65002-17-7

• 常用中文名：布溪那明
• 常用英文名：Bucillamine
• CAS号：65002-17-7
• 分子式：C₇H₁₃NO₃S₂
• 分子量：223.313
• 相关类别： 原料药 解热镇痛药 非甾抗炎药
• 发布时间：2018-02-14 08:00:00
• 更新时间：2024-01-02 19:37:43
• 布西拉明(SA96)是一种口服活性和有效的巯基供体和抗氧化剂。布西拉明也是一种具有抗血管生成特性的抗风湿剂。布西拉明可以保护高危器官移植中的缺血/再灌注损伤。布西拉明抑制VEGF的产生。布西拉明可用于研究脉络膜新生血管(CNV)和类风湿性关节炎(RA)[1][2]。

名称

• 中文名: 布溪那明
• 英文名: Bucillamine
• 中文别名: 布西拉明; 布西拉明; N-(2-巯基-2-甲基丙酰基)-L-半胱氨酸; N-(2-巯基-2-甲基-1-氧代丙基)-L-半胱氨酸
• 英文别名: L-Cysteine, N-(2-mercapto-2-methyl-1-oxopropyl)-; Bucillamine; N-(2-Mercapto-2-methylpropionyl)-L-cysteine; (2R)-2-[(2-methyl-2-sulfanylpropanoyl)amino]-3-sulfanylpropanoic acid; N-(2-Mercaptoisobutyryl)-L-cysteine; N-(2-Methyl-2-sulfanylpropanoyl)-L-cysteine; N-(2-Mercapto-2-methyl-1-oxopropyl)-L-cysteine; MFCD00867570; Thiobutarit; N-(2-Mercapto-2-methylpropanoyl)-L-cysteine

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 438.0±45.0 °C at 760 mmHg
• 熔点: 119-123ºC
• 分子式: C₇H₁₃NO₃S₂
• 分子量: 223.313
• 闪点: 218.7±28.7 °C
• 精确质量: 223.033676
• PSA: 144.00000
• LogP: 1.28
• 蒸汽压: 0.0±2.3 mmHg at 25°C
• 折射率: 1.553
• 储存条件: Hygroscopic, -20?C Freezer, Under Inert Atmosphere
• 分子结构:

  1、 摩尔折射率：55.38

  2、 摩尔体积（cm³/mol）：173.1

  3、 等张比容（90.2K）：461.6

  4、 表面张力（dyne/cm）：50.5

  5、 极化率（10-24cm3）：21.95

• 更多:

  1.性状：白色结晶或结晶性粉末，微臭。

  2.熔点：139～140℃。

  3.比旋光度：[α]_D²⁵+32.3°(C=1.0，乙醇)。

  4.溶解度：易溶于甲醇、乙醇或冰醋酸，溶于氯仿、乙醚或乙酸乙酯，极微溶于水。

生物活性

• 描述: 布西拉明(SA96)是一种口服活性和有效的巯基供体和抗氧化剂。布西拉明也是一种具有抗血管生成特性的抗风湿剂。布西拉明可以保护高危器官移植中的缺血/再灌注损伤。布西拉明抑制VEGF的产生。布西拉明可用于研究脉络膜新生血管(CNV)和类风湿性关节炎(RA)[1][2]。
• 相关类别:
  研究领域 >> 心血管疾病
  研究领域 >> 炎症/免疫
  信号通路 >> 蛋白酪氨酸激酶 >> VEGFR
• 体内研究: 布西拉明显著提高接受肝移植的大鼠的存活率并保护其免受肝损伤[1]。布西拉明(结膜下注射)显著减少大鼠实验性CNV的渗漏和大小[2]。
• 参考文献:

  [1]. Amersi F, et al. Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8915-20.

  [2]. Yanagi Y, et al. Subconjunctival administration of bucillamine suppresses choroidal neovascularization in rat. Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3495-9.

毒性和生态

毒理学数据: 急性毒性LD50小鼠(mg/kg)：2285腹腔注射，989.6静脉注射。急性毒性LD50雄、雌小鼠，雄、雌大鼠(mg/kg)：4118，3892，4074，2961口服；1546， 1250，2165，2009皮下注射；1348，1501，1375，1035静脉注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : HA2420000 CHEMICAL NAME : L-Cysteine, N-(2-mercapto-2-methyl-1-oxopropyl)- CAS REGISTRY NUMBER : 65002-17-7 LAST UPDATED : 199312 DATA ITEMS CITED : 18 MOLECULAR FORMULA : C7-H13-N-O3-S2 MOLECULAR WEIGHT : 223.33 WISWESSER LINE NOTATION : SHX1&1&VMYVQ1SH HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3900 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 353 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1021 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1006 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 4500 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 420 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1090 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 990 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4305958 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 200 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - respiratory stimulation Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,429,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18200 mg/kg/52W-C TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - changes in metals, not otherwise specified REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,429,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 15 gm/kg/30D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes in urine composition Kidney, Ureter, Bladder - changes in bladder weight Blood - other changes REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 45500 mg/kg/91D-I TOXIC EFFECTS : Blood - changes in erythrocyte (RBC) count Kidney, Ureter, Bladder - changes in bladder weight Related to Chronic Data - changes in testicular weight REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,346,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 18 gm/kg/15W-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - changes in metals, not otherwise specified REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 29,429,1985 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 4800 mg/kg SEX/DURATION : female 6-15 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 16,626,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1200 mg/kg SEX/DURATION : female 6-15 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 16,626,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3600 mg/kg SEX/DURATION : female 6-15 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 16,626,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 840 mg/kg SEX/DURATION : female 15-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 16,665,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 3900 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 16,654,1985

安全

• 危害码 (欧洲): T,N,Xi
• 风险声明 (欧洲): R23/24/25:Toxic by inhalation, in contact with skin and if swallowed . R50/53:Very Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment .
• 安全声明 (欧洲): S26-S27-S28-S45-S60-S61
• 危险品运输编码: UN 3146 6.1/PG 3
• WGK德国: 3
• 包装等级: III
• 危险类别: 6.1
• 海关编码: 2930909090

合成路线

65002-16-6 ~79% 65002-17-7

文献：Chemical and Pharmaceutical Bulletin, , vol. 29, # 4 p. 940 - 947

52-90-4 4695-31-2 ~% 65002-17-7

文献：Chemical and Pharmaceutical Bulletin, , vol. 29, # 4 p. 940 - 947

上下游产品

上游产品  3
65002-16-6 52-90-4 4695-31-2
下游产品  1
74407-28-6

制备

S-苄基-2-巯基-2-甲基丙酸(63.1g，0.30mo1)和氯化亚砜(39.3g, 0.33mo1)反应，得S-苄基-2-巯基-2-甲基丙酰氯。另外将S-苄基-L-半胱氨酸(73.9g，0.35mo1)溶于lmol/L氢氧化钠溶液(700ml，0.70mo1)，用冰浴冷却，在搅拌下滴入上述得到的丙酰氯衍生物，加毕再搅拌1h。用盐酸酸化后，用乙酸乙酯提取。提取液水洗后，无水硫酸钠干燥，浓缩。剩余物用硅胶柱层析，用苯-乙酸乙酯(1：1)洗脱。洗脱液减压蒸发至于，得89.6g的油状物，收率74%。
将上述得到的油状物(89．6g，0.222mol)溶于500ml液氨，在搅拌下，分批小量加入金属钠(21.2g，0.917mo1)。当反应完全后，加入氯化铵(59.4g，1.11mo1)，蒸出氨。剩余物加水溶解。分出水层，用乙酸乙酯洗，然后在冷却下用盐酸酸化。用乙酸乙酯提取酸化产生的沉淀。提取液用水洗，无水硫酸钠干燥，减压浓缩，乙酸乙酯重结晶，得40.1g布西拉明，收率81%，熔点139～140℃。

海关

海关编码	2930909090
中文概述	2930909090. 其他有机硫化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:30.0%
申报要素	品名, 成分含量, 用途
Summary	2930909090. other organo-sulphur compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%