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Chemical compound
R13
Other names 4-Oxo-2-phenyl-4H -chromene-7,8-diyl bis(methylcarbamate)
Routes of administration
By mouth
[1]
Metabolites
Tropoflavin
[1]
[8-(Methylcarbamoyloxy)-4-oxo-2-phenylchromen-7-yl] N -methylcarbamate
CAS Number
PubChem
CID
UNII
Formula C 19 H 16 N 2 O 6
Molar mass 368.345 g·mol−1 3D model (
JSmol )
CNC(=O)OC1=C(C2=C(C=C1)C(=O)C=C(O2)C3=CC=CC=C3)OC(=O)NC
InChI=1S/C19H16N2O6/c1-20-18(23)26-14-9-8-12-13(22)10-15(11-6-4-3-5-7-11)25-16(12)17(14)27-19(24)21-2/h3-10H,1-2H3,(H,20,23)(H,21,24)
Key:NWWRHMSYZTWUBD-UHFFFAOYSA-N
R13 is a
small-molecule
flavonoid and
orally active ,
potent , and
selective
agonist of the
tropomyosin receptor kinase B (TrkB) – the main
signaling receptor for the
neurotrophin
brain-derived neurotrophic factor (BDNF) – which is under development for the potential treatment of
Alzheimer's disease .
[1]
[2] It is a
structural modification and
prodrug of
tropoflavin (7,8-DHF) with improved potency and
pharmacokinetics , namely
oral
bioavailability and
duration .
[1] The compound is a replacement for the earlier tropoflavin prodrug
R7 and has similar properties to it.
[1]
[3] It was developed because while R7 displayed a good drug profile in animal studies, it showed almost no
conversion into tropoflavin in human
liver
microsomes .
[1] In contrast to R7, R13 is readily
hydrolyzed into tropoflavin in human liver microsomes.
[1]
See also
References
^
a
b
c
d
e
f
g Chen C, Wang Z, Zhang Z, Liu X, Kang SS, Zhang Y, Ye K (January 2018).
"The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease" . Proc. Natl. Acad. Sci. U.S.A . 115 (3): 578–583.
Bibcode :
2018PNAS..115..578C .
doi :
10.1073/pnas.1718683115 .
PMC
5777001 .
PMID
29295929 .
^
US application 20150274692 , Keqiang Ye, "7,8-Dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto", published 2015-10-01, assigned to Emory University
^ Liu C, Chan CB, Ye K (2016).
"7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders" . Transl Neurodegener . 5 : 2.
doi :
10.1186/s40035-015-0048-7 .
PMC
4702337 .
PMID
26740873 .
External links
Angiopoietin
CNTF
EGF (ErbB)
FGF
FGFR1
FGFR2
Agonists:
Ersofermin
FGF (
1 ,
2 (bFGF) ,
3 ,
4 ,
5 ,
6 ,
7 (
KGF ),
8 ,
9 ,
10 (KGF2) ,
17 ,
18 ,
22 )
Palifermin
Repifermin
Selpercatinib
Sprifermin
Trafermin
FGFR3
FGFR4 Unsorted
HGF (c-Met)
IGF
LNGF (p75NTR )
PDGF
RET (GFL)
SCF (c-Kit)
TGFβ
Trk
TrkA
Negative allosteric modulators:
VM-902A
TrkB
Agonists:
3,7-DHF
3,7,8,2'-THF
4'-DMA-7,8-DHF
7,3'-DHF
7,8-DHF
7,8,2'-THF
7,8,3'-THF
Amitriptyline
BDNF
BNN-20
Deoxygedunin
Deprenyl
Diosmetin
DMAQ-B1
HIOC
LM22A-4
N-Acetylserotonin
NT-3
NT-4
Norwogonin (5,7,8-THF)
R7
R13
TDP6
TrkC
VEGF Others
Additional growth factors:
Adrenomedullin
Colony-stimulating factors (see
here instead)
Connective tissue growth factor (CTGF)
Ephrins (
A1 ,
A2 ,
A3 ,
A4 ,
A5 ,
B1 ,
B2 ,
B3 )
Erythropoietin (see
here instead)
Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
Glia maturation factor (GMF)
Hepatoma-derived growth factor (HDGF)
Interleukins /
T-cell growth factors (see
here instead)
Leukemia inhibitory factor (LIF)
Macrophage-stimulating protein (MSP; HLP, HGFLP)
Midkine (NEGF2)
Migration-stimulating factor (MSF; PRG4)
Oncomodulin
Pituitary adenylate cyclase-activating peptide (PACAP)
Pleiotrophin
Renalase
Thrombopoietin (see
here instead)
Wnt signaling proteins
Additional growth factor receptor modulators:
Cerebrolysin (neurotrophin mixture)