4-AMINOTETRAHYDROBIOPTERIN DIHYDROCHLORIDE DIHYDRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H16N6O2.2ClH.2H2O
Molecular Weight	349.215
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of 4-AMINOTETRAHYDROBIOPTERIN DIHYDROCHLORIDE DIHYDRATE

Structure Search

SMILES

O.O.Cl.Cl.[H][C@@]1(CNC2=NC(N)=NC(N)=C2N1)[C@@H](O)[C@H](C)O

InChI

InChIKey=UWHDTHZEDSYSLS-YWUWEZHCSA-N

InChI=1S/C9H16N6O2.2ClH.2H2O/c1-3(16)6(17)4-2-12-8-5(13-4)7(10)14-9(11)15-8;;;;/h3-4,6,13,16-17H,2H2,1H3,(H5,10,11,12,14,15);2*1H;2*1H2/t3-,4+,6-;;;;/m0..../s1

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C9H16N6O2
Molecular Weight	240.2623
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.io.nihr.ac.uk/wp-content/uploads/2018/02/8276-Ronopterin-for-traumatic-brain-injury-JAN2018-V1.0-NON-CONF.pdf | https://adisinsight.springer.com/drugs/800023224 | https://www.vasopharm.com/clinical-development/disease-focus.html

Vasopharm BIOTECH is developing 4-aminotetrahydrobiopterin (ronopterin, VAS 203), a nitric oxide synthase inhibitor, for the treatment of traumatic brain injury. Ronopterin is an allosteric nitric oxide (NO) synthase inhibitor interacting with the tetrahydrobiopterinbinding site of the enzyme. Pre-clinical, proof-of-principle studies using controlled cortical impact showed that VAS203 had significant and positive effects on elevated intracranial pressure (ICP), which contributes to the deleterious consequences of TBI, as well as on neurological outcome measured with behavioural tests. By targeting both cerebral blood vessels and cerebral tissue in a region-specific manner VAS203 represents a completely novel pharmacological approach to TBI that can be administrated in addition to best standard of care. Ronopterin is currently in development for the treatment of traumatic brain injury.In the phase III clinical trial, ronopterin is administered as a 17 mg/kg intravenous infusion over 48 hours (daily dose of 8.5 mg/kg).

CNS Activity

Originator

Approval Year

PubMed

Title	Date	PubMed
A 4-amino analogue of tetrahydrobiopterin attenuates endotoxin-induced hemodynamic alterations and organ injury in rats.	2002 Aug	12166780
Effects of the nitric oxide synthase inhibitor ronopterin (VAS203) on renal function in healthy volunteers.	2019 May	30666700

Sample Use Guides

In Vivo Use Guide

In the phase III clinical trial, ronopterin is administered as a 17 mg/kg intravenous infusion over 48 hours (daily dose of 8.5 mg/kg)

Route of Administration: Intravenous

In Vitro Use Guide

Endothelium-dependent relaxations of pig pulmonary and coronary artery strips to bradykinin or calcium ionophore A23187 were inhibited by 4-aminotetrahydrobiopterin in a concentration-dependent manner. Half-maximal inhibition was observed at 60 - 65 uM (pulmonary artery) and 200 - 250 uM 4-aminotetrahydrobiopterin (coronary artery). Pig coronary artery strips precontracted with 0.1 uM 9, 11-dideoxy-9, 11-methanoepoxy-prosta-glandin F(2alpha) (U46619) showed a time-dependent relaxation (monitored for up to 18 h) upon incubation with 1 ug ml(-1) lipopolysaccharide (LPS). Addition of 10 uM 4-aminotetrahydrobiopterin 1 h after LPS led to a pronounced inhibition of the LPS-triggered relaxation. Incubation of pulmonary and coronary artery strips with 1 ug ml(-1) LPS attenuated contractile responses to norepinephrine (1 uM) and U46619 (0.1 uM). This hyporeactivity of the blood vessels to vasoconstrictor agents was inhibited by 4-aminotetrahydrobiopterin in a concentration-dependent manner [IC(50)=17.5+/-5.9 uM (pulmonary artery) and 20.7+/-3 uM (coronary artery)]. The effect of 0.1 mM 4-ABH(4) was antagonized by coincubation with 0.1 mM sepiapterin.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 18:18:37 GMT 2023` Edited by `admin` on `Sat Dec 16 18:18:37 GMT 2023`
Record UNII	ZFE6KX23QA
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

4-AMINOTETRAHYDROBIOPTERIN DIHYDROCHLORIDE DIHYDRATE

Common Name

English

RONOPTERIN DIHYDROCHLORIDE DIHYDRATE

Common Name

English

RONOPTERIN DIHYDROCHLORIDE DIHYDRATE, (6R)-

Common Name

English

1,2-PROPANEDIOL, 1-((6R)-2,4-DIAMINO-5,6,7,8-TETRAHYDRO-6-PTERIDINYL)-, HYDROCHLORIDE, HYDRATE (1:2:2), (1R,2S)-

Systematic Name

English

Code System Code Type Description

CAS

1815587-06-4