Alpha-helix mimicry by a class of organic molecules
AssigneeThe Regents of the University of California
InventorsRodney K. Guy, Irwin D. Kuntz, Felice Lu
Life of this patent
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Abstract
The present invention provides methods for making compounds and methods for using the compounds to disrupt or inhibit protein-protein interactions. Also provided are pharmaceutical compositions comprising the compounds of the current invention.
Claims24
A compound selected from:
- A-L-B-L1-A1 and 18
- in which
- A is a member selected from:
- 19
- B is a member selected from:
- 20
- A1 is a member selected from:
- 21
- R, R′, and R2 are members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycloalkyl;
- L and L1 are members independently selected from:
- —N═N—, —CH2—CH2—, —C═C—, —CH2—CH2—, —CH2—S—, —CH2—NH—, —NH—CH2,
- 22
- and a single bond;
- X, X1, X2, Y, Y1, Y2, Z, Z1, and Z2 are members independently selected from:
- —N— and —CH—;
- X3, Y3, E, E1, and E2are members independently selected from:
- —NH—, —CH2—, —S—, and —O—;
- E, E1, and E2 members independently selected from:
- —NH—, —CH2—, —S—, and —O—;
- n, m, p and q are integers independently selected from 0 to 4;
- and
- w is an integer from 0 to 2.
A method of inhibiting or disrupting the interaction between an alpha helix of a first protein and a alpha helix binding pocket of a second protein, said method comprising contacting said second protein with a compound selected from:
- A-L-B-L1-A1 and 25
- in which
- A is a member selected from:
- 26
- B is a member selected from:
- 27
- A1 is a member selected from:
- 28
- R, R1, and R2 are members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycloalkyl;
- L and L1 are members independently selected from:
- —N═N—, —CH2—CH2—, —C═C—, —CH2—CH2—, —CH2—S—, —CH2—NH—, —NH—CH2,
- 29
- and a single bond;
- X, X1, X2, Y, Y1, Y2, Z, Z1, and Z2 are members independently selected from:
- —N— and —CH—;
- X3, Y3, E, E1, and E2are members independently selected from:
- —NH—, —CH2—, —S—, and —O—;
- E, E1, and E2 members independently selected from:
- —NH—, —CH2—, —S—, and —O—;
- n, m, p and q are integers independently selected from 0 to 4;
- and
- w is an integer from 0 to 2.
A pharmaceutical composition comprising a pharmaceutically acceptable excepient in combination with a compound selected from:
- A-L-B-L1-A1 and 32
- in which
- A is a member selected from:
- 33
- B is a member selected from:
- 34
- A1 is a member selected from:
- 35
- R, R1, and R2 are members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycloalkyl;
- L and L1 are members independently selected from:
- —N═N—, —CH2—CH2—, —C═C—, —CH2—CH2—, —CH2—S—, —CH2—NH—, —NH—CH2,
- 36
- and a single bond;
- X, X1, X2, Y, Y1, Y2, Z, Z1, and Z2 are members independently selected from:
- —N— and —CH—;
- X3, Y3, E, E1, and E2are members independently selected from:
- —NH—, —CH2—, —S—, and —O—;
- E, E1, and E2 members independently selected from:
- —NH—, —CH2—, —S—, and —O—;
- n, m, p and q are integers independently selected from 0 to 4;
- and
- w is an integer from 0 to 2.
Dependencies are inferred from the claim text.