氯沙坦钾_MSDS_用途_密度_氯沙坦钾CAS号【124750-99-8】

Losartan potassium是血管紧张素II受体1型 (AT1)拮抗剂,与血管紧张素II与AT1的结合竞争,IC50为20 nM。

[ 描述 ]:

Losartan potassium是血管紧张素II受体1型 (AT1)拮抗剂,与血管紧张素II与AT1的结合竞争,IC50为20 nM。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 血管紧张素受体

研究领域 >> 心血管疾病

[ 靶点 ]

IC50: 20 nM (angiotensin II)

[体外研究]

氯沙坦与血管紧张素II与AT1受体的结合竞争。抑制50％血管紧张素II结合的浓度(IC50)为20 nM [1]。氯沙坦(40μM)影响ISC,但阻止ANGII对ISC的影响[2]。氯沙坦显着降低Ang II介导的子宫内膜癌细胞的增殖。与单独使用每种药物相比,氯沙坦和抗miR-155的组合具有显着更高的抗增殖作用[3]。

[体内研究]

与安慰剂治疗的Fbn1C1039G/+动物相比,氯沙坦(0.6g/L,po)处理的Fbn1C1039G/+小鼠显示远端空气口径减少。滴定氯沙坦和普萘洛尔的剂量以达到相当的血液动力学效果。对pSmad2核染色的分析显示氯沙坦拮抗Fbn1C1039G/+小鼠的主动脉壁中的TGF-β信号传导。氯沙坦可以改善肺部的疾病表现,这一事件与改善血液动力学无关[4]。氯沙坦(10 mg/kg,动脉内注射)使血液中的血管紧张素水平增加4到6倍。氯沙坦(10 mg/kg,ip)使血浆肾素水平增加100倍;血浆血管紧张素原水平降低至对照的24％;和血浆醛固酮水平没有变化[5]。

[细胞实验]

MTT测定用于测量细胞增殖和活力。对于测定，将每孔200μL培养基中的5000个细胞接种在96孔板中。在孵育过夜以允许细胞附着后，通过抽吸除去培养基。加入无血清培养基中1mg / mL浓度的MTT，然后在37℃下孵育4小时。除去MTT溶液后，加入100μLDMSO以溶解甲crystals晶体。然后使用酶标仪测量570nm处和600nm处的吸光度作为参考。因此，吸光度的差异与细胞存活的程度有关。

[动物实验]

雌性Fbn1C1039G / +小鼠与野生型雄性小鼠进行定时交配。在交配后14.5d，怀孕的雌性Fbn1C1039G / +小鼠用口服氯沙坦（饮用水中0.6g / L; n = 10），普萘洛尔（0.5g / L; n = 6）或安慰剂（n = 12）治疗。。在整个哺乳期和断奶后持续治疗至10个月大。使用上述技术处死小鼠并检查。普萘洛尔用于与氯沙坦进行比较，因为β-肾上腺素能受体阻断是目前虽然有争议的调节标准，用于调节MFS中主动脉根的异常生长。从7周龄开始，野生型和Fbn1C1039G / +小鼠用口服氯沙坦（饮用水中0.6 g / L; n = 5），普萘洛尔（0.5 g / L; n = 7）或安慰剂（n = 10）。小鼠继续口服治疗6个月，然后处死。

[参考文献]

[1]. Burnier, M. Angiotensin II type 1 receptor blockers. Circulation, 2001. 103(6): p. 904-12.

[2]. Ashry, O., et al. Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells. Respir Physiol Neurobiol, 2014.

[3]. Choi, C.H., et al. Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells. Gynecol Oncol, 2012. 126(1): p. 124-31.

[4]. Habashi, J.P., et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science, 2006. 312(5770): p. 117-21.

[5]. Campbell, D.J., et al. Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol, 1995. 26(2): p. 233-40.

[相关活性小分子]

[ 密度 ]:
0.986 g/mL at 25 °C(lit.)

[ 沸点 ]:
134 °C(lit.)

[ 熔点 ]:
−69 °C(lit.)

[ 分子式 ]:
C₂₂H₂₂ClKN₆O

[ 分子量 ]:
461.001

[ 闪点 ]:
76 °F

[ 精确质量 ]:
460.118073

[ PSA ]:
89.61000

[ LogP ]:
3.89590

[ 外观性状 ]:
白色至灰白色结晶粉末

[ 蒸汽压 ]:
1.55E-19mmHg at 25°C

[ 折射率 ]:
n20/D 1.387(lit.)

[ 储存条件 ]:
Desiccate at RT

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NI6755100

CHEMICAL NAME :: 1H-Imidazole-5-methanol, 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)(1,1'-bi phenyl)-4-yl) methyl)-, monopotassium salt

CAS REGISTRY NUMBER :: 124750-99-8

LAST UPDATED :: 199701

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C22-H23-Cl-N6-O.K

MOLECULAR WEIGHT :: 462.06

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea

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: 28,3959,1994

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 200 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - dehydration

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: 28,3959,1994

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - altered sleep time (including change in righting reflex) Behavioral - ataxia

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: 28,3959,1994

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 400 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Lungs, Thorax, or Respiration - respiratory depression Nutritional and Gross Metabolic - dehydration

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: 28,3959,1994

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >320 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

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: 28,3959,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16695 mg/kg/53W-I

TOXIC EFFECTS :: Behavioral - food intake (animal) Gastrointestinal - changes in structure or function of salivary glands Nutritional and Gross Metabolic - weight loss or decreased weight gain

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: 28,4001,1994

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2450 mg/kg/14W-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of salivary glands Gastrointestinal - nausea or vomiting

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: 28,3969,1994 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 763 mg/kg

SEX/DURATION :: female 15-21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - physical

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 51,367,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2943 mg/kg

SEX/DURATION :: female 15-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 51,367,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2943 mg/kg

SEX/DURATION :: female 15-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - urogenital system

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 51,367,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 9265 mg/kg

SEX/DURATION :: female 15 day(s) pre-mating female 0-19 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 51,383,1995

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危害码 (欧洲) ]:
Xi: Irritant;

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
26-36/37/39

[ 危险品运输编码 ]:
NONH for all modes of transport

[ RTECS号 ]:
NI6755100

[ 海关编码 ]:
2933290090

详细合成路线

氯沙坦钾上游产品

氯沙坦钾下游产品

1. 戊脒盐酸盐的制备

在反应瓶中加入戊腈30g(0.361mol)和无水甲醇12g(0.375mol),搅拌溶解,在冰盐浴冷却下,通入干燥的HCl气体至增加质量18g,加盖瓶塞,侧瓶颈接无水CaCl2干燥管,放置5天,得白色结晶亚氨酯.将亚氨酯用无水甲醇溶解,加入用氨饱和的无水甲醇溶液(NH4浓度不低于9%),室温搅拌6h.抽滤,滤饼为生成的NH4Cl,弃去,滤液蒸除溶剂后得戊脒盐酸盐15g,收率30.4%(从戊腈计两步收率).该品冷却时结晶#常温时融化.戊脒盐酸盐冷却时结晶成苦味酸盐,在乙酸乙酯中重结晶#得黄色针状结晶,mp192~193ºC.

2. 2-丁基-5-羟甲基咪唑的制备

在反应瓶中加入戊脒盐酸盐5.2g(38mmol)和无水甲醇25ml,搅拌下通入NH3,使其反应液增重6g,加入二羟丙酮3.8g(42mmol)的无水甲醇20ml溶液.将其加进高压釜,室温搅拌1h.升温至40ºC,在该温度搅拌45min,升温至70ºC,在70ºC搅拌反应6h.冷却,减压蒸除溶剂,剩余物中加入适量乙腈,加热至沸,然后倾倒出乙腈溶液,重复操作几次,将残留的氯化铵弃去,合并乙腈溶液,浓缩至干,剩余物用乙酸乙酯溶解后,用硅胶柱色谱纯化,乙酸乙酯洗脱,目的物组分流出液经浓缩后,得黄色油状物,用乙酸乙酯/石油醚(bp60~90ºC)结晶,得2-丁基-5-羟甲基咪唑3.8g,为浅黄色固体,mp86~88 ºC,收率70%.

3. 2-丁基-4-氯-5-羟甲基咪唑的制备

在反应瓶中加入2-丁基-5-羟甲基咪唑1g(7mmol)、无水THF10ml,搅拌溶解#再加入N-氯代丁二酰亚胺(NCS)1g(7mmol),在40 ºC搅拌反应1h.蒸除溶剂#加入乙酸乙酯和水混合液(1:1,质量比),充分振摇,静置分层,分出乙酸乙酯层,无水NaSO4干燥,过滤,滤液减压蒸除溶剂,剩余物用石油醚(bp60~90)研磨,得白色固体2-丁基-4-氯-5-羟甲基咪唑0.7g,收率57%,mp138~140 ºC.

4. 2-丁基-4-氯-5-甲酰基咪唑的制备

在反应瓶中加入2-丁基-4-氯-5-羟甲基咪唑50g(265mmol)和冰乙酸150ml,搅拌溶解,于25º搅拌滴加1mol/L硝酸铈铵水溶液595ml(595mmol),滴加时控制反应液温度25~30ºC,滴毕,在25ºC搅拌反应3h.将反应混合物冷至0ºC,加入50%NaOH水溶液210ml,产生沉淀,调至Ph6,静置后过滤,干燥得2-丁基-4-氯-5-甲酰基咪唑38.1g,收率77%,mp92.5~93.5ºC.

5. 4,4-二甲基-2-(2-甲氧基苯基)恶唑啉的制备

在反应瓶中加入2-甲氧基苯甲酸(按文献[8~10]的方法制备)30g(0.20mol)和氯化亚砜50ml(81.9g,0.69mol),在20ºC搅拌反应18h.在真空下蒸除过量的氯化亚砜,粗品2-甲氧基苯甲酰氯,其真空蒸馏,集81~83ºC/93.33Pa馏分,2-甲氧基苯甲酰氯32g,收率95%,为无色液体,于下步反应.

在反应瓶中加入2-氨基-2-甲基-1-丙醇20g(0.224mol)和二氯甲烷100ml,搅拌下冷至0 ºC,滴加2-甲氧基苯甲酰氯17g(0.100mol)溶于二氯甲烷50ml的溶液,滴毕,升至20ºC搅拌反应2h.减压蒸除溶剂,剩余物加水稀释,析出固体,过滤,滤饼用水洗,干燥,得白色固体20.5g,该产品为粗制酰胺中间体.

在反应瓶加入上述酰胺中间体20.5g(0.092mol)和氯化亚砜22ml(36g,0.302mol),于25ºC搅拌反应1h.将反应液倒入乙醚中,析出的固体过滤收集,用乙醚洗涤,干燥.然后将其溶于水中,用1mol/LNaOH水溶液调至pH10, 用乙醚提取数次,合并有机相,无水Na2SO4干燥,过滤,滤液真空下浓缩,得4,4-二甲基-2-(2-甲氧基苯基)恶唑啉18.0g,收率88%[从2-甲氧基苯甲酰氯计]mp70~72ºC].

6. 4,4-二甲基-2-(4’-甲基联苯-2-基)恶唑啉的制备

在无水干燥反应瓶中加入无水THF200ml和镁屑2.50g(0.103mol),在N2保护下,于20ºC搅拌下滴加4-溴甲苯13ml(0.106mol) ,滴毕,搅拌反应直至镁屑全部溶解(约1h),得对甲苯基溴化镁溶液.

在反应瓶中加入4,4-二甲基-2-(2-甲氧基苯基)恶唑啉10.0g(48.7mmol)和无水THF100ml,搅拌溶解,于20ºC滴加上述对甲苯基溴化镁溶液,加毕,在20ºC搅拌反应2h.将反应混合物倒入饱和的NH4Cl水溶液中,形成的乳浊液用乙酸乙酯提取,有机相用无水Na2SO4干燥,过滤,滤液减压浓缩,得油状物粗品,经硅胶柱色谱纯化,用35%的乙酸乙酯/己烷洗脱,经后处理得4,4-二甲基-2-(4’-甲基联苯-2-基)恶唑啉11.8g,收率91%,为无色液体.

7. 2-氰基-4’-甲基联苯的制备

在反应瓶中加入4,4-二甲基-2-(4’-甲基联苯-2-基)恶唑啉243.2g(0.917mol)和吡啶975ml,于10ºC搅拌下滴入POCl3 172ml(1.84mol),在滴加过程中控制内温不超过15ºC.滴毕,升温至100ºC,在该温度搅拌反应3h.冷至室温,加水终止反应,得到的乳浊液用乙酸乙酯提取,有机相合并,用水洗,用10%CuSO4水溶液洗和用饱和食盐水洗,无水MgSO4干燥,过滤,滤液减压浓缩,剩余物用庚烷重结晶,得无色针状结晶2-氰基-4’-甲基联苯169.6g,收率96%,mp48.0~49.5ºC.

8. N-(三苯基甲基)-5-(4’-甲基联苯-2-基)-四氮唑的制备

在反应瓶中加入2-氰基-4’-甲基联苯9.0g(46.6mmol)、三丁基氯化锡16.4g(50.4mmol)、叠氮化钠30g(46.2mmol)和甲苯35ml,搅拌回流70h.加入甲苯30ml稀释,并冷至20ºC.再加入10mol/LNaOH水溶液5.5ml(55mmol)和三苯基氯甲烷13.5g(48.4mmol),在20ºC搅拌反应3h.向反应液加入蒸馏水35ml和庚烷70ml,冷至0ºC搅拌1.5h.将浆状物过滤,固体用水洗和庚烷/甲苯(1:1)洗涤,抽干,得粗制品N-(三苯基甲基)-5-(4’-甲基联苯-2-基)-四氮唑,将其溶于二氯甲烷,然后依次用0.4mol/L NaOH水溶液、水和饱和食盐水洗涤,无水Na2SO4干燥,过滤,滤液减压浓缩,得N-(三苯基甲基)-5-(4’-甲基联苯-2-基)-四氮唑15.1g,收率68%,mp163~166ºC.

9. N-(三苯基甲基)-5-[4’-(溴甲基)联苯-2-基]-四氮唑的制备

在反应瓶中加入N-(三苯基甲基)-5-(4’-甲基联苯-2-基)-四氮唑31.0g(65mmol)、N-溴代丁二酰亚胺(NBS)11.50g(65mmol)和四氯化碳390ml,搅拌回流3h.冷至40ºC,过滤,滤液真空浓缩回收溶剂,得到N-(三苯基甲基)-5-[4’-(溴甲基)联苯-2-基]-四氮唑粗品,粗品不需进一步纯化,可用于下步反应.将粗品加入二异丙醚捣碎研磨,得到N-(三苯基甲基)-5-[4’-(溴甲基)联苯-2-基]-四氮唑纯品33.10g,收率92%,为类白色固体,mp135~138 ºC.

10. 2-丁基-4-氯-5-甲酰基-1-[[[2’-(三苯甲基)四氮唑-5-基]联苯-4-基]甲基]咪唑的制备

在反应瓶中加入2-丁基-4-氯-5-甲酰基咪唑3.27g(17.5mmol)、N-(三苯基甲基)-5-[4’-(溴甲基)联苯-2-基]-四氮唑10.73g(19.3mmol)、K2CO3 4.83g(35mmol)和DMF100ml,在25 ºC搅拌反应24h.过滤,滤液减压浓缩,

剩余物加水稀释,用乙酸乙酯提取,合并有机相,用水洗)饱和盐水洗,无水MgSO4干燥,过滤,滤液浓缩,浓缩液经硅胶柱色谱纯化,用乙酸乙酯/甲苯洗脱,经后处理得2-丁基-4-氯-5-甲酰基-1-[[[2’-(三苯甲基)四氮唑-5-基]联苯-4-基]甲基]咪唑5.69g,收率49%.

11. 2-丁基-4-氯-5-(羟甲基)-1-[[2’-(三苯甲基)四氮唑-5-基]联苯-4-基]甲基]咪唑的制备

在反应瓶中加入2-丁基-4-氯-5-甲酰基咪唑3.57g(21mmol)、四丁基溴化磷0.71g(21mmol)、10mol/LNaOH水溶液4.2ml(42mmol)、水15ml和二氯甲烷70ml,搅拌下加入N-(三苯基甲基)-5-[4’-(溴甲基)联苯-2-基]-四氮唑11.65g(21mmol)溶于二氯甲烷100ml的溶液,于25ºC搅拌反应24h.向反应混合物加入硼氢化钠(NaBH4)0.79g(21mmol),再继续搅拌反应24h.加水200ml,静置分层,分出有机相,用水(200ml×2)洗,无水MgSO4干燥,过滤,滤液减压蒸除溶剂,得黄色玻璃状固体2-丁基-4-氯-5-(羟甲基)-1-[[2’-(三苯甲基)四氮唑-5-基]联苯-4-基]甲基]咪唑13.3g,用硝基甲烷重结晶,得2-丁基-4-氯-5-(羟甲基)-1-[[2’-(三苯甲基)四氮唑-5-基]联苯-4-基]甲基]咪唑精品类白色粉末7.52g,收率54%,mp167~169ºC.

12. 氯沙坦钾的合成

在反应瓶中加入化合物2-丁基-4-氯-5-(羟甲基)-1-[[2’-(三苯甲基)四氮唑-5-基]联苯-4-基]甲基]咪唑9.20g(13.8mmol)、10%盐酸100ml和THF200ml,于25ºC搅拌反应4h.加入过量的10%NaOH水溶液(约100ml)减压蒸除溶剂,剩余物用水溶解,过滤除去副产物三苯甲醇,滤液用盐酸调至Ph3,析出沉淀,过滤收集沉淀,得氯沙坦粗制品,重结晶后得氯沙坦氯沙坦钾5.18g,收率89%,mp183.5~184.5ºC.

[ 海关编码 ]: 2933290090

[ 中文概述 ]:
2933290090. 其他结构含非稠合咪唑环的化合物. 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:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933290090. other compounds containing an unfused imidazole ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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