ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors (3S,3aS,6aR)-3-Isopropyl-1-(methanesulfonyl)-4-[4-(1-piperidinyl)-2(E)-butenoyl]perhydropyrrolo[3,2b]pyrrol-2(1H)-one hydrochloride

(3S,3aS,6aR)-3-Isopropyl-1-(methanesulfonyl)-4-[4-(1-piperidinyl)-2(E)-butenoyl]perhydropyrrolo[3,2b]pyrrol-2(1H)-one hydrochloride

Product Name(3S,3aS,6aR)-3-Isopropyl-1-(methanesulfonyl)-4-[4-(1-piperidinyl)-2(E)-butenoyl]perhydropyrrolo[3,2b]pyrrol-2(1H)-one hydrochloride
CAS198062-54-3
MFC19H31N3O4S
MW397.53
EINECS
MOL File198062-54-3.mol

Chemical Properties

Boiling point	583.6±60.0 °C(Predicted)
Density	1.27±0.1 g/cm3(Predicted)
storage temp.	2-8°C
solubility	H₂O: 24 mg/mL, soluble
form	solid
pka	8.53±0.10(Predicted)
color	Light brown to brown

Safety Information

Hazard Codes	Xi
Risk Statements	36/37/38
Safety Statements	26-36
WGK Germany	3

MSDS

Provider	Language
SigmaAldrich	English

Usage And Synthesis

Uses

GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophil elastase (HNE) inhibitor with IC50 value of 22 nM and Ki value of 0.31 nM[1].

Biological Activity

Potent and selective inhibitor of human leukocyte elastase (HLE) (IC 50 = 22 nM); displays > 4500-fold selectivity over other human serine proteases. Orally active in vivo .

in vivo

GW-311616 (2 mg/kg; oral administration) rapidly abolishes the circulation of neutrophil elastase (NE) in dogs, while >90% inhibition is maintained for 4 days. This prolonged effect is independent to be due to penetration of neutrophils in bone marrow by orally administrated GW-311616. GW-311616 has moderate terminal elimination half-life (t_1/2) of 1.1 hours and 1.5 hours for dog (2 mg/kg, oral), rat (2 mg/kg, oral), respectively^[3].

Animal Model:	Dogs (9-month-old)^[3]
Dosage:	0.22 mg/kg, 0.66 mg/kg and 2 mg/kg (Pharmacokinetic study)
Administration:	Oral administration
Result:	At 0.22 mg/kg, greater than 50% inhibition of elastase was achieved 6 hours after dosing, with activity returning towards control values. Single oral dose of 2 mg/kg rapidly abolished circulating enzyme activity, and greater than 90% inhibition was maintained for 4 days.

References

[1] Ohbayashi H,et al. Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80. DOI:10.1517/13543784.11.7.965
[2] Jiang KL, et al. Neutrophil elastase and its therapeutic effect on leukemia cells. Mol Med Rep. 2015 Sep;12(3):4165-4172. DOI:10.3892/mmr.2015.3946
[3] Macdonald SJ, et al. The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate. Bioorg Med Chem Lett. 2001 Apr 9;11(7):895-8. DOI:10.1016/s0960-894x(01)00078-6

(3S,3aS,6aR)-3-Isopropyl-1-(methanesulfonyl)-4-[4-(1-piperidinyl)-2(E)-butenoyl]perhydropyrrolo[3,2b]pyrrol-2(1H)-one hydrochloride Supplier

(3S,3aS,6aR)-3-Isopropyl-1-(methanesulfonyl)-4-[4-(1-piperidinyl)-2(E)-butenoyl]perhydropyrrolo[3,2b]pyrrol-2(1H)-one hydrochloride manufacturers

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