82499-02-3

Basic information

• Product Name: 2-CHLORO-N-METHYL-9H-PURIN-6-AMINE
• Synonyms: 2-CHLORO-N-METHYL-9H-PURIN-6-AMINE
• CAS NO: 82499-02-3
• Molecular Formula: C₆H₆ClN₅
• Molecular Weight: 183.6
• Product Categories: Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Purines;PurinesHeterocyclic Building Blocks;Building Blocks;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks
• Mol File: 82499-02-3.mol

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 282.1°C at 760 mmHg
• Flash Point: 124.4°C
• Appearance: /
• Density: 1.76g/cm³
• Vapor Pressure: 0.00343mmHg at 25°C
• Refractive Index: 1.807
• CAS DataBase Reference: 2-CHLORO-N-METHYL-9H-PURIN-6-AMINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-CHLORO-N-METHYL-9H-PURIN-6-AMINE(82499-02-3)
• EPA Substance Registry System: 2-CHLORO-N-METHYL-9H-PURIN-6-AMINE(82499-02-3)

Safety Data

• Hazard Codes: Xn
• Statements: 22-43-41-37/38
• Safety Statements: 36/37-39-26
• WGK Germany: 3
• Hazardous Substances Data: 82499-02-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-CHLORO-N-METHYL-9H-PURIN-6-AMINE is used as a building block for the synthesis of various pharmaceuticals and nucleoside analogs due to its structural properties that facilitate the development of new drugs.
Used in Antiviral Drug Development:
2-CHLORO-N-METHYL-9H-PURIN-6-AMINE is used as a key component in the development of antiviral drugs for its ability to inhibit enzymes involved in viral replication, thereby helping to control viral infections.
Used in Anticancer Drug Development:
2-CHLORO-N-METHYL-9H-PURIN-6-AMINE is used as a potential anticancer agent for its capacity to inhibit enzymes involved in DNA and RNA synthesis, which can disrupt the proliferation of cancer cells.
Used in Enzyme Inhibition Research:
2-CHLORO-N-METHYL-9H-PURIN-6-AMINE is used as a research tool to study the inhibition of key enzymes involved in nucleic acid synthesis, providing insights into the mechanisms of action for potential therapeutic agents.
Used in Therapeutic Applications for Various Diseases:
2-CHLORO-N-METHYL-9H-PURIN-6-AMINE is used in the exploration of its biological activities and potential therapeutic applications in treating various disease conditions, leveraging its unique chemical properties to target specific biological processes.

InChI:InChI=1/C6H6ClN5/c1-8-4-3-5(10-2-9-3)12-6(7)11-4/h2-3H,1H3,(H,8,9,10,11,12)

Upstream product

• 74-89-5 methylamine 
• 5451-40-1 2,6-dichloro-7H-purine 
• 5451-40-1 2,6 dichloropurine 

Downstream Products

• 262863-49-0 9-bis(2-dibenzylphosphatoethylamino)-acetyl-2-chloro-6-methylamino-purine 
• 264611-17-8 1,5-anhydro-2-(2-chloro-N⁶-methyladenin-9-yl)-2,3-dideoxy-D-arabino-hexitol-4,6-(dibenzyl phosphate) 
• 1027657-72-2 2-[2-(2-chloro-6-methylamino-purin-9-yl)-ethyl]-propane-1,3-bisoxy(dibenzylphosphate) 
• 262863-50-3 tetramethyl (2-chloro-6-methylamino-purin-9-yl)-acetaminophenyl-3',5'-bis(methylphosphonate) 
• 1026464-95-8 2-[2-(2-chloro-6-methylamino-purin-9-yl)-ethyl]-2-ethoxycarbonyl-malonic acid diethyl ester 

Relevant articles and documents

Synthesis and biological evaluation of aminobenzamides containing purine moiety as class I histone deacetylases inhibitors

The aminobenzamide is selective to class I histone deacetylases (HDACs) and displays unique tight-binding/slow-off HDAC-binding mechanism. Herein, we report a series of 9-substituted purine aminobenzamides that selectively inhibit class I HDACs. The activities in vitro showed compound 9d exhibited 12 folds more potent than MS-275 against HDAC1 isoform and showed excellent inhibitory activity on cancer cells, including HCT-116, MDA-MB-231, K562 cell lines. The metabolic stability of 9d was much better than that of the well-known HDAC inhibitor SAHA. Pulse exposure test of western blot assay demonstrated that 9a, 9d induced histone acetylation in a similar manner to MS-275. Further biological validation demonstrated that 9d prevented cell transition from G1 phase to S phase by reducing Cyclin D1, CDK2 and lifting p21, induced early apoptosis by upregulating BAX and downregulating Bcl-2 in HCT-116 cells.

Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead for Trypanosoma brucei Inhibitors

Human African trypanosomiasis (HAT), or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and transmitted through the bite of infected tsetse flies. The disease is considered fatal if left untreated. To identify new chemotypes against Trypanosoma brucei, previously we identified 797 potent kinase-targeting inhibitors grouped into 59 clusters plus 53 singleton compounds with at least 100-fold selectivity over HepG2 cells. From this set of hits, a cluster of diaminopurine-derived compounds was identified. Herein, we report our medicinal chemistry investigation involving the exploration of structure-activity and structure-property relationships around one of the high-throughput screening (HTS) hits, N2-(thiophen-3-yl)-N6-(2,2,2-trifluoroethyl)-9H-purine-2,6-diamine (1, NEU-1106). This work led to the identification of a potent lead compound (4aa, NEU-4854) with improved in vitro absorption, distribution, metabolism, and excretion (ADME) properties, which was progressed into proof-of-concept translation of in vitro antiparasitic activity to in vivo efficacy.

Syntheses and biological evaluation of novel hydroxamic acid derivatives containing purine moiety as histone deacetylase inhibitors

The novel hydroxamates containing purine scaffold were designed, synthesized and screened for their biological activities as histone deacetylase (HDAC) inhibitors. Some of them exhibited excellent acti-HDACs activities and antiproliferative activities, th

Rational Design of Selective Adenine-Based Scaffolds for Inactivation of Bacterial Histidine Kinases

Bacterial histidine kinases (HKs) are quintessential regulatory enzymes found ubiquitously in bacteria. Apart from their regulatory roles, they are also involved in the production of virulence factors and conferring resistance to various antibiotics in pathogenic microbes. We have previously reported compounds that inhibit multiple HKs by targeting the conserved catalytic and ATP-binding (CA) domain. Herein, we conduct a detailed structure-activity relationship assessment of adenine-based inhibitors using biochemical and docking methods. These studies have resulted in several observations. First, interaction of an inhibitor's amine group with the conserved active-site Asp is essential for activity and likely dictates its orientation in the binding pocket. Second, a N-NH-N triad in the inhibitor scaffold is highly preferred for binding to conserved Gly:Asp:Asn residues. Lastly, hydrophobic electron-withdrawing groups at several positions in the adenine core enhance potency. The selectivity of these inhibitors was tested against heat shock protein 90 (HSP90), which possesses a similar ATP-binding fold. We found that groups that target the ATP-lid portion of the catalytic domain, such as a six-membered ring, confer selectivity for HKs.

LRRK2 INHIBITORS AND METHODS OF MAKING AND USING THE SAME

Compounds having the formula (I), (II), (III) are provided. Compounds of the present disclosure are useful for the treatment of neurodegenerative diseases, such as Parkinson's Disease.

Discovery of a pyrrolopyrimidine (JH-II-127), a highly potent, selective, and brain penetrant LRRK2 inhibitor

Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here we report a 2-anilino-4-methylamino-5-chloropyrrolopyrimidine, JH-II-127 (18

Exploring 9-benzyl purines as inhibitors of glutamate racemase (MurI) in Gram-positive bacteria

An early SAR study of a screening hit series has generated a series of 9-benzyl purines as inhibitors of bacterial glutamate racemase (MurI) with micromolar enzyme potency and improved physical properties. X-ray co-crystal EI structures were obtained.

Synthesis, biological activity, and molecular modeling of ribose- modified deoxyadenosine bisphosphate analogues as P2Y1 receptor ligands

The structure-activity relationships of adenosine-3',5'-bisphosphates as P2Y1 receptor antagonists have been explored, revealing the potency- enhancing effects of the N6-methyl group and the ability to substitute the ribose moiety (Nandanan et al. J. Med. Chem. 1999, 42, 1625-1638). We have introduced constrained carbocyclic rings (to explore the role of sugar puckering), non-glycosyl bonds to the adenine moiety, and a phosphate group shift. The biological activity of each analogue at P2Y1 receptors was characterized by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit its stimulation elicited by 30 nM 2-methylthioadenosine-5'-diphosphate (antagonist effect). Addition of the N6-methyl group in several cases converted pure agonists to antagonists. A carbocyclic N6-methyl-2'-deoxyadenosine bisphosphate analogue was a pure P2Y1 receptor antagonist and equipotent to the ribose analogue (MRS 2179). In the series of ring-constrained methanocarba derivatives where a fused cyclopropane moiety constrained the pseudosugar ring of the nucleoside to either a Northern (N) or Southern (S) conformation, as defined in the pseudorotational cycle, the 6-NH2 (N)-analogue was a pure agonist of EC50 155 nM and 86-fold more potent than the corresponding (S)-isomer. The 2-chloro-N6-methyl-(N)-methanocarba analogue was an antagonist of IC50 51.6 nM. Thus, the ribose ring (N)-conformation appeared to be favored in recognition at P2Y1 receptors. A cyclobutyl analogue was an antagonist with IC50 of 805 nM, while morpholine ring-containing analogues were nearly inactive. Anhydrohexitol ring-modified bisphosphate derivatives displayed micromolar potency as agonists (6-NH2) or antagonists (N6-methyl). A molecular model of the energy-minimized structures of the potent antagonists suggested that the two phosphate groups may occupy common regions. The (N)- and (S)-methanocarba agonist analogues were docked into the putative binding site of the previously reported P2Y1 receptor model.

Anticonvulsive substituted-9-benzyl-9H-purines

The invention relates to novel 9H-purine derivatives, especially to the novel substituted 9-benzyl-9H-purines of the general formula STR1 in which Ph is a phenyl radical substituted by halogen, R1 is hydrogen or a free amino group or an amino group that is substituted aliphatically, cycloaliphatically, cycloaliphatically-aliphatically and/or by acyl, and R2 is halogen, lower alkoxy, lower alkyl, a free amino group, or an amino group that is substituted aliphatically, cycloaliphatically, cycloaliphatically-aliphatically and/or by acyl, with the proviso that R2 is other than halogen when Ph is 2-fluorophenyl or 2,5- or 2,6-difluorophenyl and R1 is a radical of the formula --N(R11)(R12) (Ia) in which either R11 is hydrogen, methyl or ethyl and R12 is hydrogen, methyl, hydroxymethyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclopenthyl or cyclopropylmethyl, or R11 is hydrogen and R12 is methoxymethyl, and with the further proviso that R2 is other than chlorine when Ph is 3-chlorophenyl, 4-chlorophenyl or 3,4-dichlorophenyl and R1 is N,N-dimethylamino, and to the novel compounds of formula I in which Ph is 2-fluorophenyl or 2,6-difluorophenyl, R1 is N-methylamino or N,N-dimethylamino and R2 is chlorine, and to the salts thereof in each case. These compounds and the salts thereof can be used as pharmaceutical active ingredients and can be manufactured in a manner known per se.