Claims for Patent: 7,816,346

Summary for Patent: 7,816,346

Title:	Analogs of ansamycin and pharmaceutical compositions thereof
Abstract:	Analogs of geldanamycin (an ansamycin), pharmaceutical formulations comprising such analogs, and methods of use (e.g., treating tumors).
Inventor(s):	Tao; Chunlin (Los Angeles, CA), Han; Hongna (Los Angeles, CA), Sun; Xiaowen (Los Angeles, CA), Desai; Neil (Los Angeles, CA), Soon-Shiong; Patrick (Los Angeles, CA)
Assignee:	Abraxis BioScience, LLC (Los Angeles, CA)
Application Number:	11/940,644
Patent Claims:	1. A compound or pharmaceutically acceptable salt thereof having the formula (I) ##STR00116## wherein X is selected from the group consisting of --N(R.sub.8)(R.sub.9), --N(R.sub.8)--C(O)R.sub.10, --N(R.sub.8)--C(O)--OR.sub.10, --N(R.sub.8)--SO.sub.2R.sub.10, --N(R.sub.8)--C(O)--NR.sub.8R.sub.10, --N(R.sub.8)--C(S)OR.sub.10, --N(R.sub.8)--C(S)--OR.sub.10, and --N(R.sub.8)--C(S)--NR.sub.8R.sub.10; wherein R.sub.8 and R.sub.9 are independently selected from the group consisting of H, (C.sub.1-C.sub.20) alkyl, (C.sub.2-C.sub.20) alkenyl, (C.sub.2-C.sub.20) alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, cycloalkyl, and heterocyclic alkyl; R.sub.8 is selected from the group consisting of H, (C.sub.1-C.sub.6) alkyl, optionally substituted (C.sub.5-C.sub.8) aryl, and an optionally substituted (C.sub.5-C.sub.8) heteroaryl, or together with R.sub.9 forms a 4-7 membered heterocyclic ring; R.sub.10 is selected from the group consisting of hydrogen, (C.sub.1-C.sub.20) alkyl, (C.sub.2-C.sub.20) alkenyl, (C.sub.2-C.sub.20) alkynyl, optionally substituted (C.sub.6-C.sub.20) aryl, optionally substituted (C.sub.3-C.sub.20) heteroaryl, optionally substituted (C.sub.7-C.sub.20) arylalkyl, optionally substituted (C.sub.4-C.sub.20) heteroarylalkyl, (C.sub.3-C.sub.20) cycloalkyl, and a (C.sub.2-C.sub.20) alicyclic heterocyclyl; R represents, hydrogen, (C.sub.1-C.sub.6) alkyl or (C.sub.1-C.sub.6) alkenyl or (C.sub.6-C.sub.10) aryl or OCOR.sub.10; R.sub.1 and R.sub.2 are each a hydrogen or R.sub.1 and R.sub.2 together form a single bond; R.sub.3, R.sub.4, Y.sub.1, Y.sub.2, Y.sub.3 are independently selected from the group consisting H, halo, --OH, O-alkyl, O-acetyl, --O-aryl, OC(O)R.sub.10, --SO.sub.2--R.sub.10, and --NHR.sub.10, or together form oxo (.dbd.O), or hydroxylamino alkoxyimine or aryloxyimine, thioketo; or R.sub.3 and R.sub.4 or Y.sub.1 and Y.sub.2 form a heterocyclic group selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, thiazolidinyl, oxazolidinyl, morpholino, piperazinyl, 4-(C.sub.1-C.sub.4) alkylpiperidinyl and N--(C.sub.1-C.sub.4) piperazinyl; and said groups may be substituted with one or more groups selected from the group consisting of (C.sub.1-C.sub.8) alkyl, halo, nitro, amino, azido and (C.sub.1-C.sub.8) alkoxyl; R.sub.5 is selected from the group consisting of a (C.sub.1-C.sub.20) alkyl, (C.sub.2-C.sub.20) alkenyl, (C.sub.2-C.sub.20) alkynyl, optionally substituted (C.sub.6-C.sub.20) aryl, optionally substituted (C.sub.3-C.sub.20) heteroaryl, optionally substituted (C.sub.7-C.sub.20) arylalkyl, optionally substituted (C.sub.4-C.sub.20) heteroarylalkyl, (C.sub.3-C.sub.20) cycloalkyl, (C.sub.2-C.sub.20) alicyclic heterocyclyl, N(R.sub.8)(R.sub.9); --OR.sub.10, --SR.sub.10, --N(R.sub.8)--C(O)R.sub.10, --N(R.sub.8)--C(O)--OR.sub.10, --N(R.sub.8)--C(O)--NR.sub.8R.sub.10, --N(R.sub.8)--C(S)OR.sub.10, --N(R.sub.8)--C(S)--OR.sub.10, and --N(R.sub.8)--C(S)--NR.sub.8R.sub.10, R.sub.6 is selected from the group consisting of, hydrogen, hallo, a (C.sub.1-C.sub.10) alkyl, (C.sub.1-C.sub.10) alkenyl, or an optionally substituted or unsubstituted (C.sub.6-C.sub.10) aryl; and R.sub.7 is selected from the group consisted of hydrogen, a (C.sub.1-C.sub.10) alkyl, optionally substituted (C.sub.5-C.sub.10) aryl and (C.sub.1-C.sub.10) acyl. 2. The compound of claim 1 wherein, X is selected from N(R.sub.8)(R.sub.9), --N(R.sub.8)--C(O)R.sub.10, --N(R.sub.8)--C(O)--OR.sub.10, --N(R.sub.8)--C(O)--NR.sub.8R.sub.10, --N(R.sub.8)--SO.sub.2R.sub.10, --N(R.sub.8)--C(S)--OR.sub.10, and --N(R.sub.8)--C(S)--NR.sub.8R.sub.10. 3. The compound of claim 1 wherein the compound is: ##STR00117## 4. The compound of claim 3, wherein X is selected from the group consisting of --N(R.sub.8)--C(O)R.sub.10, N(R.sub.8)--C(O)--OR.sub.10, --N(R.sub.8)--SO.sub.2R.sub.10, --N(R.sub.8)--C(O)--NR.sub.8R.sub.10, --N(R.sub.8)--C(S)OR.sub.10, --N(R.sub.8)--C(S)OR.sub.10, --N(R.sub.8)--C(S)--NR.sub.8R.sub.10, and --N(R.sub.8)(R.sub.9). 5. The compound of claim 4, wherein R.sub.8 is hydrogen. 6. The compound of claim 4, wherein R.sub.8 is methyl. 7. The compound of claim 4, wherein R.sub.10 is (C.sub.6-C.sub.10) aryl. 8. The compound of claim 5, wherein R.sub.10 is (C.sub.6-C.sub.10) aryl. 9. The compound of claim 6, wherein R.sub.10 is (C.sub.6-C.sub.10) aryl. 10. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. 11. The pharmaceutical composition of claim 1, wherein the composition is suitable for delivery via routes of administration selected from the group consisting of oral, parenteral, intravenous, and combinations thereof. 12. The pharmaceutical composition of claim 11, wherein said composition is suitable for oral delivery and further comprises one or more ingredients selected from the group consisting of a diluent, an edible carrier, a binder, an excipient, a disintegrating agent, a lubricant, a glidant, and a sweetening agent. 13. The pharmaceutical composition of claim 11 wherein said composition is suitable for parenteral delivery and comprises one or more ingredients selected from the group consisting of a sterile diluent, antimicrobial agents, antioxidants, buffers, tonicity adjusting agents.

Details for Patent 7,816,346

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2026-11-15