| Identification | Back Directory | [Name]
2-Thiopheneacetic acid, α-hydroxy-α-2-thienyl-, trans-4-[[3-[5-[[[(2R)-2-(1,2-dihydro-8-hydroxy-2-oxo-5-quinolinyl)-2-hydroxyethyl]amino]methyl]-1H-benzotriazol-1-yl]propyl]methylamino]cyclohexyl ester, compd. with 1,2-benzisothiazol-3(2H)-one 1,1-dioxide (1:1) | [CAS]
1648550-37-1 | [Synonyms]
AZD8871 saccharinate
AZD-8871 saccharinate
LAS191351 saccharinate
LAS-191351 saccharinate
Navafenterol saccharinate
2-Thiopheneacetic acid, α-hydroxy-α-2-thienyl-, trans-4-[[3-[5-[[[(2R)-2-(1,2-dihydro-8-hydroxy-2-oxo-5-quinolinyl)-2-hydroxyethyl]amino]methyl]-1H-benzotriazol-1-yl]propyl]methylamino]cyclohexyl ester, compd. with 1,2-benzisothiazol-3(2H)-one 1,1-dioxide (1:1) | [Molecular Formula]
C45H47N7O9S3 | [MDL Number]
MFCD34589898 | [MOL File]
1648550-37-1.mol | [Molecular Weight]
926.09 |
| Hazard Information | Back Directory | [Uses]
Navafenterol?(AZD-8871) saccharinate?is an inhaled dual-acting, potent, selective, and long-lasting M3-antagonist/β2-agonist (MABA) with long-lasting effects and favorable safety profile. The pIC50 is 9.5 for human M3?receptor, and the pEC50 is 9.5 for β2-adrenoceptor. Navafenterol saccharinate can be used for the research of chronic obstructive pulmonary disease (COPD).?Bronchoprotective and antisialagogue effects. Favorable cardiovascular profile[1]. | [in vivo]
Navafenterol?(AZD-8871) prevents acetylcholine-induced bronchoconstriction in both guinea pig and dog with minimal effects on salivation and heart rate at doses with bronchoprotective activity. Moreover, AZD8871 shows long-lasting effects in dog, with a bronchoprotective half-life longer than 24 hours. Navafenterol?shows dose-proportional bronchoprotective effect, with a nonsignificantly different potency (ID40?of 0.40 μg/kg)[1]. | Animal Model: | Male Dunkin Hartley guinea pigs (body weight 340-600 g)?bearing bronchoconstriction model[1] | | Dosage: | 10, 30, 100, and 300?μg/mL | | Administration: | Administered by aerosol | | Result: | Inhibited the bronchoconstriction in a concentration-response manner with the IC50?value of 2.1?μg/mL.
Exhibited the antisialagogue effect with a maximal inhibition of sialorrhea of 65%±11% at 300?μg/mL and an estimated IC50?of 138.4 μg/mL.
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| Animal Model: | Male anesthetized Beagle dogs[1] | | Dosage: | 0.3, 1, 3, or 10?μg/kg | | Administration: | Administered as nebulized liquid aerosols; the administration volume was 3 mL | | Result: | Showed significant effects over 24 hours at all the doses tested (0.3-10?μg/kg).
Showed long-lasting effects at 10?μg/kg, with a 79% ± 3.6% of bronchoprotection at 24 hours and a calculated half-life longer than 24 hours.?
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mAChR3 | [References]
[1] Mònica Aparici, et al. Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3?Receptor Antagonist/?β?2-Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile. J Pharmacol Exp Ther.?2019 Jul;370(1):127-136. DOI:10.1124/jpet.118.255620 |
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