2-Chloroadenine
(Synonyms: 2-氯-6-氨基嘌呤) 目录号 : GC46539
A heterocyclic building block
Cas No.:1839-18-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
2-Chloroadenine is a heterocyclic building block that has been used in the synthesis of adenosine antimetabolites with antineoplastic activity.1 It is also the major catabolite of 2-chloro-2'-deoxyadenosine.2
1.Bauta, W.E., Schulmeier, B.E., Burke, B.J., et al.A new process for antineoplastic agent clofarabineOrg. Proc. Res. Dev.8(6)889-896(2004) 2.Bontemps, F., Delacauw, A., Cardoen, S., et al.Metabolism and cytotoxic effects of 2-chloroadenine, the major catabolite of 2-chloro-29-deoxyadenosineBiochem. Pharmacol.59(10)1237-1243(2000)
| Cas No. | 1839-18-5 | SDF | |
| 别名 | 2-氯-6-氨基嘌呤 | ||
| Canonical SMILES | NC1=C2C(N=CN2)=NC(Cl)=N1 | ||
| 分子式 | C5H4ClN5 | 分子量 | 169.6 |
| 溶解度 | Ethanol: slightly soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.8962 mL | 29.4811 mL | 58.9623 mL |
| 5 mM | 1.1792 mL | 5.8962 mL | 11.7925 mL |
| 10 mM | 0.5896 mL | 2.9481 mL | 5.8962 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors
J Med Chem 2020 Dec 24;63(24):15852-15863.PMID:33291877DOI:10.1021/acs.jmedchem.0c01573.
To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-Chloroadenine derivatives based on the hit clofarabine. Structure-based design targeting Tyr748 in PDE8 resulted in the lead compound 3a (IC50 = 0.010 μM) with high selectivity with a reasonable druglike profile. In the X-ray crystal structure, 3a bound to PDE8A with a different mode from 3-isobutyl-1-methylxanthine (a pan-PDE inhibitor) and gave a H-bond of 2.7 Å with Tyr748, which possibly interprets the 220-fold selectivity of 3a against PDE2A. Additionally, oral administration of compound 3a achieved remarkable therapeutic effects against vascular dementia (VaD), indicating that PDE8 inhibitors could serve as potential anti-VaD agents.
Metabolism and cytotoxic effects of 2-Chloroadenine, the major catabolite of 2-chloro-2'-deoxyadenosine
Biochem Pharmacol 2000 May 15;59(10):1237-43.PMID:10736424DOI:10.1016/s0006-2952(00)00258-6.
EHEB cells, a continuous cell line derived from a patient with B cell chronic lymphocytic leukemia (B-CLL), synthesized, when incubated with tritiated 2-chloro-2'-deoxyadenosine (CdA), labeled mono-, di-, and triphosphate ribonucleosides at a much higher rate than CdA deoxyribonucleotides. Further analysis revealed that these ribonucleotides were formed from labeled 2-Chloroadenine (CAde), which contaminated commercial tritiated CdA at a proportion of 2-3%. Since CAde is the major catabolite of CdA measured in plasma after oral or intravenous administration of CdA to patients, its metabolism and in particular its potential cytotoxicity were investigated both in EHEB cells and in B-CLL lymphocytes. Phosphorylation of CAde was inhibited by adenine, indicating that its initial metabolism most probably proceeds via adenine phosphoribosyltransferase (EC 2.4.2.7). In both cell types, chloro-ATP was the major metabolite formed from CAde and its concentration increased proportionally at least up to 50 microM CAde. At high concentration, CAde metabolism was accompanied by a decrease in intracellular ATP. Cytotoxicity of CAde, evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, showed an IC(50) of 16 microM in EHEB cells and 5 microM in B-CLL lymphocytes. At cytotoxic concentrations, apopain/caspase-3 activation and high molecular weight DNA fragmentation were observed, indicating that CAde cytotoxicity results from induction of apoptosis. However, since CAde cytotoxicity requires higher concentrations than CdA, it probably does not play a role in the therapeutic effect of CdA in the treatment of hematologic malignancies.
Stability and analysis of 2-chloro-2'-deoxyadenosine, 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine and 2-Chloroadenine in human blood plasma
Anticancer Drugs 1997 Jun;8(5):445-53.PMID:9215606DOI:10.1097/00001813-199706000-00005.
Cladribine (2-chloro-2'-deoxyadenosine, CdA) is a purine nucleoside analog with activity against lymphoproliferative and autoimmune disorders. 2-Chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA), a derivative of CdA with better acid stability, shows a similar in vitro spectrum of activity as CdA. 2-Chloroadenine (CAde) is the major catabolite of both CdA and CAFdA. We have developed a high performance liquid chromatography method to measure CdA, CAFdA and their metabolite CAde in plasma. This method employees an internal standard, chloroadenosine (CAdo), and a C8 solid-phase extraction to isolate and concentrate the substances. Chromatographic separation was achieved using a C8 reverse-phase column, with UV detection at 265 nm, which gives a limit of detection of 1 nmol/l for all substances. The method was reproducible with intra- and inter-assay coefficients of variations below 6% at 50 nmol/l and at 5 nmol/l below 23%. The average recoveries of CdA, CAde, CAFdA and the internal standard were higher than 70%. Stability studies of authentic patient samples show that samples containing CdA should be kept in a refrigerator or on ice to prevent degradation. Plasma containing CAde should not be kept at -20 degrees C for longer than 10 weeks before analysis. CdA and CAFdA remain almost stable during storage at -20 degrees C for 12 weeks.
Anion states and fragmentation of 2-Chloroadenine upon low-energy electron collisions
Phys Chem Chem Phys 2015 Nov 21;17(43):28958-65.PMID:26456239DOI:10.1039/c5cp04967a.
We report on a joint theoretical and experimental investigation into the electron-induced fragmentation of 2-Chloroadenine, for electrons up to 12 eV. Elastic scattering calculations indicate an anion spectrum comprising a σ(CCl)* and four π* shape resonances, where the latter are systematically stabilised when compared to the analogue states of adenine. The measured ion yields indicate strong signals associated with the elimination of neutral hydrogen (peaking at 0.8 eV and with milder structures up to 2 eV), chloride ions and hydrochloric acid (both observed at around 0.2 and 0.9 eV). Bound state calculations indicate that the main feature for hydrogen abstraction arises from a vibrational Feshbach resonance on a dipole-bound state coupled to a σ(NH)* state, while the π2* and π3* resonances initiate this fragmentation process in the 1-2 eV region. On the other hand, the C-Cl bond cleavage would mainly arise from the formation of the π1* and π2* resonances, which couple to the dissociative σ(CCl)* state. Our results show that 2-Chloroadenine efficiently dissociates into reactive species upon electron attachment, corroborating its potential as a radiosensitising drug.
Ni-Catalyzed Cross-Coupling of 2-Iodoglycals and 2-Iodoribals with Grignard Reagents: A Route to 2-C-Glycosides and 2'-C-Nucleosides
Chemistry 2022 May 11;28(27):e202104311.PMID:35238093DOI:10.1002/chem.202104311.
The synthesis of 2-C-glycals and 2-C-ribals was achieved in good yields using a nickel-catalyzed cross-coupling between 2-iodoglycals and 2-iodoribal respectively and Grignard reagents. The prepared 2-C-glycals and ribals were then transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides and 2'-C-2'-deoxynucleosides. The developed method was applied to the synthesis of a 2-Chloroadenine 2'-deoxyribonucleoside - a structural analogue of cladribine (Mavenclad®, Leustatin®) and clofarabine (Clolar®, Evoltra®), two compounds used in the treatment of relapsing-remitting multiple sclerosis and hairy cell leukemia.