo nerve cell comprising the step of administering to said patient or said cell an amount of a compound sufficient to promoting neuronal repair or preventing neuronal damage, wherein said compound has the formula:
- 17. A method for promoting neuronal repair or preventing neuronal damage in a patient or in an ex vivo nerve cell, glial cell, chromafin cell or stem cell comprising the step of administering to said patient or said cell a compound according to any one of claims 1 to 10 in an amount sufficient to promote neuronal repair or prevent neuronal damage.
- 18. The method according to claim 16, comprising the additional step of administering to said patient a neurotrophic factor either as part of a multiple dosage from together with said compound or as a separate dosage form.
- 19. The method according to claim 17, comprising the additional step of administering to said patient a neurotrophic factor either as part of a multiple dosage from together with said compound or as a separate dosage form.
- 20. The method according to claim 18 or 19, wherein said neurotrophic factor is selected from nerve growth factor (NGF), insulin-like growth factor (IGF-1) and its active truncated derivatives such as gIGF-1 and Des(1-3)IGF-I, acidic and basic fibroblast growth factor (aFGF and bFGF, respectively), platelet-derived growth factors (PDGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factors (CNTF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3)and neurotrophin 4/5 (NT-4/5).
- 21. The method according to claim 16, wherein said method is used to treat a patient suffering from a disease selected from trigeminal neuralgia, glosspharyngeal neuralgia, Bell's Palsy, myasthenia gravis, muscular dystrophy, muscle injury, progressive muscular atrophy, progressive bulbar inherited muscular atrophy, herniated, ruptured, or prolapsed invertebrae disk syndrome's, cervical spondylosis, plexus disorders, thoracic outlet destruction syndromes, peripheral neuropathies, such as those caused by lead, dapsone, ticks, or porphyria, other peripheral myelin disorders, Alzheimer's disease, Gullain-Barre syndrome, Parkinson's disease and other Parkinsonian disorders, ALS, Tourette's syndrome, multiple sclerosis, other central myelin disorders, stroke and ischemia associated with stroke, neural paropathy, other neural degenerative diseases, motor neuron diseases, sciatic injury, neuropathy associated with diabetes, spinal cord injuries, facial nerve injury and other trauma, chemotherapy- and other medication-induced neuropathies, Huntington's disease, and protein fibrillization diseases, such as Diffuse Lewy Body disease, Alzheimer's disease-Lewy Body variant, Famillal British Dementia, and Frontotemporal Dementia.
- 22. The method according to claim 17, wherein said method is used to treat a patient suffering from a disease selected from trigeminal neuralgia, glosspharyngeal neuralgia, Bell's Palsy, myasthenia gravis, muscular dystrophy, muscle injury, progressive muscular atrophy, progressive bulbar inherited muscular atrophy, herniated, ruptured, or prolapsed invertebrae disk syndrome's, cervical spondylosis, plexus disorders, thoracic outlet destruction syndromes, peripheral neuropathies, such as those caused by lead, dapsone, ticks, or porphyria, other peripheral myelin disorders, Alzheimer's disease, Gullain-Barre syndrome, Parkinson's disease and other Parkinsonian disorders, ALS, Tourette's syndrome, multiple sclerosis, other central myelin disorders, stroke and ischemia associated with stroke, neural paropathy, other neural degenerative diseases, motor neuron diseases, sciatic injury, neuropathy associated with diabetes, spinal cord injuries, facial nerve injury and other trauma, chemotherapy- and other medication-induced neuropathies, Huntington's disease, and protein fibrillization diseases, such as Diffuse Lewy Body disease, Alzheimer's disease-Lewy Body variant, Famillal British Dementia, and Frontotemporal Dementia.
- 23. The method according to claim 18 or 19, wherein said method is used to treat a patient suffering from a disease selected from trigeminal neuralgia, glosspharyngeal neuralgia, Bell's Palsy, myasthenia gravis, muscular dystrophy, muscle injury, progressive muscular atrophy, progressive bulbar inherited muscular atrophy, herniated, ruptured, or prolapsed invertebrae disk syndrome's, cervical spondylosis, plexus disorders, thoracic outlet destruction syndromes, peripheral neuropathies, such as those caused by lead, dapsone, ticks, or porphyria, other peripheral myelin disorders, Alzheimer's disease, Gullain-Barre syndrome, Parkinson's disease and other Parkinsonian disorders, ALS, Tourette's syndrome, multiple sclerosis, other central myelin disorders, stroke and ischemia associated with stroke, neural paropathy, other neural degenerative diseases, motor neuron diseases, sciatic injury, neuropathy associated with diabetes, spinal cord injuries, facial nerve injury and other trauma, chemotherapy- and other medication-induced neuropathies, Huntington's disease, and protein fibrillization diseases, such as Diffuse Lewy Body disease, Alzheimer's disease-Lewy Body variant, Familial British Dementia, and Frontotemporal Dementia.
- 24. The method according to claim 20, wherein said method is used to treat a patient suffering from a disease selected from trigeminal neuralgia, glosspharyngeal neuralgia, Bell's Palsy, myasthenia gravis, muscular dystrophy, muscle injury, progressive muscular atrophy, progressive bulbar inherited muscular atrophy, herniated, ruptured, or prolapsed invertebrae disk syndrome's, cervical spondylosis, plexus disorders, thoracic outlet destruction syndromes, peripheral neuropathies, such as those caused by lead, dapsone, ticks, or porphyria, other peripheral myelin disorders, Alzheimer's disease, Gullain-Barre syndrome, Parkinson's disease and other Parkinsonian disorders, ALS, Tourette's syndrome, multiple sclerosis, other central myelin disorders, stroke and ischemia associated with stroke, neural paropathy, other neural degenerative diseases, motor neuron diseases, sciatic injury, neuropathy associated with diabetes, spinal cord injuries, facial nerve injury and other trauma, chemotherapy- and other medication-induced neuropathies, Huntington's disease, and protein fibrillization diseases, such as Diffuse Lewy Body disease, Alzheimer's disease-Lewy Body variant, Familial British Dementia, and Frontotemporal Dementia.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of International Application No. PCT/US01/04210, filed Feb. 9, 2001 which claims the benefit of U.S. Provisional Patent Application 60/181,944, filed Feb. 11, 2000 and U.S. Provisional Patent Application 60/247,330, filed Nov. 10, 2000. The above three priority applications are incorporated herein by reference.