基本情報
- 標準SMILES
C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)/C=C/[C@H](C)C(C)C)CC[C@@H]23)C[C@@H](O)C[C@@H]1O- InChIKey
HKXBNHCUPKIYDM-CGMHZMFXSA-N- 分子式
- C28H44O2
- 平均分子量
- 412.6 g/mol
- 単同位体質量
- 412.33413065
概要
Doxercalciferol is a hydroxy seco-steroid and synthetic vitamin D2 analogue that undergoes metabolic activation in vivo to form 1alpha,25-dihydroxyvitamin D2 (1alpha,25-(OH)2D2), a naturally occurring, biologically active form of vitamin D2. It is used to treat secondary hyperparathyroidism, a condition in which the body produces excess parathyroid hormone (PTH; a natural substance needed to control the amount of calcium in the blood) in certain people with chronic kidney disease. It has a role as a provitamin, a bone density conservation agent and a prohormone. It is a vitamin D and a hydroxy seco-steroid.
名称と識別子
- 優先名称
- Doxercalciferol
- IUPAC
- trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
- 現地名
- ドキセルカルシフェロール
- 英語名
- Doxercalciferol
- 分子式
- C28H44O2
- 分子量
- 412.65
名称と別名
名称をさらに表示
データベース識別子
- CAS
54573-75-0- PubChem CID
- 5281107
- DTXSID
DTXSID1034214- ChEMBL
CHEMBL1200810- ChEBI
CHEBI:4712- UNII
- 3DIZ9LF5Y9
- EC Number
- 643-005-9
- Nikkaji
- J527.612H
物性
構造計算による物性
- XLogP
- 6.3
- 極性表面積
- 40.5 Ų
- 水素結合供与体数
- 2
- 水素結合受容体数
- 2
- 回転可能結合数
- 5
- 重原子数
- 30
- 形式電荷
- 0
- 複雑度
- 712
実験および物理化学的性質
Human Drugs
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
物理化学的性質
- 融点
- 138 · 138-140°C
- 沸点
- 538.7 · 538.7±50.0 °C(Predicted)
- 比重(密度)
- 1.01 · 1.01±0.1 g/cm3(Predicted)
- 貯蔵温度
- -20 °C · Sealed in dry,Store in freezer, under -20°C
- 溶解性
- 10 mg/mL · DMSO:>10mg/mL
- 外見
- 白色結晶性固体
- 酸解離定数(Pka)
- 14.43 · 14.43±0.40(Predicted)
- 色
- White to Almost white
- InChIKey
- HKXBNHCUPKIYDM-CGMHZMFXSA-N
- SMILES
- [C@@H]1(O)C/C(=C/C=C2\CCC[C@@]3(C)[C@@]\2([H])CC[C@@H]3[C@H](C)/C=C/[C@H](C)C(C)C)/C(=C)[C@@H](O)C1
- CAS データベース
- 54573 · 54573-75-0(CAS DataBase Reference)
- EPAの化学物質情報
- Doxercalciferol (54573-75-0)
化学的性質
化学的特性Doxercalciferol is Crystalline Solid
安全と法規制
GHS分類
GHS Classification
Danger
H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]
P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 51 reports by companies from 2 notifications to the ECHA C&L Inventory.
危険有害性情報
毒性情報
Drug Induced Liver Injury
Drug Induced Liver Injury Rank (DILIrank 2.0)
Doxercalciferol
Ambiguous-DILI-concern
3
Adverse reactions
DOI:10.1016/j.drudis.2016.02.015
安全データ
- wgk
- 3
- rtecs
- VS2950000
- ridadr
- UN 2811 6.1 / PGIII
- 毒性
- LD50 orally in rats: 3.5-6.5 mg/kg (Sjden)
- hs_code
- 2936299055
- risk_code
- 28
- hazard_code
- T+
- safety_code
- 28-36/37-45
- Hazard Classifications
- Acute Tox. 1 Oral
- ストレージクラス
- 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials
化学と産業
薬理情報
ATC Code
H - Systemic hormonal preparations, excl. sex hormones and insulins
QH - Systemic hormonal preparations, excl. sex hormones and insulin
Mechanism of Action
Calcitriol (1α,25-(OH)2D3) and 1α,25-(OH)2D2 regulate blood calcium at levels required for essential body functions. Specifically, the biologically active vitamin D metabolites control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. They act directly on bone cells (osteoblasts) to stimulate skeletal growth, and on the parathyroid glands to suppress PTH (parathyroid hormone) synthesis and secretion. These functions are mediated by the interaction of these biologically active metabolites with specific receptor proteins in the various target tissues. In patients with chronic kidney disease (CKD), deficient production of biologically active vitamin D metabolites (due to lack of or insufficient 25-hydroxyvitamin D-1-alpha-hydroxylase activity) leads to secondary hyperparathyroidism, which contributes to the development of metabolic bone disease.
Metabolism/Metabolites
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.
FDA Pharmacological Classification
3DIZ9LF5Y9
DOXERCALCIFEROL
Chemical Structure [CS] - Ergocalciferols
Established Pharmacologic Class [EPC] - Vitamin D2 Analog
Doxercalciferol is a Vitamin D2 Analog.
DOXERCALCIFEROL
MeSH Pharmacological Classification
Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.
Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.
応用分野
説明Doxercalciferol is a synthetic vitamin D2 analog introduced in the US as Hectorol for the treatment of secondary hyperparathyroidism (SHPT) in patients with end-stage renal failure. It is actually 1-alpha-hydroxyvitamin D2 (one-alpha- D2) and can be synthesized by direct hydroxylation of vitamin D2 tosylate or in 5 steps from ergosterol. Doxercalciferol itself is inactive until metabolized by the liver into active 1,24-dihydroxyvitamin D2, showing a pharmacokinetic profile similar to calcitriol. During placebo-controlled clinical trials, patients with moderate to severe SHPT were treated with 1-alpha-D2 (10 μg doses) for 16 to 24 weeks; in 9 patients out of 10, blood levels of parathyroid hormone were considerably reduced, so maintaining a good control of the parathyroid hyperplasia. Moreover, only a moderate tendency to raise calcium and phosphate was observed. Doxercalciferol is orally-active and less toxic than other vitamin D analogs like alfacalcidol; it shows differentially controlled effects and has an improved safety profile compared to calcitriol.
使用Synthetic vitamin D prohormone. A new active Vitamin D analog which inhibits growth of human neuroblastoma. Antihyperparathyroid
上流・下流製品情報
上流原料
サプライヤー50 社
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