Small organic molecule regulators of cell proliferation
First Claim
Patent Images
1. A pharmaceutical preparation comprising a pharmaceutically acceptable excipient and a compound represented in general formula (III):
-
whereinAr 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.
3 Assignments
0 Petitions
Accused Products
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.
207 Citations
59 Claims
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1. 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.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
i is zero except for Mi between Ar and N; and all Y are absent.
-
-
16. The pharmaceutical preparation of claim 13, wherein
i is zero except for Mi between Ar and N; and all Y are absent.
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17. The pharmaceutical preparation of claim 1, wherein Cy represents a substituted or unsubstituted cyclohexyl group.
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18. The pharmaceutical preparation of claim 17, wherein Cy′
- represents a substituted or unsubstituted benzothiophene.
-
19. The pharmaceutical preparation of claim 18, wherein the benzothiophene ring is substituted with one or more hydrogen, methyl, ethyl, fluorine, chlorine, methoxy, or cyano groups.
-
20. The pharmaceutical preparation of claim 17, wherein each R independently represents H or a lower alkyl.
-
21. The pharmaceutical preparation of claim 11, wherein NR2 represents a secondary amine.
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22. The pharmaceutical preparation of claim 19, wherein each R independently represents H or a lower alkyl.
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23. The pharmaceutical preparation of claim 22, wherein NR2 represents a secondary amine.
-
24. The pharmaceutical preparation of claim 20, wherein
i is zero except for Mi between Ar and N; and all Y are absent.
-
25. The pharmaceutical preparation of claim 22, wherein
i is zero except for Mi between Ar and N; and all Y are absent.
-
26. The pharmaceutical preparation of claim 5, wherein each R independently represents H or a lower alkyl.
-
27. The pharmaceutical preparation of claim 26, wherein NR2 represents a secondary amine.
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28. The pharmaceutical preparation of claim 26, wherein Cy′
- represents a substituted or unsubstituted benzothiophene.
-
29. The pharmaceutical preparation of claim 28, wherein the benzothiophene ring is substituted with one or more hydrogen, methyl, ethyl, fluorine, chlorine, methoxy, or cyano groups.
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30. The pharmaceutical preparation of claim 26, wherein Cy represents a substituted or unsubstituted cyclohexyl group.
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31. The pharmaceutical preparation of claim 29, wherein
i is zero except for Mi between Ar and N; and all Y are absent.
-
32. The pharmaceutical preparation of claim 30, wherein
i is zero except for Mi between Ar and N; and all Y are absent.
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33. 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. - View Dependent Claims (34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59)
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Specification