新型多取代丁烯内酯的设计、合成及生物活性研究
|
摘要
丁烯内酯是一大类重要的天然和人工合成的生物活性分子。γ-丁烯内酯结构单元广泛存在于天然产物中,也是天然产物的重要合成中间体。丁烯内酯类化合物具有广泛的生物活性,在医药及农药等方面有广泛应用,开发应用前景广阔。丁烯内酯类化合物的全合成、类似物的合成以及生物活性研究长久以来倍受关注。
本文基于β取代和α，β双取代的γ丁烯内酯,设计合成了新型的γ取代丁烯内酯类化合物：卢帕他定类似物、罗非昔布衍生物、氯西加酮及其类似物以及其他γ取代的丁烯内酯衍生物,并对所合成化合物的相应生物活性进行了评价。具体研究工作如下：
一、以抗组胺药卢帕他定为先导,根据电子等排原理,设计合成了系列新型包含丁烯内酯结构单元的卢帕他定类似物。共合成卢帕他定类似物20个,其中新化合物18个,并通过NMR, HRMS和IR等波谱学方法对其结构进行了确证。通过组胺诱导的离体豚鼠回肠收缩试验对所合成的部分化合物的抗组胺活性进行了评价,所评价化合物均表现出了抗组胺活性,、其中化合物7,8a和8g表现出了良好的抗组胺活性,均好于阳性对照药氯雷他定,其中化合物7优于对照药地洛他定。初步的构效关系研究发现,丁烯内酯环的引入对三环类抗组胺药的活性有利。最终从所合成的化合物中筛选出了化合物7,8a和8g作为抗过敏药物研发的候选化合物。
二、罗非昔布的心血管不良反应可能是由于其内酯环结构的5位碳在体内被氧化的代谢物毒性所致。基于这一研究结果,以罗非昔布及其两个类似物为先导,本论文通过一步插烯缩合的方法设计并合成3个系列48个5位亚烷基取代的罗非昔布衍生物,所合成的化合物均未见有文献报道。用COX(ovine) Inhibitor Screening Assay Kit的方法对所合成部分化合物的选择性COX-2抑制活性进行了评价,结果表明部分化合物表现出了选择性COX-2抑制活性,其中化合物Ⅱ-3的选择性COX-2抑制活性好于阳性对照罗非昔布。上述结果表明,所发现新化合物既有选择性的COX-2抑制活性也能够避免其在体内产生心脑血管毒性的5位氧化代谢产物。除此之外,通过MTT试验评价了部分化合物对前列腺癌细胞的细胞毒活性。结果表明,化合物Ⅱ-3,Ⅱ-6,Ⅱ-7,Ⅱ-11,Ⅱ-12,Ⅲ-3,Ⅲ-11,Ⅲ-16对前列腺癌细胞的IC50值均小于50μM,其中化合物Ⅱ-7的IC50值约12.5μM,化合物Ⅱ-12的IC50值约15μM,化合物Ⅲ-3的IC50值约20μM,化合物Ⅲ-11、Ⅲ-16的IC50值约22μM,而罗非昔布对照药及其2个卤素取代基的类似物均没有表现出对前列腺癌细胞明显的细胞毒活性。通过上述研究筛选出了两个有进一步研究价值的候选化合物。
三、以异戊烯酸为起始原料通过一系列反应合成四个系列的新型3,5-取代-γ丁烯内酯类小分子化合物。评价了部分化合物的抗菌活性、细胞毒活性。部分化合物表现出中等的抗菌活性和细胞毒活性,其中化合物1d表现出中等的抗金黄色葡萄球菌活性,MIC值40μg/mL。化合物9'd对Ec9706细胞表现出了较好的抑制活性,IC50值39.39μg/mL,与阳性对照药5-氟尿嘧啶(IC50=37.74μg/mL)想当。
四、以3-甲氧基呋喃酮为原料,通过水相一步插烯缩合对3-取代的丁烯内酯药物分子氯西加酮的合成工艺进行了研究,且通过结晶的方法可得顺反选择比例大于96%(反/顺)的产物。探索了手性诱导条件下的非对映选择性合成,反/顺值约50%。除此之外合成了12个氯西加酮的类似物及其他们的非对映异构体,其中6个类似物为新化合物。
总之,通过上述研究工作,设计合成了多个系列共116个新型的多取代γ丁烯内酯类衍生物,其中新化合物105个。通过活性筛选发现,具有进一步研究价值的抗组胺药物候选化合物3个,选择性COX-2抑制剂1个,并且该化合物既有选择性的COX-2抑制活性,同时有可能避免罗非昔布的心脑血管毒副作用；抗前列腺癌增生活性候选化合物5个。为开发具有自主知识产权的新药奠定基础。
Butenolides are an important class of natural products or synthetic bioactive molecules, of whichγ-alkylidene butenolides widely present in natural products, also can be used as synthetic intermediates of natural products. For the significant physiological activity of such compounds, they have great prospects for the development and application in medicine and pesticide and so on. And in organic synthesis has a strong application value. The total synthesis of these compounds and their analogues long since have attracted researcher's attention.
In this thesis, on the basis ofβandα,βsubstituted butenolides, we designed and synthesized series of newγ-butenolide:rupatadine derivatives, rofecoxib derivatives, losigamone and its analogues and other smallγ-butenolide moleculers. Their corresponding activities were evaluated. The corresponding work was described as follows:
First, with antihistamines rupatadine as the lead compounds, replacement of the 5-methyl-3-pyridine of rupatadine byα,β-unsaturated-γ-alkylidenebutenolide, a series of derivatives were stereoselectively synthesized. The first time, tricyclic antihistamines and butenolides were combined by five-numbered lactone ring, which expanded the structural types of antihistamines. Twenty rupatadine analogues were synthesized, eighteen were new compounds. All compounds obtained were characterized by NMR, IR and HR MS spectras. Some of their anti-histamine activities were also evaluated. For the evaluation of H1 antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. A preliminary structure-activity relationship was analysized. Their H1 antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7,8a and 8g display potent activity inhibiting histamine-induced effects, which were better than the positive control loratadine.
Second, rofecoxib (vioxx) is selective COX-2 (cyclooxygenase-2) inhibitors. However, the research finding of significant elevation of adverse cardiovascular events in people already at risk has triggered the withdrawal from use of one of the most widely used COX-2 inhibitors. Studies have shown that the facile oxidation of the conjugate base of rofecoxib is a possible contributor to chronic human toxicity. In order to avoid or reduce this side effect, fourty eight rofecoxib derivatives were stereoselectively synthesised, all of them were new compounds. All compounds obtained were characterized by NMR, IR and HR MS spectras. Some of their COX-2 inhibitory activities and cytotoxic activities were evaluated. The selective COX-2 inhibitory activity of candidate compoundsⅡ-3 was better than the control drug rofecoxib. The cytotoxic activity on prostate cancer cells showed that the IC50 values of compoundsⅡ-3,Ⅱ-6,Ⅱ-7,Ⅱ-11,Ⅱ-12,Ⅲ-3,Ⅲ-11 andⅢ-16 all less than 50μM. The IC50 value of optimum structuresⅡ-7 was about 12.5μM, but the positive control rofecoxib has no antiproliferative effect. It showed that rofecoxib and its analogues onγ-alkylidene butenolides derivatives is a very effective modification.
Third, four series of newγ-alkylidene butenolide andγ-hydroxyalkyl butenolide were prepared. Their bioactivities such as antibacterial activity and cytotoxic activity were evaluated. Preliminary evaluation results showed that some of the compounds showed moderate to good antibacterial activity and cytotoxic activity, among them compound 1d exhibited good antibacterial activity against staphylococcus aureus with the MIC value was 40μg/mL.Compound 9'd showed good cytotoxic activity against Ec9706 cell, the IC50 value was 39.39μg/mL, which was comparative to the positive drug fluorouracil(IC50=37.74μg/mL).
Finally, with losigamone as the lead compounds, a series of losigamone analogues were synthesized. Twelve losigamone analogues were synthesized, six were new compounds. The de value of crystalline losigamone was about 96%. The diastereoselective synthesis conditions were explored, the de value was about 50%, less than the original process'diastereoselectivity.
In summary, more than 116 of novelγ-alkylidene butenolides derivatives were obtained.105 of them were new compounds. Some of their bioactivities and structure-bioactivity relationship were investigated. As candidates, a few compounds were valuable to further investigate for new drug development.
本文基于β取代和α，β双取代的γ丁烯内酯,设计合成了新型的γ取代丁烯内酯类化合物：卢帕他定类似物、罗非昔布衍生物、氯西加酮及其类似物以及其他γ取代的丁烯内酯衍生物,并对所合成化合物的相应生物活性进行了评价。具体研究工作如下：
一、以抗组胺药卢帕他定为先导,根据电子等排原理,设计合成了系列新型包含丁烯内酯结构单元的卢帕他定类似物。共合成卢帕他定类似物20个,其中新化合物18个,并通过NMR, HRMS和IR等波谱学方法对其结构进行了确证。通过组胺诱导的离体豚鼠回肠收缩试验对所合成的部分化合物的抗组胺活性进行了评价,所评价化合物均表现出了抗组胺活性,、其中化合物7,8a和8g表现出了良好的抗组胺活性,均好于阳性对照药氯雷他定,其中化合物7优于对照药地洛他定。初步的构效关系研究发现,丁烯内酯环的引入对三环类抗组胺药的活性有利。最终从所合成的化合物中筛选出了化合物7,8a和8g作为抗过敏药物研发的候选化合物。
二、罗非昔布的心血管不良反应可能是由于其内酯环结构的5位碳在体内被氧化的代谢物毒性所致。基于这一研究结果,以罗非昔布及其两个类似物为先导,本论文通过一步插烯缩合的方法设计并合成3个系列48个5位亚烷基取代的罗非昔布衍生物,所合成的化合物均未见有文献报道。用COX(ovine) Inhibitor Screening Assay Kit的方法对所合成部分化合物的选择性COX-2抑制活性进行了评价,结果表明部分化合物表现出了选择性COX-2抑制活性,其中化合物Ⅱ-3的选择性COX-2抑制活性好于阳性对照罗非昔布。上述结果表明,所发现新化合物既有选择性的COX-2抑制活性也能够避免其在体内产生心脑血管毒性的5位氧化代谢产物。除此之外,通过MTT试验评价了部分化合物对前列腺癌细胞的细胞毒活性。结果表明,化合物Ⅱ-3,Ⅱ-6,Ⅱ-7,Ⅱ-11,Ⅱ-12,Ⅲ-3,Ⅲ-11,Ⅲ-16对前列腺癌细胞的IC50值均小于50μM,其中化合物Ⅱ-7的IC50值约12.5μM,化合物Ⅱ-12的IC50值约15μM,化合物Ⅲ-3的IC50值约20μM,化合物Ⅲ-11、Ⅲ-16的IC50值约22μM,而罗非昔布对照药及其2个卤素取代基的类似物均没有表现出对前列腺癌细胞明显的细胞毒活性。通过上述研究筛选出了两个有进一步研究价值的候选化合物。
三、以异戊烯酸为起始原料通过一系列反应合成四个系列的新型3,5-取代-γ丁烯内酯类小分子化合物。评价了部分化合物的抗菌活性、细胞毒活性。部分化合物表现出中等的抗菌活性和细胞毒活性,其中化合物1d表现出中等的抗金黄色葡萄球菌活性,MIC值40μg/mL。化合物9'd对Ec9706细胞表现出了较好的抑制活性,IC50值39.39μg/mL,与阳性对照药5-氟尿嘧啶(IC50=37.74μg/mL)想当。
四、以3-甲氧基呋喃酮为原料,通过水相一步插烯缩合对3-取代的丁烯内酯药物分子氯西加酮的合成工艺进行了研究,且通过结晶的方法可得顺反选择比例大于96%(反/顺)的产物。探索了手性诱导条件下的非对映选择性合成,反/顺值约50%。除此之外合成了12个氯西加酮的类似物及其他们的非对映异构体,其中6个类似物为新化合物。
总之,通过上述研究工作,设计合成了多个系列共116个新型的多取代γ丁烯内酯类衍生物,其中新化合物105个。通过活性筛选发现,具有进一步研究价值的抗组胺药物候选化合物3个,选择性COX-2抑制剂1个,并且该化合物既有选择性的COX-2抑制活性,同时有可能避免罗非昔布的心脑血管毒副作用；抗前列腺癌增生活性候选化合物5个。为开发具有自主知识产权的新药奠定基础。
Butenolides are an important class of natural products or synthetic bioactive molecules, of whichγ-alkylidene butenolides widely present in natural products, also can be used as synthetic intermediates of natural products. For the significant physiological activity of such compounds, they have great prospects for the development and application in medicine and pesticide and so on. And in organic synthesis has a strong application value. The total synthesis of these compounds and their analogues long since have attracted researcher's attention.
In this thesis, on the basis ofβandα,βsubstituted butenolides, we designed and synthesized series of newγ-butenolide:rupatadine derivatives, rofecoxib derivatives, losigamone and its analogues and other smallγ-butenolide moleculers. Their corresponding activities were evaluated. The corresponding work was described as follows:
First, with antihistamines rupatadine as the lead compounds, replacement of the 5-methyl-3-pyridine of rupatadine byα,β-unsaturated-γ-alkylidenebutenolide, a series of derivatives were stereoselectively synthesized. The first time, tricyclic antihistamines and butenolides were combined by five-numbered lactone ring, which expanded the structural types of antihistamines. Twenty rupatadine analogues were synthesized, eighteen were new compounds. All compounds obtained were characterized by NMR, IR and HR MS spectras. Some of their anti-histamine activities were also evaluated. For the evaluation of H1 antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. A preliminary structure-activity relationship was analysized. Their H1 antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7,8a and 8g display potent activity inhibiting histamine-induced effects, which were better than the positive control loratadine.
Second, rofecoxib (vioxx) is selective COX-2 (cyclooxygenase-2) inhibitors. However, the research finding of significant elevation of adverse cardiovascular events in people already at risk has triggered the withdrawal from use of one of the most widely used COX-2 inhibitors. Studies have shown that the facile oxidation of the conjugate base of rofecoxib is a possible contributor to chronic human toxicity. In order to avoid or reduce this side effect, fourty eight rofecoxib derivatives were stereoselectively synthesised, all of them were new compounds. All compounds obtained were characterized by NMR, IR and HR MS spectras. Some of their COX-2 inhibitory activities and cytotoxic activities were evaluated. The selective COX-2 inhibitory activity of candidate compoundsⅡ-3 was better than the control drug rofecoxib. The cytotoxic activity on prostate cancer cells showed that the IC50 values of compoundsⅡ-3,Ⅱ-6,Ⅱ-7,Ⅱ-11,Ⅱ-12,Ⅲ-3,Ⅲ-11 andⅢ-16 all less than 50μM. The IC50 value of optimum structuresⅡ-7 was about 12.5μM, but the positive control rofecoxib has no antiproliferative effect. It showed that rofecoxib and its analogues onγ-alkylidene butenolides derivatives is a very effective modification.
Third, four series of newγ-alkylidene butenolide andγ-hydroxyalkyl butenolide were prepared. Their bioactivities such as antibacterial activity and cytotoxic activity were evaluated. Preliminary evaluation results showed that some of the compounds showed moderate to good antibacterial activity and cytotoxic activity, among them compound 1d exhibited good antibacterial activity against staphylococcus aureus with the MIC value was 40μg/mL.Compound 9'd showed good cytotoxic activity against Ec9706 cell, the IC50 value was 39.39μg/mL, which was comparative to the positive drug fluorouracil(IC50=37.74μg/mL).
Finally, with losigamone as the lead compounds, a series of losigamone analogues were synthesized. Twelve losigamone analogues were synthesized, six were new compounds. The de value of crystalline losigamone was about 96%. The diastereoselective synthesis conditions were explored, the de value was about 50%, less than the original process'diastereoselectivity.
In summary, more than 116 of novelγ-alkylidene butenolides derivatives were obtained.105 of them were new compounds. Some of their bioactivities and structure-bioactivity relationship were investigated. As candidates, a few compounds were valuable to further investigate for new drug development.
引文
[1](a) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod.1999,62,504. (b)Ratnayake, R.; Karunaratne, V.; Ratnayake Bandara, B. M.; et al [J]. J. Nat. Prod.2001,64,376. (c)Siddiqui, B. S.; Afshan, F.; Ghiasuddin; Faizi, S.; et al [J]. J. Chem. Soc., Perkin Trans.1999,2367. (d) Takahashi, S.; Maeda, K.; Hirota, S.; et al [J]. Org. Lett.1999,1,2025. (e)Ame'lia P. R.; Jose'F.; Maria I; et al [J]. Tetrahedron:Asymmetry,2001,12,1131.
[2]Ma, S.; Shi, Z.; Yu, Z. Tetrahedron 1999,55,12137. Negishi, E.; Kotora, M. Tetrahedron 1997,53(20),6707.
[3]Alberto C.; Nicoletta A.; Paolo B. et al. J. Med. Chem.2002,45,189-207
[4]刘新建；王一飞；李贵生.中药材，2003,26(2),135.
[5]贾力.药学通报，1985,20(2),101.
[6]敖桂珍,王未东,张奕华.中国医药工业杂志，2002,33(6),267.
[7]Hsieh, T.-J.; Chang,F.-R.; Chia, Y.-C.; et al [J]. J. Nat. Prod.2001,64,1157. (b) Ortega, M. J.; Zubi'a, E.; Ocan~a, J. M.; et al [J]. Tetrahedron 2000,56,3963. (c)Rao, Y. S. Chem. Rev.1964,64,353. (d)Rao, Y. S. Chem. Rev.1976,76,625. Yao, Y. K.; (e)Rao, G.; Vimalamma, C.; Rao, V.; Tzeng, Y M. Phytochemistry 2004,65,2317.
[8]Kazlauskas, R.; Murphy, P. T.; Quinn, R. J.; et al [J]. Tetrahedron. Lett.1977,37-40.
[9]Fabio, B.; Chiara, A.; Renzo, R. Tetrahedron. Lett.2002,43,2023-2027.
[10](a) Teixeira, R. R.; Barbosa, L. C. A.; Santana, J. O.; et al [J].J. Mol. Struct.2007,837, 197-205. (b) Yang, X. M.; Yuzuru, S. Tetrahedron. Lett.1993,34(5),761-764. (c) John, B.; FranCois, M.; Nicolas, L. Tetrahedron. Lett.1994,35(43),7897-7900.
[11]Kuhut, D.; Anke, T.; Besl, H.; et al [J]. J. Antibiot.1990,43,1413-1420.
[12]Helena, F., Milan, P.; Jiri, K.; Petr S. Tetrahedron. Lett.2005,46,8137-8140.
[13]Josef, E. S.; Hans-Dietrich, S.; Shyam, S. C.; et al [J]. Eur. J. Med. Chem.1998,33,665-669.
[14]Schuyler, A.; Craig, E. C.; William, Hu. D.K.; et al [J]. Bioorg. Med. Chem. Lett.2006,16, 176-180.
[15]Caufiled, C. E.; Antane, S.A.; Morris, K.M.; Naughton, S. M.; Quagliato, D. A.; Enos, A.; Chiarello, J. F.2005, WO2005019196.
[16]Gholam, H. H.; Kak, S. S.; Xue, C. H.; Shahram, H.; Ali, A. M.; Ali, A. S.; Ali, K. N.; Mohammad, N. S. R.; Valeriy, O.; Wang, K. P.; Liao, J. H.; Luo, F. T. Bioorg. Med. Chem. 2002,10,3489-3498.
[17]Brian Morgan, David Dolphin, Richard H. Jones, Terry Jones, Frederick W. B. Einstein. J. Org. Chem.1987,52,4631-4633.
[18]Charles W. Jefford, Danielle Jaggi, and John Boukouvalas. J.CHEM. SOC., CHEM. COMMUN.,1988.1595-1596.
[19]Takashi Joh, Hiroyuki Nagata and Shigetoshi Takahashi. Inorganica Chimica Acta,220 (1994) 45-53.
[20]Martha L. Quesada and Richard H. Schlessinger. J. Org. Clhem.Vol 43, No.2,1978. 346-347.
[21]Akitami Ichihara, Noriki Nio, Yoshihiko Terayama,Ryoji Kimura, and Sadao Sakamura. Tetrahedron Letters.1979,39,3731-3734.
[22]En Si Wang, Yuen Min Choy and Henry N.C. Wong. Tetrahedron, Vol.52, No.37, pp. 12137-12158,1996.
[23]Rajiv P. Balasubramaniam, David K. Moss, Justin K. Wyatt, John D. Spence, Arvin Gee, and Michael H.Nantz. Tetrahedron, Vol.53, No.22, pp.7429-7444,1997.
[24]Robert K. Boeckman, Jr., and SoO Sung KO. J. Am. Chem. SOC.1982,104,1033-1041.
[25]Robert K.Boeckman, Jr., Soo Sung KO. J.Am. Chem. SOC.1980,102,7146-7149.
[26]E.Lattmann, H.M.R. Hoffmann.Synthesis.155-163.1996.
[27]Xian Huang, Hongwei Zhou, and Wanli Chen; J. Org. Chem., Vol.69, No.3,2004.
[28]Ma, S.; Wu, S. L. J. Org. Chem.1999,64,6314.
[29](a) Takeda, Y.; Okeda, Y.; Masuda, T.; Hirata, E.; Shieato, T.;Takushi, A.; Yu, Q.; Otsuka, H. P. K.:Warkentin, J. Chem. Pharm.Bull.2000,48,752. (b) Brady, S. F.; Clardy, J.J. Nat. Prod.2000,63,1447.
[30](a) Topol, I.; Burt, S. K.; Rashin, A. A.; Erickson, J. W. J. Phys.Chem. A 2000,104,866. (b) Takeda, Y.; Okeda, Y.; Masuda, T.; Hirata,E.; Shieato, T.; Takushi, A.; Yu, Q.; Otsuka, H. P. K.:Warkentin, J.Chem. Pharm. Bull.2000,48,752. (c) Brady, S. F.; Clardy, J. J. Nat.Prod. 2000,63,1447. (d) Watanabe, H.; Watanabe, H.; Usui, T.;Kondoh, M.; Osada, H.; Kitahara, T. J. Antibiot.2000,53,540.
[31]Kortmann, I.; Werstermann, B. Synthesis 1995,931-933.
[32]von W. Haefliger and T. Petrzilka.Helv. Chim. Acta,49,1937 (1966).
[33]Rajiv P. Balasubramaniam, David K. Moss, Justin K. Wyatt, John D. Spence, Arvin Gee,and Michael H. Nantz; Tetrahedron, Vol.53, No.22, pp.7429-7444,1997.
[34]Roush, W. R.; Adam, M. A.; Peseckis, S. M. Tetrahedron Lett.1983,24,1377.
[35]Juan Ps. Cenal, Carlos R. Carreras, Carlos E. Tonn, Juan I. Padron, Miguel A. Ramirez, David D. Diaz,Fernando Garcia-Tellado, Victor S. Martin. SYNLETT.2005, No.10, 1575-157817.
[36]郑学文,江涛.氯雷他定合成工艺研究.JOURNAL OF GUANGDONG COLLEGE OF PHARMACY. Dec,2005 Vol 21 No.6655-656.
[37]隋丽娅,祝清芬,谢寅,彭新杰.盐酸氯雷他定一般药理学及毒理学实验研究.China Practical medical, January.2007, Vol.2, No.2.46-47.
[38]王道福,王莹,鲍洪军.组胺H1受体拮抗剂的临床应用近况.Prac J Med & pharm.2004 NO.1 Vol 21.71-72.
[39]徐文严.地洛他定：一种新的抗组胺药.Chin J Dermatol. November 2003, Vol 36, No.11 688-670.
[40]徐道华.第三代抗组胺药地洛他定.Chinese Journal of new drugs.2005, Vol.14 No.121486-1488.
[41]朱运贵,原海燕.去羧氯雷他定.Chinese Journal of new drugs.2002, Vol.11 No.9731-732.
[42]Carceller, E.; Recasens, N.; Almansa, C; Almansa, J.; Merlos, M.; Giral, M.; Garcia-Rafanell, J.; Forn, J. Span.1993, ES 2042421, CA 2096318, US 5407941, EP 577957.
[43]Elena, C.; Manuel, M.; Marta, G.; Dolors, B.; Carmen, A.; Javier, B.; Julian, G.R.; Javier, F. J.Med.Chem.1994,37,2697.
[44]C.L. Zhang, S.S. Chatterjee, U. Stein, U. Heinemann. Naunyn-Schmiedeberg's Arch Pharmacol. (1992).345:85-92.
[45]洪钢,章江生,王琳辉.Chin J Clin Pharmacol Ther.2005 Nov; 10(11).1201-1209.
[46](a) Laffan, David. (Lonza A.-G., Switz.). Process of preparation of threo-4-alkoxy-5-(arylhy droxymethyl)-2(5H)-furanones. Eur. Pat. Appl. (1992), EP 492347, A1 19920701.(b) Heterocycles,43(1),191-8; 1996.
[47](a)Kinga K. Borowicz, Bozena Jaszczyk, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Journal of Pharmacology.567 (2007) 110-116. (b)King K. Borowicz, Zaneta Kimber-Trojnar, Neville Ratnaraj,Philip N. Patsalos, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Neuropsycho pharmacology. (2007) 17,94-101.
[48]Andreas Draguhn, Mathias Jungclaus, Swetlana Sokolowa, Uwe Heinemann. European Journal of Pharmacology.325,1997.245-251.
[49]Francis A. Jones, John A. Davies. British Journal of Pharmacology. (1999) 128,1223-1228.
[50]S. S. Chatterjee; M. Noldner. CNS Drug Review. Vol.3. No.3,1997.225-244.
[51]Josef E. Schachtner, Hans-Dietrich Stachel, Shyam S. Chatterjee, Hermann Hauer, Kurt Polborn. Eur J. Med. Chem.33 (1998) 665-669.
[52]敖桂珍,王未东,张奕华.罗非昔布的合成[J].中国医药工业杂志，2002,33(6)：267-268.
[53]Scott L J, Lamb H M. Rofecoxib [J]. Drugs,1999,58(3):499-505.
[54]沈娟,李彬彬.柳暗花明—昔布类高选择性环氧酶抑制剂能否卷土重来[J].中国医院用药评价与分析，2006,6(2)：69-71.
[55]刘琨,罗非昔布及其衍生物的合成[D].河北医科大学硕士学位论文.2003,1-81.
[56]雷新胜,朱七庆,屈凌波等.选择性环氧合酶-2抑制剂的三维定量构效研究[J].药学学报，1999,34(8)：590-595.
[57]崔志平,特异性环氧化酶-Ⅱ抑制药-罗非昔布[J].医药导报，2002,21(6)：379-380.
[58]Chan C C, Boyce S, Brideau C, et al. Rofecoxib [Vioxx, MK20966:4-(4'-methyls ulfonyl-phenyl)-3-phenyl-2-(5H)-furanone]:a potent andorally active cyclooxygenase-2 inhibitor. Pharmacological and biochemicalprofiles [J]. J Pharmacol Exp Ther.1999,290:551-560.
[59]Van Hecken A, Depre M, Ehrich E, et al. Demonstration of specific COX-2 inhibition by MK2966 in human with supratherapeutic doses [J].Clin Pharmacol Ther,1999,65:164.
[60]王仁云.罗非昔布的药理及临床研究[J].中国新药杂志，2000,9(9)：661-664.
[61]Hawkey CJ. COX-2 inhibitors [J]. Lancet,1999,353:307-314.
[62]Ehrich EW, Dallob A, Lepeleire ID, et al. Characterization of rofecoxib as a cyclooxy-genase-2 isoform inhibitor and demonstra2tion of analgesia in the dental model [J]. Clin Pharmacol Ther,1999,65:336-347.
[63]Merck and Co. Inc. Vioxx Prescribing information[R]. New Jersey, USA.1998.
[64]Saag K, Fisher C, Mckay J, et al. MK20966, A specific COX-2 inhibitors has clinical efficacy comparable to ibuprofen in the treatment of knee and hip OA in a six-week controlled clinicaltrial [J]. A rthritis Rheum,1998,41 (Suppl 9):S84.
[65]Cannon G, Caldwell J, Holt P, et al. MK20966, a specific COX-2 inhibitor, has clinical efficacy comparable to diclofenac in the treatment of knee and hip OA in a 26 week controlled clinicaltrial [J]. A rthritis Rheum,1998,41 (Suppl 9):S83.
[66]Morrison BW, Daniels SE, Kotey P, et al. Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea:a randomized controlled trial [J]. Obstet Gynecol,1999,94 (4):504-508.
[67]张伟(译).罗非昔布首次批准用于治疗偏头疼.China Pharmacist.2005,8(6):474.
[68]钟海莹.COX-2在恶性肿瘤发生发展中的作用和机制.国外医学输血及血液学分册.2004,27(3)：203-206.
[69]Murata H, Kawano S, Tsuji S, et al, Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenicrol,1999,91:451-455.
[70]沈卫东,刘鹏飞.罗非昔布对人正常肝细胞和肝癌细胞生长及凋亡的影响.中华肝脏病杂志.2006,11(14)：863-865.
[71]李小翠,凌桂琴等.选择性COX-2抑制剂罗非昔布对胃癌细胞增殖的影响.徐州医学院学报.2005,25(3)：203-206.
[72]段瑞钦,刘建霞等.选择性环氧合酶-2抑制剂罗非昔布对胆囊癌生长的影响.山东医药.2007,47(27)：17-19.
[73]F. Conrad Engelhardt, Yao-Jun Shi, Cameron J, et al. Synthesis of a NO-Releasing Prodrug of Rofecoxib, J. Org. Chem.2006,71,480-491.
[74]刘琨,罗非昔布及其衍生物的合成[D],河北医科大学硕士学位论文，2003,1-81
[75]Amgad G. Habeeb, P. N. Praveen Rao, and Edward E. Knaus, Design and Synthesis of Celecoxib and Rofecoxib Analogues as Selective Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Sulfonamide and Methylsulfonyl Pharmacophores by an Azido Bioisostere, Journal of Medicinal Chemistry,2001,44(18):3039-3042.
[76]Latifeh Navidpour, Mohsen Amini, Hamed Shafaroodi, et al. Design and synthesis of new water-soluble tetrazolide derivatives of celecoxib and rofecoxib as selective cyclooxygenase-2 (COX-2) inhibitors, Bioorganic & Medicinal Chemistry Letters,2006, 16:4483-4487.
[77]Afshin Zarghi, P. N. Praveen Rao and Edward E. Knaus, Sulfonamido, azidosulfonyl and N-acetylsulfonamido analogues of rofecoxib:4-[4-(N-acetylsulfonamido)phenyl]-3-(4-methanesulfonylphenyl)-2(5H)furanone is a potent and selective cyclooxygenase-2inhibitor, Bioorganic & Medicinal Chemistry Letters,2004,14:1957-1960.
[78]Qiao-Hong Chen, P. N. Praveen Rao and Edward E. Knaus, Synthesis and biological evaluation of a novel class of rofecoxib analogues as dual inhibitors of cyclooxygenases (COXs) and lipoxygenases (LOXs), Bioorganic & Medicinal Chemistry,2006, 14:7898-7909.
[79]Francisco Caturla, Merce Amat, Raquel F. Reinoso, et al. Racemic and chiral sulfoxides as potential prodrugs of the COX-2 inhibitors Vioxx and Arcoxia, Bioorganic & Medicinal Chemistry Letters,2006,16:3209-3212.
[80]Nicholas D. Smith, Thomas S. Reger, Joseph Payne, et al. Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia, Bioorganic & Medicinal Chemistry Letters,2005,15:3197-3200.
[81]W. Cameron Black, Christine Brideau, Chi-Chung Chan, et al.3,4-Diaryl-5-hydroxyfuran ones:Highly Selective Inhibitors of Cyclooxygenase-2 with Aqueous Solubility, Bioorganic & Medicinal Chemistry Letters,2003,13:1195-1198.
[82]Afshin Zarghi, P. N. Praveen Rao and Edward E. Knaus, Sulfonamido, azidosulfonyl and N-acetylsulfonamido analogues of rofecoxib:4-[4-(N-acetylsulfonamido)phenyl]-3-(4-methanesulfonylphenyl)-2(5H)furanone is a potent and selective cyclooxygenase-2inhibitor, Bioorganic & Medicinal Chemistry Letters,2004,14:1957-1960.
[83]Vale'rie Weber, Catherine Rubat, Eliane Duroux, et al. New 3-and 4-hydroxyfuranones as anti-oxidants and anti-inflammatory agents, Bioorganic & Medicinal Chemistry,2005,13: 4552-4564.
[84]Desmond Richard, et al, Process for making phenyl heterocycles useful as COX-2 inhibitors [P], WO 9608482,1996-03-21.
[85]Atkinson, Joseph, G. et al, Stilbene derivatives useful as cyclooxygenase-2 inhibitors [P], WO 9613483,1996-05-09.
[86]Desmond Richard, etal, Process for preparing phenyl heterocycles useful as COX-2 inhibitors [P], WO 9800416,1996-01-08.
[87]Therien, Michel; Gauthier, Jacques Yves, et al, Synthesis of Rofecoxib, (MK 0966, Vioxx(?) 4-(4'-Methylsulfonylphenyl)-3-Phenyl-2(5H)-Furanone), a Selective and Orally Active Inhibitor of Cyclooxygenase-2, Synthesis,2001,12:1778-1779.
[88]敖桂珍,王未东,张奕华.罗非昔布的合成[J].中国医药工业杂志,2002,33(6)：267-268.
[89]Leleti Rajender Reddy and E. J. Corey. Facile air oxidation of the conjugate base of rofecoxib (VioxxTM), a possible contributor to chronic human toxicity. Tetrahedron Letters. 2005,46,927.
[1]Pata, Y. S. Antiinflamm. Antiallergy. Agents. Med. Chem.2008,7(1),32.
[2]Camelo-Nunes, I. C. Jornal de pediatria.2006,82(5),173.
[3]Kruszewski, J.; Klinika, C. I.; Alergolog, W.; Instytutu, M. The Polish otolaryngology.2007, 61(4),522.
[4]Salmun, L. M. Eepert. Opin. Inv. Drug.2002,11(2),259.
[5]Jesingbhai, J. K.; Sekhar, U. R.; Sivaramchandra, K.; Rao, C. T.; Rajamamannar, T. Indian Pat. Appl.2005,16pp. IN 2003MU00406
[6]Affrime, M. B.; Banfield, C. R.; Gupta, S. K. U.S. Pat. Appl. Publ.2006,9pp. US 2006154948.
[7]Tibor, M.; Bala'zs, V.; Imre, K.; Gyula, S. Abstracts of Papers. Organic process research and development--fifth international conference.2008,12,855.
[8]Schumacher, D. P.; Lee, J.; Rogers, L. R.; Eckhart, C. H.; Sawant, N. S.; Mitchell, M. B. PCT Int. Appl. WO 9901450,1999.
[9]Carceller, E.; Recasens, N.; Almansa, C.; Almansa, J.; Merlos, M.; Giral, M.; Garcia-Rafanell, J.; Forn, J. Span.1993, ES 2042421, CA 2096318, US 5407941, EP 577957.
[10]Elena, C.; Manuel, M.; Marta, G.; Dolors, B.; Carmen, A.; Javier, B.; Julian, G.R.; Javier, F. J. Med.Chem.1994,37,2697.
[11]Mullol, J.; Bousquet, J; Bachert, C; Canonica, W.G; Gimenez, A. A.; Kowalski, M. L.; Marti, G. E.; Maurer, M.; Picado, C.; Scadding, G.; Van, C. P. Allergy.2008,63,87,5.
[12]Guadano, E. M.; Serra-Batlles, J.; Meseguer, J.; Castillo, J. A.; de Molina, M.; Valero, A.; Picado,C. Allergy (Oxford, United Kingdom).2004,59(7),766.
[13]Arnau, A. G.; Ianosi, S.; Perez, I.; Donado, E.; Arnaiz, E.; Kaszuba, A.; Malbran, A.; Poop, G.. Abstracts of Papers. European Academy of Dermatology and Venereology, EADV, Proceedings of the Congress,15th, Greece, Oct.4-8,2006,841.
[14]Keam, Susan J.; Plosker, Greg L. Drugs.2007,67(3),457.
[15]Van, D. A. R.; Natella, Y. Curr. Opin. Investig. Drugs.2000,2(2),127.
[16]Izquierdo, I.; Merlos, M.; Garcia, R. J. Drugs of Today.2003,39(6),451.
[17]Merlos, M.; Giral, M.; Balsa, D.; Ferrando, R.; Queralt, M.; Puigdemont, A.; Garcia, R. J.; Forn, J. The Journal of pharmacology experimental therapeutics.1997,280(1),114.
[18]Xu, H.W.; Wang, J. F.; Liu, G. Z.; Hong, G. F.; Liu, H. M. Org. Biomol. Chem.2007,5, 1247.
[19]Xu, H.W.; Dai, G.F.; Liu, G. Z.; Wang, J. F.; Liu, H. M. Bioorg. Med. Chem.2007,15,4247.
[20]Xu, H.W.; Liu, G. Z.; Dai, G. F.; Wu, C. L.; Liu, H. M. Drug. Discov. Ther.2007,1(1),73.
[21]Dai, G. F.; Xu, H.W.; Wang, J. F.; Liu, F. W. Liu, H. M. Bioorg. Med. Chem. Lett.2006,16, 2710.
[22]Wang, E. S.; Choy, Y. M.; Henry, N. C. W. Tetrahedron.1996.52(37),12137.
[23]Robert, K.; Boeckman, J.; Soo, S. K.J. Am. Chem. Soc.1982,104,1033.
[24]Fan, H.; Tian, Y.; Guan, K.; Fu, Y. Q.; Wang, H.; Wang, Y.; Sun, K. F. J. Tradit. Chin. Med. 2008,10(2),145.
[1]Masferrer, J. L.; Zweifel, B. S.; Manning, P. T.; Hauser, S. D.; Leahy, K. M.; Smith, W. G.; Isakson, P. C.; Seibert, K. Selective inhibition of inducible cyclooxygenase-2 in vivo is anti-inflammatory and nonulcerogenic. Proc. Natl Acad. Sci. U.S.A.1994,91,3228-3232.
[2]Chan, C. C.; Boyce, S.; Brideau, C.; Ford-Hutchinson, A. W.; Gordon, R.; Guay, D.; Hill, R. G.; Li, C. S.; Mancini, J.; Penneton, M.; Prasit, P.; Rasori, R.; Riendeau, D.; Roy, P.; Tagari, P.; Vickers, P.; Wong, E.; Rodger, I. W. Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337:a novel nonsteroidal antiinflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J. Pharmacol. Exp. Ther.1995,274, 1531-1537.
[3]Silverstein, F. E.; Faich, G.; Goldstein, J. L.; Simon, L. S.; Pincus, T.; Whelton, A.; Makuch, R.; Eisen, G.; Agrawal, N. M.; Stenson, W. F.; Burr, A. M.; Zhao, W. W.; Kent, J. D.; Lefkowith, J. B.; Verburg, K. M.; Geis, G. S. Gastrointestinal toxicity with celecoxib vs nonsteroidal antiinflammatory drugs for osteoarthritis and rheumatoid rrthrits. The class study:a randomized controlled trial. JAMA 2000,284,1247-1255.
[4]Hawkey, C.; Laine, L.; Simon, T.; Beaulieu, A.; Maldonado, C. J.; Acevedo, E.; Shahane, A.; Quan, H.; Bolognese, J.; Mortensen, E. Comparison of the effect of rofecoxib (a cyclooxygenase-2 inhibitor), ibuprofen and placebo on the gastroduodenal mucosa of patients with osteoarthritis:a randomized, double-blind, placebo-controlled trial. The rofecoxib osteoarthritis endoscopy multinational study group. Arthritis Rheum.2000,43, 370-377.
[5]Penning, T.; Talley, J. J.; Bertenshaw, S.; Carter, J.; Collins, P.; Docter, S.; Graneto, M.; Lee, L.; Malecha, J.; Miyashiro, J.; Rogers, R.; Rogier, D.; Yu, S.; Anderson, G.; Burton, E.; Cogburn, J.; Gregory, S.; Koboldt, C.; Perkins, W.; Seibert, K.; Veenhuizen, A.; Zhang, Y. Isakson, P. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors:identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1Hpyrazol-1-yl)] benzenesulfonamide (SC-58635, Celecoxib). J. Med. Chem.1997,40,1347-1365.
[6]Chan, C. C.; Boyce, S.; Brideau, C.; Charleson, S.; Cromlish, W.; Ethier, D.; Evans, J.; Ford-Hutchinson, A. W.; Forrest, M. J.; Gauthier, J. Y.; Gordon, R.; Gresser, M.; Guay, J.; Kargman, S.; Kennedy, B.; Leblanc, Y.; Leger, S.; Mancini, J.; O(?)Neill, G. P.; Ouellet, M.; Patrick, D.; Percival, M. D.; Perrier, H.; Prasit, P.; Rodger, I. Rofecoxib [Vioxx, MK-0966; 4-(4(?)-methylsulfonylpheny])-3-pheny]-2-(5H)-furanone]:a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J. Pharmacol. Exp. Ther.1999,290,551-560.
[7]Kawamori, T.; Rao, C. V.; Seibert, K.; Reddy, B. S. Chemopreventive activity of celecoxib, a specific cylooxygenase-2 inhibitor, against colon carcinogenesis. Cancer. Res.1998,58, 409-412.
[8]Ghosh, A. J.; Hirasawa, N.; Niki, H.; Ohuchi, K. Cyclooxygenase-2 mediated Angiogenesis in carrageenan-induced granulation tissue in rats. J. Pharmacol. Exp. Ther.2000,295, 802-809.
[9]Katori, M.; Majima, M. Cyclooxygenase-2:its rich diversity of roles and possible application of its selective inhibitors. Inflamm. Res.2000,49,367-392.
[10]Subbaramaiah, K.; Dannenberg, A. J. Cyclooxygenase-2:a molecular target for cancer prevention and treatment. Trends Pharmacol. Sci.2003,24,96-102.
[11]Fujita, H.; Koshida, K.; Keller, E. T.; Takahashi, Y.; Yoshimito, T.; Namiki, M.; Mizokami, A. Cyclooxygenase-2 promotes prostate cancer progression. Prostate 2002,53,232-240.
[12]Xiang, Z.; Ho, L.; Yemul, S.; Zhao, Z.; Qing, W.; Pompl, P.; Kelley, K.; Dang, A.; Qing, W.; Teplow, D,; Pasinetti, G. M. Cyclooxygenase-2 promotes amyloid plaque deposition in a mouse model of Alzheimer's disease neuropathology. Gene Expr.2002,10,271-278.
[13]Teismann, P.; Tieu, K.; Choi, D. K.; Wu, D. C.; Naini, A.; Hunot, S.; Vila, M.; Jackson-Lewis, V.; Przedborski, S. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc. Natl. Acad. Sci. U S A.2003,100,5473-5478.
[14]Talley, J. J. Selective inhibitors of cyclooxygenase-2 (COX-2). Progr. Med. Chem.1999,36, 201-233.
[15]Rao, P. N. P.; Amini, M.; Li, H.; Habeeb, A. G.; Knaus, E. E.6-Alkyl, alkoxy, or alkylthio-substituted 3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones:a novel class of diarylheterocyclic selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett.2003,13, 2205-2209.
[16]Leleti Rajender Reddy and E. J. Corey. Facile air oxidation of the conjugate base of rofecoxib (VioxxTM), a possible contributor to chronic human toxicity. Tetrahedron Letters. 2005,46,927.
[17]敖桂珍,王未东,张奕华.罗非昔布的合成[J].中国医药工业杂志,2002,33(6)：267-268.
[18]Praveen Rao, P.N., Uddin, J., Knaus, E.E. Design, Synthesis, and Structure-Activity Relationship Studies of 3,4,6 Triphenylpyran-2-ones as Selective Cyclooxgenase-2 Inhibitors. J. Med. Chem.2004.47 (16):3972-3990.
[19]Praveen Rao, P.N., Amini, M. Li, H., Habeeb, A.G., Knaus, E.E. Design, Synthesis, and Biological Evaluation of 6-Substituted-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones: A Novel Class of Diarylheterocyclic Selective Cyclooxygenase-2 Inhibitors. J. Med. Chem. 2009.46 (23):4872-4822.
[20]Fosslien, E. Review:Molecular Pathology of Cyclooxygenase-2 in Cancer-induced Angiogenesis. Annals of Clin. Lab. Science.2001.31 (4):325-329.
[1]Amr, A. E.; Hegab, M. I.; Ibrahim, A. A.; Abdalah, M. M. Monatschefte fur Chemie.2003, 134,1395-1409.
[2](a) Amr, A. E.; Abou-Ghalia, M. H. Amino Acids,2004,26,283-289; (b) Brana, M. F.; Castellano, J. M.; Mpran, M.; Perez de Vega, M. J.; Gian, X. D.; Romerdahl, C. A.; Keihauer, G. Eur.J. Med. Chem,1995,30,235-239; (c) Kojima, N.; Fushimi, T.; Maezaki, N.; Tanaka, T.; Yamori, T. Bioorg. Med. Chem. Lett.2008,18,1637-1641.
[3]Kuhut, D.; Anke, T.; Besl, H.; Bross, M.; Herrmann, R.; Mocek, U. J. Antibiot.1990,43, 1413.
[4]Helena F., Milan P.; Jir i K.; Petr S. Tetrahedron.Lett.2005,46,8137.
[5]Schuyler, A.; Craig, E. C.; William, Hu. D.K.; Pornpen, L.; Koi, M.; Shaughnessy, M. N.; Peter, J. P.; Beth, A. R.; Guy, S.; Yang, Y. J. Bioorg. Med.Chem. Lett.2006,16,176.
[6]Caufiled, C. E.; Antane, S. A.; Morris, K.M.; Naughton, S. M.; Quagliato, D. A.; Enos, A.; Chiarello, J. F. 2005,WO2005019196.
[7]E. S. Wang, Y. M. Choy, N. C. W. Henry, Tetrahedron.52 (1996)12137-12158.
[8]K. Robert, J. Boeckman, S. K. Soo, J. Am. Chem Soc.104 (1982)1033-1041.
[9]H.W. Xu,; J. F.Wang, G. Z. Liu, G. F. Hong, H. M. Liu, Org. Biomol. Chem.5 (2007)1247-1250.
[10]H.W. Xu, G.F. Dai, G. Z. Liu, J. F.Wang, H. M. Liu, Bioorg. Med. Chem.15 (2007)4247-4251.
[11]H.W. Xu, G. Z. Liu, G. F. Dai, C. L. Wu, H. M. Liu, Drug. Discov. Ther.1(2007)73-77.
[12]G. F. Dai, H.W. Xu, J. F. Wang, F. W. Liu, H. M. Liu, Bioorg. Med. Chem. Lett. 16(2006)2710-2713.
[13]C. Caufield, S. A. Antane, K. M. Morris, S. M. Naughton, D. A.Quagliato, P. M. Andrae, A. Enos, J.F. Chiarello, PCT Int. Appl. (2005),118 pp. WO 2005019196 A1 20050303
[14]Y.H. Li, H. L iao, Yang, Gungdong yao xue.13(2003)37-39.
[15]Y Q. Liu, Y. Z. Zhang, S. G. Yan, C. C. Cheng, Y. Li, P. J. Gao, Jouranl of Shangdong Agricultural University.34(2003) 181-184.
[1]C.L. Zhang, S.S. Chatterjee, U. Stein, U. Heinemann. Naunyn-Schmiedeberg's Arch Pharmacol. (1992).345:85-92.
[2]洪钢,章江生,王琳辉.Chin J Clin Pharmacol Ther.2005 Nov; 10(11).1201-1209.
[3]Kinga K. Borowicz, Bozena Jaszczyk, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Journal of Pharmacology.567 (2007) 110-116.
[4]King K. Borowicz, Zaneta Kimber-Trojnar, Neville Ratnaraj,Philip N. Patsalos, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Neuropsycho pharmacology. (2007) 17, 94-101.
[5]Andreas Draguhn, Mathias Jungclaus, Swetlana Sokolowa, Uwe Heinemann. European Journal of Pharmacology.325,1997.245-251.
[6]Francis A. Jones, John A. Davies. British Journal of Pharmacology. (1999) 128,1223-1228.
[7]S. S. Chatterjee; M. Noldner. CNS Drug Review. Vol.3. No.3,1997.225-244.
[8]Josef E. Schachtner, Hans-Dietrich Stachel, Shyam S. Chatterjee, Hermann Hauer, Kurt Polborn. Eur J. Med. Chem.33 (1998) 665-669.
[2]Ma, S.; Shi, Z.; Yu, Z. Tetrahedron 1999,55,12137. Negishi, E.; Kotora, M. Tetrahedron 1997,53(20),6707.
[3]Alberto C.; Nicoletta A.; Paolo B. et al. J. Med. Chem.2002,45,189-207
[4]刘新建；王一飞；李贵生.中药材，2003,26(2),135.
[5]贾力.药学通报，1985,20(2),101.
[6]敖桂珍,王未东,张奕华.中国医药工业杂志，2002,33(6),267.
[7]Hsieh, T.-J.; Chang,F.-R.; Chia, Y.-C.; et al [J]. J. Nat. Prod.2001,64,1157. (b) Ortega, M. J.; Zubi'a, E.; Ocan~a, J. M.; et al [J]. Tetrahedron 2000,56,3963. (c)Rao, Y. S. Chem. Rev.1964,64,353. (d)Rao, Y. S. Chem. Rev.1976,76,625. Yao, Y. K.; (e)Rao, G.; Vimalamma, C.; Rao, V.; Tzeng, Y M. Phytochemistry 2004,65,2317.
[8]Kazlauskas, R.; Murphy, P. T.; Quinn, R. J.; et al [J]. Tetrahedron. Lett.1977,37-40.
[9]Fabio, B.; Chiara, A.; Renzo, R. Tetrahedron. Lett.2002,43,2023-2027.
[10](a) Teixeira, R. R.; Barbosa, L. C. A.; Santana, J. O.; et al [J].J. Mol. Struct.2007,837, 197-205. (b) Yang, X. M.; Yuzuru, S. Tetrahedron. Lett.1993,34(5),761-764. (c) John, B.; FranCois, M.; Nicolas, L. Tetrahedron. Lett.1994,35(43),7897-7900.
[11]Kuhut, D.; Anke, T.; Besl, H.; et al [J]. J. Antibiot.1990,43,1413-1420.
[12]Helena, F., Milan, P.; Jiri, K.; Petr S. Tetrahedron. Lett.2005,46,8137-8140.
[13]Josef, E. S.; Hans-Dietrich, S.; Shyam, S. C.; et al [J]. Eur. J. Med. Chem.1998,33,665-669.
[14]Schuyler, A.; Craig, E. C.; William, Hu. D.K.; et al [J]. Bioorg. Med. Chem. Lett.2006,16, 176-180.
[15]Caufiled, C. E.; Antane, S.A.; Morris, K.M.; Naughton, S. M.; Quagliato, D. A.; Enos, A.; Chiarello, J. F.2005, WO2005019196.
[16]Gholam, H. H.; Kak, S. S.; Xue, C. H.; Shahram, H.; Ali, A. M.; Ali, A. S.; Ali, K. N.; Mohammad, N. S. R.; Valeriy, O.; Wang, K. P.; Liao, J. H.; Luo, F. T. Bioorg. Med. Chem. 2002,10,3489-3498.
[17]Brian Morgan, David Dolphin, Richard H. Jones, Terry Jones, Frederick W. B. Einstein. J. Org. Chem.1987,52,4631-4633.
[18]Charles W. Jefford, Danielle Jaggi, and John Boukouvalas. J.CHEM. SOC., CHEM. COMMUN.,1988.1595-1596.
[19]Takashi Joh, Hiroyuki Nagata and Shigetoshi Takahashi. Inorganica Chimica Acta,220 (1994) 45-53.
[20]Martha L. Quesada and Richard H. Schlessinger. J. Org. Clhem.Vol 43, No.2,1978. 346-347.
[21]Akitami Ichihara, Noriki Nio, Yoshihiko Terayama,Ryoji Kimura, and Sadao Sakamura. Tetrahedron Letters.1979,39,3731-3734.
[22]En Si Wang, Yuen Min Choy and Henry N.C. Wong. Tetrahedron, Vol.52, No.37, pp. 12137-12158,1996.
[23]Rajiv P. Balasubramaniam, David K. Moss, Justin K. Wyatt, John D. Spence, Arvin Gee, and Michael H.Nantz. Tetrahedron, Vol.53, No.22, pp.7429-7444,1997.
[24]Robert K. Boeckman, Jr., and SoO Sung KO. J. Am. Chem. SOC.1982,104,1033-1041.
[25]Robert K.Boeckman, Jr., Soo Sung KO. J.Am. Chem. SOC.1980,102,7146-7149.
[26]E.Lattmann, H.M.R. Hoffmann.Synthesis.155-163.1996.
[27]Xian Huang, Hongwei Zhou, and Wanli Chen; J. Org. Chem., Vol.69, No.3,2004.
[28]Ma, S.; Wu, S. L. J. Org. Chem.1999,64,6314.
[29](a) Takeda, Y.; Okeda, Y.; Masuda, T.; Hirata, E.; Shieato, T.;Takushi, A.; Yu, Q.; Otsuka, H. P. K.:Warkentin, J. Chem. Pharm.Bull.2000,48,752. (b) Brady, S. F.; Clardy, J.J. Nat. Prod.2000,63,1447.
[30](a) Topol, I.; Burt, S. K.; Rashin, A. A.; Erickson, J. W. J. Phys.Chem. A 2000,104,866. (b) Takeda, Y.; Okeda, Y.; Masuda, T.; Hirata,E.; Shieato, T.; Takushi, A.; Yu, Q.; Otsuka, H. P. K.:Warkentin, J.Chem. Pharm. Bull.2000,48,752. (c) Brady, S. F.; Clardy, J. J. Nat.Prod. 2000,63,1447. (d) Watanabe, H.; Watanabe, H.; Usui, T.;Kondoh, M.; Osada, H.; Kitahara, T. J. Antibiot.2000,53,540.
[31]Kortmann, I.; Werstermann, B. Synthesis 1995,931-933.
[32]von W. Haefliger and T. Petrzilka.Helv. Chim. Acta,49,1937 (1966).
[33]Rajiv P. Balasubramaniam, David K. Moss, Justin K. Wyatt, John D. Spence, Arvin Gee,and Michael H. Nantz; Tetrahedron, Vol.53, No.22, pp.7429-7444,1997.
[34]Roush, W. R.; Adam, M. A.; Peseckis, S. M. Tetrahedron Lett.1983,24,1377.
[35]Juan Ps. Cenal, Carlos R. Carreras, Carlos E. Tonn, Juan I. Padron, Miguel A. Ramirez, David D. Diaz,Fernando Garcia-Tellado, Victor S. Martin. SYNLETT.2005, No.10, 1575-157817.
[36]郑学文,江涛.氯雷他定合成工艺研究.JOURNAL OF GUANGDONG COLLEGE OF PHARMACY. Dec,2005 Vol 21 No.6655-656.
[37]隋丽娅,祝清芬,谢寅,彭新杰.盐酸氯雷他定一般药理学及毒理学实验研究.China Practical medical, January.2007, Vol.2, No.2.46-47.
[38]王道福,王莹,鲍洪军.组胺H1受体拮抗剂的临床应用近况.Prac J Med & pharm.2004 NO.1 Vol 21.71-72.
[39]徐文严.地洛他定：一种新的抗组胺药.Chin J Dermatol. November 2003, Vol 36, No.11 688-670.
[40]徐道华.第三代抗组胺药地洛他定.Chinese Journal of new drugs.2005, Vol.14 No.121486-1488.
[41]朱运贵,原海燕.去羧氯雷他定.Chinese Journal of new drugs.2002, Vol.11 No.9731-732.
[42]Carceller, E.; Recasens, N.; Almansa, C; Almansa, J.; Merlos, M.; Giral, M.; Garcia-Rafanell, J.; Forn, J. Span.1993, ES 2042421, CA 2096318, US 5407941, EP 577957.
[43]Elena, C.; Manuel, M.; Marta, G.; Dolors, B.; Carmen, A.; Javier, B.; Julian, G.R.; Javier, F. J.Med.Chem.1994,37,2697.
[44]C.L. Zhang, S.S. Chatterjee, U. Stein, U. Heinemann. Naunyn-Schmiedeberg's Arch Pharmacol. (1992).345:85-92.
[45]洪钢,章江生,王琳辉.Chin J Clin Pharmacol Ther.2005 Nov; 10(11).1201-1209.
[46](a) Laffan, David. (Lonza A.-G., Switz.). Process of preparation of threo-4-alkoxy-5-(arylhy droxymethyl)-2(5H)-furanones. Eur. Pat. Appl. (1992), EP 492347, A1 19920701.(b) Heterocycles,43(1),191-8; 1996.
[47](a)Kinga K. Borowicz, Bozena Jaszczyk, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Journal of Pharmacology.567 (2007) 110-116. (b)King K. Borowicz, Zaneta Kimber-Trojnar, Neville Ratnaraj,Philip N. Patsalos, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Neuropsycho pharmacology. (2007) 17,94-101.
[48]Andreas Draguhn, Mathias Jungclaus, Swetlana Sokolowa, Uwe Heinemann. European Journal of Pharmacology.325,1997.245-251.
[49]Francis A. Jones, John A. Davies. British Journal of Pharmacology. (1999) 128,1223-1228.
[50]S. S. Chatterjee; M. Noldner. CNS Drug Review. Vol.3. No.3,1997.225-244.
[51]Josef E. Schachtner, Hans-Dietrich Stachel, Shyam S. Chatterjee, Hermann Hauer, Kurt Polborn. Eur J. Med. Chem.33 (1998) 665-669.
[52]敖桂珍,王未东,张奕华.罗非昔布的合成[J].中国医药工业杂志，2002,33(6)：267-268.
[53]Scott L J, Lamb H M. Rofecoxib [J]. Drugs,1999,58(3):499-505.
[54]沈娟,李彬彬.柳暗花明—昔布类高选择性环氧酶抑制剂能否卷土重来[J].中国医院用药评价与分析，2006,6(2)：69-71.
[55]刘琨,罗非昔布及其衍生物的合成[D].河北医科大学硕士学位论文.2003,1-81.
[56]雷新胜,朱七庆,屈凌波等.选择性环氧合酶-2抑制剂的三维定量构效研究[J].药学学报，1999,34(8)：590-595.
[57]崔志平,特异性环氧化酶-Ⅱ抑制药-罗非昔布[J].医药导报，2002,21(6)：379-380.
[58]Chan C C, Boyce S, Brideau C, et al. Rofecoxib [Vioxx, MK20966:4-(4'-methyls ulfonyl-phenyl)-3-phenyl-2-(5H)-furanone]:a potent andorally active cyclooxygenase-2 inhibitor. Pharmacological and biochemicalprofiles [J]. J Pharmacol Exp Ther.1999,290:551-560.
[59]Van Hecken A, Depre M, Ehrich E, et al. Demonstration of specific COX-2 inhibition by MK2966 in human with supratherapeutic doses [J].Clin Pharmacol Ther,1999,65:164.
[60]王仁云.罗非昔布的药理及临床研究[J].中国新药杂志，2000,9(9)：661-664.
[61]Hawkey CJ. COX-2 inhibitors [J]. Lancet,1999,353:307-314.
[62]Ehrich EW, Dallob A, Lepeleire ID, et al. Characterization of rofecoxib as a cyclooxy-genase-2 isoform inhibitor and demonstra2tion of analgesia in the dental model [J]. Clin Pharmacol Ther,1999,65:336-347.
[63]Merck and Co. Inc. Vioxx Prescribing information[R]. New Jersey, USA.1998.
[64]Saag K, Fisher C, Mckay J, et al. MK20966, A specific COX-2 inhibitors has clinical efficacy comparable to ibuprofen in the treatment of knee and hip OA in a six-week controlled clinicaltrial [J]. A rthritis Rheum,1998,41 (Suppl 9):S84.
[65]Cannon G, Caldwell J, Holt P, et al. MK20966, a specific COX-2 inhibitor, has clinical efficacy comparable to diclofenac in the treatment of knee and hip OA in a 26 week controlled clinicaltrial [J]. A rthritis Rheum,1998,41 (Suppl 9):S83.
[66]Morrison BW, Daniels SE, Kotey P, et al. Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea:a randomized controlled trial [J]. Obstet Gynecol,1999,94 (4):504-508.
[67]张伟(译).罗非昔布首次批准用于治疗偏头疼.China Pharmacist.2005,8(6):474.
[68]钟海莹.COX-2在恶性肿瘤发生发展中的作用和机制.国外医学输血及血液学分册.2004,27(3)：203-206.
[69]Murata H, Kawano S, Tsuji S, et al, Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenicrol,1999,91:451-455.
[70]沈卫东,刘鹏飞.罗非昔布对人正常肝细胞和肝癌细胞生长及凋亡的影响.中华肝脏病杂志.2006,11(14)：863-865.
[71]李小翠,凌桂琴等.选择性COX-2抑制剂罗非昔布对胃癌细胞增殖的影响.徐州医学院学报.2005,25(3)：203-206.
[72]段瑞钦,刘建霞等.选择性环氧合酶-2抑制剂罗非昔布对胆囊癌生长的影响.山东医药.2007,47(27)：17-19.
[73]F. Conrad Engelhardt, Yao-Jun Shi, Cameron J, et al. Synthesis of a NO-Releasing Prodrug of Rofecoxib, J. Org. Chem.2006,71,480-491.
[74]刘琨,罗非昔布及其衍生物的合成[D],河北医科大学硕士学位论文，2003,1-81
[75]Amgad G. Habeeb, P. N. Praveen Rao, and Edward E. Knaus, Design and Synthesis of Celecoxib and Rofecoxib Analogues as Selective Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Sulfonamide and Methylsulfonyl Pharmacophores by an Azido Bioisostere, Journal of Medicinal Chemistry,2001,44(18):3039-3042.
[76]Latifeh Navidpour, Mohsen Amini, Hamed Shafaroodi, et al. Design and synthesis of new water-soluble tetrazolide derivatives of celecoxib and rofecoxib as selective cyclooxygenase-2 (COX-2) inhibitors, Bioorganic & Medicinal Chemistry Letters,2006, 16:4483-4487.
[77]Afshin Zarghi, P. N. Praveen Rao and Edward E. Knaus, Sulfonamido, azidosulfonyl and N-acetylsulfonamido analogues of rofecoxib:4-[4-(N-acetylsulfonamido)phenyl]-3-(4-methanesulfonylphenyl)-2(5H)furanone is a potent and selective cyclooxygenase-2inhibitor, Bioorganic & Medicinal Chemistry Letters,2004,14:1957-1960.
[78]Qiao-Hong Chen, P. N. Praveen Rao and Edward E. Knaus, Synthesis and biological evaluation of a novel class of rofecoxib analogues as dual inhibitors of cyclooxygenases (COXs) and lipoxygenases (LOXs), Bioorganic & Medicinal Chemistry,2006, 14:7898-7909.
[79]Francisco Caturla, Merce Amat, Raquel F. Reinoso, et al. Racemic and chiral sulfoxides as potential prodrugs of the COX-2 inhibitors Vioxx and Arcoxia, Bioorganic & Medicinal Chemistry Letters,2006,16:3209-3212.
[80]Nicholas D. Smith, Thomas S. Reger, Joseph Payne, et al. Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia, Bioorganic & Medicinal Chemistry Letters,2005,15:3197-3200.
[81]W. Cameron Black, Christine Brideau, Chi-Chung Chan, et al.3,4-Diaryl-5-hydroxyfuran ones:Highly Selective Inhibitors of Cyclooxygenase-2 with Aqueous Solubility, Bioorganic & Medicinal Chemistry Letters,2003,13:1195-1198.
[82]Afshin Zarghi, P. N. Praveen Rao and Edward E. Knaus, Sulfonamido, azidosulfonyl and N-acetylsulfonamido analogues of rofecoxib:4-[4-(N-acetylsulfonamido)phenyl]-3-(4-methanesulfonylphenyl)-2(5H)furanone is a potent and selective cyclooxygenase-2inhibitor, Bioorganic & Medicinal Chemistry Letters,2004,14:1957-1960.
[83]Vale'rie Weber, Catherine Rubat, Eliane Duroux, et al. New 3-and 4-hydroxyfuranones as anti-oxidants and anti-inflammatory agents, Bioorganic & Medicinal Chemistry,2005,13: 4552-4564.
[84]Desmond Richard, et al, Process for making phenyl heterocycles useful as COX-2 inhibitors [P], WO 9608482,1996-03-21.
[85]Atkinson, Joseph, G. et al, Stilbene derivatives useful as cyclooxygenase-2 inhibitors [P], WO 9613483,1996-05-09.
[86]Desmond Richard, etal, Process for preparing phenyl heterocycles useful as COX-2 inhibitors [P], WO 9800416,1996-01-08.
[87]Therien, Michel; Gauthier, Jacques Yves, et al, Synthesis of Rofecoxib, (MK 0966, Vioxx(?) 4-(4'-Methylsulfonylphenyl)-3-Phenyl-2(5H)-Furanone), a Selective and Orally Active Inhibitor of Cyclooxygenase-2, Synthesis,2001,12:1778-1779.
[88]敖桂珍,王未东,张奕华.罗非昔布的合成[J].中国医药工业杂志,2002,33(6)：267-268.
[89]Leleti Rajender Reddy and E. J. Corey. Facile air oxidation of the conjugate base of rofecoxib (VioxxTM), a possible contributor to chronic human toxicity. Tetrahedron Letters. 2005,46,927.
[1]Pata, Y. S. Antiinflamm. Antiallergy. Agents. Med. Chem.2008,7(1),32.
[2]Camelo-Nunes, I. C. Jornal de pediatria.2006,82(5),173.
[3]Kruszewski, J.; Klinika, C. I.; Alergolog, W.; Instytutu, M. The Polish otolaryngology.2007, 61(4),522.
[4]Salmun, L. M. Eepert. Opin. Inv. Drug.2002,11(2),259.
[5]Jesingbhai, J. K.; Sekhar, U. R.; Sivaramchandra, K.; Rao, C. T.; Rajamamannar, T. Indian Pat. Appl.2005,16pp. IN 2003MU00406
[6]Affrime, M. B.; Banfield, C. R.; Gupta, S. K. U.S. Pat. Appl. Publ.2006,9pp. US 2006154948.
[7]Tibor, M.; Bala'zs, V.; Imre, K.; Gyula, S. Abstracts of Papers. Organic process research and development--fifth international conference.2008,12,855.
[8]Schumacher, D. P.; Lee, J.; Rogers, L. R.; Eckhart, C. H.; Sawant, N. S.; Mitchell, M. B. PCT Int. Appl. WO 9901450,1999.
[9]Carceller, E.; Recasens, N.; Almansa, C.; Almansa, J.; Merlos, M.; Giral, M.; Garcia-Rafanell, J.; Forn, J. Span.1993, ES 2042421, CA 2096318, US 5407941, EP 577957.
[10]Elena, C.; Manuel, M.; Marta, G.; Dolors, B.; Carmen, A.; Javier, B.; Julian, G.R.; Javier, F. J. Med.Chem.1994,37,2697.
[11]Mullol, J.; Bousquet, J; Bachert, C; Canonica, W.G; Gimenez, A. A.; Kowalski, M. L.; Marti, G. E.; Maurer, M.; Picado, C.; Scadding, G.; Van, C. P. Allergy.2008,63,87,5.
[12]Guadano, E. M.; Serra-Batlles, J.; Meseguer, J.; Castillo, J. A.; de Molina, M.; Valero, A.; Picado,C. Allergy (Oxford, United Kingdom).2004,59(7),766.
[13]Arnau, A. G.; Ianosi, S.; Perez, I.; Donado, E.; Arnaiz, E.; Kaszuba, A.; Malbran, A.; Poop, G.. Abstracts of Papers. European Academy of Dermatology and Venereology, EADV, Proceedings of the Congress,15th, Greece, Oct.4-8,2006,841.
[14]Keam, Susan J.; Plosker, Greg L. Drugs.2007,67(3),457.
[15]Van, D. A. R.; Natella, Y. Curr. Opin. Investig. Drugs.2000,2(2),127.
[16]Izquierdo, I.; Merlos, M.; Garcia, R. J. Drugs of Today.2003,39(6),451.
[17]Merlos, M.; Giral, M.; Balsa, D.; Ferrando, R.; Queralt, M.; Puigdemont, A.; Garcia, R. J.; Forn, J. The Journal of pharmacology experimental therapeutics.1997,280(1),114.
[18]Xu, H.W.; Wang, J. F.; Liu, G. Z.; Hong, G. F.; Liu, H. M. Org. Biomol. Chem.2007,5, 1247.
[19]Xu, H.W.; Dai, G.F.; Liu, G. Z.; Wang, J. F.; Liu, H. M. Bioorg. Med. Chem.2007,15,4247.
[20]Xu, H.W.; Liu, G. Z.; Dai, G. F.; Wu, C. L.; Liu, H. M. Drug. Discov. Ther.2007,1(1),73.
[21]Dai, G. F.; Xu, H.W.; Wang, J. F.; Liu, F. W. Liu, H. M. Bioorg. Med. Chem. Lett.2006,16, 2710.
[22]Wang, E. S.; Choy, Y. M.; Henry, N. C. W. Tetrahedron.1996.52(37),12137.
[23]Robert, K.; Boeckman, J.; Soo, S. K.J. Am. Chem. Soc.1982,104,1033.
[24]Fan, H.; Tian, Y.; Guan, K.; Fu, Y. Q.; Wang, H.; Wang, Y.; Sun, K. F. J. Tradit. Chin. Med. 2008,10(2),145.
[1]Masferrer, J. L.; Zweifel, B. S.; Manning, P. T.; Hauser, S. D.; Leahy, K. M.; Smith, W. G.; Isakson, P. C.; Seibert, K. Selective inhibition of inducible cyclooxygenase-2 in vivo is anti-inflammatory and nonulcerogenic. Proc. Natl Acad. Sci. U.S.A.1994,91,3228-3232.
[2]Chan, C. C.; Boyce, S.; Brideau, C.; Ford-Hutchinson, A. W.; Gordon, R.; Guay, D.; Hill, R. G.; Li, C. S.; Mancini, J.; Penneton, M.; Prasit, P.; Rasori, R.; Riendeau, D.; Roy, P.; Tagari, P.; Vickers, P.; Wong, E.; Rodger, I. W. Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337:a novel nonsteroidal antiinflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J. Pharmacol. Exp. Ther.1995,274, 1531-1537.
[3]Silverstein, F. E.; Faich, G.; Goldstein, J. L.; Simon, L. S.; Pincus, T.; Whelton, A.; Makuch, R.; Eisen, G.; Agrawal, N. M.; Stenson, W. F.; Burr, A. M.; Zhao, W. W.; Kent, J. D.; Lefkowith, J. B.; Verburg, K. M.; Geis, G. S. Gastrointestinal toxicity with celecoxib vs nonsteroidal antiinflammatory drugs for osteoarthritis and rheumatoid rrthrits. The class study:a randomized controlled trial. JAMA 2000,284,1247-1255.
[4]Hawkey, C.; Laine, L.; Simon, T.; Beaulieu, A.; Maldonado, C. J.; Acevedo, E.; Shahane, A.; Quan, H.; Bolognese, J.; Mortensen, E. Comparison of the effect of rofecoxib (a cyclooxygenase-2 inhibitor), ibuprofen and placebo on the gastroduodenal mucosa of patients with osteoarthritis:a randomized, double-blind, placebo-controlled trial. The rofecoxib osteoarthritis endoscopy multinational study group. Arthritis Rheum.2000,43, 370-377.
[5]Penning, T.; Talley, J. J.; Bertenshaw, S.; Carter, J.; Collins, P.; Docter, S.; Graneto, M.; Lee, L.; Malecha, J.; Miyashiro, J.; Rogers, R.; Rogier, D.; Yu, S.; Anderson, G.; Burton, E.; Cogburn, J.; Gregory, S.; Koboldt, C.; Perkins, W.; Seibert, K.; Veenhuizen, A.; Zhang, Y. Isakson, P. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors:identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1Hpyrazol-1-yl)] benzenesulfonamide (SC-58635, Celecoxib). J. Med. Chem.1997,40,1347-1365.
[6]Chan, C. C.; Boyce, S.; Brideau, C.; Charleson, S.; Cromlish, W.; Ethier, D.; Evans, J.; Ford-Hutchinson, A. W.; Forrest, M. J.; Gauthier, J. Y.; Gordon, R.; Gresser, M.; Guay, J.; Kargman, S.; Kennedy, B.; Leblanc, Y.; Leger, S.; Mancini, J.; O(?)Neill, G. P.; Ouellet, M.; Patrick, D.; Percival, M. D.; Perrier, H.; Prasit, P.; Rodger, I. Rofecoxib [Vioxx, MK-0966; 4-(4(?)-methylsulfonylpheny])-3-pheny]-2-(5H)-furanone]:a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J. Pharmacol. Exp. Ther.1999,290,551-560.
[7]Kawamori, T.; Rao, C. V.; Seibert, K.; Reddy, B. S. Chemopreventive activity of celecoxib, a specific cylooxygenase-2 inhibitor, against colon carcinogenesis. Cancer. Res.1998,58, 409-412.
[8]Ghosh, A. J.; Hirasawa, N.; Niki, H.; Ohuchi, K. Cyclooxygenase-2 mediated Angiogenesis in carrageenan-induced granulation tissue in rats. J. Pharmacol. Exp. Ther.2000,295, 802-809.
[9]Katori, M.; Majima, M. Cyclooxygenase-2:its rich diversity of roles and possible application of its selective inhibitors. Inflamm. Res.2000,49,367-392.
[10]Subbaramaiah, K.; Dannenberg, A. J. Cyclooxygenase-2:a molecular target for cancer prevention and treatment. Trends Pharmacol. Sci.2003,24,96-102.
[11]Fujita, H.; Koshida, K.; Keller, E. T.; Takahashi, Y.; Yoshimito, T.; Namiki, M.; Mizokami, A. Cyclooxygenase-2 promotes prostate cancer progression. Prostate 2002,53,232-240.
[12]Xiang, Z.; Ho, L.; Yemul, S.; Zhao, Z.; Qing, W.; Pompl, P.; Kelley, K.; Dang, A.; Qing, W.; Teplow, D,; Pasinetti, G. M. Cyclooxygenase-2 promotes amyloid plaque deposition in a mouse model of Alzheimer's disease neuropathology. Gene Expr.2002,10,271-278.
[13]Teismann, P.; Tieu, K.; Choi, D. K.; Wu, D. C.; Naini, A.; Hunot, S.; Vila, M.; Jackson-Lewis, V.; Przedborski, S. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc. Natl. Acad. Sci. U S A.2003,100,5473-5478.
[14]Talley, J. J. Selective inhibitors of cyclooxygenase-2 (COX-2). Progr. Med. Chem.1999,36, 201-233.
[15]Rao, P. N. P.; Amini, M.; Li, H.; Habeeb, A. G.; Knaus, E. E.6-Alkyl, alkoxy, or alkylthio-substituted 3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones:a novel class of diarylheterocyclic selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett.2003,13, 2205-2209.
[16]Leleti Rajender Reddy and E. J. Corey. Facile air oxidation of the conjugate base of rofecoxib (VioxxTM), a possible contributor to chronic human toxicity. Tetrahedron Letters. 2005,46,927.
[17]敖桂珍,王未东,张奕华.罗非昔布的合成[J].中国医药工业杂志,2002,33(6)：267-268.
[18]Praveen Rao, P.N., Uddin, J., Knaus, E.E. Design, Synthesis, and Structure-Activity Relationship Studies of 3,4,6 Triphenylpyran-2-ones as Selective Cyclooxgenase-2 Inhibitors. J. Med. Chem.2004.47 (16):3972-3990.
[19]Praveen Rao, P.N., Amini, M. Li, H., Habeeb, A.G., Knaus, E.E. Design, Synthesis, and Biological Evaluation of 6-Substituted-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones: A Novel Class of Diarylheterocyclic Selective Cyclooxygenase-2 Inhibitors. J. Med. Chem. 2009.46 (23):4872-4822.
[20]Fosslien, E. Review:Molecular Pathology of Cyclooxygenase-2 in Cancer-induced Angiogenesis. Annals of Clin. Lab. Science.2001.31 (4):325-329.
[1]Amr, A. E.; Hegab, M. I.; Ibrahim, A. A.; Abdalah, M. M. Monatschefte fur Chemie.2003, 134,1395-1409.
[2](a) Amr, A. E.; Abou-Ghalia, M. H. Amino Acids,2004,26,283-289; (b) Brana, M. F.; Castellano, J. M.; Mpran, M.; Perez de Vega, M. J.; Gian, X. D.; Romerdahl, C. A.; Keihauer, G. Eur.J. Med. Chem,1995,30,235-239; (c) Kojima, N.; Fushimi, T.; Maezaki, N.; Tanaka, T.; Yamori, T. Bioorg. Med. Chem. Lett.2008,18,1637-1641.
[3]Kuhut, D.; Anke, T.; Besl, H.; Bross, M.; Herrmann, R.; Mocek, U. J. Antibiot.1990,43, 1413.
[4]Helena F., Milan P.; Jir i K.; Petr S. Tetrahedron.Lett.2005,46,8137.
[5]Schuyler, A.; Craig, E. C.; William, Hu. D.K.; Pornpen, L.; Koi, M.; Shaughnessy, M. N.; Peter, J. P.; Beth, A. R.; Guy, S.; Yang, Y. J. Bioorg. Med.Chem. Lett.2006,16,176.
[6]Caufiled, C. E.; Antane, S. A.; Morris, K.M.; Naughton, S. M.; Quagliato, D. A.; Enos, A.; Chiarello, J. F. 2005,WO2005019196.
[7]E. S. Wang, Y. M. Choy, N. C. W. Henry, Tetrahedron.52 (1996)12137-12158.
[8]K. Robert, J. Boeckman, S. K. Soo, J. Am. Chem Soc.104 (1982)1033-1041.
[9]H.W. Xu,; J. F.Wang, G. Z. Liu, G. F. Hong, H. M. Liu, Org. Biomol. Chem.5 (2007)1247-1250.
[10]H.W. Xu, G.F. Dai, G. Z. Liu, J. F.Wang, H. M. Liu, Bioorg. Med. Chem.15 (2007)4247-4251.
[11]H.W. Xu, G. Z. Liu, G. F. Dai, C. L. Wu, H. M. Liu, Drug. Discov. Ther.1(2007)73-77.
[12]G. F. Dai, H.W. Xu, J. F. Wang, F. W. Liu, H. M. Liu, Bioorg. Med. Chem. Lett. 16(2006)2710-2713.
[13]C. Caufield, S. A. Antane, K. M. Morris, S. M. Naughton, D. A.Quagliato, P. M. Andrae, A. Enos, J.F. Chiarello, PCT Int. Appl. (2005),118 pp. WO 2005019196 A1 20050303
[14]Y.H. Li, H. L iao, Yang, Gungdong yao xue.13(2003)37-39.
[15]Y Q. Liu, Y. Z. Zhang, S. G. Yan, C. C. Cheng, Y. Li, P. J. Gao, Jouranl of Shangdong Agricultural University.34(2003) 181-184.
[1]C.L. Zhang, S.S. Chatterjee, U. Stein, U. Heinemann. Naunyn-Schmiedeberg's Arch Pharmacol. (1992).345:85-92.
[2]洪钢,章江生,王琳辉.Chin J Clin Pharmacol Ther.2005 Nov; 10(11).1201-1209.
[3]Kinga K. Borowicz, Bozena Jaszczyk, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Journal of Pharmacology.567 (2007) 110-116.
[4]King K. Borowicz, Zaneta Kimber-Trojnar, Neville Ratnaraj,Philip N. Patsalos, Jarogniew J. Luszczki, Stanislaw J. Czuczwar. European Neuropsycho pharmacology. (2007) 17, 94-101.
[5]Andreas Draguhn, Mathias Jungclaus, Swetlana Sokolowa, Uwe Heinemann. European Journal of Pharmacology.325,1997.245-251.
[6]Francis A. Jones, John A. Davies. British Journal of Pharmacology. (1999) 128,1223-1228.
[7]S. S. Chatterjee; M. Noldner. CNS Drug Review. Vol.3. No.3,1997.225-244.
[8]Josef E. Schachtner, Hans-Dietrich Stachel, Shyam S. Chatterjee, Hermann Hauer, Kurt Polborn. Eur J. Med. Chem.33 (1998) 665-669.