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氯诺昔康

氯诺昔康用途

Lornoxicam是高活性COX-1和COX-2抑制剂,IC50分别为5nM和8nM,是一个新型非甾体抗炎化合物。

氯诺昔康名称

[ CAS 号 ]:
70374-39-9

[ 中文名 ]:
氯诺昔康

[ 英文名 ]:
Lornoxicam

[中文别名 ]:

劳洛克西

[英文别名 ]:

Lorcam
CTX
Lornoxicam
Chlortenoxicam
Telos
MFCD00866163
Xefocam
Lornoxicamum
Ro 13-9297
Taigalor

氯诺昔康生物活性

[ 描述 ]:

Lornoxicam是高活性COX-1和COX-2抑制剂,IC50分别为5nM和8nM,是一个新型非甾体抗炎化合物。

[ 相关类别 ]:

研究领域 >> 炎症/免疫

[ 靶点 ]

COX-1:5 nM (IC50, in cells)

COX-2:45 nM (IC50, in cells)

[参考文献]

[1]. Spyra S, et al. COX-2-selective inhibitors celecoxib and deracoxib modulate transient receptor potential vanilloid 3 channels. Br J Pharmacol. 2017 Aug;174(16):2696-2705.

[2]. Rose, P. and C. Steinhauser, Comparison of Lornoxicam and Rofecoxib in Patients with Activated Osteoarthritis (COLOR Study). Clin Drug Investig, 2004. 24(4): p. 227-36.

[3]. Bianchi, M. and A.E. Panerai, Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail. Pharmacol Res, 2002. 45(2): p. 101-5.

[相关活性小分子]

氯诺昔康物理化学性质

[ 密度 ]:
1.7±0.1 g/cm3

[ 熔点 ]:
225-230°C (dec.)

[ 分子式 ]:
C₁₃H₁₀ClN₃O₄S₂

[ 分子量 ]:
371.819

[ 精确质量 ]:
370.980133

[ PSA ]:
136.22000

[ LogP ]:
2.18

[ 外观性状 ]:
结晶固体

[ 折射率 ]:
1.741

[ 储存条件 ]:
-20°C Freezer

[ 水溶解性 ]:
可溶于：二甲基甲酰胺

氯诺昔康MSDS

详细MSDS(安全技术说明书)

氯诺昔康毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XJ9095000

CHEMICAL NAME :: 2H-Thieno(2,3-e)-1,2-thiazine-3-carboxamide, 6-chloro-4-hydroxy-2-methyl-N-2-pyridinyl-, 1,1-dioxide

CAS REGISTRY NUMBER :: 70374-39-9

LAST UPDATED :: 199806

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C13-H10-Cl-N3-O4-S2

MOLECULAR WEIGHT :: 371.83

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 :: 5730 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 94,61,1989 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 58240 ug/kg/1Y-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - pigmented or nucleated red blood cells Related to Chronic Data - death

REFERENCE :: FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 35,909,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 42 mg/kg/6W-I

TOXIC EFFECTS :: Gastrointestinal - ulceration or bleeding from stomach Gastrointestinal - hypermotility, diarrhea Related to Chronic Data - death

REFERENCE :: FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 35,465,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 192 mg/kg/52W-I

TOXIC EFFECTS :: Gastrointestinal - alteration in gastric secretion Blood - other changes Biochemical - Metabolism (Intermediary) - other proteins

REFERENCE :: FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 35,465,1997

氯诺昔康安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H300

[ 警示性声明 ]:
P264-P301 + P310

[ 危害码 (欧洲) ]:
Xi: Irritant;

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
26-36

[ 危险品运输编码 ]:
UN 2811 6.1 / PGII

[ RTECS号 ]:
XJ9095000

[ 海关编码 ]:
2934999090

氯诺昔康制备

1. 2,5-二氯噻吩(Ⅰ)用氯磺酸在氯化亚砜存在下进行氯磺化反应,得到磺酰氯(Ⅱ).接着和甲胺在氯仿中酰化,得到磺酰胺(Ⅲ).再和二氧化碳及丁基锂在乙醚中进行羧化反应,得到羧酸(Ⅳ).(Ⅳ)先和五氯化磷作用,再加入甲醇,酯化得到羧酸酯(V).(V)在二甲基甲酰胺中,氢化钠存在下,和碘乙酸甲酯反应,生成叔胺(犞犐).再在甲醇钠作用下,环合得到噻嗪衍生物(Ⅶ).最后和2-氨基吡啶,在二甲苯中回流,得氯诺昔康.

2,5-二氯噻吩-3-磺酰甲胺的制备

在反应瓶中加入氯磺酸123g(1.055mol)和亚硫酰氯10g(0.084mol),在冰浴冷却下降温至5ºC,然后在搅拌下小心慢慢加入2,5-二氯噻吩(市售试剂)64.7g(0.422mol),反应混合物必须要保持<7ºC,在加料过程中有大量气体逸出,加毕,将反应液于15 ºC搅拌反应1.5h.反应液变成淡红色溶液后,将其倾入碎冰中,混合物再搅拌数分钟,则生成的磺酰氯化合物大块结晶被分散.除去过量的冰后,抽滤,用蒸馏水洗滤饼,压干,得微红色磺酰氯化合物粗品,将其溶于二氯甲烷400ml,用无水MgSO4干燥,过滤,滤液浓缩回收溶剂.剩余物再真空抽干除净溶剂,于-20 ºC下冷藏,则2,5-二氯噻吩-3-磺酰氯形成结晶磺酰氯化合物,不经进一步纯化直接用于下步反应.如将其用石油醚重结晶后25~27ºC.

在反应瓶中加入氯仿350ml和磺酰氯化合物53.3g,搅拌溶解,于20ºC搅拌下通入干燥的甲胺,直至反应液呈碱性.将反应混合物再在室温下搅拌反应1.5h,然后用0.5mol/L盐酸提取数次,有机相用无水NaSO4干燥,过滤,滤液真空浓缩,得到的油状物置于冷藏室(冰箱)低温固化结晶.所得结晶用150ml四氯化碳重结晶,过滤出的结晶于真空干燥器40ºC下干燥,得2,5-二氯噻吩-3-磺酰甲胺白色针状结晶,mp59~61ºC.

3. 5-氯-3-甲氨基磺酰噻吩-2-羧酸的制备

在反应瓶中加2,5-二氯噻吩-3-磺酰甲胺25g(0.102mol)和干燥的乙醚150ml(之前反应瓶要用干燥N2置换空气和清洗干净),在搅拌下,连续N2保护下于1h内慢慢滴加正丁基锂[16.27(0.254mol)] 的乙醚(200ml)溶液,滴毕,将反应混合物加热至沸,则有白色沉淀析出,并逐渐变成灰色,此时开始搅拌回流反应5h.冷至25ºC,向悬浮液中通入干燥的CO2气体30min,并连续搅拌.通气毕,将反应液倾入200ml水中,然后加入浓盐酸,直至其水相呈强酸性反应.水相用乙醚提取,合并全部乙醚相,用5%NaHCO3溶(30ml×3)提取.合并NaHCO3提取液相,用浓盐酸酸化至pH1~2,400ml乙醚提取.其乙醚相用无水MgSO4干燥,过滤.滤液浓缩,得淡黄色粗制品结晶,用冰醋酸重结晶得纯化的5-氯-3-甲氨基磺酰噻吩-2-羧酸.

4. 5-氯-3-甲氨基磺酰噻吩-2-羧酸甲酯的制备

在反应瓶中加入干燥的氯仿150ml和5-氯-3-甲氨基磺酰噻吩-2-羧酸9g搅拌悬浮混合,然后加入五氯化磷8.52g,将溶液加热至35 ºC,15min后其混合液变澄清,该过程必须防止高温,否则参加反应原料会发生闭环反应.共搅拌反应20~30min后,停止加热,再滴加入干燥甲醇25ml.滴毕,将反应液加热至沸,搅拌回流10min.冷却,氯仿相用少量的NaHCO3溶液洗涤数次,用水洗涤,无水Na2SO4干燥,过滤,滤液真空浓缩,研磨所得的剩余油状物,得结晶,用甲醇重结晶得5-氯-3-甲氨基磺酰噻吩-2-羧酸甲酯,mp103~104 ºC.

5. 5-氯-3-(N-甲氧基羰基亚甲基- N-甲基)氨基磺酰噻吩-2-羧酸甲酯的制备

在反应瓶中加入DMF700ml,将悬浮于矿物油中的NaH(55%)9.7g,用干燥苯洗涤后迅速加入,在N2保护下滴加5-氯-3-甲氨基磺酰噻吩-2-羧酸甲酯60g溶于干燥的DMF(525ml)溶液,控制滴加时的温度0 ºC,在1h内滴加完并连续搅拌.加毕,继续搅拌20min.于0~5 ºC2h内搅拌滴加碘乙酸甲酯44.5g溶于无水DMF(65ml)溶液.滴毕,在室温进行搅拌反应,直至反应液呈中性(用潮湿试纸检测).将反应液真空浓缩(真空度近似于133.322Pa), 剩余物加入0.5mol/L盐酸400ml和二氯甲烷400ml,充分搅拌,静置分相.水相用少量二氯甲烷提取,合并有机相,用5%NaHCO3溶液洗涤,无水Na2SO4干燥,过滤,滤液真空浓缩,得剩余物结晶,用乙醇重结晶,得5-氯-3-(N-甲氧基羰基亚甲基- N-甲基)氨基磺酰噻吩-2-羧酸甲酯50g, mp103~104 ºC.

6. 6-氯-4-羟基-2-甲基-2H-噻吩并[2,3-e]-1,2-噻嗪-3-羧酸甲酯-1,1-二氧化物的制备

在反应瓶中加入二烷140ml和粉状甲醇钠5g,搅拌混合,加入5-氯-3-(N-甲氧基羰基亚甲基- N-甲基)氨基磺酰噻吩-2-羧酸甲酯32g(0.096mol),升至50 ºC,在该温度搅拌反应5h.冷却,倒入2mol/L盐酸300ml和二氯甲烷160ml中,充分搅拌后分相,水相用(20ml×2)二氯甲烷提取,合并有机相.用10%乙酸钠水溶液(100ml×2)、10%Na2CO3溶液(80ml×2)洗涤有机相,析出大量黄色固体.过滤,滤饼转入水100ml和CH2Cl2 160ml组成的混合液中,剧烈搅拌分散后,用浓盐酸酸化至pH2,分层,取有机相,用无水Na2SO4干燥.过滤,滤液浓缩至干后用甲醇60ml浸泡,过滤,干燥,得浅黄色晶体6-氯-4-羟基-2-甲基-2H-噻吩并[2,3-e]-1,2-噻嗪-3-羧酸甲酯-1,1-二氧化物22.4g,收率77.2%(文献[3,4]报道mp200~203 ºC,收率24.2%)mp200~202 ºC.

7. 氯诺昔康的合成

在反应瓶中加入二甲苯150ml和6-氯-4-羟基-2-甲基-2H-噻吩并[2,3-e]-1,2-噻嗪-3-羧酸甲酯-1,1-二氧化物16g(0.052mol),在N2保护下搅拌回流,并不断通入新鲜N2以夹带走生成的甲醇,于3h内滴入2-氨基吡啶的DMF-二甲苯溶液[2-氨基吡啶6.4g(0.068mol)溶于DMF15ml和二甲苯15ml混合液].滴毕,缓慢蒸出二甲苯约500ml.冷却析晶,过滤,干燥后得土黄色固体16.8g, 用二烷重结晶得亮黄色晶体氯诺昔康16.1g,收率83.7%,mp223~227 ºC.(分解)(文献[3,4]报道mp225~230 ºC)

氯诺昔康海关

[ 海关编码 ]: 2934999090

[ 中文概述 ]:
2934999090. 其他杂环化合物. 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

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

氯诺昔康文献

Intra-articular levobupivacaine, lornoxicam and morphine analgesia after knee arthroscopy: a randomized, controlled trial.

Acta Orthop. Traumatol. Turc. 46(6) , 411-5, (2012)

The aim of this study was to compare the analgesic effects of intra-articular levobupivacaine alone, intra-articular levobupivacaine in combination with lornoxicam, and intra-articular levobupivacaine...

Characterization of two polymorphs of lornoxicam.

J. Pharm. Pharmacol. 65(1) , 44-52, (2013)

The aim of the study was to prepare and to characterize two polymorphs of lornoxicam, a water-insoluble non-steroidal anti-inflammatory drug, which has thus far received no exploration of its polymorp...

Investigation on the micelle-sensitized Ce(IV)-lornoxicam-Rh B chemiluminescence system and its application.

J. Fluoresc. 22(1) , 529-35, (2012)

Based on the micelle synergism mechanism, a simple and sensitive flow injection chemiluminescence (FI-CL) method for the assay of lornoxicam was described. The CL signal generated from the reaction of...

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