Claims for Patent: 9,526,737

Summary for Patent: 9,526,737

Title:	Oxysterols for activation of hedgehog signaling, osteoinduction, antiadipogenesis, and Wnt signaling
Abstract:	Synthetic oxysterols can be made and can be used for the treatment of bone disorders, obesity, cardiovascular disorders, and neurological disorders.
Inventor(s):	Parhami; Farhad (Los Angeles, CA), Jung; Michael E. (Los Angeles, CA), Nguyen; Khanhlinh (Los Angeles, CA), Yoo; Dongwon (Los Angeles, CA), Kim; Woo-Kyun (Los Angeles, CA)
Assignee:	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA (Oakland, CA)
Application Number:	12/745,888
Patent Claims:	1. A compound having Formula I, ##STR00032## wherein q is a single bond or a double bond, wherein t is a single bond, wherein at least one of q and t is a single bond, wherein M is selected from the group consisting of hydrogen (--H), hydroxy (--OH), formoxy (--O(C.dbd.O)H), acyloxy (--O(C.dbd.O)--C.sub.1-6alkyl), alkoxy (--O--C.sub.1-6alkyl), sulfhydryl (--SH), alkylthio (--S--C.sub.1-6alkyl), amino (--NH.sub.2), methylamino (--NHCH.sub.3), alkylamino (--NH--C.sub.1-6alkyl), formamido (--NH(C.dbd.O)H), acetamido (--NH(C.dbd.O)CH.sub.3), and alkylamido (--NH(C.dbd.O)--C.sub.1-6alkyl), wherein E is C.sub.1-6 alkyl, wherein R.sub.2is selected from the group consisting of C.sub.2-6 alkyl, C.sub.2-6 alkenys, C.sub.8-12 phenalkyl, thiophene-substituted C.sub.5-11 alkyl, C.sub.5-12 aralkenyl, C.sub.5-12 aralkynyl, halogen-substituted C.sub.4-12 aralkyl, halogen-substituted C.sub.5-12 aralkenyl halogen-substituted C.sub.5-12 aralkynyl, alkyl-substituted C.sub.5-18 aralkyl alkyl-substituted C.sub.6-18 aralkenyl, alkyl-substituted C.sub.6-18 aralkynyl, hydroxy-substituted C.sub.6 alkyl, and hydroxy-substituted C.sub.2-6 alkenyl, wherein when q is a single bond, M is hydroxy, and E is methyl, then R.sub.2 is not 4-methylpentyl vinyl, 1-hydroxzy-4-methylpentyl, 3-hydroxy-3-methylbutyl, 4-hydroxy-4methylpentyl 1,4-dihydroxy-4-methylpentyl, 1,5-dihydroxy-4-methylpentyl, or 2-phenylethenyl, wherein when q is a single bond, M is hydroxy, and E is methyl, then R.sub.2 is not 4-methylpentyl or 4-methyl-pent-3-enyl, wherein when q is a double bond, M is hydrogen, and E is methyl, then R.sub.2 is not ethyl, vinyl, n-propyl, allyl, 1-propenyl, n-butyl, t-butyl, 1-methylpropyl, n-pentyl, 3-methylbutyl, 3-methylpentyl, 4-methylpentyl, 4-methylpent-3-enyl, 4-methylpent-4-enyl, 1-hydroxy-4-methylpentyl, 4-hydroxy-4-methylpentyl, 4-hydroxy-4-methylpent-1-enyl, 4-hydroxy-4-methylpent-2-enyl, 1,4-dihydroxy-4-methylpentyl, 1-(2-pyridinyl)ethyl, or 3 -methyl-4-hydroxybutyl, wherein when q is a double bond, M is hydrogen, and E is 4-methylpentyl, then R.sub.2 is not hydroxymethyl, wherein when q is a double bond and M is hydrogen, then R.sub.2 is not methyl-substituted benzyl, wherein the compound is not ##STR00033## and wherein the compound is inductive of a biological response in a mammalian cell, the response selected from the group consisting of stimulated osteoblastic differentiation, inhibited adipocyte differentiation, stimulated cartilage formation, stimulated hair growth, and/or stimulated angiogenesis. 2. The compound of claim 1, wherein the compound is selected from the group consisting of ##STR00034## ##STR00035## ##STR00036## ##STR00037## 3. A bioactive composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. 4. The bioactive composition of claim 3, further comprising at least one additional agent, selected from the group consisting of parathyroid hormone, sodium fluoride, insulin-like growth factor I (ILGF-I), insulin-like growth factor II (ILGF-II), transforming growth factor beta (TGF-.beta.), a cytochrome P450 inhibitor, an osteogenic prostanoid, bone morphogenetic protein 2 (BMP 2), bone morphogenetic protein 4 (BMP 4), bone morphogenetic protein 7 (BMP 7), and bone morphogenetic protein 14 (BMP 14). 5. The compound of claim 1, wherein q is a single bond. 6. The compound of claim 5, wherein E is --CH.sub.3. 7. The compound of claim 6, wherein M is --OH or --O(C.dbd.O)CH.sub.3. 8. The compound of claim 7, wherein R.sub.2 is selected from the group consisting of C.sub.2-6 alkyl, C.sub.2-6 alkenyl, C.sub.8-12 phenalkyl, thiophene-substituted C.sub.5-11 alkyl, C.sub.5-12 aralkynyl, and hydroxy-substituted C.sub.6 alkyl. 9. The compound of claim 8, wherein the compound is ##STR00038## 10. The compound of claim 8, wherein the compound is ##STR00039## 11. The compound of claim 1, wherein q is a double bond. 12. The compound of claim 11, wherein E is --CH.sub.3. 13. The compound of claim 12, wherein M is hydrogen. 14. The compound of claim 13, wherein R.sub.2 is selected from the group consisting of C.sub.2-6 alkenyl, C.sub.8-12 phenalkyl, thiophene-substituted C.sub.5-11 alkyl, C.sub.5-12 aralkynyl, and halogen-substituted C.sub.4-12 aralkyl.

Details for Patent 9,526,737

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2027-12-03