Small organic molecule regulators of cell proliferation
AssigneeCuris, Inc.
InventorsAnthony David Baxter, Edward Andrew Boyd, Maria Frank-Kamenetsky, Oivin Guicherit, Jeffery Porter, Stephen Price, Lee L. Rubin, John Harry Alexander Stibbard
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.
Claims29
A compound represented in general formula (IX):
- wherein, as valence and stability permit,
- Ar represents a substituted or unsubstituted aryl ring;
- X is selected from —C(═O)—, —C(═S)—, —S(O2)—, —S(O)—, and a methylene group optionally substituted with 1–2 lower alkyls;
- Y is absent for each occurrence;
- Z is absent or represents a substituted or unsubstituted aryl or carbocyclyl ring, or a lower alkyl, nitro, cyano, or halogen substituent;
- M represents, independently for each occurrence, a substituted or unsubstituted methylene group, or two M taken together represent substituted or unsubstituted ethene or ethyne;
- Cy represents a substituted or unsubstituted piperidine ring or cycloalkyl;
- Cy′ represents a 3-chloro-benzo(b)thien-2-yl, 3-fluoro-benzo(b)thien-2-yl, or 3-methyl-benzo(b)thien-2-yl, wherein the benzo ring is substituted with from 1–4 substituents selected from halogen, nitro, cyano, methyl, and ethyl;
- i represents 0 for all occurrences except in the sequence N-Mi-Y—Ar, where i represents 1;
- and
- k represents 0;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical preparation comprising a sterile pharmaceutical excipient and a compound represented in general formula (I):
- wherein
- Ar and Ar′ independently represent substituted or unsubstituted aryl rings;
- Y, independently for each occurrence, is absent or represents —N(R)—, —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 M taken together represent substituted or unsubstituted etbene or ethyne;
- R represents, independently for each occurrence, H or substituted or unsubstituted aryl, heterocyclyl, heteroaryl, aralkyl, heteroaralkyl, alkynyl, ailcenyl, or alkyl, or two R taken together may form a 4- to 8-membered ring;
- Cy represents a substituted or unsubstituted piperidine ring or cycloalkyl;
- Cy′ represents a 3-chloro-benzo(b)thien-2-yl, 3-fluoro-benzo(b)thien-2-yl, or 3-methyl-benzo(b)thien-2-yl, wherein the benzo ring is substituted with from 1–4 substituents selected from halogen, intro, cyano, methyl, and ethyl;
- i represents, independently for each occurrence, an integer from 0 to 5;
- and
- n, individually for each occurrence, represents an integer from 0 to 10;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.