R13 (drug)

R13
Clinical data
Other names	4-Oxo-2-phenyl-4H-chromene-7,8-diyl bis(methylcarbamate)
Routes of; administration	By mouth
Pharmacokinetic data
Metabolites	Tropoflavin
Identifiers
	IUPAC name [8-(Methylcarbamoyloxy)-4-oxo-2-phenylchromen-7-yl] N-methylcarbamate;
CAS Number	1609067-49-3 ;
PubChem CID	90117609;
UNII	OGG19T0LU2;
Chemical and physical data
Formula	C19H16N2O6
Molar mass	368.345 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CNC(=O)OC1=C(C2=C(C=C1)C(=O)C=C(O2)C3=CC=CC=C3)OC(=O)NC;
	InChI 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]

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.

Clinical data

Other names	4-Oxo-2-phenyl-4H-chromene-7,8-diyl bis(methylcarbamate)
Routes of administration	By mouth^[1]
Pharmacokinetic data
Metabolites	Tropoflavin^[1]
Identifiers
IUPAC name [8-(Methylcarbamoyloxy)-4-oxo-2-phenylchromen-7-yl] N-methylcarbamate
CAS Number	1609067-49-3^Y
PubChem CID	90117609
UNII	OGG19T0LU2
Chemical and physical data
Formula	C₁₉H₁₆N₂O₆
Molar mass	368.345 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CNC(=O)OC1=C(C2=C(C=C1)C(=O)C=C(O2)C3=CC=CC=C3)OC(=O)NC
InChI 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