| Identification | Back Directory | [Name]
(S)-BI 665915 | [CAS]
1360550-05-5 | [Synonyms]
(S)-BI 665915
(S) BI 665915,(S)BI 665915
1H-Pyrazole-1-acetamide, 4-[3-[(1S)-1-[4-(2-amino-5-pyrimidinyl)phenyl]-1-cyclopropylethyl]-1,2,4-oxadiazol-5-yl]-N,N-dimethyl- | [Molecular Formula]
C24H26N8O2 | [MDL Number]
MFCD32664445 | [MOL File]
1360550-05-5.mol | [Molecular Weight]
458.52 |
| Hazard Information | Back Directory | [Uses]
(S)-BI 665915 is an orally active oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitor with an IC50 of 1.7 nM for FLAP binding. (S)-BI 665915 inhibits FLAP functional in human whole blood with an IC50 of 45 nM. (S)-BI 665915 demonstrates an excellent cross-species agent metabolism and pharmacokinetics (DMPK) profile and a dose-dependent inhibition of LTB4 production[1]. | [in vivo]
(S)-BI 665915 (oral; 1-100 mg/kg) demonstrates dose-dependent LTB4 production inhibition in mouse whole blood, 2 h after single oral dose[1].
(S)-BI 665915 (iv of 1 mg/kg or po of 10 mg/kg) shows low iv plasma clearance in all three species, with clearance values of 7 % Qh in rat, 2.8 % Qh in dog, and 3.6 % Qh in cynomolgus monkey, respectively. The volume of distribution (Vss) across species tested is in a range of 0.5 to 1.2 L/kg, and the bioavailability was good (45 to 63 %) in all species tested[1].
| Animal Model: | C57BL/6 mice[1] | | Dosage: | 1, 3, 10, 30, 100 mg/kg (Pharmacokinetic Analysis) | | Administration: | Oral | | Result: | Demonstrated dose-dependent LTB4 production inhibition in mouse whole blood, 2 h after single oral dose.
|
| Animal Model: | Rat; dog; cynomolgus monkey[1] | | Dosage: | 1 mg/kg (iv) or 10 mg/kg (po) | | Administration: | Iv or po | | Result: | Showed low iv plasma clearance in all three species, with clearance values of 7 % Qh in rat, 2.8 % Qh in dog, and 3.6 % Qh in cynomolgus monkey, respectively.
|
| [References]
[1] Takahashi H, et al. Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915). J Med Chem. 2015 Feb 26;58(4):1669-90. DOI:10.1021/jm501185j |
|
|