74150-27-9

• 常用中文名：匹莫苯丹
• 常用英文名：Pimobendan
• CAS号：74150-27-9
• 分子式：C₁₉H₁₈N₄O₂
• 分子量：334.372
• 相关类别： 生物化工 抑制剂 代谢(Metabolism) PDE 抑制剂
• 发布时间：2018-02-07 08:00:00
• 更新时间：2026-07-07 11:42:26
• Pimobendan是PDE3选择性抑制剂,IC50为320nM.

名称

• 中文名: 匹莫苯
• 英文名: pimobendan
• 中文别名: 皮莫本达; 匹莫苯丹,10 MM DMSO 溶液; ACDI|||PIMOBENDANE|||UD-CG 115 BS|||匹莫苯丹|||UD-CG115; 匹莫苯,匹莫苯丹; 心血管系统用药-匹莫苯丹; 乙腈中匹莫苯丹; 4,5-二氢-5-甲基-6-[2-(4-甲氧基苯基)-1H-苯并咪唑-5-基]-3(2H)一哒嗪酮; Pimobendan (Vetmedin) 10mM * 1mL in DMSO试剂; 6-[2-(4-甲氧基苯基)-1H-苯并咪唑-5-基]-5-甲基-4,5-二氢-3(2H)-哒嗪酮; 匹莫莱挥; 匹莫苯丹 Pimobendan; 匹莫苯旦; Pimobendan (Vetmedin) 5mg试剂; 6-(2-(4-甲氧基苯基)-1H-苯并[D]咪唑-5-基)-5-甲基-4,5-二氢哒嗪-3(2H)-酮; 匹莫苯丹系统适用性 标准品
• 英文别名: Racemic pimobendan; Pimobendan 100 μg/mL in Acetonitrile; Pimobendan //BP; 6-[2-(4-Methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one; 6-(2-(4-Methoxyphenyl)-4,5-dihydro-1H-benzimidazol-5-yl)-5-methyl-3(2H)-pyridazinone; PIMOBENDAN; Vetmedin; 3(2H)-Pyridazinone,4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-5-methyl; 6-[2-(4-Methoxyphenyl)-1H-benzimidazol-6-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one; 6-(2-(4-Methoxyphenyl)-1H-benzo[d]iMidazol-5-yl)-5-Methyl-4,5-dihydropyridazin-3(2H)-one; Pimobendan in Acetonitrile; Pimobendanum; UD-CG 115; Piperidinoimidazopyridazinone; 6-[2-(4-Methoxyphenyl)-1H-benzimidazol-6-yl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone; Pimobendane [inn-french]; Pimobendan, 10 mM in DMSO; 6-[2-(4-Methoxy-phenyl)-1H-benzoiMidazol-5-yl]-5-Methyl-4,5-dihydro-2H-pyridazin-3-one; MFCD00761648; Pimobendan [inn-spanish]; Pimobendan D3Q: What is Pimobendan D3 Q: What is the CAS Number of Pimobendan D3; UNII:9HTU209Z0N; 2-(4-methoxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl) benzimidazole; Pimobendan for system suitability CRS; Acdi|||Pimobendane|||UD-CG 115 BS|||UD-CG115; UD-CG; Pimobendane; Acardi; 6-[2-(4-Methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone; UD-CG115 BS; VetMedin; 4,5-dihydro-6-[2-(4-methoxyphenyl)-1h-benzimidazol-5-yl]-5-methyl-3(2h)-pyridazinone; Pimobendan Impurity; (RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one; Pimobendan/UD-CG115; 4,5-Dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-3(2H)-pyridazinone; VETMEDIN; ACDI; PIMOBENDANE; (±)-UD CG 115BS; Pimobendan (Vetmedin), Ca2+ channel sensitizer; (5RS)-6-[2-(4-Methoxyphenyl)-1H-benzimidazol-5-yl]-5- methyl-4,5-dihydropyridazin-3(2H)-one; dl-Pimobendan; UD-CG 115BS; rac PiMobendan; Pimobendan CRS; UD CG 115 BS; PIMOBENDANE HCL; 6-(2-(4-methoxyphenyl)-1H-benzo[d]imidazol-6-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one; Pimobendam; 3(2H)-Pyridazinone, 4,5-dihydro-(4-methoxyphenyl)-1H-benzimidazol-5-yl-5-methyl; Acdi; UNII:34AP3BBP9T; 2-(4-methoxyphenyl)-5(6)-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl)benzimidazole; PiMobendan(VetMedin); 4,5-Dihydro-6-[2-(4-Methoxyphenyl)-1H-benziMidazol-6-yl]-5-Methyl- 3(2H)-pyridazinone; UNII:613JXV89SU; 2-(2-Methyl-1-oxopropyl)isoindole-1,3-dione; Pimobendan-D4; 4，5-Dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-y1]-5-methyl-3(2H)-pyridazinone; 3(2H)-Pyridazinone, 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl- (9CI); Pimobendan 13CD3Q: What is Pimobendan 13CD3 Q: What is the CAS Number of Pimobendan 13CD3

物化性质

• 密度: 1.4±0.1 g/cm3
• 熔点: 249 °C(dec.)
• 分子式: C₁₉H₁₈N₄O₂
• 分子量: 334.372
• 精确质量: 334.142975
• PSA: 79.37000
• LogP: 1.81
• 外观性状: 固体;White to Almost white powder to crystal
• 折射率: 1.693
• 储存条件: 0-10°C;存放于惰性气体之中;避免空气,加热
• 分子结构:

  1、 摩尔折射率：94.00

  2、 摩尔体积（cm³/mol）：245.2

  3、 等张比容（90.2K）：657.6

  4、 表面张力（dyne/cm）：51.7

  5、 极化率（10-24cm3）：37.26

• 计算化学:

  1.疏水参数计算参考值（XlogP）:2.7

  2.氢键供体数量:2

  3.氢键受体数量:4

  4.可旋转化学键数量:3

  5.互变异构体数量:15

  6.拓扑分子极性表面积79.4

  7.重原子数量:25

  8.表面电荷:0

  9.复杂度:530

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:1

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

生物活性

• 描述: Pimobendan是PDE3选择性抑制剂,IC50为320nM.
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> 磷酸二酯酶(PDE)
  研究领域 >> 心血管疾病
• 参考文献:

  [1]. Kajimoto K, et al. Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes. Br J Pharmacol. 1997 Aug;121(8):1549-56.

  [2]. Iwasaki A, et al. Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis. J Am Coll Cardiol. 1999 Apr;33(5):1400-7.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : UR6373000 CHEMICAL NAME : 3(2H)-Pyridazinone, 4,5-dihydro-6-(2-(4-methoxyphenyl)-1H-benzimidazol-5- yl)-5-methyl- CAS REGISTRY NUMBER : 74150-27-9 LAST UPDATED : 199612 DATA ITEMS CITED : 15 MOLECULAR FORMULA : C19-H18-N4-O2 MOLECULAR WEIGHT : 334.41 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 : 950 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Endocrine - other changes REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >300 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value 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: 25,815,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 72 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - acute pulmonary edema Gastrointestinal - other changes REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value 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: 25,815,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 16800 mg/kg/4W-I TOXIC EFFECTS : Endocrine - changes in adrenal weight Blood - normocytic anemia Related to Chronic Data - death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1911 mg/kg/39W-I TOXIC EFFECTS : Gastrointestinal - other changes REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18200 mg/kg/52W-I TOXIC EFFECTS : Gastrointestinal - other changes Blood - changes in other cell count (unspecified) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 56 mg/kg/4W-I TOXIC EFFECTS : Gastrointestinal - other changes REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1400 mg/kg/4W-I TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 56 mg/kg/4W-I TOXIC EFFECTS : Cardiac - pericarditis REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,561,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 27300 mg/kg/26W-C TOXIC EFFECTS : Cardiac - change in rate Cardiac - other changes REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,529,1991 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 24 gm/kg SEX/DURATION : male 8 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,415,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 390 mg/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,415,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1300 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 43,415,1992

安全

• 符号: GHS06
• 信号词: Danger
• 危害声明: H301
• 警示性声明: Missing Phrase - N15.00950417
• 危害码 (欧洲): Xi
• 风险声明 (欧洲): R36/37/38:Irritating to eyes, respiratory system and skin .
• 安全声明 (欧洲): S26-S37/39
• 危险品运输编码: UN 2811 6.1 / PGIII
• WGK德国: 3
• RTECS号: CY8980000
• 海关编码: 29310095

制备

在搅拌下，往二硫化碳、无水三氯化铝和乙酰苯胺的溶液中，缓慢滴加丙酰氯，回流。冷至室温，将下层反应液缓慢倒入碎冰中。滤集固体，乙醇重结晶，得化合物(I)，收率51.3%。
二甲胺盐酸盐和36%甲醛溶液，室温反应。加入醋酐，搅拌至反应液澄清。然后加入化合物(Ⅰ)，100℃反应。60～65℃下减压蒸出低沸物，加丙酮回流。蒸出丙酮，加水溶解，用二氯甲烷洗3次。水层再加二氯甲烷，冷却下用2.5mol/L，氢氧化钠中和至Ph=10。分出有机层，水层用二氯甲烷提取。合并有机层，用饱和盐水洗2次，干燥，浓缩。再和碘甲烷在丙酮中，室温反应。过滤，干燥，得化合物(Ⅱ)。 化合物(Ⅱ)溶于含水甲醇，再加入氰化钾的水溶液，室温搅拌。滤集固体，用大量水洗至无CN^-离子，干燥，乙醇重结晶得化合物(Ⅲ)，收率76.6%。
在搅拌和-5～0℃下，把化合物(Ⅲ)加到混酸中，反应。倾入碎冰中，加乙酸乙酯。滤集固体，水洗至中性，干燥，得化合物(Ⅳ)，收率62.8%。
化合物(Ⅳ)和6mol/L盐酸，回流。冷至室温，过滤，干燥，得化合物(V)，收率77.3%。
化合物(V)、95%乙醇和水合肼，搅拌回流。冷至室温，过滤，干燥，得化合物(VI)，收翠92.3%。
化合物(Ⅵ)、对甲氧基苯甲酰氯和无水吡啶，40～50℃反应。倾入冷水中，滤集固体，干燥，然后和丙酮搅拌回流，冷至室温，过滤，干燥，得化合物(Ⅶ)，收率51.4%。
化合物(Ⅶ)、10%钯-炭和95%乙醇，在0.49MPa的氢压下，振荡搅拌。过滤得化合物(Ⅷ)和钯-炭的混合物，可直接用于下步反应。母液回收的产物用丙酮-二甲基甲酰胺重结晶，可得化合物(Ⅷ)。
化合物(Ⅷ)和钯-炭的混合物在述雕酸中，回流。冷至室温，过滤。滤液加冰水，用25%氢氧化钠中和。滤集固体，干燥，用硅胶G柱层析，得匹莫苯，熔点175~178℃，收率68.7%[以化合物(Ⅶ)计]。往匹莫苯中滴加氯化氢饱和的乙醇，搅拌。滤集固体，干燥，得盐酸匹莫苯，收率79.4%，熔点＞300℃。
方法2：乙酰苯胺、丙酰氯和三氯化铝在二硫化碳中反应，得化合物(I)，收率76%。
化合物(I)、冰醋酸和溴反应，粗品经硅胶G柱层析，得化合物(Ⅱ)，收率74%。
在冰浴搅拌下，往氢化钠的四氢呋喃中，缓慢滴加丙二酸二乙酯，反应。把该反应液加到化合物(Ⅱ)的四氢呋喃溶液中，室温搅拌。用2mol/L盐酸酸化至Ph=1，加入乙醚。分出有机层，水层用乙醚萃取3次。合并有机层，用饱和碳酸氢钠、氯化钠水溶液洗至中性，干燥。蒸出乙醚，用硅胶G柱层析，得化合物(Ⅲ)，收率89.4%。
化合物(Ⅲ)经混酸硝化，粗品经硅胶G柱层析，得化合物(Ⅳ)，收率89%。
化合物(Ⅱ)先经混酸硝化，再和丙二酸二乙酯反应，同样得化合物(Ⅳ)，二步收率68.8%。
化合物(Ⅳ)溶于乙醇，加入5%氢氧化钠，70～80℃：搅拌。用3mol/L盐酸酸化至Ph=1，70～80℃再搅拌。冷至室温，加入乙酸乙酯。分出有机层，水层用乙酸乙酯提取3次。合并有机层，干燥。蒸出溶剂，用硅胶G柱层析，得化合物(V)，收率85%。
化合物(V)溶于二苯醚，在160～170℃搅拌至无二氧化碳气泡放出。冷却，滤集固体，用少量石油醚洗，干燥得化合物(Ⅵ)，收率82%。
化合物(Ⅵ)、无水乙醇和85%水合肼回流反应，得化合物(Ⅶ)，收率92%。
化合物(Ⅶ)溶于无水乙醇，在5%钯-炭存在下，用85%水合肼在70～80℃还原后，再经硅胶G柱层析，得化合物(Ⅷ)，收率88%。
在偏重亚硫酸钠、水和甲醇中，化合物(Ⅷ)和对甲氧基苯甲醛在25～60℃缩合，粗品经硅胶G柱层析，得匹莫苯，收率92%，熔点240～241℃(分解)(该熔点和方法1中匹莫苯的熔点有很大出入)。匹莫苯再和盐酸-乙醇饱和溶液反应，得盐酸匹莫苯，收率80%，熔点＞310℃(分解)。

海关

海关编码	29310095