基本信息
- 标准SMILES
O=C(O)c1nn(Cc2ccc(Cl)cc2Cl)c2ccccc12- InChIKey
WDRYRZXSPDWGEB-UHFFFAOYSA-N- 分子式
- C15H10Cl2N2O2
- 平均分子量
- 321.2 g/mol
- 单同位素质量
- 320.01193292
概述
Lonidamine is a member of the class of indazoles that is 1H-indazole that is substituted at positions 1 and 3 by 2,4-dichlorobenzyl and carboxy groups, respectively. It has a role as an antispermatogenic agent, a geroprotector, an antineoplastic agent and an EC 2.7.1.1 (hexokinase) inhibitor. It is a dichlorobenzene, a monocarboxylic acid and a member of indazoles.
名称与标识
- 首选名称
- Lonidamine
- IUPAC
- 1-[(2,4-dichlorophenyl)methyl]indazole-3-carboxylic acid
- 中文名
- 氯尼达明
- 英文名
- Lonidamine
- 分子式
- C15H10Cl2N2O2
- 分子量
- 321.16
名称与别名
展开更多名称
数据库标识
- CAS
50264-69-2- PubChem CID
- 39562
- DTXSID
DTXSID5020782- ChEMBL
CHEMBL1257030- ChEBI
CHEBI:50138- UNII
- U78804BIDR
- EC Number
- 256-510-0
- Nikkaji
- J10.376D
性质
结构计算性质
- XLogP
- 4.3
- 极性表面积
- 55.1 Ų
- 氢键供体
- 1
- 氢键受体
- 3
- 可旋转键
- 3
- 重原子
- 21
- 形式电荷
- 0
- 复杂度
- 396
实验与物化性质
物理化学性质
- 熔点
- 207 · 207-209°C
- 沸点
- 537.9 · 537.9±45.0 °C(Predicted)
- 密度
- 1.4835 · 1.4835 (rough estimate)
- 折射率
- 1.607 · 1.6070 (estimate)
- 储存条件
- 2 · Sealed in dry,2-8°C
- 溶解度
- Soluble in DMSO (up to 25 mg/ml).
- 形态
- solid
- 酸度系数(pKa)
- 3 · 3.00±0.10(Predicted)
- 颜色
- White
- 稳定性
- 1 year · Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
- InChI
- InChI=1S/C15H10Cl2N2O2/c16-10-6-5-9(12(17)7-10)8-19-13-4-2-1-3-11(13)14(18-19)15(20)21/h1-7H,8H2,(H,20,21)
- InChIKey
- WDRYRZXSPDWGEB-UHFFFAOYSA-N
- SMILES
- N1(CC2=CC=C(Cl)C=C2Cl)C2=C(C=CC=C2)C(C(O)=O)=N1
- CAS 数据库
- 50264 · 50264-69-2(CAS DataBase Reference)
化学性质
从乙醇结晶,熔点207℃。溶于甲醇或乙酸。急性毒性LD50小鼠,大鼠(mg/kg):900,1700口服;435,525腹腔注射。
安全与法规
GHS分类
GHS Classification
Danger
H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 42 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
危害信息
安全数据
- wgk
- 3
- 毒性
- LD50 in mice, rats (mg/kg): 900, 1700 orally; 435, 525 i.p. (Heywood)
- RTECS号
- NK7886000
- 存储类别
- 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
- 安全说明
- 53-22-36/37/39-45
- 海关编码
- 29339900
- 危险品标志
- T
- 危险性类别
- Acute Tox. 4 OralCarc. 2Repr. 1B
- 危险类别码
- 60-22-40
化学与工业
药理信息
ATC Code
L - Antineoplastic and immunomodulating agents
QL - Antineoplastic and immunomodulating agents
Mechanism of Action
Lonidamine is an orally administered small molecule that inhibits glycolysis by the inactivation of hexokinase. Hexokinase is an enzyme that catalyzes glucose, the first step in glycolysis. The inhibition of hexokinase by lonidamine is well established. In addition, there is evidence that lonidamine may increase programmed cell death. This stems from the observation that mitochondria and mitochondria-bound hexokinase are crucial for induction of apoptosis; agents that directly effect mitochondria may, therefore, trigger apoptosis. Indeed, in vitro models with lonidamine exhibit the hallmarks of apoptosis, including mitochondrial membrane depolarization, release of cytochrome C, phosphatidylserine externalization, and DNA fragmentation. [PMID: 16986057]
MeSH Pharmacological Classification
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Agents, either mechanical or chemical, which destroy spermatozoa in the male genitalia and block spermatogenesis.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA.
应用领域
用途窄谱抗肿瘤药。可用于各种肿瘤,如乳腺癌、前列腺癌、肺癌及脑瘤等。另外也是一种杀精子药。
用途广谱抗肿瘤药,可用于各种肿瘤如乳腺癌、前列腺癌、肺癌及脑瘤等的治疗
制备方法
生产方法吲哚醌加入氢氧化钠的水溶液中,水解开环得到化合物(I)。将化合物(I)在0℃和亚硝酸钠水溶液混合,再将该混合液滴入硫酸水溶液中,保持在4℃以下,滴完继续搅拌得重氮盐溶液。于0℃和搅拌下,滴入氯化亚锡的浓盐酸溶液,继续搅拌。过滤得黄棕色固体,冰醋酸重结晶得黄色针状的吲唑-3-羧酸(Ⅲ)的结晶,收率51.2%。将该吲唑羧酸、氢氧化钠、水和碘化钾一起,在氮气保护下,在100℃和搅拌下,缓慢滴加2,4-二氯苄基氯,加毕继续反应。滤集晶体,用乙醇重结晶,得氯尼达明,收率87.5%,熔点205~206℃。其最后一步反应也可如下进行:1H-吲脞-3-羧酸溶于8g氢氧化钠和160ml水的溶液中,在水浴加热及搅拌下加入2,4-二氯苄基氯,加毕继续加热3h,冷却,用稀盐酸调至酸性,沉淀出的粗氯尼达明用醋酸重结晶,收率。70%,熔点207℃。
上下游产品信息
上游原料
试剂价格
- HY-B0486R · 5 mg
- 氯尼达明Lonidamine (Standard) — 1050元
- HY-B0486R · 10 mg
- 氯尼达明Lonidamine (Standard) — 1680元
供应商50 家
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