Tìm theo
Denufosol
Thuốc Gốc
Small Molecule
CAS: 318250-11-2
CTHH: C18H27N5O21P4
PTK: 773.3229
Denufosol (INN) is an inhaled drug for the treatment of cystic fibrosis, being developed by Inspire Pharmaceuticals and sponsored by the Cystic Fibrosis Foundation. It was tested in two Phase III clinical trials, TIGER-1 and TIGER-2. Initially, in the first Phase III trial, TIGER-1, the compound showed significant results as compared with placebo. In the second Phase III trial, TIGER-2, the compound did not meet the primary endpoint, a significant change in baseline FEV1 (forced expiratory volume in one second) at the week 48 endpoint as compared to placebo. As of 2011, no additional clinical studies are being conducted with the compound. The drug was also investigated for the treatment of retinal detachment and other retinal diseases, but trials were terminated in 2006. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H27N5O21P4
Phân tử khối
773.3229
Monoisotopic mass
773.014898999
InChI
InChI=1S/C18H27N5O21P4/c19-11-1-3-22(17(28)20-11)13-5-8(24)9(40-13)6-38-45(30,31)42-47(34,35)44-48(36,37)43-46(32,33)39-7-10-14(26)15(27)16(41-10)23-4-2-12(25)21-18(23)29/h1-4,8-10,13-16,24,26-27H,5-7H2,(H,30,31)(H,32,33)(H,34,35)(H,36,37)(H2,19,20,28)(H,21,25,29)/t8-,9?,10+,13+,14+,15+,16+/m0/s1
InChI Key
InChIKey=FPNPSEMJLALQSA-QWQWSIRXSA-N
IUPAC Name
{[({[({[(3S,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)(hydroxy)phosphoryl]oxy}({[(2R,3S,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy})phosphinic acid
Traditional IUPAC Name
[({[(3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxy(hydroxy)phosphoryl)oxy(hydroxy)phosphoryl]oxy[(2R,3S,4R,5R)-5-(2,4-dioxo-3H-pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxyphosphinic acid
SMILES
NC1=NC(=O)N(C=C1)[C@H]1C[C@H](O)C(COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=CC(=O)NC2=O)O1
Độ hòa tan
2.23e+01 g/l
logP
-5.4
logS
-1.5
pKa (strongest acidic)
0.76
pKa (Strongest Basic)
0.13
PSA
382.6 Å2
Refractivity
145.31 m3·mol-1
Polarizability
60.36 Å3
Rotatable Bond Count
14
H Bond Acceptor Count
18
H Bond Donor Count
9
Physiological Charge
-4
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Denufosol is designed to enhance the lung's innate mucosal hydration and mucociliary clearance through stimulation of the P2Y2 receptor. The pharmacologic profile of denufosol parallels that of UTP, leading to increased chloride and water secretion, increased cilia beat frequency, and increased mucin release.
Cơ Chế Tác Dụng : Denufosol (INN) is an inhaled drug for the treatment of cystic fibrosis, being developed by Inspire Pharmaceuticals and sponsored by the Cystic Fibrosis Foundation. It was tested in two Phase III clinical trials, TIGER-1 and TIGER-2. Initially, in the first Phase III trial, TIGER-1, the compound showed significant results as compared with placebo. In the second Phase III trial, TIGER-2, the compound did not meet the primary endpoint, a significant change in baseline FEV1 (forced expiratory volume in one second) at the week 48 endpoint as compared to placebo. As of 2011, no additional clinical studies are being conducted with the compound. The drug was also investigated for the treatment of retinal detachment and other retinal diseases, but trials were terminated in 2006. [Wikipedia] Denufosol tetrasodium is a selective P2Y2 agonist designed to enhance the lung's innate mucosal hydration and mucociliary clearance mechanisms by activating an alternative ion channel that acts in the same way as the defective ion channel in moving salt and water to the surface of the airways. Based on pre-clinical and clinical work, denufosol has several pharmacological actions contributing to its mechanism of action: hydration of the airways by stimulating chloride and liquid secretions on the epithelial cell surface; inhibition of epithelial sodium absorption; enhancement of ciliary beat frequency; and stimulation of mucin secretion. This unique mechanism of action represents a differentiated approach relative to other approved CF products and may be important in intervening in the early clinical course of CF lung disease.
Chỉ Định : For use as an inhaled treatment for cystic fibrosis.
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04983
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03685
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