Pyrimidine-4-Carboxylic Acid
(Synonyms: 4-嘧啶甲酸) 目录号 : GC44788
Synthetic intermediate
Cas No.:31462-59-6
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
Pyrimidine-4-carboxylic acid is a synthetic intermediate useful for pharmaceutical synthesis.
| Cas No. | 31462-59-6 | SDF | |
| 别名 | 4-嘧啶甲酸 | ||
| Canonical SMILES | OC(=O)c1ccncn1 | ||
| 分子式 | C5H4N2O2 | 分子量 | 124.1 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 20 mg/ml,Ethanol: 0.25 mg/ml,PBS (pH 7.2): 1 mg/ml | 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 | 8.058 mL | 40.2901 mL | 80.5802 mL |
| 5 mM | 1.6116 mL | 8.058 mL | 16.116 mL |
| 10 mM | 0.8058 mL | 4.029 mL | 8.058 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。
Intramolecular hydrogen bond interruption and scaffold hopping of TMC-5 led to 2-(4-alkoxy-3-cyanophenyl)pyrimidine-4/5-carboxylic acids and 6-(4-alkoxy-3-cyanophenyl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-ones as potent pyrimidine-based xanthine oxidase inhibitors
Eur J Med Chem 2022 Feb 5;229:114086.PMID:34992040DOI:10.1016/j.ejmech.2021.114086.
Many pyrimidine-based xanthine oxidase (XO) inhibitors with diverse chemotypes have been reported recently. Our previous study revealed that 2-(4-alkoxy-3-cyano)phenyl-6-imino-1,6-dihydropyrimidine-5-carboxylic acid derivatives exhibited remarkable XO inhibitory potency. Notably, an intramolecular hydrogen bond (IMHB) formed between amino and carboxylic groups could be observed. With the hope to expand the structure-activity relationships (SARs) and obtain potential pyrimidine-based XO inhibitors, IMHB interruption and scaffold hopping were carried out on these compounds to design 2-(4-alkoxy-3-cyanophenyl)pyrimidine-4/5-carboxylic acids (11a-11n and 15a-15j) and 6-(4-alkoxy-3-cyanophenyl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-ones (19a-19j). Among them, compound 19a (IC50 = 0.039 μM) was identified as the most promising compound with substantially higher in vitro inhibitory potency than allopurinol (IC50 = 7.590 μM) and comparable to febuxostat (IC50 = 0.028 μM). The SAR analysis revealed that interrupting the IMHB through the removal of the amino group could damage the XO inhibitory potency; Pyrimidine-4-Carboxylic Acid moiety was more beneficial for the XO inhibitory potency than the pyrimidine-5-carboxylic acid moiety. Additionally, enzyme kinetics studies suggested that compounds 11a, 15a and 19a acted as mixed-type inhibitors for XO and the removal of 6-position amino group resulted in a weakened affinity to the free enzyme, but an enhanced binding to the enzyme-substrate complex. Molecular modeling provided a reasonable explanation for the SARs observed in this study. Furthermore, in vivo hypouricemic effects demonstrated that compounds 15a and 19a could effectively reduce serum uric acid levels at an oral dose of 10 mg/kg, with 19a demonstrating a stronger effect than 15a. Therefore, our study proved that 6-(4-alkoxy-3-cyanophenyl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-ones were potent pyrimidine-based XO inhibitors and compound 19a required further structural optimization as a potential and efficacious agents for the treatment of hyperuricemia and gout.
Ruthenium(II) complexes incorporating 2-(2'-pyridyl)Pyrimidine-4-Carboxylic Acid
Inorg Chem 2009 Jan 5;48(1):68-81.PMID:19053847DOI:10.1021/ic800972x.
A new bidentate ligand bearing a single carboxylate functionality, 2-(2'-pyridyl)Pyrimidine-4-Carboxylic Acid (cppH), has been prepared and applied in the synthesis of a series of ruthenium(II) complexes. Reaction of this new ligand with Ru(II)(bpy)(2)Cl(2) led to the unexpected oxidation of the starting material to give [Ru(III)(bpy)(2)Cl(2)]Cl.H(2)O and a low yield of [Ru(II)(bpy)(2)(cppH)](PF(6))(2).H(2)O (1) on addition of an aqueous KPF(6) solution (bpy = 2,2'-bipyridine and cpp = 4-carboxylate-2'-pyridyl-2-pyrimidine). An X-ray crystal structure determination on crystals of 1a, [Ru(II)(bpy)(2)(cpp)](PF(6)), obtained from slow evaporation of an aqueous solution of 1 revealed that the nitrogen para to the carboxylate group in the cpp(-) ligand coordinates to the ruthenium(II) center rather than that ortho to this group. The same complex was prepared via decarbonylation of [Ru(II)(cppH)(CO)(2)Cl(2)].H(2)O in the presence of bpy and an excess of trimethylamine-N-oxide (Me(3)NO), as the decarbonylation agent. The coordination of cppH in the precursor is the same as in the final product. The related complex [Ru(II)(phen)(2)(cppH)](PF(6))(2).2H(2)O (2) (phen = 1,10-phenanthroline) was similarly synthesized. [Ru(II)(bpy)(dppz)(cppH)](PF(6))(2).CH(3)CN (3) (dppz = dipyrido[3,2,-a;2',3-c]phenazine) was also prepared by photochemical decarbonylation of [Ru(II)(bpy)(CO)(2)Cl(2)] giving [Ru(II)(bpy)(CO)Cl(2)](2) followed by bridge splitting with dppz to generate [Ru(II)(bpy)(dppz)(CO)Cl](PF(6)).H(2)O. This intermediate was then reacted with cppH to produce 3, as a mixture of geometric isomers. In contrast to 1, X-ray crystallography on the major product isolated from this mixture, [Ru(II)(bpy)(dppz)(cpp)](NO(3)).10H(2)O, 3(N3) indicated that the nitrogen adjacent to the carboxylate was coordinated to ruthenium(II). Full characterization of these complexes has been undertaken including the measurement of UV-visible and emission spectra. Electrochemical and spectroelectrochemical studies in acetonitrile show that these complexes undergo reversible oxidation from Ru(II) to Ru(III) at potentials of 983 +/- 3 mV, 1004 +/- 5 mV, and 1023 +/- 3 mV versus Fc(0/+) (Fc = Ferrocene) for 1, 2, and 3(N3), respectively.
Bis(dipyridophenazine)(2-(2'-pyridyl)Pyrimidine-4-Carboxylic Acid)ruthenium(II) hexafluorophosphate: a lesson in stubbornness
ChemMedChem 2014 Jul;9(7):1419-27.PMID:24591361DOI:10.1002/cmdc.201400029.
Ruthenium complexes are currently considered to be among the most promising alternatives to platinum anticancer drugs. In this work, thirteen structural analogues and organelle/receptor-targeting peptide bioconjugates of a cytotoxic bis(dppz)-Ru(II) complex [Ru(dppz)2 (CppH)](PF6 )2 (1) were prepared, characterized, and assessed for their cytotoxicity and cellular localization (CppH=2-(2'-pyridyl)Pyrimidine-4-Carboxylic Acid; dppz=dipyrido[3,2-a:2',3'-c]phenazine). It was observed that structural modifications (lipophilicity, charge, and size-based) result in the cytotoxic potency of 1 being compromised. Confocal microscopy studies revealed that unlike 1, the screened complexes/bioconjugates do not have a preferential accumulation in mitochondria. The results of this important structure-activity relationship strongly support our initial hypothesis that accumulation in mitochondria is crucial for 1 to exert its cytotoxic action.
A bis(dipyridophenazine)(2-(2-pyridyl)Pyrimidine-4-Carboxylic Acid)ruthenium(II) complex with anticancer action upon photodeprotection
Angew Chem Int Ed Engl 2014 Mar 10;53(11):2960-3.PMID:24500767DOI:10.1002/anie.201309576.
Improving the selectivity of anticancer drugs towards cancer cells is one of the main goals of drug optimization; the prodrug strategy has been one of the most promising. A light-triggered prodrug strategy is presented as an efficient approach for controlling cytotoxicity of the substitutionally inert cytotoxic complex [Ru(dppz)2(CppH)](PF6)2(C1; CppH=2-(2-pyridyl)Pyrimidine-4-Carboxylic Acid; dppz=dipyrido[3,2-a:2',3'-c]phenazine). Attachment of a photolabile 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) ester ("photocaging") makes the otherwise active complex C1 innocuous to both cancerous (HeLa and U2OS) and non-cancerous (MRC-5) cells. The cytotoxic action can be successfully unleashed in living cells upon light illumination (350 nm), reaching similar level of activity as the parent cytotoxic compound C1. This is the first substitutionally inert cytotoxic metal complex to be used as a light-triggered prodrug candidate.
Ru(ii)-Peptide bioconjugates with the cppH linker (cppH = 2-(2'-pyridyl)Pyrimidine-4-Carboxylic Acid): synthesis, structural characterization, and different stereochemical features between organic and aqueous solvents
Dalton Trans 2019 Jan 2;48(2):400-414.PMID:30285015DOI:10.1039/c8dt03575j.
Three new Ru(ii) bioconjugates with the C-terminal hexapeptide sequence of neurotensin, RRPYIL, namely trans,cis-RuCl2(CO)2(cppH-RRPYIL-κNp) (7), [Ru([9]aneS3)(cppH-RRPYIL-κNp)(PTA)](Cl)2 (8), and [Ru([9]aneS3)Cl(cppH-RRPYIL-κNp)]Cl (11), where cppH is the asymmetric linker 2-(2'-pyridyl)Pyrimidine-4-Carboxylic Acid, were prepared in pure form and structurally characterized in solution. The cppH linker is capable of forming stereoisomers (i.e. linkage isomers), depending on whether the nitrogen atom ortho (No) or para (Np) to the carboxylate on C4 in the pyrimidine ring binds the metal ion. Thus, one of the aims of this work was to obtain pairs of stereoisomeric conjugates and investigate their biological (anticancer, antibacterial) activity. A thorough NMR characterization clearly indicated that in all cases exclusively Np conjugates were obtained in pure form. In addition, the NMR studies showed that, whereas in DMSO-d6 each conjugate exists as a single species, in D2O two (7) or even three if not four (8 and 11) very similar stable species form (each one corresponding to an individual compound). Similar results were observed for the cppH-RRPYIL ligand alone. Overall, the NMR findings are consistent with the occurrence of a strong intramolecular stacking interaction between the phenol ring of tyrosine and the pyridyl ring of cppH. Such stacking interactions between aromatic rings are expected to be stronger in water. This interaction leads to two stereoisomeric species in the free cppH-RRPYIL ligand and in the bioconjugate 7, and is somehow modulated by the less symmetrical Ru coordination environments in 8 and 11, affording three to four very similar species.