2-Aminoisocytosine

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H6N4O
Molecular Weight	126.1168
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=CC(=O)N=C(N)N1

InChI

InChIKey=SWELIMKTDYHAOY-UHFFFAOYSA-N

InChI=1S/C4H6N4O/c5-2-1-3(9)8-4(6)7-2/h1H,(H5,5,6,7,8,9)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9694862 | https://www.ncbi.nlm.nih.gov/pubmed/12441764

2,4-Diamino-6-hydroxypyrimidine is a selective, specific inhibitor of GTP cyclohydrolase I, a rate-limiting enzyme for the de novo biosynthesis of biopterin. Experiments in rats have shown that 4-Diamino-6-hydroxypyrimidine possesses protective effects against postburn Staphylococcus aureus sepsis.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GTP cyclohydrolase 1 2 Target ID: P30793 Gene ID: 2643.0 Gene Symbol: GCH1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9694862	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postburn Staphylococcal sepsis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12441764	Preventing		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
2,6-Diamino-4-oxo-3,4-dihydropyrim-idin-1-ium chloride dihydrate.	2010-08-11	21588646
Design, synthesis and evaluation of 2-amino-4-m-bromoanilino-6-arylmethyl-7H-pyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors and antiangiogenic agents.	2010-07-15	20558072
Synthesis and biological activity of N(4)-phenylsubstituted-6-(2,4-dichloro phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as vascular endothelial growth factor receptor-2 inhibitors and antiangiogenic and antitumor agents.	2010-05-15	20403700
Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats.	2010-05	20185690
Novel riboswitch ligand analogs as selective inhibitors of guanine-related metabolic pathways.	2010-04-22	20421948
Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry.	2010-02-11	20085328
Role of tetrahydrobiopterin in resistance to myocardial ischemia in Brown Norway and Dahl S rats.	2009-11	19717731
DFT simulations and vibrational analysis of FT-IR and FT-Raman spectra of 2,4-diamino-6-hydroxypyrimidine.	2009-08-15	19406685
Highly diastereoselective domino synthesis of 6-spirosubstituted pyrido[2,3-d]pyrimidine derivatives in water.	2009-06-23	19537742
A facile synthetic approach to 7-deazaguanine nucleosides via a Boc protection strategy.	2009-06-04	19422208
Metallothionein abrogates GTP cyclohydrolase I inhibition-induced cardiac contractile and morphological defects: role of mitochondrial biogenesis.	2009-06	19398661
Acute inhibition of guanosine triphosphate cyclohydrolase 1 uncouples endothelial nitric oxide synthase and elevates blood pressure.	2008-09	18645049
Three-day tetrahydrobiopterin therapy increases in vivo hepatic NOS activity and reduces portal pressure in CCl4 cirrhotic rats.	2008-08	18534709
Effect of decreased levels of intrinsic tetrahydrobiopterin on endothelial function in anesthetized rats.	2008-05	18446004
2,4-Diamino-6-hydroxypyrimidine (DAHP) suppresses cytokine-induced VCAM-1 expression on the cell surface of human umbilical vein endothelial cells in a BH(4)-independent manner.	2007-11-05	18423409
Regulation of tetrahydrobiopterin biosynthesis by shear stress.	2007-10-12	17704208
Alu recombination-mediated structural deletions in the chimpanzee genome.	2007-10	17953488
An efficient route for the synthesis of a new class of pyrido[2,3-d]pyrimidine derivatives.	2007-05-07	17464415
C-Reactive protein-induced endothelial microparticle generation in HUVECs is related to BH4-dependent NO formation.	2007	17351328
Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats.	2006-04-29	16645543
Folic acid reverses endothelial dysfunction induced by inhibition of tetrahydrobiopterin biosynthesis.	2006-01-20	16387296
Neural tube closure depends on nitric oxide synthase activity.	2006-01	16300634
Synthesis and antitumor activity of some novel quinazoline derivatives bearing the biologically active thione moiety.	2006	17063643
Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase.	2005-12-07	16216381
Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates cerebral infarction via reducing inducible NO synthase and peroxynitrite in ischemic stroke.	2005-12	16282548
Immobilization stress causes increases in tetrahydrobiopterin, dopamine, and neuromelanin and oxidative damage in the nigrostriatal system.	2005-10	16181415
Crystal structure and luminescence of lanthanide monodentate complexes [Ln(C(4)N(4)H(6)O)(2)(H(2)O)(6)]Cl(3) and [Ln(C(4)N(4)H(6)O)(2)(H(2)O)(3)(NO(3))(3)] (Ln = Tb or Eu).	2005-06-13	15934740
Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.	2004-12-30	15615538
Effect of tetrahydrobiopterin on nitric oxide synthase-containing cells in the rat hippocampus.	2004-10	15380323
The mechanism of potent GTP cyclohydrolase I inhibition by 2,4-diamino-6-hydroxypyrimidine: requirement of the GTP cyclohydrolase I feedback regulatory protein.	2004-09-24	15292175
A new and efficient synthesis of pyrrolo[2,3-d]pyrimidine anticancer agents: Alimta (LY231514, MTA), homo-Alimta, TNP-351, and some aryl 5-substituted pyrrolo[2,3-d]pyrimidines.	2003-12-26	14682686
Tetrahydrobiopterin, a critical factor in the production and role of nitric oxide in mast cells.	2003-12-12	14514683
Antiangiogenic and antitumor agents. Design, synthesis, and evaluation of novel 2-amino-4-(3-bromoanilino)-6-benzylsubstituted pyrrolo[2,3-d]pyrimidines as inhibitors of receptor tyrosine kinases.	2003-11-17	14604679
GTP cyclohydrolase 1 inhibition attenuates vasodilation and increases blood pressure in rats.	2003-11	12855421
Kainic acid lesion-induced nigral neuronal death.	2003-08	12954531
Exogenous biopterins requirement for iNOS function in vascular smooth muscle cells.	2003-08	12883322
Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase.	2003-06-20	12692136
Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures.	2003-04	12641743
Increased vulnerability to ischemia/reperfusion-induced ventricular tachyarrhythmias by pre-ischemic inhibition of nitric oxide synthase in isolated rat hearts.	2003-02-25	12598018
HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells.	2003-02-01	12588756
Wavelength-dependent induction of a mycosporine-like amino acid in a rice-field cyanobacterium, Nostoc commune: role of inhibitors and salt stress.	2003-02	12664980
Role of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts.	2003-02	12627070
Non-classical antifolates, 5-(N-phenylpyrrolidin-3-yl)-2,4,6-triaminopyrimidines and 2,4-Diamino-6(5H)-oxopyrimidines, synthesis and antitumor studies.	2003-01-02	12467717
Effect of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats.	2002-11	12441764
Tetrahydrobiopterin deficiency increases neuronal vulnerability to hypoxia.	2002-09	12358762
Possible involvement of tetrahydrobiopterin in the trophic effect of insulin-like growth factor-1 on rat pheochromocytoma-12 (PC12) cells.	2002-08-09	12133588
Lack of nitric oxide mediation of flow-dependent arteriolar dilation in type I diabetes is restored by sepiapterin.	2002-05-02	12644725
[The protective effects and its underlying mechanism of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats].	2002-04	12515652
A new one-pot three-component condensation reaction for the synthesis of 5-deaza-5,8-dihydropterins.	2001-12-07	12240003
Guanosine triphosphate cyclohydrolase I regulates nitric oxide synthesis in renal proximal tubules.	1995-02	7756597

Patents

Sample Use Guides

In Vivo Use Guide

Male Wistar rats: animals were intraperitoneally injected with a dose of 1 g/kg 2,4-diamino-6-hydroxy-pyrimidine (DAHP) before Staphylococcus aureus challenge and then were further divided into 2- and 6-hr groups

Route of Administration: Intraperitoneal

In Vitro Use Guide

In interferon-gamma-activated murine peritoneal macrophages 2,4-diamino-6-hydroxy-pyrimidine suppresses the expression of iNOS mRNA and protein in a tetrahydrobiopterin (BH4)-independent manner and, thus, acts by a novel mechanism.

Name

Type

Language

2-Aminoisocytosine

Common Name

English

2,4-DIAMINO-6-HYDROXYPYRIMIDINE

Preferred Name

English

NSC-9302

Code

English

NSC-680818

Code

English

4(1H)-PYRIMIDINONE, 2,6-DIAMINO-

Systematic Name

English

NSC-44914

Code

English

2,6-DIAMINO-4(3H)-PYRIMIDINONE

Systematic Name

English

4(3H)-PYRIMIDINONE, 2,6-DIAMINO-

Systematic Name

English

2,4-DIAMINO-6-HYDROXYPYRIMIDINE [MI]

Common Name

English

Code System Code Type Description

PUBCHEM

135408763