التفاصيل البيبلوغرافية
| العنوان: |
Inhibitors of p97 |
| Document Number: |
20090253717 |
| تاريخ النشر: |
October 8, 2009 |
| Appl. No: |
12/321463 |
| Application Filed: |
January 20, 2009 |
| مستخلص: |
One aspect of the invention relates to compounds that inhibit the activity of p97, such as by binding covalently to a cysteine residue in the active site. In certain embodiments, the invention relates to the treatment of disease, such as cancer, comprising administering a compound of the invention. |
| Inventors: |
Brown, Steven J. (San Diego, CA, US); Chou, Tsui-Fen (Pasadena, CA, US); Deshaies, Raymond (Claremont, CA, US); Jones, Amanda C. (Pasadena, CA, US); Rosen, Hugh (La Jolla, CA, US); Stoltz, Brian M. (San Marino, CA, US) |
| Claim: |
1. A method for inhibiting the activity of p97, comprising contacting a cell with a compound that binds to and inhibits p97. |
| Claim: |
2. The method of claim 1, wherein the compound covalently binds to an active site of p97. |
| Claim: |
3. The method of claim 2, wherein the compound forms a covalent bond with a cysteine residue of the active site. |
| Claim: |
4. The method of claim 3, wherein the cysteine residue is Cys522. |
| Claim: |
5. The method of claim 1, wherein the compound has a structure of Formula I: Ar-E (I) wherein E is selected from [chemical expression included] Ar is selected from [chemical expression included] [chemical expression included] R1 is selected from hydrogen and substituted or unsubstituted haloalkyl, aziridine, epoxide, vinyl sulfone, acrylyl, alkenyl, acetyl, cyanoalkyl, acyl, sulfonyl carbonyl, or sulfinyl carbonyl; R3 is selected from hydrogen and substituted or unsubstituted haloalkyl, aziridine, epoxide, vinyl sulfone, acrylyl, alkenyl, acetyl, cyanoalkyl, acyl, sulfonyl carbonyl, sulfinyl carbonyl, alkyl, aralkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heteroaralkyl, cycloalkylalkyl, heterocyclylalkyl, acyl, sulfonyl, sulfamoyl, or sulfonamido; R2 and R4, independently and for each occurrence, are selected from hydrogen and substituted or unsubstituted alkyl, alkenyl, alkynyl, heteroalkyl, aralkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heteroaralkyl, cycloalkylalkyl, heterocyclylalkyl, halogen, acyl, carboxyl, ester, hydroxyl, alkoxyl, alkylthio, acyloxy, amino, acylamino, carbamate, amido, amidino, cyano, sulfonyl, sulfoxido, sulfamoyl, or sulfonamido; and R5 is selected from hydrogen and substituted or unsubstituted alkyl, aralkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heteroaralkyl, cycloalkylalkyl, heterocyclylalkyl, acyl, sulfonyl, sulfamoyl, or sulfonamido; or a pharmaceutically acceptable salt or prodrug thereof. |
| Claim: |
6. A method of treating cancer in a patient, comprising administering an effective dose of a compound that inhibits the activity of p97. |
| Claim: |
7. The method of claim 6, wherein the compound covalently binds to an active site of p97. |
| Claim: |
8. The method of claim 7, wherein the compound forms a covalent bond with a cysteine residue of the active site. |
| Claim: |
9. The method of claim 8, wherein the cysteine residue is Cys522. |
| Claim: |
10. The method of claim 6, wherein the compound has a structure of Formula I: Ar-E (I) wherein E is selected from [chemical expression included] Ar is selected from [chemical expression included] [chemical expression included] R1 is selected from hydrogen and substituted or unsubstituted haloalkyl, aziridine, epoxide, vinyl sulfone, acrylyl, alkenyl, acetyl, cyanoalkyl, acyl, sulfonyl carbonyl, or sulfinyl carbonyl; R3 is selected from hydrogen and substituted or unsubstituted haloalkyl, aziridine, epoxide, vinyl sulfone, acrylyl, alkenyl, acetyl, cyanoalkyl, acyl, sulfonyl carbonyl, sulfinyl carbonyl, alkyl, aralkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heteroaralkyl, cycloalkylalkyl, heterocyclylalkyl, acyl, sulfonyl, sulfamoyl, or sulfonamido; R2 and R4, independently and for each occurrence, are selected from hydrogen and substituted or unsubstituted alkyl, alkenyl, alkynyl, heteroalkyl, aralkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heteroaralkyl, cycloalkylalkyl, heterocyclylalkyl, halogen, acyl, carboxyl, ester, hydroxyl, alkoxyl, alkylthio, acyloxy, amino, acylamino, carbamate, amido, amidino, cyano, sulfonyl, sulfoxido, sulfamoyl, or sulfonamido; and R5 is selected from hydrogen and substituted or unsubstituted alkyl, aralkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, heteroaralkyl, cycloalkylalkyl, heterocyclylalkyl, acyl, sulfonyl, sulfamoyl, or sulfonamido; or a pharmaceutically acceptable salt or prodrug thereof. |
| Current U.S. Class: |
5142/621 |
| Current International Class: |
61; 61 |
| رقم الانضمام: |
edspap.20090253717 |
| قاعدة البيانات: |
USPTO Patent Applications |
