170569-88-7
170569-88-7 結(jié)構(gòu)式
基本信息
Mavacoxib
PHA 739521
Mavacoxibd
4-[5-(4-Fluoro-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-benzenesulfonamide
4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE
4-[5-(4-Fluorophenyl)-3-trifluoroMethyl-1H-pyrazol-1-yl] benzenesulfonaMide
BenzenesulfonaMide, 4-[5-(4-fluorophenyl)-3-(trifluoroMethyl)-1H-pyrazol-1-yl]-
4-[5-(4-FLUOROPHENYL)-3-(TRIFLUOROMETHYL)PYRAZOL-1-YL]BENZENE-1-SULFONAMIDE USP/EP/BP
物理化學(xué)性質(zhì)
常見問題列表
嗎伐考昔又叫馬氟考昔，是一種新一代的化合物，具有獨(dú)特的作用機(jī)制即特異性地抑制環(huán)氧化酶?2（COX?2）。炎癥刺激可誘導(dǎo)COX?2生成，因而導(dǎo)致炎性前列腺素類物質(zhì)的合成和聚積，尤其是前列腺素E2，引起炎癥、水腫和疼痛。嗎伐考昔可通過抑制COX?2阻止炎性前列腺素類物質(zhì)的產(chǎn)生，達(dá)到抗炎、鎮(zhèn)痛及退熱作用。
向一個250ml三頸瓶中依次投入三氟乙酸乙酯（13.60g，0.0958mol），乙醇（20ml），28.4%甲醇鈉的甲醇溶液(16.50g，0.0868mol)，然后邊攪拌邊滴加4?氟苯乙酮（10.00g，0.0725mol）。滴畢，將反應(yīng)液升溫至10?15℃反應(yīng)2.5小時。然后滴加乙酸（6.54g，0.109mol），滴畢，慢慢加入4?氨基磺酰基苯肼鹽酸鹽。然后將反應(yīng)液在15℃反應(yīng)2小時。將反應(yīng)液冷至5℃，然后用50%氫氧化鈉調(diào)PH至7。加入乙醇（37ml）和水（31ml），升溫至30℃。緩慢加水（32ml）至反應(yīng)液。將反應(yīng)液冷至5℃，過濾，濾餅用50%乙醇?水溶液（v/v，50克）洗滌倆次。濾餅真空干燥得終產(chǎn)品20.109克，產(chǎn)率72.0%。
| Target | Value |
|
COX-2
() |
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. |
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.