Delamanid
Grundinformationen
- CAS
681492-22-8- Standard-SMILES
C[C@]1(COc2ccc(N3CCC(Oc4ccc(OC(F)(F)F)cc4)CC3)cc2)Cn2cc([N+](=O)[O-])nc2O1- InChIKey
XDAOLTSRNUSPPH-XMMPIXPASA-N- Summenformel
- C25H25F3N4O6
- Durchschnittliche Molmasse
- 534,5 g/mol
- Monoisotopische Masse
- 534,17261918
Überblick
Delamanid is a member of piperidines.
Namen und Bezeichner
- Bevorzugter Name
- 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
- Englischer Name
- Delamanid
- Summenformel
- C25H25F3N4O6
- Molmasse
- 534.48
Namen und Synonyme
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
Weitere Namen anzeigen
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
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 5,6
- Polarare Oberfläche (TPSA)
- 104 Ų
- H-Brücken-Donoren
- 0
- H-Brücken-Akzeptoren
- 11
- Frei drehbare Bindungen
- 7
- Schwere Atome
- 38
- Formalladung
- 0
- Komplexität
- 795
Experimentelle und physikochemische Eigenschaften
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
Physikochemische Eigenschaften
- Schmelzpunkt
- 195 · 195-196℃
- Siedepunkt
- 653.7 · 653.7±65.0 °C(Predicted)
- Dichte
- 1.45 · 1.45
- storage temp.
- -20 °C · Hygroscopic, -20°C Freezer, Under inert atmosphere
- Löslichkeit
- Chloroform (Sparingly), Ethyl Acetate (Slightly, Sonicated)
- pka
- 3.99 · 3.99±0.20(Predicted)
- Aggregatzustand
- Solid
- Farbe
- Off-White to Light Yellow
- Stabilität
- Hygroscopic
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
GHS-Klassifizierung
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.
Gefahrenhinweise
Hazard Classes and CategoriesSTOT SE 3 (33.3%)
Toxikologische Informationen
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
Sicherheitsdaten
- wgk
- WGK 3
- Speicherklasse
- 11 - Combustible Solids
- Hazard Classifications
- Repr. 2
Chemie und Industrie
Pharmakologische Informationen
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.
Zugehörige Reaktionen
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