吗伐考昔

概述制备生物活性靶点体外研究体内研究吗伐考昔试剂级价格

吗伐考昔

CAS号:170569-88-7
英文名:4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE
中文名:吗伐考昔
CBNumber:CB41479083
分子式:C16H11F4N3O2S
分子量:385.34
MOL File:170569-88-7.mol

吗伐考昔化学性质

熔点 :167-169°C
沸点 :519.8±60.0 °C(Predicted)
密度 :1.51±0.1 g/cm3(Predicted)
储存条件 :2-8°C
溶解度 :DMSO (Slightly), Methanol (Slightly)
酸度系数(pKa) :9.67±0.10(Predicted)
形态 :Solid
颜色 :Off-White to Pale Beige

吗伐考昔性质、用途与生产工艺

概述
吗伐考昔又叫马氟考昔，是一种新一代的化合物，具有独特的作用机制即特异性地抑制环氧化酶‑2（COX‑2）。炎症刺激可诱导COX‑2生成，因而导致炎性前列腺素类物质的合成和聚积，尤其是前列腺素E2，引起炎症、水肿和疼痛。吗伐考昔可通过抑制COX‑2阻止炎性前列腺素类物质的产生，达到抗炎、镇痛及退热作用。
制备
向一个250ml三颈瓶中依次投入三氟乙酸乙酯（13.60g，0.0958mol），乙醇（20ml），28.4%甲醇钠的甲醇溶液(16.50g，0.0868mol)，然后边搅拌边滴加4?氟苯乙酮（10.00g，0.0725mol）。滴毕，将反应液升温至10?15℃反应2.5小时。然后滴加乙酸（6.54g，0.109mol），滴毕，慢慢加入4?氨基磺酰基苯肼盐酸盐。然后将反应液在15℃反应2小时。将反应液冷至5℃，然后用50%氢氧化钠调PH至7。加入乙醇（37ml）和水（31ml），升温至30℃。缓慢加水（32ml）至反应液。将反应液冷至5℃，过滤，滤饼用50%乙醇?水溶液（v/v，50克）洗涤俩次。滤饼真空干燥得终产品20.109克，产率72.0%。
生物活性 Mavacoxib (Trocoxil)是一种选择性的、长效的 cyclooxygenase-2 (COX-2) 抑制剂。Mavacoxib是一种新型的非甾体抗炎药（NSAID）。
靶点
Target Value
COX-2
()

体外研究

Mavacoxib (0-200 μM; 72 hours; CSKOS, U2OS, REM, K9TCC and T24 cells) treatment reduces cell viability in a dose-dependent manner. However, sensitivity to Mavacoxib varied between the cell lines, with IC ₅₀ values ranging from 34.5 μM to 157.7 μM. The IC ₅₀ values of U2OS, KTOSA5, CSKOS, REM, LILY, K9TCC, K9TCC-AXA, K9TCC-In, K9TCC-Sh, T24, 5637 and HT-1376 cells are 52.6 μM, 89.8 μM, 106.3 μM, 66.6 μM, 97.5 μM, 54.9 μM, 34.5 μM, 78.7 μM, 50.7 μM, 63.4 μM, 72.5 μM and 157.7 μM, respectively.
Mavacoxib (0-200 μM; 48 hours; KTOSA5, REM, LILY, K9TCC, U2OS, and T24 cells) treatment can induce caspase-dependent apoptosis in a number of cell lines.
Mavacoxib (0-75 μM; 24 hours; CSKOS, U2OS, REM, K9TCC and T24 cells) treatment down-regulates the expression of p-Akt in CSKOS cells in in a dose-dependent manner, as is total Akt in U2OS cells. In REM cells, both p-ERK and p-Akt are increased in expression with increasing doses of Mavacoxib, and in K9TCC cells p-ERK expression is also increased with Mavacoxib treatment.

Cell Viability Assay

Cell Line:	CSKOS, U2OS, REM, K9TCC and T24 cells
Concentration:	0 μM, 0.04 μM, 25 μM, 50 μM, 75 μM, 100 μM, 125 μM, 150 μM, 175 μM, 200 μM
Incubation Time:	72 hours
Result:	Cell viability was reduced in a dose-dependent manner.

Apoptosis Analysis

Cell Line:	KTOSA5, REM, LILY, K9TCC, U2OS, and T24 cells
Concentration:	0 μM, 50 μM, 100 μM, 200 μM
Incubation Time:	48 hours
Result:	Induced apoptosis in canine and human cancer cell lines.

Cell Viability Assay

Cell Line:	CSKOS, U2OS, REM, K9TCC and T24 cells
Concentration:	0 μM, 25 μM, 50 μM or 75 μM
Incubation Time:	24 hours
Result:	In CSKOS cells, p-Akt was downregulated, as was total Akt in U2OS cells. In REM cells, both p-ERK and p-Akt were increased in expression, and in K9TCC cells p-ERK expression was also increased.

体内研究

Osteoarthritic dogs enrolled in the studies are randomized to receive treatment with Mavacoxib and daily placebo for carprofen or placebo for Mavacoxib and daily carprofen at a nominal dose of 4 mg/kg BW. Mavacoxib is administered in both studies with a 2-week interval between the first and second doses but with monthly dosing thereafter. The nominal Mavacoxib doses in Studies 1 and 2 are 4 and 2 mg/kg BW, respectively. Seven Mavacoxib doses are administered in Study 1, but only five doses in Study 2. In Study 1, Mavacoxib is administered without regard to the timing of meals, but in Study 2, all of the Mavacoxib doses are administered with food.