| Identification | Back Directory | [Name]
SSTR5 antagonist 1 | [CAS]
1628741-91-2 | [Synonyms]
SSTR5 antagonist 1
SSTR5 antagonist 1,SSTR-5 antagonist 1
4-Piperidinecarboxylic acid, 1-[2-[(2,6-diethoxy-4'-fluoro[1,1'-biphenyl]-4-yl)methyl]-5-oxa-2,6-diazaspiro[3.4]oct-6-en-7-yl]- | [Molecular Formula]
C28H34FN3O5 | [MOL File]
1628741-91-2.mol | [Molecular Weight]
511.59 |
| Chemical Properties | Back Directory | [Boiling point ]
614.2±65.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 90 mg/mL (175.92 mM; Need ultrasonic) | [form ]
Solid | [pka]
4.48±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
SSTR5 antagonist 1 (compound 25a) is a selective and orally available somatostatin receptor subtype 5 (SSTR5) antagonist with IC50s of 9.6 and 57 nM for hSSTR5 and mSSTR5, respectively[1]. | [in vivo]
SSTR5 antagonist 1 (compound 25a) (1 mg/kg; p.o.; single dose) is orally available with acceptable plasma exposure in mice in pharmacokinetic screening and exhibits excellent solubility (260 μg/mL, pH=6.8)[1].
SSTR5 antagonist 1 (100 mg/kg; p.o.; single dose; measured at 0-120 min) augments insulin secretion in a glucose-dependent manner and lowers blood glucose concentration in high-fat diet fed C57BL/6J mice[1].
SSTR5 antagonist 1 (1, 3, 10, and 30 mg/kg; p.o.; single dose) shows dose-dependent effect on glucose excursion measured during the oral glucose tolerance test in HFD fed C57BL/6J mice[1].
Pharmacokinetic profiles in male ICR mouse (8-week-old)[1] | Route | Dose (mg/kg) | CLtotal (mL/h/kg) | Vss (mL/kg) | MRT (h) | | | iv | 0.1 | 1761 | 3052 | 1.7 | / | | Route | Dose (mg/kg) | Cmax (ng/mL) | Tmax (h) | AUC0-8 h (ng·h/mL) | F (%) | | po | 1 | 74.8 | 2.0 | 332 | 58 |
| Animal Model: | High-fat diet fed C57BL/6J mice[1] | | Dosage: | 100 mg/kg | | Administration: | Oral gavage; single dose; monitored over 2 h | | Result: | Showed the maximum efficacy superior to that of 10 mg/kg Glibenclamide (HY-15206) and comparable to that of 30 mg/kg Alogliptin (HY-A0023A).
Augmented insulin secretion in a glucose-dependent manner and displayed a blood glucose-lowering effect, indicating its anti-diabetic efficacy in vivo. |
| [References]
[1] Hirose H, et al. Discovery of novel 5-oxa-2,6-diazaspiro[3.4]oct-6-ene derivatives as potent, selective, and orally available somatostatin receptor subtype 5 (SSTR5) antagonists for treatment of type 2 diabetes mellitus. Bioorg Med Chem. 2017 Aug 1;25(15):4175-4193. DOI:10.1016/j.bmc.2017.06.007 |
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