Claims for Patent: 8,637,560

Summary for Patent: 8,637,560

Title:	Imidazolidinone compounds, methods to inhibit deubiquitination and methods of treatment
Abstract:	The present invention features imidazolidinone compounds and pharmaceutical compositions of imidazolidinone compounds. The compounds of the invention are utilized in methods of treating a deubiquitination-related disorder in a subject and inhibiting p97-associated deubiquitination.
Inventor(s):	Trenkle; William (Bethesda, MD), Wiestner; Adrian (Bethesda, MD), Wang; Qiuyan (Bethesda, MD), Ye; Yihong (Germantown, MD), Mora-Jensen; Helena (Copenhagen, DK)
Assignee:	The United States of America as Represented by the Secretary of the Department of Health and Human Services (Washington, DC) N/A (N/A)
Application Number:	12/669,361
Patent Claims:	1. A method of inhibiting p97 associated deubiquitination and/or inducing ER stress in a subject in need thereof, comprising administering to said subject, an effective amount of a compound of the following Formula (II), or pharmaceutically acceptable salt, solvate or hydrate thereof: ##STR00038## wherein Q is O, S, or NR.sub.A; R.sub.1 is selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl, optionally substituted alkoxy, optionally substituted cycloalkoxy, optionally substituted (cycloalkyl)alkoxy, and optionally substituted heterocycloalkyl; R.sub.2 is selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl, optionally substituted alkoxy, optionally substituted cycloalkoxy, optionally substituted (cycloalkyl)alkoxy, and optionally substituted heterocycloalkyl; Z is an optionally substituted aryl or an optionally substituted heteroaryl; and n is 0-3. 2. A method of claim 1, wherein the subject is suffering from leukemia, multiple myeloma or lymphoma. 3. The method of claim 2 additionally comprising administering a proteasome inhibitor to the subject. 4. The method of claim 3, wherein the proteasome inhibitor is BORTEZOMIB. 5. A method for treating for leukemia, lymphoma, or multiple myeloma in a subject, the method comprising administering to said subject an effective amount of a compound of formula II: ##STR00039## wherein Q is O, S, or NR.sub.A; R.sub.1 is selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl, optionally substituted alkoxy, optionally substituted cycloalkoxy, optionally substituted (cycloalkyl)alkoxy, and optionally substituted heterocycloalkyl; R.sub.2 is selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl, optionally substituted alkoxy, optionally substituted cycloalkoxy, optionally substituted (cycloalkyl)alkoxy, and optionally substituted heterocycloalkyl; wherein X is O, S, or NR.sub.B; Z is an optionally substituted aryl or an optionally substituted heteroaryl; and n is 0-3. 6. The method of claim 5, wherein the compound of formula II is: ##STR00040## 7. The method of claim 5, further comprising an additional therapeutic agent, wherein the additional therapeutic agent is an antineoplastic agent selected from wherein the additional therapeutic agent is an antineoplastic agent selected from an alkylating agent, a folate antagonist, a purine antagonist, a pyrimidine antagonist, a taxane, a topoisomerase, or a therapeutic antibody directed against CD20 or VEGF, or a combination of any of the foregoing. 8. A method of treating a treating a subject suffering from a retroviral infection, comprising administering a compound of the following Formula (II), or pharmaceutically acceptable salt, solvate or hydrate thereof to the subject: ##STR00041## wherein Q is O, S, or NR.sub.A; R.sub.1 is selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl, optionally substituted alkoxy, optionally substituted cycloalkoxy, optionally substituted (cycloalkyl)alkoxy, and optionally substituted heterocycloalkyl; R.sub.2 is selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl, optionally substituted alkoxy, optionally substituted cycloalkoxy, optionally substituted (cycloalkyl)alkoxy, and optionally substituted heterocycloalkyl; Z is an optionally substituted aryl or an optionally substituted heteroaryl; and n is 0-3. 9. The method of claim 2, wherein the subject is resistant to treatment with a proteasome inhibitor. 10. The method of claim 2, wherein the subject is resistant to treatment with BORTEZOMIB. 11. The method of claim 5, wherein the subject is resistant to treatment with a proteasome inhibitor. 12. The method of claim 5, wherein the subject is resistant to treatment with BORTEZOMIB. 13. The method of claim 5, further comprising administering an additional therapeutic agent to the subject, wherein the additional therapeutic agent is an antineoplastic agent selected from an alkylating agent, a folate antagonist, a purine antagonist, a pyrimidine antagonist, a taxane, a topoisomerase, or a therapeutic antibody directed against CD20 or VEGF, or a combination of any of the foregoing. 14. The method of claim 7, wherein the additional therapeutic agent is an anticancer compound, chosen from mechloroethamine, chlorambucil, cyclophosamide, melphalan, ifosfamide, methotrexate, 6-mercaptopurine, 5-fluorouracil, rituximab, bevacizumab, or a combination of any of the foregoing. 15. The method of claim 5, wherein the step of administering the compound comprises administering the compound orally, topically, parentally, intravenously or intramuscularly. 16. The method of claim 8, wherein the compound is ##STR00042## 17. The method of claim 5 additionally comprising administering a proteasome inhibitor to the subject. 18. The method of claim 17, wherein the proteasome inhibitor is BORTEZOMIB.

Details for Patent 8,637,560

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2027-06-18
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2027-06-18
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2027-06-18
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2027-06-18