基本情報
- CAS
681492-22-8- 標準SMILES
C[C@]1(COc2ccc(N3CCC(Oc4ccc(OC(F)(F)F)cc4)CC3)cc2)Cn2cc([N+](=O)[O-])nc2O1- InChIKey
XDAOLTSRNUSPPH-XMMPIXPASA-N- 分子式
- C25H25F3N4O6
- 平均分子量
- 534.5 g/mol
- 単同位体質量
- 534.17261918
概要
Delamanid is a member of piperidines.
名称と識別子
- 優先名称
- Delamanid
- IUPAC
- (2R)-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl]phenoxy]methyl]-3H-imidazo[2,1-b][1,3]oxazole
- 現地名
- デラマニド
- 英語名
- Delamanid
- 分子式
- C25H25F3N4O6
- 分子量
- 534.48
名称と別名
Delamanid681492-22-8OPC-67683deltybaOPC 676838OOT6M1PC7OPC67683DTXSID60218326Imidazo(2,1-b)oxazole, 2,3-dihydro-2-methyl-6-nitro-2-((4-(4-(4-(trifluoromethoxy)phenoxy)-1-piperidinyl)phenoxy)methyl)-, (2R)-(2R)-2-METHYL-6-NITRO-2-((4-(4-(4-(TRIFLUOROMETHOXY)PHENOXY)PIPERIDIN-1-YL)PHENOXY)METHYL)-2,3-DIHYDROIMIDAZO(2,1-B)(1,3)OXAZOLE1-(4-{[(2R)-2-methyl-6-nitro-2H,3H-imidazo[2,1-b][1,3]oxazol-2-yl]methoxy}phenyl)-4-[4-(trifluoromethoxy)phenoxy]piperidinedelamanidum
名称をさらに表示
デラマニドデラマニド (JAN)デルティバ1-(4-{[(2R)-2-メチル-6-ニトロ-2H,3H-イミダゾ[2,1-b][1,3]オキサゾール-2-イル]メトキシ}フェニル)-4-(トリフルオロメトキシ)ピペリジン(2R)-2-メチル-6-ニトロ-2-[[4-[4-(トリフルオロメトキシ)ピペリジノ]フェノキシ]メチル]-2,3-ジヒドロイミダゾ[2,1-b]オキサゾールCS-2255DramaniDilamaniDelamanid (Standard)Delamanid (OPC-67683)Deflazacort Impurity 13Delamanid, 10 mM in DMSO
(2R)-2-Methyl-6-nitro-2-[(4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenoxy)methyl]-2,3-dihydroimidazo[2,1-b][1,3]oxazole1-(4-(((2R)-2-methyl-6-nitro-2H,3H-imidazo(2,1-b)(1,3)oxazol-2-yl)methoxy)phenyl)-4-(4-(trifluoromethoxy)phenoxy)piperidineImidazo[2,1-b]oxazole, 2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl]phenoxy]methyl]-, (2R)-RefChem:585666DTXCID80140817J04AK06(2R)-2-METHYL-6-NITRO-2-((4-(4-(4-(TRIFLUOROMETHOXY)PHENOXY)PIPERIDIN-1-YL)PHENOXY)METHYL)-2,3-DIHYDROIMIDAZO(2,1-B)OXAZOLE(R)-2-Methyl-6-nitro-2-((4-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)phenoxy)methyl)-2,3-dihydroimidazo[2,1-b]oxazole
物性
構造計算による物性
- XLogP
- 5.6
- 極性表面積
- 104 Ų
- 水素結合供与体数
- 0
- 水素結合受容体数
- 11
- 回転可能結合数
- 7
- 重原子数
- 38
- 形式電荷
- 0
- 複雑度
- 795
実験および物理化学的性質
Drugs
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Anti infectives for systemic use -> Antimycobacterials
Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-infective Agents; Antitubercular Agents
EMA approved medicines: Human medicine
Antituberculosis medicines
物理化学的性質
- 融点
- 195 · 195-196℃
- 沸点
- 653.7 · 653.7±65.0 °C(Predicted)
- 比重(密度)
- 1.45 · 1.45
- 貯蔵温度
- -20 °C · Hygroscopic, -20°C Freezer, Under inert atmosphere
- 溶解性
- クロロホルム (少量)、酢酸エチル (わずかに、超音波処理)
- 酸解離定数(Pka)
- 3.99 · 3.99±0.20(Predicted)
- 外見
- 個体
- 色
- オフホワイトからライトイエロー
- 安定性
- 吸湿性
- InChIKey
- XDAOLTSRNUSPPH-XMMPIXPASA-N
- SMILES
- O1[C@@](C)(COC2=CC=C(N3CCC(OC4=CC=C(OC(F)(F)F)C=C4)CC3)C=C2)CN2C=C([N+]([O-])=O)N=C12
安全と法規制
安全情報は参考情報です。供給元の安全データシート（SDS）、適用法令、専門家による評価に代わるものではありません。
GHS分類
GHS Classification
Warning
H336 (33.3%): May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure; Narcotic effects]
P203, P260, P261, P263, P264, P270, P271, P280, P304+P340, P318, P319, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
危険有害性情報
Hazard Classes and CategoriesSTOT SE 3 (33.3%)
毒性情報
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
安全データ
- wgk
- WGK 3
- Hazard Classifications
- Repr. 2
- ストレージクラス
- 11 - Combustible Solids
化学と産業
薬理情報
ATC Code
J - Antiinfectives for systemic use
QJ - Antiinfectives for systemic use
J04AK06
Protein BindingDelamanid highly binds to all plasma proteins with a binding to total proteins of ≥99.5%.
Pharmacodynamics
The minimum inhibitory concentrations (MIC) of delamanid against _Mycobacterium tuberculosis_ isolates ranges from 0.006 to 0.024 g/mL. Among non-tuberculosis mycobacteria, delamanid has _in vitro_ activity against _M. kansasii_ and _M. bovis_. Delamanid has no in vitro activity against Gram negative or positive bacterial species and does not display cross-resistance to other anti-tuberculosis drugs. In murine models of chronic tuberculosis, the reduction of _M. tuberculosis_ colony counts by delamanid was demonstrated in a dose-dependent manner. Repeated dosing of delamanid may cause QTc-prolongation via inhibition of cardiac potassium channel (hERG channel), and this effect is mostly contributed by the main metabolite of delamanid, DM-6705. Animal studies indicate that delamanid may attenuate vitamin K-dependent blood clotting, increase prothrombin time (PT), and activated partial thromboplastin time (APTT).
Mechanism of Action
Delamanid is a prodrug that requires biotransformation via via the mycobacterial F420 coenzyme system, including the deazaflavin dependent nitroreductase (Rv3547), to mediate its antimycobacterial activity against both growing and nongrowing mycobacteria. Mutations in one of five coenzyme F420 genes, _fgd, Rv3547, fbiA, fbiB, and fbiC_ has been proposed as the mechanism of resistance to delamanid. Upon activation, the radical intermediate formed between delamanid and desnitro-imidazooxazole derivative is thought to mediate antimycobacterial actions via inhibition of methoxy-mycolic and keto-mycolic acid synthesis, leading to depletion of mycobacterial cell wall components and destruction of the mycobacteria. Nitroimidazooxazole derivative is thought to generate reactive nitrogen species, including nitrogen oxide (NO). However unlike isoniazid, delamanid does not alpha-mycolic acid.
Biological Half-LifeThe half life ranges from 30 to 38 hours.
関連反応
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化合物ノート
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