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US 2010/0143499 A1Published application
Dimeric iap inhibitors
AssigneeTetralogic Pharmaceuticals Corporation
InventorStephen M. Condon
Life of this patent
Estimating the term…
Abstract
Compounds, compositions, and methods of using such compounds to modulate apoptosis including IAP antagonists are provided herein. Compositions including mimetics of the invention and, optionally, secondary agents, may be used to treat proliferative disorders such as, cancer and autoimmune diseases.
Claims20
A compound comprising a homodimer or heterodimer of a monomeric unit of formula (I):
- wherein:
- each X1, X2, and X3 is, independently, O or S;
- each Y is, independently, (CHR10), O, or S(O)n;
- wherein n is 0, 1, or 2 and R10 is H, halogen, alkyl, aryl, arylalkyl, amino, arylamino, arylalkylamino, alkoxy, aryloxy, or arylalkyloxy;
- each A is, independently, a 5-member heterocycle comprising 1 to 4 heteroatoms optionally substituted with amino, nitro, cyano, hydroxyl, mercapto, halo, carboxyl, amidino, gaunidino, alkyl, alkyloxy, aryl, aryloxy, acyl, acyloxy, acylamino, alkyloxycarbonylamino, cycloalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, alkylsulfonylamino, or a heterocycle wherein each alkyl, alkoxy, aryl, aryloxy, acyl, acyloxy, acylamino, cycloalkyl, and heterocycle is optionally substituted with hydroxyl, halogen, mercapto, carboxyl, alkyl, alkoxy, haloalkyl, amino, nitro, cyano, cycloalkyl, aryl, or heterocycle;
- or
- each A is, independently, a bond, —C(X4)—, —C(X4)NR11, or —C(X4)O— wherein X4 is O or S and R11 is H or R8 when the monomeric units are linked through A;
- each R1 and R2 are, independently, H, hydroxyl, amino, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroarylalkyl wherein each alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, and heteroarylalkyl is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, alkoxy, amino, or nitro;
- each R3 is, independently, H or alkyl;
- each R4 is, independently, H or alkyl;
- each R5 is, independently, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, a heterocycle or heterocyclylalkyl;
- each optionally substituted with hydroxyl, mercapto, halogen, amino, carboxyl, alkyl, haloalkyl, alkoxy, or alkylthio;
- each R6 is, independently, H or alkyl;
- or
- each independent R5 and R6 together forms a 5-8 member ring;
- each R7 is, independently, H, alkyl, aryl, or arylalkyl;
- each R8 is, independently, alkyl, a carbocycle, carbocycle-substituted alkyl, a heterocycle or heterocycle-substituted alkyl wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, haloalkyl, alkoxy, alkylsulfonyl, amino, nitro, aryl, or heteroaryl;
- and
- each R9 is, independently, H or alkyl;
- or
- a pharmaceutically acceptable salt or hydrate thereof.
18 more elements
A pharmaceutical composition comprising a compound of formula (II):
- wherein:
- X1, X1′, X2, X2′, X3, and X3′ are each, independently, O or S;
- Y and Y′ are each, independently, (CHR10), O, or S(O)n;
- wherein n is 0, 1, or 2 and R10 is H, halogen, alkyl, aryl, arylalkyl, amino, arylamino, arylalkylamino, alkoxy, aryloxy or arylalkyloxy;
- A and A′ are each, independently, a bond, —C(X4)—, —C(X4)NR11, or —C(X4)O— wherein X4 is O or S and R11 is H or R8 when L is all or a part of A or A′;
- or
- A and A′ are each, independently, a 5-member heterocycle comprising 1 to 4 heteroatoms optionally substituted with amino, hydroxyl, mercapto, halo, carboxyl, amidino, gaunidino, alkyl, alkyloxy, aryl, aryloxy, acyl, acyloxy, acylamino, alkyloxycarbonylamino, cycloalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, alkylsulfonylamino or a heterocycle;
- wherein each alkyl, alkyloxy, aryl, aryloxy, acyl, acyloxy, acylamino, cycloalkyl and heterocycle is optionally substituted with hydroxyl, halogen, mercapto, carboxyl, alkyl, alkyloxy, haloalkyl, amino, nitro, cyano, cycloalkyl, aryl, or heterocycle;
- R1, R1′, R2 and R2′ are each, independently, H, hydroxyl, amino, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroarylalkyl wherein each alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl and heteroarylalkyl is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, alkoxy, amino, or nitro;
- R3 and R3′ are each, independently, H or alkyl;
- R4 and R4′ are each, independently, H or alkyl;
- R5 and R5′ are each, independently, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, a heterocycle or heterocyclylalkyl;
- each optionally substituted with hydroxyl, mercapto, halogen, amino, carboxyl, alkyl, haloalkyl, alkoxy, or alkylthio;
- R6 and R6′ are each, independently, H or alkyl;
- or
- R5 and R6 or R5′ and R6′ each, independently, together form a 5-8 member ring;
- R7 and R7′ are each, independently, H, alkyl, aryl, or arylalkyl;
- R8 and R8′ are each, independently, alkyl, a carbocycle, carbocycle-substituted alkyl, a heterocycle or heterocycle-substituted alkyl wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, haloalkyl, alkoxy, alkylsulfonyl, amino, nitro, aryl, or heteroaryl;
- R9 and R9′ are each, independently, H, or alkyl;
- and
- L is one or more independent bonds or one or more independent linkers;
- or
- a pharmaceutically acceptable excipient or carrier.
20 more elements
Dependencies are inferred from the claim text.