Pyrrolidinone, Pyrrolidine-2, 5-Dione, Pyrrolidine and Thiosuccinimide Derivatives, Compositions and Methods for Treatment of Cancer
First Claim
1. A compound of formula I, II, III, or IV, or pharmaceutically acceptable salts thereof:
- wherein;
R1, R2, and R3 are independently selected from the group consisting of H, F, Cl, Br, I, —
NR7R8, —
(C1-C6) alkyl, —
(C1-C6) substituted alkyl, —
(C3-C9) cycloalkyl, —
(C3-C9) substituted cycloalkyl, —
O—
(C1-C6) alkyl, —
O—
(C3-C9) cycloalkyl, and —
O—
(C3-C9) substituted cycloalkyl, aryl, heteroaryl, and heterocyclyl;
R4 is selected from the group consisting of H, —
(C1-C4) alkyl, and —
(C1-C4) substituted alkyl;
R5 is selected from the group consisting of H, —
(C1-C6) alkyl, —
CH2R6, —
CONHR9, —
COR10, and SO2R11;
R6 is selected from the group consisting of —
O—
P(═
O)(OH)2, —
O—
P(═
O)(—
OH)(—
O—
(C1-C6) alkyl), —
O—
P(═
O)(—
O—
(C1-C6) alkyl)2, —
O—
P(═
O)(—
OH) (—
O—
(CH2)-phenyl), —
O—
P(═
O)(—
O—
(CH2)-phenyl)2, a carboxylic acid group, an amino carboxylic acid group, and a peptide;
R7 and R8 are independently selected from the group consisting of H and —
(C1-C6) alkyl;
R9, R10, and R11 are independently selected from the group consisting of H, NHR12, —
(C1-C6)alkyl, —
(C1-C6)substituted alkyl, —
(C3-C9)cycloalkyl, —
(C3-C9) substituted cycloalkyl, aryl, heteroaryl, and heterocyclyl;
Q is selected from the group consisting of indolyl, substituted indolyl, aryl, heteroaryl, heterocyclyl, and alkyl;
V and Z are independently selected from the group consisting of O, S, H2;
when both V and Z are O, R4 is —
(C1-C4) alkyl, or —
(C1-C4) substituted alkyl;
when both Z and V are not H2, R5 is H, —
(C1-C6) alkyl, or —
CH2R6;
X is selected from the group consisting of —
CH2—
, —
NR12, S, O, and a bond;
R12 is selected from the group consisting of H, —
(C1-C6) alkyl, —
(C1-C6) substituted alkyl, —
(C3-C9) cycloalkyl, —
(C3-C9) substituted cycloalkyl, —
O—
(C1-C6) alkyl, C(═
O)—
O—
(C1-C6) alkyl, and —
C(═
O)—
O—
(C1-C6) substituted alkyl;
W is selected from the group consisting of —
CH2—
, CO, and a bond; and
m is 0, 1 or 2.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention relates to pyrrolidin-2-one, pyrrolidin-2,5-dione, pyrrolidine and thiosucciniroide compounds of formulae (I)-(IV), and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising pyrrolidin-2-one, pyrrolidin-2,5-dione, pyrrolidine and thiosuccinimide compounds. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a compound of pyrrolidin-2-one, pyrrolidin-2,5-dione, pyrrolidine and thiosuccinimide compound of the present invention.
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Citations
33 Claims
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1. A compound of formula I, II, III, or IV, or pharmaceutically acceptable salts thereof:
-
wherein; R1, R2, and R3 are independently selected from the group consisting of H, F, Cl, Br, I, —
NR7R8, —
(C1-C6) alkyl, —
(C1-C6) substituted alkyl, —
(C3-C9) cycloalkyl, —
(C3-C9) substituted cycloalkyl, —
O—
(C1-C6) alkyl, —
O—
(C3-C9) cycloalkyl, and —
O—
(C3-C9) substituted cycloalkyl, aryl, heteroaryl, and heterocyclyl;R4 is selected from the group consisting of H, —
(C1-C4) alkyl, and —
(C1-C4) substituted alkyl;R5 is selected from the group consisting of H, —
(C1-C6) alkyl, —
CH2R6, —
CONHR9, —
COR10, and SO2R11;R6 is selected from the group consisting of —
O—
P(═
O)(OH)2, —
O—
P(═
O)(—
OH)(—
O—
(C1-C6) alkyl), —
O—
P(═
O)(—
O—
(C1-C6) alkyl)2, —
O—
P(═
O)(—
OH) (—
O—
(CH2)-phenyl), —
O—
P(═
O)(—
O—
(CH2)-phenyl)2, a carboxylic acid group, an amino carboxylic acid group, and a peptide;R7 and R8 are independently selected from the group consisting of H and —
(C1-C6) alkyl;R9, R10, and R11 are independently selected from the group consisting of H, NHR12, —
(C1-C6)alkyl, —
(C1-C6)substituted alkyl, —
(C3-C9)cycloalkyl, —
(C3-C9) substituted cycloalkyl, aryl, heteroaryl, and heterocyclyl;Q is selected from the group consisting of indolyl, substituted indolyl, aryl, heteroaryl, heterocyclyl, and alkyl; V and Z are independently selected from the group consisting of O, S, H2;
when both V and Z are O, R4 is —
(C1-C4) alkyl, or —
(C1-C4) substituted alkyl;
when both Z and V are not H2, R5 is H, —
(C1-C6) alkyl, or —
CH2R6;X is selected from the group consisting of —
CH2—
, —
NR12, S, O, and a bond;R12 is selected from the group consisting of H, —
(C1-C6) alkyl, —
(C1-C6) substituted alkyl, —
(C3-C9) cycloalkyl, —
(C3-C9) substituted cycloalkyl, —
O—
(C1-C6) alkyl, C(═
O)—
O—
(C1-C6) alkyl, and —
C(═
O)—
O—
(C1-C6) substituted alkyl;W is selected from the group consisting of —
CH2—
, CO, and a bond; andm is 0, 1 or 2. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
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17. The pharmaceutical composition of 16, wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen, raloxifene, anastrozole, exemestane, letrozole, trastuzumab, imatanib, paclitaxel, cyclophosphamide, lovastatin, minosine, gemcitabine, araC, 5-fluorouracil, methotrexate, docetaxel, goserelin, vincristin, vinblastin, nocodazole, teniposide, etoposide, gemcitabine, epothilone, navelbine, camptothecin, daunonibicin, dactinomycin, mitoxantrone, amsacrine, doxorubicin, epirubicin, and idarubicin.
Specification