Doxercalciferol is absorbed from the gastrointestinal tract and activated by CYP 27 in the liver to form 1α,25-(OH)2D2 (major metabolite) and 1α,24-dihydroxyvitamin D2 (minor metabolite). Activation of doxercalciferol does not require the involvement of the kidneys.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
3-Desoxy-2-Methylene-Vitamin D Analogs and Their Uses
申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION
公开号：US20130102567A1
公开（公告）日：2013-04-25
This invention discloses 3-desoxy-2-methylene-vitamin D analogs, and specifically (20S)-3-desoxy-1α,25-dihydroxy-2-methylene-vitamin D
3
and (20R)-3-desoxy-1α, 25-dihydroxy-2-methylene-vitamin D
3
as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to monocytes thus evidencing use as anti-cancer agents especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also exhibit relatively high calcemic activity evidencing use in the treatment of bone diseases.
This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-25-hydroxy-2-methylene-vitamin D
3
and (20R)-25-hydroxy-2-methylene-vitamin D
3
, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.
[EN] VITAMIN D ANALOGUES, COMPOSITIONS COMPRISING SAID ANALOGUES AND THEIR USE<br/>[FR] ANALOGUES DE LA VITAMINE D, COMPOSITIONS COMPRENANT LESDITS ANALOGUES ET LEUR UTILISATION
申请人：LEO PHARMA AS
公开号：WO2004037781A1
公开（公告）日：2004-05-06
Compounds according to formula I: in which formula R1 and R2, which may be the same or different, represent halogen, (C1-C6) hydrocarbyl, optionally substituted with one or two hydroxyl group on one or more fluorine atoms, or, together with the carbon atom to which they are both attached, R1 and R2 form a (C3-C6)carbocyclic ring, or one of R1 and R2 taken together with R3 forms a direct bond, such that a triple bond is constituted, or R1 and R2 represent both hydrogen; R3 when not forming a direct bond with one of R1 and R2 represents hydrogen or (C1-C3)hydrocarbyl; X represents (E)-ethylene, (Z)-ethylene, ethynylene, or a bond; Y and Z independently represent hydrogen or methyl; the bond between C#16 and C#17 is depicted with a dotted line to illustrate that said bond may be either a single bond, in which case the projection of the ring substituents is beta, or a double bond; A represents hydroxyl, fluorine or hydrogen; B represents CH2 or H2; the configuration is the 3-position corresponds to the same configuration as in natural vitamine D3 (normal), or the configuration in the configuration in the 3-position is opposite to that of natural vitamin D3(epi); with the proviso that when X represents (E)-ethylene or (Z)-ethylene, one of R1 and R2 taken together with R3 may not form a direct bond, such that a triple bond is constituted; with the further proviso that when X represents a bond R1 ands R2 are nor hydrogen; with the further proviso that the compound of formula I is not 3(S)-hyroxy-9, 10-secocholesta-5(Z),7(E),10(19),22(E),24-penta-ene; and prodrugs and stereo isomeric forms thereof are provided together with their use in therapy, and their use in the manufacture of medicaments.
Disclosed are (22E)-2-methylene-22-dehydro-1,24,25-trihydroxy-19-nor-vitamin D
3
compounds, their biological activities, and various pharmaceutical uses for these compounds. Particularly disclosed are (22E)-(24R)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D
3
and (22E)-(24S)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D
3
, their biological activities, and various pharmaceutical uses for these compounds.
2-Methylene-(22E)-25-Hexanoyl-24-OXO-26,27-Cyclo-22-Dehydro-19-Nor-Vitamin D Analogs
申请人：DeLuca Hector F.
公开号：US20130005686A1
公开（公告）日：2013-01-03
This invention discloses 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-vitamin D analogs, and specifically 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α-hydroxyvitamin D
3
, and pharmaceutical uses therefor. This compound exhibits relatively high transcription activity as well as pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also shows low activity in vivo on bone calcium mobilization, and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.
