DNA alkylating agents

A method of treating cancer expressing AKR1C3 reductase, comprising:

• administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or a composition comprising the compound and at least a pharmaceutically acceptable excipient or carrier thereby treating the cancer
• or a pharmaceutically acceptable salt, or a solvate of each thereof, wherein
• X10 is O, S, SO, or SO2;
• A is C6-C10 aryl, 5-15 membered heteroaryl, or —N═CR1R2;
• each R1 and R2 independently is hydrogen, —CN, C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4-15 membered heterocycle, 5-15 membered heteroaryl, ether, —CONR13R14, or —NR13COR14;
• each X and Z independently is hydrogen or C1-C6 alkyl;
• Y is hydrogen, halo, or C1-C6 alkyl;
• R is hydrogen or C1-C6 alkyl;
• each R13 and R14 independently is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4-15 membered heterocycle, 5-15 membered heteroaryl, or ether;
• T is OP(Z1)(NHCH2CH2Cl)2, OP(Z1)(NHCH2CH2Br)2, OP(Z1)(NH2)(N(CH2CH2X1)2), OP(Z1)(N(CH2)2)2, or OP(Z1)(N(CH2CH2Cl)2)2, wherein Z1 is O or S, and X1 is Cl, Br, or OMs;
• and
• wherein the alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, ether groups are optionally substituted, and wherein the cancer is selected from the group consisting of a cancer of the adrenal gland, bone, brain, breast, bronchi, colon and/or rectum, gallbladder, head and neck, kidneys, larynx, liver, lung, neural tissue, pancreas, prostate, parathyroid, skin, stomach, and thyroid;
• and acute and chronic lymphocytic and granulocytic tumors, adenocarcinoma, adenoma, basal cell carcinoma, cervical dysplasia and in situ carcinoma, Ewing's sarcoma, epidermoid carcinomas, giant cell tumor, glioblastoma multiforma, hairy-cell tumor, intestinal ganglioneuroma, hyperplastic corneal nerve tumor, islet cell carcinoma, Kaposi's sarcoma, leiomyoma, leukemias, lymphomas, malignant carcinoid, malignant melanomas, malignant hypercalcemia, marfanoid habitus tumor, medullary carcinoma, metastatic skin carcinoma, mucosal neuroma, myeloma, mycosis fungoides, neuroblastoma, osteo sarcoma, osteogenic and other sarcoma, ovarian tumor, pheochromocytoma, polycythermia vera, primary brain tumor, small-cell lung tumor, squamous cell carcinoma of both ulcerating and papillary type, hyperplasia, seminoma, soft tissue sarcoma, retinoblastoma, rhabdomyo sarcoma, renal cell tumor, topical skin lesion, veticulum cell sarcoma, and Wilm's tumor.