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编 号：F750663
分子式：C21H27N3O2
分子量：353.46
分子式：C21H27N3O2
分子量：353.46
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CAS No: 2255311-93-2
产品详情
生物活性：
HPGDS inhibitor 3 is an orally active and highly potent peripherally restricted hematopoietic prostaglandin D synthase (H-PGDS) inhibitor with IC50 value of 9.4 nM and EC50 of 42 nM, respectively. HPGDS inhibitor 3 exhibits good selectivity, good pharmacokinetic parameters in mouse, rat, and dog, and no CNS toxicity. HPGDS inhibitor 3 has anti-inflammatory activity.
体内研究：
HPGDS inhibitor 3 (compound 1y) (1-3 mg/kg; PO and IV; single) has a lower IV clearance, similar steady state volume of distribution, longer terminal half-life, and high oral bioavailability, as well as very low brain exposures in mouse, rat and dog.HPGDS inhibitor 3 (0.003-1 mg/kg; PO; single) attenuates PGD2 release to baseline levels in a dose-dependent manner; also inhibits LPS-induced PGD2 increase in plasma and skeletal muscle in a dose-dependent manner.HPGDS inhibitor 3 (0.003-1 mg/kg; PO; single) .HPGDS inhibitor 3 (1, 3, and 10 mg/kg; PO; q.d., for 16 days) significantly enhances functional recovery of injured limbs, and hastens the time to full functional recovery of injured limb muscles.HPGDS inhibitor 3 (10, 30 and 100 mg/kg; PO; once daily, for 7 days or 4 days) exhibits well tolerated at 30 mg/kg/day in rat but not tolerated at 100 mg/kg/day; shows well tolerated at 30 mg/kg/day in dogs but not tolerated at 75 mg/kg/day.Pharmacokinetic Parameters of HPGDS inhibitor 3 in mice, rats and dogs.MouseIV, 1 mg/kgPO, 3 mg/kg RatIV, 0.4 mg/kgPO, 2.4 mg/kg DogIV, 0.5 mg/kgPO, 1 mg/kg
T1/2 (h)2.95.16.2
CL (mL/min/kg)9.04.51.9
Vss (L/kg)1.61.61.0
F (%)7110092
Brain:blood ratio0.06
Animal Model:Male C57BL/6J mice (murine mast cell degranulation model of inflammation)
Dosage:0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg
Administration:PO; single (anesthetized 1 hour later, intraperitoneally injected with 0.2 mL PBS or 48/80 (0.75 mg/mL))
Result:Attenuated PGD2 release to baseline levels in a dose-dependent manner with an ED50 of 0.009 mg/kg (blood EC50 = 3.4 nM) in this acute inflammation model.
Animal Model:Male C57BL6/N mice (12 weeks, n=6)
Dosage:0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg
Administration:PO; single (intraperitoneally injection of PBS or 20 ng/kg LPS 1 hour later)
Result:Inhibited LPS-induced PGD2 increase in plasma and skeletal muscle in a dose-dependent manner.
Animal Model:Male C57Bl/6 mice (10-12 weeks, n=7-8; chronic eccentric contraction-induced muscle injury models)
Dosage:1, 3, and 10 mg/kg
Administration:PO; q.d., for 16 days
Result:Significantly enhanced functional recovery of injured limbs, and significantly hastened the time to full functional recovery of injured limb muscles, with maximal efficacy observed at ≥ 10 mg/kg q.d..
Animal Model:Mdx mouse (6-8 mouths, duchenne muscular dystrophy model)
Dosage:0.1, 0.3, 1, 3, and 10 mg/kg
Administration:PO; q.d., for 43 days
Result:Significantly improved functional recovery (~90% to 100% restoration), following eccentric contraction-induced muscle injury in mdx mice.
Animal Model:Male Wistar Han rat and dog
Dosage:10, 30 and 100 mg/kg for rat; 10, 30, and 75 mg/kg for dog
Administration:PO; once daily; for 7 days (rat) or for 4 days (dog)
Result:In rat, the AUC values at 10, 30, and 100 mg/kg/day were 120, 410, and 820 μg?hr/mL, respectively; respective Cmax values were 8.7, 24, and 57 μg/mL. In dog, it showed well tolerated at dose levels up to 30 mg/kg/day with no abnormal microscopic findings; but exhibited discoloration in the small intestine and esophagus (female) at 75 mg/kg/day.
Animal Model:Mice, rats, dongs
Dosage:1 mg/kg IV and 3 mg/kg p.o in mice, 0.4 mg/kg IV and 2.4 mg/kg PO in rat, 0.5 mg/kg IV and 1 mg/kg PO in dog
Administration:IV and PO; single (Pharmacokinetics Analysis)
Result:Had a lower IV clearance, similar steady state volume of distribution, longer terminal half-life, and high oral bioavailability, as well as very low brain exposures in mouse, rat and dog.
HPGDS inhibitor 3 is an orally active and highly potent peripherally restricted hematopoietic prostaglandin D synthase (H-PGDS) inhibitor with IC50 value of 9.4 nM and EC50 of 42 nM, respectively. HPGDS inhibitor 3 exhibits good selectivity, good pharmacokinetic parameters in mouse, rat, and dog, and no CNS toxicity. HPGDS inhibitor 3 has anti-inflammatory activity.
体内研究：
HPGDS inhibitor 3 (compound 1y) (1-3 mg/kg; PO and IV; single) has a lower IV clearance, similar steady state volume of distribution, longer terminal half-life, and high oral bioavailability, as well as very low brain exposures in mouse, rat and dog.HPGDS inhibitor 3 (0.003-1 mg/kg; PO; single) attenuates PGD2 release to baseline levels in a dose-dependent manner; also inhibits LPS-induced PGD2 increase in plasma and skeletal muscle in a dose-dependent manner.HPGDS inhibitor 3 (0.003-1 mg/kg; PO; single) .HPGDS inhibitor 3 (1, 3, and 10 mg/kg; PO; q.d., for 16 days) significantly enhances functional recovery of injured limbs, and hastens the time to full functional recovery of injured limb muscles.HPGDS inhibitor 3 (10, 30 and 100 mg/kg; PO; once daily, for 7 days or 4 days) exhibits well tolerated at 30 mg/kg/day in rat but not tolerated at 100 mg/kg/day; shows well tolerated at 30 mg/kg/day in dogs but not tolerated at 75 mg/kg/day.Pharmacokinetic Parameters of HPGDS inhibitor 3 in mice, rats and dogs.MouseIV, 1 mg/kgPO, 3 mg/kg RatIV, 0.4 mg/kgPO, 2.4 mg/kg DogIV, 0.5 mg/kgPO, 1 mg/kg
T1/2 (h)2.95.16.2
CL (mL/min/kg)9.04.51.9
Vss (L/kg)1.61.61.0
F (%)7110092
Brain:blood ratio0.06
Animal Model:Male C57BL/6J mice (murine mast cell degranulation model of inflammation)
Dosage:0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg
Administration:PO; single (anesthetized 1 hour later, intraperitoneally injected with 0.2 mL PBS or 48/80 (0.75 mg/mL))
Result:Attenuated PGD2 release to baseline levels in a dose-dependent manner with an ED50 of 0.009 mg/kg (blood EC50 = 3.4 nM) in this acute inflammation model.
Animal Model:Male C57BL6/N mice (12 weeks, n=6)
Dosage:0.003, 0.01, 0.03, 0.1, 0.3 and 1.0 mg/kg
Administration:PO; single (intraperitoneally injection of PBS or 20 ng/kg LPS 1 hour later)
Result:Inhibited LPS-induced PGD2 increase in plasma and skeletal muscle in a dose-dependent manner.
Animal Model:Male C57Bl/6 mice (10-12 weeks, n=7-8; chronic eccentric contraction-induced muscle injury models)
Dosage:1, 3, and 10 mg/kg
Administration:PO; q.d., for 16 days
Result:Significantly enhanced functional recovery of injured limbs, and significantly hastened the time to full functional recovery of injured limb muscles, with maximal efficacy observed at ≥ 10 mg/kg q.d..
Animal Model:Mdx mouse (6-8 mouths, duchenne muscular dystrophy model)
Dosage:0.1, 0.3, 1, 3, and 10 mg/kg
Administration:PO; q.d., for 43 days
Result:Significantly improved functional recovery (~90% to 100% restoration), following eccentric contraction-induced muscle injury in mdx mice.
Animal Model:Male Wistar Han rat and dog
Dosage:10, 30 and 100 mg/kg for rat; 10, 30, and 75 mg/kg for dog
Administration:PO; once daily; for 7 days (rat) or for 4 days (dog)
Result:In rat, the AUC values at 10, 30, and 100 mg/kg/day were 120, 410, and 820 μg?hr/mL, respectively; respective Cmax values were 8.7, 24, and 57 μg/mL. In dog, it showed well tolerated at dose levels up to 30 mg/kg/day with no abnormal microscopic findings; but exhibited discoloration in the small intestine and esophagus (female) at 75 mg/kg/day.
Animal Model:Mice, rats, dongs
Dosage:1 mg/kg IV and 3 mg/kg p.o in mice, 0.4 mg/kg IV and 2.4 mg/kg PO in rat, 0.5 mg/kg IV and 1 mg/kg PO in dog
Administration:IV and PO; single (Pharmacokinetics Analysis)
Result:Had a lower IV clearance, similar steady state volume of distribution, longer terminal half-life, and high oral bioavailability, as well as very low brain exposures in mouse, rat and dog.
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