基本情報
- CAS
112828-00-9- 標準SMILES
C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)/C=C/[C@@H](O)C4CC4)CC[C@@H]23)C[C@@H](O)C[C@@H]1O- InChIKey
LWQQLNNNIPYSNX-UROSTWAQSA-N- 分子式
- C27H40O3
- 平均分子量
- 412.6 g/mol
- 単同位体質量
- 412.29774514
概要
Calcipotriol is a seco-cholestane that is 26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene carrying additional hydroxy substituents at positions 1, 3 and 24. It is used (as its hydrate) in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. It has a role as an antipsoriatic and a drug allergen. It is a triol, a secondary alcohol, a seco-cholestane, a hydroxy seco-steroid and a member of cyclopropanes.
名称と識別子
- 優先名称
- Calcipotriol
- IUPAC
- trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5S)-5-cyclopropyl-5-hydroxypent-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
- カルシポトリオール
- 英語名
- Calcipotriene
- 分子式
- C27H40O3
- 分子量
- 412.6
名称と別名
名称をさらに表示
データベース識別子
- CAS
112828-00-9、112965-21-6- PubChem CID
- 5288783
- DTXSID
DTXSID0046648- ChEMBL
CHEMBL1200666- ChEBI
CHEBI:50749- UNII
- 143NQ3779B
- EC Number
- 601-218-4、686-849-3
- Nikkaji
- J367.434G
物性
構造計算による物性
- XLogP
- 4.3
- 極性表面積
- 60.7 Ų
- 水素結合供与体数
- 3
- 水素結合受容体数
- 3
- 回転可能結合数
- 5
- 重原子数
- 30
- 形式電荷
- 0
- 複雑度
- 743
実験および物理化学的性質
Human Drugs
Breast Feeding; Lactation; Milk, Human; Dermatologic Agents
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Dermatological medicines > Medicines affecting skin differentiation and proliferation
物理化学的性質
- 融点
- 166 · 166-168°C
- 沸点
- 582 · 582.0±50.0 °C(Predicted)
- 比重(密度)
- 1.12 · 1.12±0.1 g/cm3(Predicted)
- 貯蔵温度
- -20 °C · Desiccate at -20°C
- 溶解性
- 15 mg/mL、透明 · DMSO:可溶15mg/mL、透明
- 外見
- 粉
- 酸解離定数(Pka)
- 14.29 · 14.29±0.20(Predicted)
- 色
- White to off-white
- 安定性
- Light and Temperature Sensitive, Light And Temperature Sensitive
- InChIKey
- LWQQLNNNIPYSNX-HCHVWAPNSA-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](C2CC2)O)/C(=C)[C@@H](O)C1
- CAS データベース
- 112965 · 112965-21-6(CAS DataBase Reference)
化学的性質
化学的特性White Crystalline Solid
安全と法規制
GHS分類
GHS Classification
Danger
H300+H310 (16.7%): Fatal if swallowed or in contact with skin [Danger Acute toxicity, oral; acute toxicity, dermal]
P203, P260, P261, P262, P263, P264, P264+P265, P270, P271, P272, P280, P284, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P318, P319, P320, P321, P330, P332+P317, P333+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 6 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Danger
H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]
危険有害性情報
Hazard Classes and Categories
Acute Tox. 2 (83.3%)
Acute Tox. 3 (100%)
毒性情報
Exposure Routes
Clinical studies with radiolabeled ointment indicate that approximately 6% (+3%, SD) of the applied dose of calcipotriene is absorbed systemically when the ointment is applied topically to psoriasis plaques or 5% (+2.6%, SO) when applied to normal skin.
Toxicity Summary
The precise mechanism of calcipotriol in remitting psoriasis is not well-understood. However, it has been shown to have comparable affinity with calcitriol for the Vitamin D receptor, while being less than 1% as active as the calcitriol in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes.
安全データ
- wgk
- 3
- ridadr
- UN 2811 6.1 / PGIII
- 毒性
- dog,LD50,skin,> 1500ug/kg (1.5mg/kg),BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)MUSCULOSKELETAL: OTHER CHANGESGASTROINTESTINAL: NAUSEA OR VOMITING,Journal of Toxicological Sciences. Vol. 21(Suppl,
- hs_code
- 2906195000
- risk_code
- 36/37/38
- hazard_code
- Xi
- safety_code
- 26
- Hazard Classifications
- Acute Tox. 1 DermalAcute Tox. 2 OralEye Irrit. 2Repr. 2Skin Sens. 1BSTOT RE 1
- 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
D05AX52
D - Dermatologicals
QD - Dermatologicals
D05AX02
Mechanism of Action
The precise mechanism of calcipotriol in remitting psoriasis is not well-understood, however, it has been shown to have comparable affinity with calcitriol for the Vitamin D receptor while being less than 1% the activity in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis and are believed to undergo modulation of gene expression with binding of calcipotriol to the VDR. This modulation is thought to affect gene products related to cell differentiation and proliferation.
Metabolism/Metabolites
Hepatic. Calcipotriene metabolism following systemic uptake is rapid, and occurs via a similar pathway to the natural hormone. The primary metabolites are much less potent than the parent compound.
Hepatic. Calcipotriene metabolism following systemic uptake is rapid, and occurs via a similar pathway to the natural hormone. The primary metabolites are much less potent than the parent compound. Route of Elimination: The active form of the vitamin, 1,25-dihydroxy vitamin D3 (calcitriol), is known to be recycled via the liver and excreted in the bile. There is evidence that maternal 1,25-dihydroxy vitamin D3 (calcitriol) may enter the fetal circulation, but it is not known whether it is excreted in human milk.
FDA Pharmacological Classification
143NQ3779B
CALCIPOTRIENE
Chemical Structure [CS] - Vitamin D
Established Pharmacologic Class [EPC] - Vitamin D Analog
Calcipotriene is a Vitamin D Analog.
CALCIPOTRIENE
Absorption, Distribution and Excretion
Clinical studies with radiolabeled ointment indicate that approximately 6% (+3%, SD) of the applied dose of calcipotriene is absorbed systemically when the ointment is applied topically to psoriasis plaques or 5% (+2.6%, SO) when applied to normal skin.
The active form of the vitamin, 1,25-dihydroxy vitamin D3 (calcitriol), is known to be recycled via the liver and excreted in the bile. There is evidence that maternal 1,25-dihydroxy vitamin D3 (calcitriol) may enter the fetal circulation, but it is not known whether it is excreted in human milk.
用途と製造
Uses
Use (kg) in USA (2002): 4
For the treatment of moderate plaque psoriasis in adults.
応用分野
説明Calcipotriene also known as Calcipotriol, is a topical vitaminD3 derivative effective in the treatment of psoriasis vulgaris. The drug acts by binding to vitamin D3 receptors in the skin keratinocytes, producing an elevation in cell differentiation and a reduction in cell proliferation. Although its efficacy is comparable to calcitriol, calcipotriol exhibits at least 100 times less effect on calcium metabolism in rats.
使用Calcipotriene is an antipsoriatic that is a vitamin D3 analogue with low calcemic activity. It works by regulating the production and growth of skin cells. In the United States, this drug was first marketed under the trade name Dovonex and is used mainly for the treatment of psoriasis. It is one of the most effective non glucocorticoid topical drugs for the treatment of localized psoriasis.This drug has many off-label applications that are alternative therapies for many dermatologic diseases.
調製方法
製造方法A convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven Vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described.A Synthesis of calcipotriol via a Key Electroreductive Cross-coupling ApproachCalcipotriol is currently the most successful VitD analog and is prescribed for the treatment of psoriasis, an autoimmune skin disease.
上流・下流製品情報
上流原料
下流製品
サプライヤー100 社
補足説明
定義ChEBI: Calcipotriol is a seco-cholestane that is 26,27-cyclo-9,10-secocholesta-5,7,10,22-tetraene carrying additional hydroxy substituents at positions 1, 3 and 24. It is used (as its hydrate) in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. It has a role as a drug allergen and an antipsoriatic. It is a member of cyclopropanes, a secondary alcohol, a triol, a hydroxy seco-steroid and a seco-cholestane.
関連反応
化合物ノート
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