| US 7,470,709 B2 | ||
| Benzimidazole quinolinones and uses thereof | ||
| Paul A. Barsanti, Pleasant Hill, Calif. (US); Dirksen Bussiere, San Leandro, Calif. (US); Stephen D. Harrison, Albany, Calif. (US); Carla C. Heise, Benicia, Calif. (US); Johanna M. Jansen, San Francisco, Calif. (US); Elisa Jazan, Richmond, Calif. (US); Timothy D. Machajewski, Martinez, Calif. (US); Christopher McBride, Oakland, Calif. (US); William R. McCrea, Jr., Berkeley, Calif. (US); Simon Ng, Walnut Creek, Calif. (US); Zhi-Jie Ni, Fremont, Calif. (US); Sabina Pecchi, Oakland, Calif. (US); Keith B. Pfister, San Ramon, Calif. (US); Savithri Ramurthy, Walnut Creek, Calif. (US); Paul A. Renhowe, Danville, Calif. (US); Cynthia M. Shafer, El Sobrante, Calif. (US); Joel B. Silver, Santa Cruz, Calif. (US); Allan S. Wagman, Belmont, Calif. (US); Marion Wiesmann, Brisbane, Calif. (US); and Kelly Wayman, San Rafael, Calif. (US) | ||
| Assigned to Novartis Vaccines and Diagnostics, Inc., Emeryville, Calif. (US) | ||
| Filed on Aug. 19, 2003, as Appl. No. 10/644,055. | ||
| Claims priority of provisional application 60/405729, filed on Aug. 23, 2002. | ||
| Claims priority of provisional application 60/426107, filed on Nov. 13, 2002. | ||
| Claims priority of provisional application 60/426226, filed on Nov. 13, 2002. | ||
| Claims priority of provisional application 60/426282, filed on Nov. 13, 2002. | ||
| Claims priority of provisional application 60/428210, filed on Nov. 21, 2002. | ||
| Claims priority of provisional application 60/460328, filed on Apr. 03, 2003. | ||
| Claims priority of provisional application 60/460493, filed on Apr. 03, 2003. | ||
| Claims priority of provisional application 60/460327, filed on Apr. 03, 2003. | ||
| Claims priority of provisional application 60/478916, filed on Jun. 16, 2003. | ||
| Claims priority of provisional application 60/484048, filed on Jul. 01, 2003. | ||
| Prior Publication US 2004/0092535 A1, May 13, 2004 | ||
| Int. Cl. A61K 31/47 (2006.01) | ||
| U.S. Cl. 514—312 [514/314; 514/313] | 17 Claims |
1. A method of treating cancer comprising: administering to a cancer patient an effective amount of a compound of Structure
I, a tautomer of the compound, a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable salt of the
tautomer, or mixtures thereof, wherein the cancer is selected from hematologic cancers, acute myelogenous leukemia, ovarian
carcinoma, breast carcinoma, lung cancer, colon cancer, prostate cancer, pituitary cancer, chronic myelogenous leukemia, or
acute lymphoblastic leukemia, and Structure I has the following formula:
 wherein,
A, B, C, and D are all carbon or one of A or D is nitrogen, and B and C are both carbon;
R1 is selected from the group consisting of —H, —F, —Cl, —Br, —I, substituted and unsubstituted straight and branched chain alkyl
groups having from 1 to 8 carbon atoms, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocyclyl
groups, substituted and unsubstituted heterocyclylalkyl groups, substituted and unsubstituted alkoxy groups, substituted and
unsubstituted heterocyclyloxy groups, or substituted and unsubstituted heterocyclylalkoxy groups;
R2 is selected from —H, —F, —Cl, —Br, —I, —NO2, —CN, substituted and unsubstituted straight and branched chain alkyl groups having from 1 to 12 carbon atoms, substituted
and unsubstituted cycloalkyl groups, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups,
substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted
and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH2, substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl)2 groups, —C(═O)—NH2, substituted and unsubstituted —C(═O)—N(H)(aryl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aryl) groups, substituted
and unsubstituted —C(═O)—N(aryl)2 groups, substituted and unsubstituted —C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aralkyl)
groups, substituted and unsubstituted —C(═O)—N(aralkyl)2 groups, or —CO2H;
R3 is selected from —H, —F, —Cl, —Br, —I, —CN, substituted and unsubstituted straight or branched chain alkyl groups having from
1 to 8 carbon atoms, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted aryl groups, substituted
and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl
groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted
and unsubstituted heterocyclylalkoxy groups, substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted
—N(alkyl)2 groups, or substituted and unsubstituted —N(H)(heterocyclylalkyl) groups;
R4 is selected from the group consisting of —H and substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms;
R5 and R8 are independently selected from —H, —F, —OH, or saturated heterocyclyl groups; or R5 is absent if A is nitrogen; or R8 is absent if D is nitrogen;
R6 and R7 are independently selected from —H, —F, —Cl, —Br, —I, —CN, substituted and unsubstituted straight and branched chain alkyl
groups having from 1 to 8 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl
groups, substituted and unsubstituted —S(═O)2—N(H)(alkyl) groups, substituted and unsubstituted —S(═O)2—N(alkyl)2 groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted
and unsubstituted heterocyclylalkoxy groups, substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted
—N(alkyl)2 groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups,
substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl)
groups, substituted and unsubstituted —C(═O)—heterocyclyl groups, substituted and unsubstituted —C(═O)—N(H)(alkyl) groups,
substituted and unsubstituted —C(═O)—N(alkyl)2 groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclyl) groups, or substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclyl)
groups;
R9 is selected from the group consisting of —H, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms,
substituted and unsubstituted alkenyl groups having from 1 to 12 carbons, substituted and unsubstituted aryl groups, substituted
and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl
groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, —NH2, and substituted and unsubstituted heterocyclylaminoalkyl; and
R10 is —H.
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