Claims for Patent: 8,389,570

Summary for Patent: 8,389,570

Title:	Hydroxamates as therapeutic agents
Abstract:	The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.
Inventor(s):	Verner; Erik J. (Belmont, CA), Sendzik; Martin (San Mateo, CA), Baskaran; Chitra (Foster City, CA), Buggy; Joseph J. (Mountain View, CA), Robinson; James (Sacramento, CA)
Assignee:	Pharmacyclics, Inc. (Sunnyvale, CA)
Application Number:	13/209,147
Patent Claims:	1. A method for treating lung cancer, colon cancer, skin cancer, breast cancer, ovarian cancer, prostate cancer, liver cancer, brain cancer, stomach cancer, pancreatic cancer, neuroblastoma, T-cell lymphoma, or leukemia in a human comprising administering to the human a therapeutically effective amount of a compound having the structure of Formula (I): ##STR00026## wherein: R.sup.1 is hydrogen or alkyl; X is --O--, --NR.sup.2--, or --S(O).sub.n where n is 0-2 and R.sup.2 is hydrogen or alkyl; Y is alkylene optionally substituted with cycloalkyl, optionally substituted phenyl, alkylthio, alkylsulfinyl, alkysulfonyl, optionally substituted phenylalkylthio, optionally substituted phenylalkylsulfonyl, hydroxyl, or optionally substituted phenoxy; Ar.sup.1 is phenylene or heteroarylene wherein said Ar.sup.1 is optionally substituted with one or two groups independently selected from alkyl, halo, hydroxyl, alkoxy, haloalkoxy, or haloalkyl; R.sup.3 is hydrogen, alkyl, hydroxyalkyl, or optionally substituted phenyl; and Ar.sup.2 is aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heteroaralkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, or heterocycloalkylalkyl; wherein aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heteroaralkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, and heterocycloalkylalkyl are each optionally substituted with one or two substituents independently selected from alkyl, halo, haloalkyl, alkoxy, alkoxyalkyl, hydroxyalkoxy, hydroxyalkoxyalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, aminoalkyl, aminoalkoxy, haloalkoxy, haloalkoxyalkyl, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted phenylalkyloxy, optionally substituted phenylalkyl, optionally substituted phenyloxyalkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyloxy, optionally substituted heteroaryloxyalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heterocycloalkyloxy, optionally substituted heterocycloalkylalkyloxy, -alkylene-S(O).sub.nR.sup.1 (where n is 0 to 2 and R.sup.a is hydroxyalkyl or optionally substituted phenyl), -alkylene-NR.sup.e-alkyleneCONR.sup.cR.sup.d (where R.sup.c is hydroxyl and R.sup.d and R.sup.e are independently hydrogen or alkyl), or carboxyalkylaminoalkyl; or a pharmaceutically acceptable salt thereof. 2. The method of claim 1 wherein R.sup.1 is hydrogen. 3. The method of claim 1 wherein Ar.sup.1 is phenylene. 4. The method of claim 1 wherein X is --O--. 5. The method of claim 1 wherein Y is alkylene. 6. The method of claim 5 wherein alkylene is --CH.sub.2CH.sub.2--. 7. The method of claim 1 wherein R.sup.3 is hydrogen. 8. The method of claim 1 wherein Ar.sup.2 is monosubstituted. 9. The method of claim 8 wherein Ar.sup.2 is substituted with aminoalkyl. 10. The method of claim 1 wherein the leukemia is myelogenous leukemia (MML) or acute myelogenous leukemia (AML). 11. The method of claim 1 wherein the compound is in a pharmaceutical composition. 12. The method of claim 11 wherein the pharmaceutical composition is administered in combination with one or more compound(s) independently selected from an estrogen receptor modulator, an androgen receptor modulator, retinoid receptor modulator, a cytotoxic agent, another antiproliferative agent, a prenyl-protein transferase inhibitor, an HMG-CoA reductase inhibitor, an HIV protease inhibitor, a reverse transcriptase inhibitor, DNA methyltransferase inhibitor, an angiogenesis inhibitor, or an antineoplastic agent. 13. The method of claim 1 further comprising radiation therapy. 14. The method of claim 11 further comprising radiation therapy. 15. The method of claim 12 wherein the one or more compound(s) are independently selected from doxorubicin, caminomycin, daunorubicin, aminopterin, methotrexate, methopeterin, dichloro-methotrexate, mitomycin C, porfiromycin, Trastuzumab, Rituximab, 5-fluorouracil, 6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin, cochicines, etoposide, etoposide phosphate, teniposide, melphalan, vinblastine, vincristine, leurosidine, vindesine, leurosine, paclitaxel, estramustine, cisplatin, carboplatin, cycloophosphamide, belomycin, tamoxifen, ifosamide, melphalan, hexamethyl melamine, thiotepa, cytarabin, idatrexate, trimetrexate, dacarbazine, L-asparaginase, camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide, leuprolide, pyridobenzoindole derivatives, interferons and interleukins.

Details for Patent 8,389,570

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2023-04-07
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2023-04-07
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Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2023-04-07