832714-46-2

中文名称 ISOPROPYL 4-(1-(2-FLUORO-4-(METHYLSULFONYL)PHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLOXY)PIPERIDINE-1-CARBOXYLATE

英文名称 APD668

CAS 832714-46-2

分子式 C21H24FN5O5S

分子量 477.51

MOL 文件 832714-46-2.mol

更新日期 2023/03/20 15:41:25

832714-46-2 结构式

基本信息物理化学性质图谱信息常见问题列表

基本信息

中文别名

4-(1-(2-氟-4-(甲磺酰基)苯基)-1H-吡唑并[3,4-D]嘧啶-4-氧基)哌啶-1-羧酸异丙酯
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

英文别名

APD668
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

所属类别

生物化工：激动剂抑制剂

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

图谱信息

APD668(832714-46-2)核磁图(¹HNMR)

常见问题列表

生物活性

APD668是有效的GPR119激动剂，对人源GPR119和大鼠GPR119的EC50值分别为2.7 nM和33 nM。

靶点

Target	Value
human GPR119 ()	2.7 nM(EC50)
rat GPR119 ()	33 nM(EC50)

体外研究

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.

体内研究

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.