5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine

• ChemBase编号: 90
• 分子式: C12H13ClN4
• 平均质量: 248.71142
• 单一同位素质量: 248.08287412
• SMILES: Clc1ccc(c2c(nc(nc2N)N)CC)cc1
• Canonical SMILES: CCc1nc(N)nc(c1c1ccc(cc1)Cl)N
• InChI: InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
• InChIKey: WKSAUQYGYAYLPV-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
• IUPAC传统名: pyrimethamine
• 商标名: Darachlor; Daraclor; Darapram; Daraprim; Daraprime; Disulone; Erbaprelina; Fansidar; Khloridin; Malacid; Malocid; Malocide; Maloprim; Pirimecidan; Tindurin; Tinduring
• 别名: 6-乙基-5-(4-氯苯基)-2,4-嘧啶二胺; 乙胺嘧啶; 2,4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidine; Khloridin; Pirimetmin; NSC 3061; RP 4753; Pyrimethamine; Daraprim; Malocide; Pirimecidan; 5-(4-Chlorophenyl)-6-ethyl-2,4-pyrimidinediamine; 5-[4-Chlorophenyl]-6-ethyl-2,4-pyrimidinediamine; Pirimetamin; Chloridyn; Pyrimethamine; Pyrimethamine Hcl; Pyrimethamin; Pyremethamine; Ethylpyrimidine; Diaminopyritamin; CD; Chloridin; Chloridine; Primethamine; Pirimetamina; 5-(4-Chlorophenyl)-6-ethylpyriMidine-2,4-diaMine

登记号

• CAS号: 58-14-0
• EC号: 200-364-2
• MDL号: MFCD00057350
• Beilstein号: 219864
• PubChem SID: 24870381; 160963553; 46505987; 24898876
• PubChem CID: 4993
• CHEBI ID: 8673
• ATC码: P01BD01
• CHEMBL: 36
• Chemspider ID: 4819
• DrugBank ID: DB00205
• KEGG ID: D00488
• 美国药典/FDA物质标识码: Z3614QOX8W
• 维基百科标题: Pyrimethamine
• Medline Plus: a601050

理论计算性质

JChem

• Acid pKa: 17.222044
• 质子受体: 4
• 质子供体: 2
• LogD (pH = 5.5): 0.9725773
• LogD (pH = 7.4): 2.2334282
• Log P: 2.7483032
• 摩尔折射率: 71.542 cm^3
• 极化性: 27.221851 Å^3
• 极化表面积: 77.82 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.62
• LOG S: -3.14
• 溶解度: 1.79e-01 g/l

分子性质

理化性质

• 溶解度: 121 mg/L; DMSO; Ethanol (hot)
• 外观: White Solid
• 熔点: 233-234°C
• 疏水性(logP): 2.7

安全信息

• 保存条件: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• RTECS编号: UV8140000
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 22; R:22
• 安全公开号: S:36/37/39
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H302
• 个人保护装置: dust mask type N95 (US), Eyeshields, Faceshields, Gloves

药理学性质

• 给药途径: Oral
• 生物利用度: well-absorbed
• 排泄: Renal
• 半衰期: 96 hours
• 代谢: Hepatic
• 蛋白结合率: 87%
• 法定药品分级: Rx-only
• 妊娠期药物分类: B3 (Australia); C (US)
• 相关基因信息: human ... CYP2C9(1559), DHFRP1(573971)rat ... Dhfr(24312)

产品相关信息

• 纯度: 97%
• 级别: VETRANAL™, analytical standard
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C12H13ClN4

详细说明

MP Biomedicals - 02194180

Antiprotozoal compound
For Research Use Only

DrugBank - DB00205

• Drug Groups: approved
• Description: One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. [PubChem]
• Indication: For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine
• Pharmacology: Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.
• Affected Organisms: Plasmodium
• Biotransformation: Hepatic
• Absorption: Well absorbed with peak levels occurring between 2 to 6 hours following administration
• Half Life: 96 hours
• Protein Binding: 87%
• References: Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. [Pubmed] ; Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S2006

Research Area: Infection
Biological Activity:
Pyrimethamine is a dihydrofolate reductase(DHFR) inhibitor with an IC50 of 15.4 nM. It is a medication used for protozoal infections. It is commonly used as an antimalarial drug (for both treatment and prevention of malaria), and is also used (combined with sulfadiazine) in the treatment of Toxoplasma gondii infections in immune-compromised patients, such as HIV-positive individuals. It interferes with folic acid synthesis by inhibiting the enzyme dihydrofolate reductase (DHFR). Folic acid is needed for DNA and RNA synthesis in many species, including protozoa. [1]

Sigma Aldrich - 46706

法律信息
VETRANAL 商标 Sigma-Aldrich Co. LLC

Toronto Research Chemicals - P997240

Dihydrofolate reductase inhibitor; generally used in combination with other antimicrobial agents. Antiprotozoal (Toxoplasma); antimalarial.

参考文献

• Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. Pubmed
• Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. Pubmed
• http://en.wikipedia.org/wiki/Pyrimethamine
• Loutfy, M.A., et al.: Anal. Profiles Drug Subs., 12, 463 (1983)
• Leport, C., et al.: Am. J. Med., 84, 94 (1983)
• McIntosh, H.M., et al.: Ann. Trop. Med., Parasitol., 93, 265 (1983)
• Plowe, C.V., et al.: Br. Med. J., 328, 545 (1983)