Therapeutic potential of the 2-alkyl and 2-alkylidene-19-nor-(20 S)-modified analogs of 1α,25-dihydroxyvitamin D 3

Abstract

Five analogs of 19-nor-1α,25-dihydroxyvitamin D 3 are described that show highly selective and potent activities. The 2-methylene-19-nor-(20 S)-1α25-dihydroxyvitamin D 3 (2MD) and its 2α-methyl sister are selectively active on the osteoblast. 2MD is bone anabolic and causes bone formation in vivo and in vitro and is being developed as a therapy for bone loss diseases such as osteoporosis. 2-Methylene-19-nor (20 S)-bishomo-1α-hydroxypregnacalciferol (2BMP) has no activity on calcium in vivo while totally suppressing circulating parathyroid hormone. Its homologs, i.e. 2-methylene-19-nor-1α-hydroxy-homopregnacalciferol (2MP) and 2-methylene-19-nor-1α-hydroxypregnacalciferol (2MPC) act similarly but are either less selective (2MP) or not as potent (2MPC). These abbreviated side chain analogs will be developed for diseases where a rise in serum calcium is not desired, as for example, cancer, renal osteodystrophy, psoriasis and autoimmune diseases.