| Identification | Back Directory | [Name]
(3S,3AS,6AR)-3-ISOPROPYL-1-(METHANESULFONYL)-4-[4-(1-PIPERIDINYL)-2(E)-BUTENOYL]PERHYDROPYRROLO[3,2B]PYRROL-2(1H)-ONE HYDROCHLORIDE | [CAS]
198062-54-3 | [Synonyms]
CS-1261
GW311616
GW311616A
GW311616HCl
GW 311616 HYDROCHLORIDE
(3S,3aS,6aR)-Hexahydro-3-(1-methylethyl)-1-(methylsulfonyl)-4-((2E)-1-oxo-4-(1-piperidinyl)-2-butenyl)pyrrolo[3.2-b]pyrr
(3S,3AS,6AR)-3-ISOPROPYL-1-(METHANESULFONYL)-4-[4-(1-PIPERIDINYL)-2(E)-BUTENOYL]PERHYDROPYRROLO[3,2B]PYRROL-2(1H)-ONE HYDROCHLORIDE
Pyrrolo[3,2-b]pyrrol-2(1H)-one, hexahydro-3-(1-methylethyl)-1-(methylsulfonyl)-4-[(2E)-1-oxo-4-(1-piperidinyl)-2-buten-1-yl]-, (3S,3aS,6aR)-
(3S,3AS,6AR)-HEXAHYDRO-3-(1-METHYLETHYL)-1-(METHYLSULFONYL)-4-[(2E)-1-OXO-4-(1-PIPERIDINYL)-2-BUTENYL]PYRROLO[3,2-B]PYRROL-2(1H)-ONE HYDROCHLORIDE | [Molecular Formula]
C19H31N3O4S | [MDL Number]
MFCD06411566 | [MOL File]
198062-54-3.mol | [Molecular Weight]
397.53 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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 (t1/2) 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.
|
| [storage]
Store at -20°C | [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 |
|
| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
SPIRO PHARMA
|
| Telephone: |
|
| Website: |
www.spiropharma.com.cn |
|