Tìm theo
GTS-21
Các tên gọi khác (2) :
  • DMXB-A
  • DMXB-Anabaseine
nicotinic agonists
Thuốc Gốc
Small Molecule
CAS: 156223-05-1
CTHH: C19H22Cl2N2O2
PTK: 381.296
GTS-21 (also known as DMBX-A), is a novel, small-molecule, orally active and selective alpha-7 nicotinic acetylcholine (nACh) receptor agonist that has demonstrated memory and cognition enhancement activity in human clinical trials. Athenagen licensed the exclusive rights to the compound and a related library of analogs as part of the acquisition of Osprey Pharmaceutical Company in April 2006. GTS-21 has been studied in multiple Phase I studies in healthy volunteers and one Phase I/II study in schizophrenic patients. In all studies, the compound was well tolerated. In a Phase I multi-dose, double-blind, placebo controlled study in healthy adults, GTS-21 also demonstrated cognitive enhancement across all doses, with a statistically significant improvement in attention related and memory related tasks (Kitagawa, et al. Neuropsychopharmacology (2003), 28, 542-551).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H22Cl2N2O2
Phân tử khối
381.296
Monoisotopic mass
380.105833372
InChI
InChI=1S/C19H20N2O2.2ClH/c1-22-17-8-7-14(18(12-17)23-2)11-15-5-4-10-21-19(15)16-6-3-9-20-13-16;;/h3,6-9,11-13H,4-5,10H2,1-2H3;2*1H/b15-11+;;
InChI Key
InChIKey=BXKYFUGAAFLYJL-BXGYHSFXSA-N
IUPAC Name
3-[(3E)-3-[(2,4-dimethoxyphenyl)methylidene]-3,4,5,6-tetrahydropyridin-2-yl]pyridine dihydrochloride
Traditional IUPAC Name
3-[(3E)-3-[(2,4-dimethoxyphenyl)methylidene]-5,6-dihydro-4H-pyridin-2-yl]pyridine dihydrochloride
SMILES
Cl.Cl.COC1=CC(OC)=C(\C=C2/CCCN=C2C2=CN=CC=C2)C=C1
logP
2.96
pKa (Strongest Basic)
5.89
PSA
43.71 Å2
Refractivity
91.83 m3·mol-1
Polarizability
33.94 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
4
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Cơ Chế Tác Dụng : GTS-21 (also known as DMBX-A), is a novel, small-molecule, orally active and selective alpha-7 nicotinic acetylcholine (nACh) receptor agonist that has demonstrated memory and cognition enhancement activity in human clinical trials. Athenagen licensed the exclusive rights to the compound and a related library of analogs as part of the acquisition of Osprey Pharmaceutical Company in April 2006. GTS-21 has been studied in multiple Phase I studies in healthy volunteers and one Phase I/II study in schizophrenic patients. In all studies, the compound was well tolerated. In a Phase I multi-dose, double-blind, placebo controlled study in healthy adults, GTS-21 also demonstrated cognitive enhancement across all doses, with a statistically significant improvement in attention related and memory related tasks (Kitagawa, et al. Neuropsychopharmacology (2003), 28, 542-551). Auditory sensory gating, a biological measurement of the ability to suppress the evoked response to the second of two auditory stimuli, is diminished in people with schizophrenia. Deficits in sensory gating are associated with attentional impairment, and may contribute to cognitive symptoms and perceptual disturbances. This inhibitory process, which involves the alpha(7) nicotinic receptor mediated release of gamma-aminobutyric acid (GABA) by hippocampal interneurons, represents a potential new target for therapeutic intervention in schizophrenia. GTS-21 is an orally active alpha-7 nicotinic acetylcholine (nACh) receptor agonist.
Dược Động Học :
▧ Absorption :
Rapidly and extensively absorbed after oral administration. In rat, GTS-21 showed linear pharmacokinetics over doses ranging from 1 to 10 mg/kg with an absolute bioavailability of 23%. In dog, the absolute bioavailability was 27% at an oral dose of 3 mg/kg.
▧ Metabolism :
GTS-21 was O-demethylated to yield compounds that were then subject to glucuronidation. Three of the metabolites in rat urine were isolated and characterized as 4-OH-GTS-21, 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. The major urinary metabolites were 4-OH-GTS-21 glucuronide and 2-OH-GTS-21 glucuronide. In vitro chemical inhibition of cytochrome P450 in human liver microsomes indicated that CYPIA2 and CYP2E1 were the isoforms primarily responsible for the O-demethylation of GTS-21, with some contribution from CYP3A.
Chỉ Định : Investigated for use/treatment in alzheimer's disease and schizophrenia and schizoaffective disorders.
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05708
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=6438361
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=43031369
ChemSpider
http://www.chemspider.com/Chemical-Structure.4942844.html
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