Claims
- 1. A compound having formula (I): or a pharmaceutically acceptable salt thereof, wherein:X is NR1; A, B and R1 are independently (C1-C10)-straight or branched alkyl, (C2-C10)-straight or branched alkenyl or alkynyl, wherein 1 or 2 hydrogen atoms in said alkyl, alkenyl or alkynyl are optionally and independently replaced with a monocyclic aromatic ring comprising 5-7 ring atoms independently selected from C, N, O, or S, and wherein 1-4 ring atoms are independently selected from N, O, or S; or R1 is independently hydrogen; wherein R3 is selected from hydrogen, (C1-C4)-straight or branched alkyl, (C3-C4)-straight or branched alkenyl or alkynyl, or (C1-C4) bridging alkyl, wherein said bridge is formed between the nitrogen atom to which said R3 is bound and any carbon atom of said alkyl, alkenyl or alkynyl to form a ring, and wherein said ring is optionally benzofused; wherein E is a saturated, partially saturated or unsaturated, or aromatic monocyclic or bicyclic ring system, wherein each ring comprises 5 to 7 ring atoms independently selected from C, N, O or S; and wherein no more than 4 ring atoms are selected from N, O or S; wherein 1 to 4 hydrogen atoms in E are optionally and independently replaced with halogen, hydroxyl, hydroxymethyl, nitro, SO3H, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O—[(C1-C6)-straight or branched alkyl], O—[(C3-C6)-straight or branched alkenyl], (CH2)n—N(R4)(R5), (CH2)n—NH(R4)—(CH2)n—Z, (CH2)n—N(R4—(CH2)n—Z)(R5—(CH2)n—Z, (CH2)n—Z, O—(CH2)n—Z, (CH2)n—O—Z, S—(CH2)n—Z, CH═CH—Z, 1,2-methylenedioxy, C(O)OH, C(O)O—[(C1-C6)-straight or branched alkyl], C(O)O—(CH2)n—Z or C(O)—N(R4)(R5); wherein each of R4 and R5 are independently hydrogen, (C1-C6)-straight or branched alkyl, (C3-C5)-straight or branched alkenyl, or wherein R4 and R5, when bound to the same nitrogen atom, are taken together with the nitrogen atom to form a 5 or 6 membered ring, wherein said ring optionally contains 1 to 3 additional heteroatoms independently selected from N, O or S; wherein said alkyl, alkenyl or alkynyl groups in R4 and R5 are optionally substituted with Z, each n is independently 0 to 4; each Z is independently selected from a saturated, partially saturated or unsaturated, monocyclic or bicyclic ring system, wherein each ring comprises 5 to 7 ring atoms independently selected from C, N, O or S; and wherein no more than 4 ring atoms are selected from N, O or S; wherein 1 to 4 hydrogen atoms in Z are optionally and independently replaced with halo, hydroxy, nitro, cyano, C(O)OH, (C1-C3)-straight or branched alkyl, O—(C1-C3)-straight or branched alkyl, C(O)O—[(C1-C3)-straight or branched alkyl], amino, NH[(C1-C3)-straight or branched alkyl], or N—[(C1-C3)-straight or branched alkyl]2; K is selected from E, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl, wherein 1 to 2 hydrogen atoms in said alkyl, alkenyl or alkynyl is optionally and independently replaced with E; wherein K is optionally substituted with up to 3 substituents selected from halogen, OH, O—(C1-C6)-alkyl, O—(CH2)n-Z, NO2, CO2H, C(O)—O—(C1-C6)-alkyl, C(O)NR4R5, NR4R5 and (CH2)n—Z; or, G-, —C(O)—C(O)—; Y is oxygen, or N(R6); wherein R6 is hydrogen, E, (C1-C6)-straight or branched alkyl, (C3-C6)-straight or branched alkenyl or alkynyl; or wherein R6 and D are taken together with the atoms to which they are bound to form a 5 to 7 membered ring system wherein said ring optionally contains 1 to 3 additional heteroatoms independently selected from O, S, N, NH, SO, or SO2; and wherein said ring is optionally benzofused; D is hydrogen, (C1-C7)-straight or branched alkyl, (C2-C7)-straight or branched alkenyl or alkynyl, or phenyl; wherein 1 to 2 of the CH2 groups of said alkyl, alkenyl or alkynyl chains in D is optionally replaced by —O—, —S—, —S(O)—, —S(O2)—, or —N(R3).
- 2. The compound according to claim 1, wherein:each of A and B is independently selected from —CH2—CH2—E or —CH2—CH2—CH2—E; and E is a monocyclic aromatic ring system, wherein said ring comprises 5-7 ring atoms independently selected from C, N, O or S, and wherein 1 to 4 ring atoms are independently selected from N, O or S; wherein 1 to 4 hydrogen atoms in E are optionally and independently replaced with halogen, hydroxyl, hydroxymethyl, nitro, SO3H, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O—[(C1-C6)-straight or branched alkyl], O—[(C3—C6)-straight or branched alkenyl], (CH2)n—N(R4)(R5), (CH2)n—NH(R4)—(CH2)n—Z, (CH2)n—N(R4—(CH2)n—Z)(R5—(CH2)n—Z), (CH2)n—Z, O—(CH2)n—Z, (CH2)n—O—Z, S—(CH2)n—Z, CH═CH—Z, 1,2-methylenedioxy, C(O)OH, or C(O)—N(R4)(R5).
- 3. The compound according to claim 2, wherein G is —C(O)C(O)—.
- 4. A compound of having the formula below:
- 5. The compound according to claim 2, wherein each of A and B is independently selected from —CH2—CH2—E or —CH2—CH2—CH2—E; and E is pyridyl.
- 6. A composition comprising a compound according to claim 1 and a pharmaceutically effective carrier.
- 7. The composition according to claim 6, further comprising a neurotrophic factor.
- 8. The composition according to claim 7, wherein said neurotrophic factor is selected from nerve growth factor (NGF), insulin-like growth factor (IGF-1), 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).
- 9. The composition according to claim 8, wherein said neurotrophic factor is nerve growth factor (NGF).
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuing application of co-pending International Patent Application PCT/US00/18564, filed Jul. 6, 2000, which claims priority of U.S. provisional patent No. 60/142,568, filed Jul. 6, 1999.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3712924 |
Kruger et al. |
Jan 1973 |
A |
5543423 |
Zelle et al. |
Aug 1996 |
A |
5614547 |
Hamilton et al. |
Mar 1997 |
A |
Foreign Referenced Citations (9)
Number |
Date |
Country |
22 56 484 |
Jun 1973 |
DE |
25 44 132 |
May 1976 |
DE |
34 19 994 |
Dec 1985 |
DE |
0 144 290 |
Jun 1985 |
EP |
0 338 892 |
Oct 1989 |
EP |
WO 9640140 |
Dec 1996 |
WO |
WO 9641609 |
Dec 1996 |
WO |
WO 9716190 |
May 1997 |
WO |
WO 9745115 |
Dec 1997 |
WO |
Non-Patent Literature Citations (1)
Entry |
Van der Steen, F.H., et al., “Synthesis and Molecular Structure of Novel α-Amino Organoaluminum Ester Enolates. Key Intermediates in the Selective Formation of trans-3-Amino-2-azetidinones,” J. Am. Chem. Soc., 113(15):5742-5750 (1991). |
Provisional Applications (1)
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Number |
Date |
Country |
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60/142568 |
Jul 1999 |
US |
Continuations (1)
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Number |
Date |
Country |
Parent |
PCT/US00/18564 |
Jul 2000 |
US |
Child |
10/039896 |
|
US |