Claims
- 1. A compound of the following formula:
43
- 2. The compound of claim 1, the ring Q is a 4 to 8-membered ring that includes the illustrated ring nitrogen, with the remaining ring atoms being carbon.
- 3. The compound of claim 1, wherein (A) at least one of Rxa, Rya and R2a is substituted with fluoro, chloro, bromo, hydroxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, (C3-C8) alkyl, Rq, RrO—, RsS—, (B) R3 is hydrogen, (C1-C6) alkyl, or phenyl or phenylalkyl wherein the alkyl is C1 to C6 and either such phenyl can be substituted with the same substituents defined above for the aryl or heteroaryl of Rxa or (C) the ring stuctures of Rxa, Rya and R2a, including substituents thereto, otherwise include at least two aromatic ring structures that together include from 15 to 20 ring atoms.
- 4. The compound of claim 3, wherein at least one of Rxa, Rya and R2a is substituted with fluoro, trifluoromethyl, trifluoromethoxy, nitro, cyano, or (C3-C8) alkyl.
- 5. The compound of claim 1, wherein at least one of Rxa, Rya and R2a is substituted with Rq, RrO—, or RsS—.
- 6. The compound of claim 1, wherein an aryl or heteroaryl of at least one of Rxa, Rya and R2a is phenyl.
- 7. The compound of claim 1, wherein Ryb is oxa, methyleneoxy, thia, methylenethia.
- 8. The compound of claim, wherein Ryb is oxa or thia.
- 9. The compound of claim 1, wherein R5 is (CO)NR13R14, (CO)OR15 or (CO)SR16.
- 10. The compound of claim 9, wherein R15 is (C2-C6) alkyl, (C2-C4) hydroxyalkyl, phenyl, phenylalkyl wherein the alkyl is C1-C3, or aminoalkyl where the alkyl is C2-C6 and the amino can be substituted with up to two independent (C1-C3) alkyls, wherein the phenyl or the phenyl of phenylalkyl can be substituted.
- 11. The compound of claim 9, wherein R15 is hydrogen.
- 12. The compound of claim 1, wherein R4 is hydrogen, methyl or hydroxymethyl and R4* is hydrogen.
- 13. The compound of claim 1, wherein at least one of Rxa, Rya and R2a is a heteroaryl comprising diazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, thiolyl, diazinyl, triazinyl, benzoazolyl, benzodiazolyl, benzothiazolyl, benzoxazolyl, benzoxolyl, benzothiolyl, quinolyl, isoquinolyl, benzodiazinyl, benzotriazinyl, pyridyl, thienyl, furanyl, pyrrolyl, indolyl, isoindoyl or pyrimidyl.
- 14. The compound of claim 1, wherein R1 is —O—R8 or —S—R8*.
- 15. The compound of claim 1, wherein said second bridge between two of Rxa, Rya and R2a is L, and satisfies the following formula:
45
- 16. The compound of claim 14, wherein Rxa—Rxb—, Rya—Ryb— and X form:
46
- 17. The compound of claim 16, wherein R21 is CH2CH2 or CH═CH.
- 18. The compound of claim 1, wherein the alkyenedioxy substitution of Rxa, Rya or R2a is as follows:
47
- 19. The compound of claim 1, wherein Rxa and Rya together can be substituted with up to six substituents, R2a, Rq, Rr and Rs can each be substituted with up to 3 substituents, and wherein the presence of each of Rq, Rr or Rs is considered a substitution to the respective ring structure of Rxa, Rya and R2a.
- 20. The compound of claim 1, wherein a phenyl of R3 is substituted with up to three substituents.
- 21. The compound of claim 1, wherein the aryl, heteroaryl, aryl of arylalkyl or the heteroaryl of heteroarylalkyl of R13, R14, R15, R16 R17, R18 R19 or R20 is substituted with up to three substituents.
- 22. The compound of claim 1, wherein the compound is an optically pure enantiomer.
- 23. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
- 24. The pharmaceutical composition of claim 23, wherein the compound of claim 1 is present in an effective amount for:
(1) treating or preventing schizophrenia, (2) enhancing treating or preventing dementia, (3) treating or preventing epilepsy, (4) treating or preventing spasticity, (5) treating or preventing muscle spasm, (6) treating or preventing pain, (7) preventing neural cell death after stroke, (8) preventing neural cell death in an animal suffering from a neurodegenerative disease, (9) treating or preventing mood disorders, (10) enhancing memory or learning, or (11) treating or preventing learning disorders.
- 25. A method (1) of treating or preventing schizophrenia comprising administering a schizophrenia treating or preventing effective amount of a compound, (2) of treating or preventing dementia comprising administering a dementia treating or preventing effective amount of a compound, (3) of treating or preventing epilepsy comprising administering an epilepsy treating or preventing effective amount of a compound, (4) of treating or preventing spasticity comprising administering a spasticity treating or preventing effective amount of a compound, (5) of treating or preventing muscle spasm comprising administering a muscle spasm treating or preventing effective amount of a compound, (6) of treating or preventing pain comprising administering a pain treating or preventing effective amount of a compound, (7) of preventing neural cell death after stroke comprising administering a neural cell death preventing effective amount of a compound, (8) of preventing neural cell death in an animal suffering from a neurodegenerative disease, (9) treating or preventing mood disorders. (10) enhancing memory or learning, or (I 1) treating or preventing learning disorders, comprising administering an amount effective for said treating, preventing or enhancing of a compound of formula:
48
- 26. The method of claim 25, wherein the spasticity is associated with epilepsy, stroke, head trauma, multiple sclerosis, spinal cord injury or dystonia.
- 27. The method of claim 26, wherein the neurodegenerative disease is Alzheimer's disease, multi-infarct dementia, AIDS dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis or stroke or head trauma.
- 28. A method of synthesizing a compound of claim 1 comprising:
A) reacting a compound of one of the following formulas
1)
50wherein L1 is a nucleophilic substitution leaving group, with a compound of the formula 2)
51or B) reacting a compound of the formula
1)
52with a compound of the formula 2)
53wherein L2 is a nucleophilic substitution leaving group.
- 29. A method of synthesizing a compound of claim 1 comprising:
A) reductively alkylating a compound of the formula
1)
54with a compound of the formula 2)
55where R1* differs from R1 in that it lacks the carbon that is part of the illustrated aldehyde carbonyl, OR B) reductively alkylating a compound of the formula
1)
56with a compound of the formula 2)
57
- 30. A method of synthesizing a compound of claim 1 comprising reductively alkylating RdNH2 with a compound of the formula
58
- 31. A method of synthesizing a compound of claim 1 comprising reacting RfOH or Rf*SH with a compound of the formula
59
- 32. The method of claim 31 further comprising synthesizing the compound of formula
60
- 33. The method of claim 32, comprising reacting a compound of formula
62
- 34. A method of synthesizing a compound of claim 1 comprising reacting ReM with a compound of the formula
63
- 35. A method of synthesizing a compound of claim 1 comprising dehydrating a compound of the formula
65
- 36. A method of synthesizing a compound of claim 1 comprising reducing a compound of the formula
67
- 37. A method of synthesizing a compound that can be used to synthesize the compound of claim 1, the method comprising synthesizing the compound of formula:
69
- 38. A method of synthesizing of a compound of claim 1, the method comprising reacting a compound of formula
72
- 39. A method of synthesizing a compound that can be used to synthesize the compound of claim 1, the method comprising synthesizing a compound of formula X:
74
- 40. The method of claim 39, further comprising converting the compound of formula X to:
76
- 41. A method of synthesizing a compound that can be used to synthesize the compound of claim 1, the method comprising reacting a compound of formula
77
- 42. A method of synthesizing a compound that can be used to synthesize the compound of claim 1, the method comprising synthesizing the compound of formula:
80
- 43. A compound of the following formula:
82
- 44. The compound of claim 43, wherein at least one of Rxa, Rya, Rq, Rr and Rs is thienyl or furanyl.
- 45. The compound of claim 43, wherein at least one of Rxa and Rya is thienyl or furanyl.
- 47. The compound of claim 46, wherein at least one of Rxa, Rya, Rq, Rr and Rs is substituted with fluoro, trifluoromethyl, trifluoromethoxy, nitro, cyano, or (C3-C8) alkyl.
- 53. The compound of claim 51, wherein R5 is (CO)OR15 and R15 is (C2-C6) alkyl, (C2-C4) hydroxyalkyl, phenyl, phenylalkyl wherein the alkyl is C1-C3, or aminoalkyl where the alkyl is C2-C6 and the amino can be substituted with up to two independent (C1-C3) alkyls, wherein the phenyl or the phenyl of phenylalkyl can be substituted.
- 54. The compound of claim 51, wherein R5 is (CO)OR15 and R15 is hydrogen.
- 62. The compound of claim 43, wherein R3 is hydrogen, (C1-6) alkyl, or phenyl or phenylalkyl wherein the alkyl is C1 to C6 and the phenyl or phenyl of phenylalkyl can be substituted with the same substituents defined above for the phenyl of Rxa.
- 66. The compound of claim 43 wherein:
(1) 2R is hydrogen, (2) Rxa and Rya are phenyl, thienyl or furanyl, and can be substituted, (3) R is a single bond and Ryb is a single bond or oxy, and (4) Rs is (CO)NR13R14 or (CO)OR15, wherein R13, R14, and R15 are independently hydrogen; (C1-C8) alkyl which can include a (C3-C8) cycloalkyl, wherein the carbon linked to the oxygen of OR has no more than secondary branching; (C2-C6) hydroxyalkyl or aminoalkyl where the alkyl is C2 to C6 and the amino can be substituted with up to two independent (C1-C6) alkyl or phenylalkyl, wherein the alkyl is C1-C6 and the phenyl can be substituted with substituents selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, hydroxy, trifluoromethyl, amidosulfonyl which can have up to two independent (C1-C6) N-alkyl substitutions, (C1-C6) alkyl, (C2-C6) alkenyl, (C1-C6) alkylamine, dialkylamine wherein each alkyl is independently C1 to C6, amino, (C1-C6) alkoxy, (C2-C7) alkanoyl, (C2-C7) alkanoyloxy, trifluoromethoxy, hydroxycarbonyl, (C2-C7) alkyloxycarbonyl, aminocarbonyl that can be N-substituted with up to two independent (C1-C6) alkyl, (C1-C6) alkylsulfonyl, amidino that can substituted with up to three (C1-C6) alkyl.
- 67. The compound of claim 66, wherein R2 forms a double bond with an adjacent carbon from R1.
Parent Case Info
[0001] The present application is a continuation-in-part of: U.S. Ser. No. 08/656,063, filed May 31, 1996, U.S. Ser. No. 08/655,912, filed May 31, 1996, U.S. Ser. No. 08/807,682, filed Feb. 27, 1997, and U.S. Ser. No. 08/808,754, filed Feb. 27,1997, each of which applications are now converted to provisional applications.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60041503 |
May 1996 |
US |
|
60044387 |
Feb 1997 |
US |
|
60041504 |
May 1996 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
08866007 |
May 1997 |
US |
Child |
09757011 |
Jan 2001 |
US |
Continuation in Parts (4)
|
Number |
Date |
Country |
Parent |
08808754 |
Feb 1997 |
US |
Child |
08866007 |
May 1997 |
US |
Parent |
08656063 |
May 1996 |
US |
Child |
08808754 |
Feb 1997 |
US |
Parent |
08655912 |
May 1996 |
US |
Child |
08808754 |
Feb 1997 |
US |
Parent |
08807682 |
Feb 1997 |
US |
Child |
08808754 |
Feb 1997 |
US |