| Stereochemistry | ABSOLUTE |
| Molecular Formula | C9H16N6O2 |
| Molecular Weight | 240.2623 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]1(CNC2=NC(N)=NC(N)=C2N1)[C@@H](O)[C@H](C)O
InChI
InChIKey=NDSDGUULXHNXGA-RPDRRWSUSA-N
InChI=1S/C9H16N6O2/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)/t3-,4+,6-/m0/s1
| Molecular Formula | C9H16N6O2 |
| Molecular Weight | 240.2623 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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
Sample Use Guides
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
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.
