Small organic molecule regulators of cell proliferation
AssigneeCuris, Inc.
InventorsJeffrey Porter, Oivin M. Guicherit, Lee Rubin, Anthony David Baxter, Edward Andrew Boyd, Stephen Price
Life of this patent
Estimating the term…
Abstract
The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.
Claims59
A pharmaceutical preparation comprising a pharmaceutically acceptable excipient and a compound represented in general formula (III):
- wherein
- Ar and Ar′ independently represent substituted or unsubstituted aryl or heteroaryl rings;
- Y, independently for each occurrence, is absent or represents —NR—, —O—, —S—, or —Se—;
- X is selected from —C(═O)—, —C(═S)—, —S(O2)—, —S(O)—, —C(═NCN)—, —P(═O)(OR2)—, and a methylene group optionally substituted with 1-2 groups selected from lower alkyl, alkenyl, and alkynyl groups;
- M represents, independently for each occurrence, a substituted or unsubstituted methylene group, or two adjacent M taken together represent substituted or unsubstituted ethene or ethyne;
- R represents, independently for each occurrence, H or substituted or unsubstituted aryl, heterocyclyl, heteroaryl, aralkyl, heteroaralkyl, alkynyl, alkenyl, or alkyl, or two R taken together may form a 4- to 8-membered ring;
- Cy and Cy′ independently represent substituted or unsubstituted aryl, heterocyclyl, heteroaryl, or cycloalkyl;
- i represents, independently for each occurrence, an integer from 0 to 5;
- and
- wherein in —Cy—Y—Mi—NR2 i is zero and Y is absent.
A pharmaceutical preparation comprising a pharmaceutical excipient and a compound represented in general formula (VII):
- wherein
- Cy represents a substituted or unsubstituted heterocyclyl or cycloalkyl;
- Ar is a substituted or unsubstituted aryl or heteroaryl ring;
- W is O or S;
- R represents, independently for each occurrence, H or substituted or unsubstituted aryl, heterocyclyl, heteroaryl, aralkyl, heteroaralkyl, alkynyl, alkenyl, or alkyl, or two R taken together may form a 4- to 8-membered ring;
- R1 and R2 represent, independently and as valency permits, from 0-5 substituents on the ring to which each is attached, selected from halogen, lower alkyl, lower alkenyl, aryl, heteroaryl, carbonyl, thiocarbonyl, ketone, aldehyde, amino, acylamino, amido, amidino, cyano, nitro, hydroxyl, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, sulfonamido, phosphoryl, phosphonate, phosphinate, —(CH2)palkyl, —(CH2)palkenyl, —(CH2)palkynyl, —(CH2)paryl, —(CH2)paralkyl, —(CH2)pOH, —(CH2)pO-lower alkyl, —(CH2)pO-lower alkenyl, —O(CH2)nR, —(CH2)pSH, —(CH2)pS-lower alkyl, —(CH2)pS-lower alkenyl, —S(CH2)nR, —(CH2)pNR2, —(CH2)pNR-lower alkyl, —(CH2)pNR-lower alkenyl, —NR(CH2)nR, and protected forms of the above;
- and
- n and p, individually for each occurrence, represent integers from 0 to 10.
Dependencies are inferred from the claim text.