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75706-12-6 分子结构
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5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide

ChemBase编号:968
分子式:C12H9F3N2O2
平均质量:270.2072696
单一同位素质量:270.0616122
SMILES和InChIs

SMILES:
FC(F)(F)c1ccc(NC(=O)c2c(onc2)C)cc1
Canonical SMILES:
O=C(c1cnoc1C)Nc1ccc(cc1)C(F)(F)F
InChI:
InChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18)
InChIKey:
VHOGYURTWQBHIL-UHFFFAOYSA-N

引用这个纪录

CBID:968 http://www.chembase.cn/molecule-968.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
IUPAC传统名
leflunomide
5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
商标名
Arava
别名
Leflunomidum [INN-Latin]
Lefunomide [INN-Spanish]
leflunomide
Leflunomide
5-Methylisoxazole-4-[4-trifluoromethylcarboxanilide]
Leflunomida
5-Methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide
Leflunomidum
5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
5-Methylisoxazole-4-(4-trifluoromethyl)carboxanilide
Leflunomide
Arava
CAS号
75706-12-6
MDL号
MFCD00867593
PubChem SID
46506013
24278516
160964431
PubChem CID
3899

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 10.412348  质子受体
质子供体 LogD (pH = 5.5) 2.5070803 
LogD (pH = 7.4) 2.506685  Log P 2.5070858 
摩尔折射率 64.1569 cm3 极化性 21.993195 Å3
极化表面积 55.13 Å2 可自由旋转的化学键
里宾斯基五规则 true 
Log P 2.52  LOG S -3.51 
溶解度 8.44e-02 g/l 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
21 mg/L (poorly soluble) expand 查看数据来源
Dichloromethane expand 查看数据来源
DMSO expand 查看数据来源
Ether expand 查看数据来源
Ethyl Acetate expand 查看数据来源
Methanol expand 查看数据来源
外观
Off White Solid expand 查看数据来源
熔点
153-156°C expand 查看数据来源
疏水性(logP)
2.324 expand 查看数据来源
2.8 expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer expand 查看数据来源
RTECS编号
NY2354200 expand 查看数据来源
欧盟危险性物质标志
有害性(Harmful) 有害性(Harmful) (Xn) expand 查看数据来源
联合国危险货物编号
2811 expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
联合国危险货物等级
6.1 expand 查看数据来源
联合国危险货物包装类别(PG)
3 expand 查看数据来源
危险公开号
22-36/37/38 expand 查看数据来源
安全公开号
26 expand 查看数据来源
GHS危险品标识
GHS06 expand 查看数据来源
GHS警示词
Danger expand 查看数据来源
GHS危险声明
H301-H315-H319-H335 expand 查看数据来源
GHS警示性声明
P261-P301 + P310-P305 + P351 + P338 expand 查看数据来源
个人保护装置
dust mask type N95 (US), Eyeshields, Faceshields, Gloves expand 查看数据来源
RID/ADR
UN 2811 6.1/PG 3 expand 查看数据来源
保存温度
2-8°C expand 查看数据来源
相关基因信息
human ... DHODH(1723) expand 查看数据来源
纯度
95% expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源
Empirical Formula (Hill Notation)
C12H9F3N2O2 expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich TRC TRC
DrugBank -  DB01097 external link
Item Information
Drug Groups approved; investigational
Description Leflunomide is a pyrimidine synthesis inhibitor belonging to the DMARD (disease-modifying antirheumatic drug) class of drugs, which are chemically and pharmacologically very heterogeneous. Leflunomide was approved by FDA and in many other countries (e.g., Canada, Europe) in 1999.
Indication For the management of the signs and symptoms of active rheumatoid arthritis (RA) to improve physical function and to slow the progression of structural damage associated with the disease. Has also been used for the prevention of acute and chronic rejection in recipients of solid organ trasnplants and is designated by the FDA as an orphan drug for this use.
Pharmacology Leflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis.
Toxicity LD50=100-250 mg/kg (acute oral toxicity)
Affected Organisms
Humans and other mammals
Biotransformation Primarily hepatic. Leflunomide is converted to its active form following oral intake.
Absorption Well absorbed, peak plasma concentrations appear 6-12 hours after dosing
Half Life 2 weeks
Protein Binding >99.3%
Elimination The active metabolite is eliminated by further metabolism and subsequent renal excretion as well as by direct biliary excretion. In a 28 day study of drug elimination (n=3) using a single dose of radiolabeled compound, approximately 43% of the total radioactivity was eliminated in the urine and 48% was eliminated in the feces. It is not known whether leflunomide is excreted in human milk.
Many drugs are excreted in human milk, and there is a potential for serious adverse reactions in nursing infants from leflunomide.
Distribution * 0.13 L/kg
References
Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. [Pubmed]
Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [Pubmed]
Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3. [Pubmed]
Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9. \ [Pubmed]
Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [Pubmed]
Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89. [Pubmed]
Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8. [Pubmed]
Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Selleck Chemicals -  S1247 external link
Research Area: Anaplastic astrocytoma
Biological Activity:
Leflunomide is a pyrimidine synthesis inhibitor belonging to the DMARD (disease-modifying antirheumatic drug) class of drugs. Leflunomide is used to relieve symptoms caused by rheumatoid arthritis, such as inflammation, swelling, stiffness, and joint pain. This medicine works by stopping the body from producing too many of the immune cells that are responsible for the swelling and inflammation. [1]
Sigma Aldrich -  L5025 external link
Biochem/physiol Actions
Immunosuppressive; inhibits T and B cell proliferation. Activity is attributed mainly to its metabolite, a malononitrile derivative, which is believed to inhibit dihydroorotate dehydrogenase (in the de novo pyrimidine synthesis pathway) as well as several protein tyrosine kinases.
Application
By virtue of its immunosuppressant effects, leflunomide has found use in organ transplantation1 and treatment of rheumatoid arthritis2 and other autoimmune diseases.
Toronto Research Chemicals -  L322750 external link
An immunosuppressive. Inhibits T and B cell proliferation. Activity is attributed mainly to its metabolite, a malononitrile derivative, which is beleived to inhibit dihydroorotate dehydrogenase as well as several protein tyrosine kinases. Therapeutical

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. Pubmed
  • Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. Pubmed
  • Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3. Pubmed
  • Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9. Pubmed\
  • Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. Pubmed
  • Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89. Pubmed
  • Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8. Pubmed
  • Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. Pubmed
  • www.mayoclinic.com/health/drug-information/DR60155
  • Vrenken, T., et al.: J. Hepatol., 49, 799 (2008)
  • Mazzucco, G., et al.: Clin. Nephrol., 70, 163 (2008)
  • Davies, M., et al.: J. Med. Chem., 52, 2683 (2008)
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专利

专利

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