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US 8,410,144 B2Granted
Substituted indolo-pyridinone compounds
AssigneeArQule, Inc.
InventorsNivedita Namdev, Manish Tandon, Jianqiang Wang, Audra Dalton, David Vensel, Rocio Palma, Mark A. Ashwell, Neil Westlund
Life of this patent
Estimating the term…
Abstract
The present invention relates to substituted indolo-pyridinone compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted indolo-pyridinone compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.
Claims18
A compound of formula I:
- or a salt or ester thereof, wherein:
- W, X and Y are each independently H, C(O)R4, NR11C(O)R7, —(CH2)p—NR5R6, unsubstituted or substituted C1-C6 alkyl, hydroxyl, halogen, unsubstituted or substituted C5-C6 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C6 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- Z is H, C(O)R4, NR11C(O)R7, —(CH2)p—NR5R6, unsubstituted or substituted C1-C6 alkyl, hydroxyl, halogen, unsubstituted or substituted C5-C6 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C6 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S, or Z together with R2, forms a 5- to 7-member ring optionally comprising 1-2 additional heteroatoms selected from N and O;
- R1 is halogen, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- R2 is H or unsubstituted or substituted C1-C6 alkyl, or R2 together with Z, forms a 5- to 7-member ring optionally comprising 1-2 additional heteroatoms selected from N and O;
- R3 is H or unsubstituted or substituted C1-C6 alkyl;
- R4 and R7 are each independently NR5R6 or OR8;
- R5 and R6 are each independently H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or —(CH2)n—R9, or R5 and R6, together with the nitrogen atom to which they are attached, form a 5- to 7-member ring which optionally comprises 1-2 additional heteroatoms selected from N and O and optionally is substituted;
- R8 is H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or —(CH2)n-R9;
- R9 is unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1-C6 alkylamino, unsubstituted or substituted di(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryloxyl, unsubstituted or substituted C1-C6 alkylthio, unsubstituted or substituted acyl or amide;
- R11 is H or unsubstituted or substituted C1-C6 alkyl;
- p is 0, 1, 2, 3, 4, 5 or 6;
- and
- n is 1, 2, 3, 4, 5 or 6.
12 more elements
A compound of formula II:
- or a salt or ester thereof, wherein:
- Y is C(O)R4, NR11C(O)R7, —(CH2)p—NR5R6, unsubstituted or substituted C1-C6 alkyl, hydroxyl, halogen, unsubstituted or substituted C5-C6 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C6 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- R1 is H, halogen, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle or unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- R2 is H or unsubstituted or substituted C1-C6 alkyl, or R2, together with Z, forms a 5- to 7-member ring optionally comprising 1-2 additional heteroatoms selected from N and O;
- R3 is H or unsubstituted or substituted C1-C6 alkyl
- R4 and R7 are each independently NR5R6 or OR8;
- R5 and R6 are each independently H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or —(CH2)n—R9, or R5 and R6, together with the nitrogen atom to which they are attached, form a 5- to 7-member ring optionally comprising 1-2 additional heteroatoms selected from N and O and the ring is optionally substituted;
- R8 is H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or —(CH2)n—R9;
- R9 is unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1-C6 alkylamino, unsubstituted or substituted di(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryloxyl, unsubstituted or substituted C1-C6 alkylthio, unsubstituted or substituted acyl or amide;
- R11 is H or unsubstituted or substituted C1-C6 alkyl;
- p is 0, 1, 2, 3, 4, 5 or 6;
- and
- n is 1, 2, 3, 4, 5 or 6.
11 more elements
A compound of formula III:
- or a salt or ester thereof, wherein:
- R2a and R3a are each independently H or unsubstituted or substituted C1-C6 alkyl;
- R5 and R6 are each independently H, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S or —(CH2)n—R9, or R5 and R6, together with the nitrogen atom to which they are attached, form a 5- to 7-member ring which optionally comprises 1-2 additional heteroatoms selected from N and O and optionally is substituted;
- R9 is unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1-C6 alkylamino, unsubstituted or substituted di(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryloxyl, unsubstituted or substituted C1-C6 alkylthio, unsubstituted or substituted acyl or amide;
- each R10 is independently hydroxyl, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C5-C10 aryl, unsubstituted or substituted heteroaryl comprising 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C3-C10 carbocycle, unsubstituted or substituted heterocycle comprising 1-4 heteroatoms selected from N, O and S;
- unsubstituted or substituted C1-C6 alkoxyl, amino, unsubstituted or substituted C1-C6 alkylamino, unsubstituted or substituted di(C1-C6) alkylamino, unsubstituted or substituted C5-C10 aryloxyl, unsubstituted or substituted C1-C6 alkylthio, unsubstituted or substituted acyl, amide, nitro or cyano;
- n is 1, 2, 3, 4, 5 or 6;
- and
- m is 0, 1, 2, 3, 4 or 5.
7 more elements
Dependencies are inferred from the claim text.