FEBRIFUGINE DIHYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H19N3O3.2ClH
Molecular Weight	374.262
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of FEBRIFUGINE DIHYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.O[C@H]1CCCN[C@@H]1CC(=O)CN2C=NC3=CC=CC=C3C2=O

InChI

InChIKey=RDUHYEILHQUTIR-AMTWEWDESA-N

InChI=1S/C16H19N3O3.2ClH/c20-11(8-14-15(21)6-3-7-17-14)9-19-10-18-13-5-2-1-4-12(13)16(19)22;;/h1-2,4-5,10,14-15,17,21H,3,6-9H2;2*1H/t14-,15+;;/m1../s1

HIDE SMILES / InChI

Description
Sources: http://wiredspace.wits.ac.za/bitstream/handle/10539/1743/01chapter1.pdf
Curator's Comment: description was created based on several sources, including: Weici Tang, Gerhard Eisenbrand (2013) "Chinese Drugs of Plant Origin", p.455-457 Retrieved from https://books.google.ru/books?id=xmHwCAAAQBAJ

The alkaloids febrifugine was originally isolated from the roots of the Chinese shrub Dichroa febrifuga. Febrifugine showed an antimalarial activity 50-100 times higher than that of quinine. Febrifugine acts by causing an increase in NO production during the immunological response - increased production of NO by febrifugine plays an important role in host defense against malaria infection in mice. Also, febrifugine are known to inhibit prolyl-tRNA synthetase of malaria parasite Plasmodium falciparum.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Proline--tRNA ligase 2 Target ID: Q8I5R7 Gene ID: 811187.0 Gene Symbol: proRS Target Organism: Plasmodium falciparum (isolate 3D7) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22327401 \| https://www.ncbi.nlm.nih.gov/pubmed/25047712 \| https://www.ncbi.nlm.nih.gov/pubmed/25995223	Inhibitor 8297
nitric oxide biosynthetic process 17 Target ID: GO:0006809 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9644055	Activator 1430
Hemozoin formation 2 Target ID: Hemozoin formation Sources: Teng, W.-C. et al. (2016) "Medicinal Plants and Malaria: Applications, Trends, and Prospects", chapter.4.1.3.1 Retrieved from \| https://books.google.ru/books?id=CBXYCwAAQBAJ	Modulator 828

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 95 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10535750 https://www.ncbi.nlm.nih.gov/pubmed/12820231 https://www.ncbi.nlm.nih.gov/pubmed/11009379 https://www.ncbi.nlm.nih.gov/pubmed/9644055	Curative		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Lewis acid-catalyzed ring-opening reactions of semicyclic N,O-acetals possessing an exocyclic nitrogen atom: mechanistic aspect and application to piperidine alkaloid synthesis.	2001 Dec 19	11741414
Re-revision of the stereo structure of piperidine lactone, an intermediate in the synthesis of febrifugine.	2002 Jul	12130869
Potent antimalarial febrifugine analogues against the plasmodium malaria parasite.	2002 Jun 6	12036365
Combination effects of chloroquine with the febrifugine and isofebrifugine mixture against a blood-induced infection with chloroquine-resistant Plasmodium berghei NK65 in ICR mice.	2003 Dec	14669265
Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite.	2003 Sep 25	13678413
Concise synthesis of dl-febrifugine.	2005 Jul	15997158
Antimalarials: shortages and searches.	2005 Oct	16249521
Synthesis and evaluation of febrifugine analogues as potential antimalarial agents.	2006 Apr 1	16434194
Recent advances in antimalarial compounds and their patents.	2007	17346161
Asymmetric synthesis of (+)-isofebrifugine and (-)-sedacryptine from a common chiral nonracemic building block.	2008 Sep 4	18672881
Complementary chemoenzymatic routes to both enantiomers of febrifugine.	2009 Jul 21	19582308
A new reaction motif: "homo-S(N)2'-like" direct nucleophilic addition to neutral eta(3)-allylmolybdenum complexes. total synthesis of the antimalarial (+)-isofebrifugine.	2009 Sep 9	19678704

Patents

Sample Use Guides

In Vivo Use Guide

dosage range - 50 ug/kg/day - 5.00 mg/kg/day once daily

Route of Administration: Oral

In Vitro Use Guide

Febrifugine exhibits extreme potency against P. falciparum. Its activity is approximately 10-fold that of the effective antimalarial artemisinin, and 25-fold that of the well-known drug (EC50=0.7 nM). chloroquine.

Name

Type

Language

FEBRIFUGINE DIHYDROCHLORIDE

Common Name

English

FEBRIFUGINE DIHYDROCHLORIDE [MI]

Common Name

English

4(3H)-QUINAZOLINONE, 3-(3-((2R,3S)-3-HYDROXY-2-PIPERIDINYL)-2-OXOPROPYL)-, HYDROCHLORIDE (1:2)

Systematic Name

English

PROPYLDAZINE HYDROCHLORIDE

Common Name

English

3-(3-((2R,3S)-3-HYDROXY-2-PIPERIDINYL)-2-OXOPROPYL)-4(3H)-QUINAZOLINONE DIHYDROCHLORIDE

Systematic Name

English

2-PROPANOL, 1-((6-HYDRAZINYL-3-PYRIDAZINYL)METHYLAMINO)-, HYDROCHLORIDE (1:2)

Systematic Name

English

FEBRIFUGINE, DIHYDROCHLORIDE

Common Name

English

1-((6-HYDRAZINYL-3-PYRIDAZINYL)METHYLAMINO)-2-PROPANOL

Systematic Name

English

(+)-FEBRIFUGINE DIHYDROCHLORIDE

Common Name

English

Code System Code Type Description

FDA UNII

K922TFG9SM