痛风药物研究进展
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摘要
痛风是由高尿酸血症和关节周围的尿酸盐(MSU)晶体沉积引起的病症。综述了用于痛风治疗的相关药物,包括已经在临床上应用的传统药物、正处于临床研究阶段的新药,以及临床前研究阶段的新化合物。为其他研究者在痛风领域的研究提供参考与借鉴。
Gout is caused by hyperuricemia and deposition of monosodiumurate(MSU) crystals around the joints. This review summarized related drugs for gout treatment, including traditional drugs used clinically, new drugs in clinical research stage and new compounds under pre-clinical research. The review is to provide references for other researchers in the field of gout.
Gout is caused by hyperuricemia and deposition of monosodiumurate(MSU) crystals around the joints. This review summarized related drugs for gout treatment, including traditional drugs used clinically, new drugs in clinical research stage and new compounds under pre-clinical research. The review is to provide references for other researchers in the field of gout.
引文
[1] VanWert AL, Gionfriddo MR, Sweet DH. Organic anion transporters:discovery, pharmacology, regulation and roles in pathophysiology[J].Biopharm Drug Dispos, 2010, 31(1):1-71.
[2] Tan PK, Liu S, Gunic E, et al. Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout[J]. Sci Rep, 2017, 7(1):665.
[3] Kannangara DR, Phipps-Green AJ, Dalbeth N, et al. Hyperuricaemia:contributions of urate transporter ABCG2 and the fractional renal clearance of urate[J]. Ann Rheum Dis, 2016, 75(7):1363-6.
[4] Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment:results of a double-blind, randomised study[J]. Ann Rheum Dis, 2011, 70(71):1264-71.
[5] Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options:results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions[J]. Ann Rheum Dis, 2012, 71(11):1839-48.
[6] Ottaviani S, MoltóA, Ea HK, et al. Efficacy of anakinra in gouty arthritis:a retrospective study of 40 cases[J]. Arthritis Res Ther,2013, 15(5):R123.
[7] Yun J, Marcaida MJ, Eriksson KK, et al. Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01[J]. J Immunol, 2014, 192(7):2984-93.
[8]高杰,张晶晶,王进,等.别嘌醇致严重皮肤不良反应与江苏汉族人HLA-B*5801等位基因的相关性研究[J].药物不良反应杂志,2013,15(5):258-5.
[9] Malik UZ, Hundley NJ, Romero G, et al. Febuxostat inhibition of endothelial-bound XO:implications for targeting vascular ROS production[J]. Free Radical Biol Med, 2011, 51(1):179-84.
[10]王丽英,赵燕,郑毅,等.随机双盲三模拟对照多中心临床研究非布索坦降低痛风患者高尿酸水平的疗效和安全性[J].中华临床医师杂志(电子版),2013,7(7):2798-803.
[11]单瑞,程爱娟,吴尚勤.苯溴马隆与别嘌醇对心力衰竭伴高尿酸血症患者炎症因子及心功能的影响[J].中华高血压杂志,2014,22(4):380-3.
[12]余芬,何静.苯溴马隆片与别嘌醇片治疗急性脑梗死伴高尿酸血症的临床研究[J].中国临床药理学杂志,2017,33(19):1862-4+1881.
[13]黄映红.苯溴马隆和别嘌醇对高尿酸血症和痛风患者降尿酸疗效及安全性分析[J].中国实用医药,2018,13(33):137-8.
[14] McGillicuddy FC, de la Llera Moya M, Hinkle CC, et al. Inflammation impairs reverse cholesterol transport in vivo[J]. Circulation,2009, 119(8):1135-45.
[15] Shen Z, Rowlings C, Kerr B, et al. Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males[J]. Drug Des Dev Ther,2015, 9:3423-34.
[16] LüJM, Yao Q, Chen C. 3,4-Dihydroxy-5-nitrobenzaldehyde(DHNB)is a potent inhibitor of xanthine oxidase:a potential therapeutic agent for treatment of hyperuricemia and gout[J]. Biochem Pharmacol, 2013, 86(9):1328-37.
[17]马小双,刘艳军. 3,4-二羟基-5-硝基苯甲醛的合成[J].广东化工,2015,42(20):65.
[18] Hosoya T, Ogawa Y, Hashimoto H, et al. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout:a phase 3, multicentre, randomized, double-blind,double-dummy, active-controlled, parallel-group study[J]. J Clin Pharm Ther, 2016, 41(3):290-7.
[19]高瑞,王德才,许斌,等.托匹司他的合成工艺[J].中国医药工业杂志,2016,47(7):835-7.
[20] Fleischmann R, Winkle P, Hall J, et al. Pharmacodynamic effects and safety of verinurad in combination with febuxostat versus febuxostat alone in adults with gout:a phase 2a, open-label study[C]//Arthritis Rheumatol, New Jersey:WILEY, 2016.
[21] Fleischmann R, Winkle P, Miner JN, et al. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout:a phase IIa, open-label study[J]. RMD Open, 2018, 4(1):e000584.
[22] Ahn SO, Ohtomo S, Kiyokawa J, et al. Stronger uricosuric effects of the novel selective URAT1 inhibitor UR-1102 lowered plasma urate in tufted capuchin monkeys to a greater extent than benzbromarone[J]. J Pharmacol Exp Ther, 2016, 357(1):157-66.
[23] Lee HA, Park SI, Yoon S, et al. A pharmacokinetic and pharmacodynamic evaluation of URC102, a potent and selective inhibitor of URAT1, after single and multiple oral administrations in healthy volunteers[C]//Arthritis Rheumatol, New Jersey:WILEY,2017.
[24] Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment:two randomized controlled trials[J]. JAMA, 2011, 306(7):711-20.
[25] Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase:results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy[J]. Arthritis Res Ther, 2013, 15(5):R137.
[26] Fabbrini E, Serafini M, Colic Baric I, et al. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects[J]. Diabetes, 2014, 63(3):976-81.
[27] Becker MA, Baraf HS, Yood RA, et al. Long-term safety of pegloticase in chronic gout refractory to conventional treatment[J].Ann Rheum Dis, 2013, 72(9):1469-74.
[28] Lipsky PE, Calabrese LH, Kavanaugh A, et al. Pegloticase immunogenicity:the relationship between efficacy and antibody development in patients treated for refractory chronic gout[J]. Arthritis Res Ther, 2014, 16(2):R60.
[29] Nyborg AC, Ward C, Zacco A, et al. A therapeutic uricase with reduced immunogenicity risk and improved development properties[J]. Plos One, 2016, 11(12):e0167935.
[30] Sands E, Kivitz AJ, DeHaan W, et al. Initial phase 2 clinical data of SEL-212 in symptomatic gout patients:Monthly dosing of a pegylated uricase(pegsiticase)with svp-rapamycin enables sustained reduction of serum uric acid levels by mitigating formation of anti-drug antibodies[C]//Arthritis Rheumatol, New Jersey:WILEY, 2017.
[31]杨旭娟,黄茜,田周,等.以PNP酶为靶点的急性高尿酸血症小鼠模型组建[J].中国药理学通报,2017,33(6):882-5.
[32] Steinberg AS, Vince BD, Choi YJ, et al. The pharmacodynamics,pharmacokinetics, and safety of arhalofenate in combination with febuxostat when treating hyperuricemia associated with gout[J]. J Rheumatol, 2017, 44(3):374-9.
[33] Cai W, Wu J, Liu W, et al. Systematic structure-activity relationship(SAR)exploration of diarylmethane backbone and discovery of a highly potent novel uric acid transporter 1(URAT1)inhibitor[J].Molecules, 2018, 23(2):252.
[34] Tang HJ, Li W, Zhou M, et al. Design, synthesis and biological evaluation of novel xanthine oxidase inhibitors bearing a 2-arylbenzo[b] furan scaffold[J]. Eur J Med Chem, 2018, 151:849-60.
[35] Sun ZG, Zhou XJ, Zhu ML, et al. Synthesis and biological evaluation of novel aryl-2H-pyrazole derivatives as potent non-purine xanthine oxidase inhibitors[J]. Chem Pharm Bull(Tokyo), 2015, 63(8):603-7.
[36] Chen S, Zhang T, Wang J, et al. Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives as non-purine xanthine oxidase inhibitors[J]. Eur J Med Chem, 2015, 103:343-53.
[37]张雷,吴芳萍,李晶,等.一种黄嘌呤氧化还原酶抑制剂及其制备方法与应用:中国,106279024[P]. 2017-01-04.
[38]杨新业,黄常伟,马发城,等.羧酸取代的(杂)芳环类衍生物及其制备方法和用途:中国,106478500[P]. 2017-03-08.
[39]张雷,吴芳萍,李晶,等.氮取代基苯基吡唑类黄嘌呤氧化还原酶抑制剂及其制备:中国,106632245[P]. 2017-05-10.
[40]龙亚秋,许忠良,王贺瑶,等.一类4,5-二取代咪唑衍生物及其制备方法和用途:中国,106892871[P]. 2017-06-27.
[41]黄常伟,王晓军,杨新业,等.磺酰胺类衍生物及其制备方法和用途:中国,107089955[P]. 2017-08-25.
[42]陈磊邢,肖兰,刘玉先,等.作为URAT1抑制剂的化合物:中国,107814795[P]. 2018-03-20.
[43]杨琰,王奇昌,扈占坤,等.吲哚类或氮杂吲哚类衍生物、其制备方法和应用:中国,107987006[P]. 2018-05-04.
[44]夏增华.没食子酰葡萄糖苷类衍生物的应用及用于治疗高尿酸血症的药物组合物:中国,108451959[P]. 2018-08-28.
[45]张为革,石爱龙,王赫,等. 6-(3,4-取代苯基)-2-巯基嘧啶-4-甲酸类化合物及其制备方法和用途:中国,108689948[P]. 2018-10-23.
[2] Tan PK, Liu S, Gunic E, et al. Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout[J]. Sci Rep, 2017, 7(1):665.
[3] Kannangara DR, Phipps-Green AJ, Dalbeth N, et al. Hyperuricaemia:contributions of urate transporter ABCG2 and the fractional renal clearance of urate[J]. Ann Rheum Dis, 2016, 75(7):1363-6.
[4] Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment:results of a double-blind, randomised study[J]. Ann Rheum Dis, 2011, 70(71):1264-71.
[5] Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options:results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions[J]. Ann Rheum Dis, 2012, 71(11):1839-48.
[6] Ottaviani S, MoltóA, Ea HK, et al. Efficacy of anakinra in gouty arthritis:a retrospective study of 40 cases[J]. Arthritis Res Ther,2013, 15(5):R123.
[7] Yun J, Marcaida MJ, Eriksson KK, et al. Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01[J]. J Immunol, 2014, 192(7):2984-93.
[8]高杰,张晶晶,王进,等.别嘌醇致严重皮肤不良反应与江苏汉族人HLA-B*5801等位基因的相关性研究[J].药物不良反应杂志,2013,15(5):258-5.
[9] Malik UZ, Hundley NJ, Romero G, et al. Febuxostat inhibition of endothelial-bound XO:implications for targeting vascular ROS production[J]. Free Radical Biol Med, 2011, 51(1):179-84.
[10]王丽英,赵燕,郑毅,等.随机双盲三模拟对照多中心临床研究非布索坦降低痛风患者高尿酸水平的疗效和安全性[J].中华临床医师杂志(电子版),2013,7(7):2798-803.
[11]单瑞,程爱娟,吴尚勤.苯溴马隆与别嘌醇对心力衰竭伴高尿酸血症患者炎症因子及心功能的影响[J].中华高血压杂志,2014,22(4):380-3.
[12]余芬,何静.苯溴马隆片与别嘌醇片治疗急性脑梗死伴高尿酸血症的临床研究[J].中国临床药理学杂志,2017,33(19):1862-4+1881.
[13]黄映红.苯溴马隆和别嘌醇对高尿酸血症和痛风患者降尿酸疗效及安全性分析[J].中国实用医药,2018,13(33):137-8.
[14] McGillicuddy FC, de la Llera Moya M, Hinkle CC, et al. Inflammation impairs reverse cholesterol transport in vivo[J]. Circulation,2009, 119(8):1135-45.
[15] Shen Z, Rowlings C, Kerr B, et al. Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males[J]. Drug Des Dev Ther,2015, 9:3423-34.
[16] LüJM, Yao Q, Chen C. 3,4-Dihydroxy-5-nitrobenzaldehyde(DHNB)is a potent inhibitor of xanthine oxidase:a potential therapeutic agent for treatment of hyperuricemia and gout[J]. Biochem Pharmacol, 2013, 86(9):1328-37.
[17]马小双,刘艳军. 3,4-二羟基-5-硝基苯甲醛的合成[J].广东化工,2015,42(20):65.
[18] Hosoya T, Ogawa Y, Hashimoto H, et al. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout:a phase 3, multicentre, randomized, double-blind,double-dummy, active-controlled, parallel-group study[J]. J Clin Pharm Ther, 2016, 41(3):290-7.
[19]高瑞,王德才,许斌,等.托匹司他的合成工艺[J].中国医药工业杂志,2016,47(7):835-7.
[20] Fleischmann R, Winkle P, Hall J, et al. Pharmacodynamic effects and safety of verinurad in combination with febuxostat versus febuxostat alone in adults with gout:a phase 2a, open-label study[C]//Arthritis Rheumatol, New Jersey:WILEY, 2016.
[21] Fleischmann R, Winkle P, Miner JN, et al. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout:a phase IIa, open-label study[J]. RMD Open, 2018, 4(1):e000584.
[22] Ahn SO, Ohtomo S, Kiyokawa J, et al. Stronger uricosuric effects of the novel selective URAT1 inhibitor UR-1102 lowered plasma urate in tufted capuchin monkeys to a greater extent than benzbromarone[J]. J Pharmacol Exp Ther, 2016, 357(1):157-66.
[23] Lee HA, Park SI, Yoon S, et al. A pharmacokinetic and pharmacodynamic evaluation of URC102, a potent and selective inhibitor of URAT1, after single and multiple oral administrations in healthy volunteers[C]//Arthritis Rheumatol, New Jersey:WILEY,2017.
[24] Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment:two randomized controlled trials[J]. JAMA, 2011, 306(7):711-20.
[25] Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase:results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy[J]. Arthritis Res Ther, 2013, 15(5):R137.
[26] Fabbrini E, Serafini M, Colic Baric I, et al. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects[J]. Diabetes, 2014, 63(3):976-81.
[27] Becker MA, Baraf HS, Yood RA, et al. Long-term safety of pegloticase in chronic gout refractory to conventional treatment[J].Ann Rheum Dis, 2013, 72(9):1469-74.
[28] Lipsky PE, Calabrese LH, Kavanaugh A, et al. Pegloticase immunogenicity:the relationship between efficacy and antibody development in patients treated for refractory chronic gout[J]. Arthritis Res Ther, 2014, 16(2):R60.
[29] Nyborg AC, Ward C, Zacco A, et al. A therapeutic uricase with reduced immunogenicity risk and improved development properties[J]. Plos One, 2016, 11(12):e0167935.
[30] Sands E, Kivitz AJ, DeHaan W, et al. Initial phase 2 clinical data of SEL-212 in symptomatic gout patients:Monthly dosing of a pegylated uricase(pegsiticase)with svp-rapamycin enables sustained reduction of serum uric acid levels by mitigating formation of anti-drug antibodies[C]//Arthritis Rheumatol, New Jersey:WILEY, 2017.
[31]杨旭娟,黄茜,田周,等.以PNP酶为靶点的急性高尿酸血症小鼠模型组建[J].中国药理学通报,2017,33(6):882-5.
[32] Steinberg AS, Vince BD, Choi YJ, et al. The pharmacodynamics,pharmacokinetics, and safety of arhalofenate in combination with febuxostat when treating hyperuricemia associated with gout[J]. J Rheumatol, 2017, 44(3):374-9.
[33] Cai W, Wu J, Liu W, et al. Systematic structure-activity relationship(SAR)exploration of diarylmethane backbone and discovery of a highly potent novel uric acid transporter 1(URAT1)inhibitor[J].Molecules, 2018, 23(2):252.
[34] Tang HJ, Li W, Zhou M, et al. Design, synthesis and biological evaluation of novel xanthine oxidase inhibitors bearing a 2-arylbenzo[b] furan scaffold[J]. Eur J Med Chem, 2018, 151:849-60.
[35] Sun ZG, Zhou XJ, Zhu ML, et al. Synthesis and biological evaluation of novel aryl-2H-pyrazole derivatives as potent non-purine xanthine oxidase inhibitors[J]. Chem Pharm Bull(Tokyo), 2015, 63(8):603-7.
[36] Chen S, Zhang T, Wang J, et al. Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives as non-purine xanthine oxidase inhibitors[J]. Eur J Med Chem, 2015, 103:343-53.
[37]张雷,吴芳萍,李晶,等.一种黄嘌呤氧化还原酶抑制剂及其制备方法与应用:中国,106279024[P]. 2017-01-04.
[38]杨新业,黄常伟,马发城,等.羧酸取代的(杂)芳环类衍生物及其制备方法和用途:中国,106478500[P]. 2017-03-08.
[39]张雷,吴芳萍,李晶,等.氮取代基苯基吡唑类黄嘌呤氧化还原酶抑制剂及其制备:中国,106632245[P]. 2017-05-10.
[40]龙亚秋,许忠良,王贺瑶,等.一类4,5-二取代咪唑衍生物及其制备方法和用途:中国,106892871[P]. 2017-06-27.
[41]黄常伟,王晓军,杨新业,等.磺酰胺类衍生物及其制备方法和用途:中国,107089955[P]. 2017-08-25.
[42]陈磊邢,肖兰,刘玉先,等.作为URAT1抑制剂的化合物:中国,107814795[P]. 2018-03-20.
[43]杨琰,王奇昌,扈占坤,等.吲哚类或氮杂吲哚类衍生物、其制备方法和应用:中国,107987006[P]. 2018-05-04.
[44]夏增华.没食子酰葡萄糖苷类衍生物的应用及用于治疗高尿酸血症的药物组合物:中国,108451959[P]. 2018-08-28.
[45]张为革,石爱龙,王赫,等. 6-(3,4-取代苯基)-2-巯基嘧啶-4-甲酸类化合物及其制备方法和用途:中国,108689948[P]. 2018-10-23.