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Inhibitors of cellular necrosis |
| 7345076 |
Inhibitors of cellular necrosis
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| Patent Drawings: | |
| Inventor: |
Cuny, et al. |
| Date Issued: |
March 18, 2008 |
| Application: |
10/930,690 |
| Filed: |
August 30, 2004 |
| Inventors: |
Cuny; Gregory D. (Somerville, MA)
Yuan; Junying (Newton, MA)
Jagtap; Prakash (Beverly, MA)
Degterev; Alexei (Brookline, MA)
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| Assignee: |
President and Fellows of Harvard College (Cambridge, MA) |
| Primary Examiner: |
Shiao; Rei-tsang |
| Assistant Examiner: |
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| Attorney Or Agent: |
Clark & Elbing LLPBieker-Brady; Kristina |
| U.S. Class: |
514/397; 514/398; 548/312.1 |
| Field Of Search: |
548/312.1; 514/397; 514/398 |
| International Class: |
A61K 31/415; C07D 403/02 |
| U.S Patent Documents: |
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| Foreign Patent Documents: |
02019363 |
| Other References: |
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| Abstract: |
The present invention relates to compounds and pharmaceutical preparations and their use in therapy for preventing or treating trauma, ischemia, stroke and degenerative diseases associated with cell death. Methods and compositions of the invention are particularly useful for treating neurological disorders associated with cellular necrosis. |
| Claim: |
What is claimed is:
1. A compound of the formula: ##STR00073## a stereoisomeric form thereof, a pharmaceutically acceptable acid or base addition salt thereof; wherein X represents O; Yrepresents NR.sub.8; G represents NR.sub.7; R.sub.1, R.sub.2, and R.sub.3 represent independently H, OH, OR.sub.8, F, Cl, Br, I, N(R.sub.8).sub.2, COOH, CO.sub.2R.sub.8, NO.sub.2, NHC(O)R.sub.8, lower alkyl, substituted lower alkyl, or aryl; R.sub.4represents independently OH, OR.sub.8, F, Cl, Br, I, N(R.sub.8).sub.2, COOH, CO.sub.2R.sub.8, NO.sub.2, NHC(O)R.sub.8, methyl, methoxyl, lower alkyl, substituted lower alkyl, aryl, or amine; R.sub.5, R.sub.6, and R.sub.7 represent independently H orlower alkyl; each R.sub.8 represents independently H, lower alkyl, substituted lower alkyl, aryl, substituted aryl, arylalkyl, alkenyl, or alkynyl; R.sub.9, R.sub.10, R.sub.9', and R.sub.10' represent independently H, F, Cl, Br, I, lower alkyl, orsubstituted lower alkyl, or a three to six membered cycloalkyl that includes C.sub.n and/or C.sub.n'; and n and n' equals an integer from zero to five.
2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2, wherein the pharmaceutically acceptable carrier is chosen from a diluent, a solid filler, and a solvent encapsulating material.
4. The pharmaceutical composition of claim 2, wherein the pharmaceutically acceptable carrier is chosen from a sugar, a starch, cellulose, powdered tragacanth, malt, gelatin, talc, an excipient, an oil, a glycol, a polyoi, an ester, an agar, abuffering agent, alginic acid, pyrogen free water, isotonic saline, Ringer's solution, ethyl alcohol, a pH buffered solution, a polyester, a polyanhydride, and a polycarbonate.
5. The compound of claim 1, wherein said compound is of the formula: ##STR00074##
6. The compound of claim 5, wherein said compound is an enantiomer of the formula: ##STR00075##
7. The compound of claim 5, wherein said compound is an enantiomer of the formula: ##STR00076##
8. A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising a compound of claim 6 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier.
11. The compound of claim 1, wherein R.sub.9, R.sub.10, R.sub.9', and R.sub.10' represent independently H, F, Cl, Br, I, lower alkyl, or substituted lower alkyl; and n and n' are independently zero or one.
12. The compound of claim 11, wherein R.sub.9, R.sub.10, R.sub.9', and R.sub.10' each represent H.
13. The compound of claim 12, wherein R.sub.4 represents Cl, Br, F, or I.
14. The compound of claim 13, wherein R.sub.6 represents methyl.
15. A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising a compound of claim 12 and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising a compound of claim 13 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising a compound of claim 14 and a pharmaceutically acceptable carrier. |
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