Indole derivatives as inhibitors of histone deacetylase

1. A method of alleviating, abating or ameliorating T-cell lymphoma or leukemia in a subject in need thereof, comprising administering to the subject a pharmaceutical composition containing a therapeutically effective amount of a 1,3-disubstituted-1H-indole-6-carboxylic acid hydroxyamide compound,

wherein the substituent at the 1-position is —X 2 —R 2 and the substituent at the 3-position is R 3 ,

wherein:

X 2 is a substituted or unsubstituted group selected from among C 2 -C 6 alkylene, C 1 -C 6 heteroalkylene; —C(═O)—, and —C(═O)—C 1 -C 6 alkylene;

R 2 is a substituted or unsubstituted group selected from among aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;

where if R 2 is substituted, then each substituent on R 2 is selected from among hydrogen, halogen, —CN, —NO 2 , —S(═O) 2 NH 2 , —CO 2 H, —CO 2 R 10 , —C(═O)R 11 , —S—R 11 , —S(═O)—R 11 —S(═O) 2 —R 11 , —NR 10 C(═O)—R 11 , —C(═O)N(R 10 ) 2 , —S(═O) 2 N(R 10 ) 2 , OC(═O)N(R 10 ) 2 , NR 10 C(═O)O—R 11 , —OC(═O)O—R 11 , —NHC(═O)NH—R 11 , —OC(═O)—R 11 , —N(R 10 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 10 is hydrogen, or a substituted or unsubstituted group selected from among C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 3 -C 8 cycloalkyl, C 2 -C 8 heterocycloalkyl, aryl, or heteroaryl;

R 11 is a substituted or unsubstituted group selected from among C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 2 -C 8 heterocycloalkyl, aryl, or heteroaryl;

R 3 is hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 6 alkenyl, substituted or unsubstituted C 2 -C 6 alkynyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted phenyl, or —X 6 —R 6 ;

X 6 is a C 1 -C 6 alkylene, C 1 -C 6 fluoroalkylene, C 2 -C 6 alkenylene, C 2 -C 6 heteroalkylene;

R 6 is hydrogen, halogen, —CN, hydroxy, amino, C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl)amino, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkyl, C 2 -C 8 heterocycloalkyl, phenyl, heteroaryl, or —X 7 —R 7

X 7 is a bond, —O—, —S—, —S(═O)—, —S(═O) 2 —, —NR a —, —C(═O)—, —C(═O)O—, —OC(═O)—, —NHC(═O)—, —C(═O)NR a —, —S(═O) 2 NR a —, —NHS(═O) 2 —, —OC(═O)NR a —, —NHC(═O)O—, —OC(═O)O—, or —NHC(═O)NR a —;

R 7 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl, C 2 -C 8 heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,

R a is selected from among hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 fluoroalkoxy, C 1 -C 6 heteroalkyl; or

R a and R 7 together with the N atom to which they are attached form a 5-, 6-, or 7-membered heterocycloalkyl;

or a pharmaceutically acceptable salt, pharmaceutically acceptable N-oxide, or pharmaceutically acceptable prodrug thereof.

2. The method of claim 1 , further comprising administering to the subject a second therapeutic agent, selected from among abarelix (Plenaxis®); aldesleukin (Prokine®); Aldesleukin (Proleukin®); Alemtuzumab (Campath®); alitretinoin (Panretin®); allopurinol (Zyloprim®); altretamine (Hexalen®); amifostine (Ethyol®); anastrozole (Arimidex®); arsenic trioxide (Trisenox®); asparaginase (Elspar®); azacitidine (Vidaza®); bevacizumab (Avastin®); bexarotene (Targretin®); bleomycin (Blenoxane®); bortezomib (Velcade®); busulfan (Busulfex®); busulfan (Myleran®); calusterone (Methosarb®); capecitabine (Xeloda®); carboplatin Paraplatin®); carmustine (BCNU, BiCNU); carmustine (Gliadel®); celecoxib (Celebrex®); cetuximab (Erbitux®); chlorambucil (Leukeran®); cisplatin (Platinol®); cladribine (Leustatin®); clofarabine (Clolar®); cyclophosphamide (Cytoxan®); cytarabine (Cytosar-U®); cytarabine liposomal (DepoCyt); dacarbazine (DTIC-Dome); dactinomycin (actinomycin D, Cosmegen®); Darbepoetin alfa (Aranesp®); dasatinib (Sprycel®); daunorubicin liposomal (DanuoXome); daunorubicin (daunomycin, Daunorubicin®); daunorubicin (daunomycin, Cerubidine®); decitabine (Dacogen®); denileukin (Ontak®); dexrazoxane (Zinecard®); docetaxel (Taxotere®); doxorubicin (Adriamycin®); doxorubicin liposomnal (Doxil®); dromostanolone propionate; epirubicin (Ellence®); Epirubicin; Epoetin alfa (EPOGEN®); erlotinib (Tarceva®); estramustine (Emcyt®); etoposide phosphate (Etopophos®); etoposide (VP-16; Vepesid®); exemestane (AROMASIN®); Filgrastim (Neupogen®); floxuridine (FUDR); fludarabine (Fludara®); fluorouracil (5-FU, Adrucil®); fulvestrant (Faslodex®), gefitinib (Iressa™); gemcitabine (Gemzar®); gemtuzumab ozogamicin (Mylotarg®); goserelin acetate (Zoladex®); histrelin acetate (Histrelin®); hydroxyurea (Hydrea®); Ibritumomab Tiuxetan (Zevalin®); idarubicin (Idamycin®); ifosfamide (IFEX®); imatinib mesylate (Gleevec®); interferon alfa 2a (Roferon A®); Interferon alfa-2b (Intron A®); irinotecan (Camptosar®); lenalidomide (Revlimid®); letrozole (Femara®); leucovorin (Leucovorin®); Leuprolide Acetate (Eligard®); levamisole (Ergamisol®); lomustine, CCNU CeeBU®); meclorethamine (nitrogen mustard, Mustargen®); megestrol acetate (Megace®); melphalan (Alkeran®); mercaptopurine (6-MP, Purinethol®); methotrexate (Rheumatrex®, Trexall®); methoxsalen (Uvadex®); mitomycin C (Mutamycin®); mitomycin C (Mitozytrex®); mitotane (Lysodren®); mitoxantrone (Novantrone®); nandrolone phenpropionate (Durabolin-50); nelarabine (Arranon®); Nofetumomab (Verluma®); Oprelvekin (Neumega®); oxaliplatin (Eloxatin®); paclitaxel (Paxene®); paclitaxel (Taxol®); paclitaxel protein-bound particles (Abraxane®); palifermin (Kepivance®); pamidronate (Aredia®); panitumumab (Vectibix®); pegademase (Adagen®); pegaspargase (Oncaspar®); Pegfilgrastim (Neulasta®); pemetrexed disodium (Alimta®); pentostatin (Nipent®); pipobroman (Vercyte®); plicamycin, mithramycin (Mithracin®); porfimer sodium (Photofrin®); procarbazine (Matulane®); quinacrine (Atabrine®); Rasburicase (Elitek®); rituximab (Rituxan®); sargramostim (Leukine®); Sargramostim (Prokine®); sorafenib (Nexavar®); streptozocin (Zanosar®); sunitinib maleate (Sutent®); tamoxifen (Nolvadex®); temozolomide (Terodar™); teniposide (VM-26, Vumon®); testolactone (Teslac®); thalidomide (Thalomid®); thioguanine (6-TG, Thioguanine®); thiotepa (Thioplex®); topotecan (Hycamtin®); toremifene (Fareston®); tositumomab (Bexxar®); tositumomab/I-131 tositumomab (Bexxar®); trastuzumab (Herceptin®); tretinoin (ATRA, Vesanoid®); Uracil Mustard; valrubicin (Valstar®); vinblastine (Velban®); vincristine (Oncovin®): vinorelbine (Navelbine®); vorinostat (Zolinza®); zoledronate (Zometa®); or zoledronic acid (Zometa®).