832714-46-2
基本信息
异丙基 4-(1-(2-氟-4-(甲基磺酰基)苯基)-1H-吡唑并[3,4-D]嘧啶-4-基氧基)哌啶-1-羧酸
CS-1179
APD 668, >=98%
APD 668
APD-668
4-[[1-(2-Fluoro-4-methylsulfonylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy]piperidine-1-carboxylic acid isopropyl ester
1-Piperidinecarboxylic acid,4-[[1-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy]-, 1-methylethyl ester
isopropyl 4-((1-(2-fluoro-4-(methylsulfonyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate APD668
APD668 ISOPROPYL 4-(1-(2-FLUORO-4-(METHYLSULFONYL)PHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLOXY)PIPERIDINE-1-CARBOXYLATE
物理化学性质
| 沸点 | 611.6±55.0 °C(Predicted) |
| 密度 | 1.47±0.1 g/cm3(Predicted) |
| 储存条件 | -20°C储存 |
| 溶解度 | insoluble in H2O; ≥17.4 mg/mL in DMSO; ≥2.61 mg/mL in EtOH with gentle warming and ultrasonic |
| 酸度系数(pKa) | 2.13±0.30(Predicted) |
| 形态 | 固体 |
常见问题列表
| Target | Value |
|
human GPR119
() | 2.7 nM(EC50) |
|
rat GPR119
() | 33 nM(EC50) |
APD668 increases adenylate cyclase activation in HEK293 cells transfected with human GPR119 in a concentration-dependent manner with an EC
50
of 23 nM.
APD668 is highly bound to plasma proteins of male and female cynomolgus monkeys and humans (⩾99%), but is less extensively bound to male (93.0%) and female (96.6%) rats.
APD668 (10-30 mg/kg; p.o. once daily for 8 weeks) significantly reduces blood glucose and glycated hemoglobin (HbA1c) levels, with no desensitization of the acute drug response.
APD668 (1-10 mg/kg; a single p.o.) markedly reduces blood glucose levels during oral glucose tolerance test in a dose-dependent manner in mice.
APD668 (0.08 mg/kg/min; i.v.) shows no effect during euglycemic condition, but significantly stimulates insulin release when blood glucose levels are raised to approximately 300 mg/dl in a hyperglycemic clamp model in the Sprague-Dawley rat.
APD668 (p.o.) exhibits rapid to moderate absorption (t
max
≤2 h) in mice, rats, and monkeys, but slower in dogs (t
max
=6 h), and moderate to good absolute oral bioavailability (44-79%) in mice, rats, and monkeys, but lower in dogs (22%).
| Animal Model: | Male Zucker Diabetic Fatty (ZDF) rats (6 weeks old, 200-250 g) |
| Dosage: | 10, 30 mg/kg |
| Administration: | P.o. once daily for 8 weeks |
| Result: |
Decreased the blood glucose and HbA1c levels at 30 mg/kg/day.
Did not develop diabetes, whereas the vehicle treated rats did. |