دورية أكاديمية
Design, synthesis, molecular modeling, and biological evaluation of acrylamide derivatives as potent inhibitors of human dihydroorotate dehydrogenase for the treatment of rheumatoid arthritis.
العنوان: | Design, synthesis, molecular modeling, and biological evaluation of acrylamide derivatives as potent inhibitors of human dihydroorotate dehydrogenase for the treatment of rheumatoid arthritis. |
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المؤلفون: | Zeng F; Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Li S; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Yang G; Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Luo Y; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Qi T; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Liang Y; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Yang T; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Zhang L; Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Wang R; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Zhu L; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Li H; Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China., Xu X; Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China. |
المصدر: | Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2020 Oct 15. Date of Electronic Publication: 2020 Oct 15. |
Publication Model: | Ahead of Print |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101600560 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2211-3835 (Print) Linking ISSN: 22113835 NLM ISO Abbreviation: Acta Pharm Sin B |
أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier, 2011- |
مستخلص: | Human dihydroorotate dehydrogenase (DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis (RA), psoriasis and multiple sclerosis (MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog 11 was identified as the lead compound for structure-activity relationship (SAR) studies. The replacement of the phenyl group with naphthyl moieties improved inhibitory activity significantly to double-digit nanomolar range. Further structure optimization revealed that an acrylamide with small hydrophobic groups (Me, Cl or Br) at the 2-position was preferred. Moreover, adding a fluoro atom at the 5-position of the benzoic acid enhanced the potency. The optimization efforts led to potent compounds 42 and 53 ‒ 55 with IC (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.) |
References: | Int Urol Nephrol. 2019 Nov;51(11):1987-1998. (PMID: 31515666) Inflamm Bowel Dis. 2010 Oct;16(10):1763-77. (PMID: 20310011) Med Princ Pract. 2018;27(6):501-507. (PMID: 30173215) J Crohns Colitis. 2013 Sep;7(8):636-43. (PMID: 23078909) Trends Mol Med. 2005 Sep;11(9):430-7. (PMID: 16098809) J Clin Rheumatol. 2019 Apr;25(3):127-132. (PMID: 29794514) J Med Chem. 2015 Feb 12;58(3):1123-39. (PMID: 25580811) Nat Protoc. 2007;2(5):1269-75. (PMID: 17546023) Cancer Discov. 2017 Apr;7(4):391-399. (PMID: 28255083) Arthritis Rheum. 2008 Jan;58(1):15-25. (PMID: 18163481) Bioorg Med Chem Lett. 2006 Jan 1;16(1):88-92. (PMID: 16236496) Cell Metab. 2019 Feb 5;29(2):399-416.e10. (PMID: 30449682) J Ethnopharmacol. 2013 Jan 30;145(2):465-75. (PMID: 23183090) Ann Rheum Dis. 2015 Apr;74(4):694-702. (PMID: 24368514) CNS Drugs. 2016 Jan;30(1):41-51. (PMID: 26758290) Cancer Discov. 2017 Apr;7(4):380-390. (PMID: 28255082) Nat Rev Rheumatol. 2009 Oct;5(10):531-41. (PMID: 19798027) Structure. 2002 Sep;10(9):1211-23. (PMID: 12220493) J Med Chem. 2012 Oct 11;55(19):8341-9. (PMID: 22984987) Nature. 2003 May 15;423(6937):356-61. (PMID: 12748655) Cancer Chemother Pharmacol. 1993;32(1):64-6. (PMID: 8384937) Ann Rheum Dis. 2017 Jun;76(6):1101-1136. (PMID: 28298374) Drugs Aging. 2009;26(4):273-93. (PMID: 19476397) Transplantation. 2012 Jun 15;93(11):1101-7. (PMID: 22609757) Structure. 2000 Jan 15;8(1):25-33. (PMID: 10673429) Recent Pat Anticancer Drug Discov. 2018;13(1):86-105. (PMID: 29119937) Am J Pathol. 2010 Jun;176(6):2840-7. (PMID: 20413687) Leukemia. 2019 Oct;33(10):2403-2415. (PMID: 30940908) Biochim Biophys Acta. 1995 Apr 13;1243(3):351-60. (PMID: 7727509) Cancer Res. 1985 Nov;45(11 Pt 1):5563-8. (PMID: 4053030) Am J Med Sci. 1997 May;313(5):289-301. (PMID: 9145039) J Am Soc Nephrol. 1999 Jun;10(6):1366-80. (PMID: 10361877) Sci Rep. 2015 Oct 07;5:14836. (PMID: 26443076) Cell. 2016 Sep 22;167(1):171-186.e15. (PMID: 27641501) J Med Chem. 2015 Jan 8;58(1):512-6. (PMID: 24712864) Immunity. 2017 Feb 21;46(2):183-196. (PMID: 28228278) J Med Chem. 2014 Jun 26;57(12):5023-38. (PMID: 24417533) Drug Saf. 2009;32(12):1123-34. (PMID: 19916579) Biochemistry. 2000 Jul 11;39(27):7990-7. (PMID: 10891080) J Med Chem. 2018 Jun 28;61(12):5162-5186. (PMID: 29727569) Clin Immunol. 2018 Jan;186:59-62. (PMID: 28736274) Transplantation. 1992 Feb;53(2):303-8. (PMID: 1531394) J Med Chem. 2013 Apr 25;56(8):3148-67. (PMID: 23452331) Sci Transl Med. 2019 Nov 6;11(517):. (PMID: 31694929) Cell Chem Biol. 2018 Jun 21;25(6):705-717.e11. (PMID: 29628435) J Nutr Biochem. 2014 Dec;25(12):1275-81. (PMID: 25294776) Arthritis Rheumatol. 2016 Jan;68(1):1-26. (PMID: 26545940) ChemMedChem. 2010 Apr 6;5(4):608-17. (PMID: 20183850) Medchemcomm. 2017 Apr 26;8(6):1297-1302. (PMID: 30108840) Mult Scler Relat Disord. 2020 Aug;43:102129. (PMID: 32428844) Nature. 2011 Mar 24;471(7339):518-22. (PMID: 21430780) Am J Clin Oncol. 1993 Dec;16(6):526-8. (PMID: 8256771) J Pharmacol Exp Ther. 2012 Sep;342(3):850-60. (PMID: 22691298) Mini Rev Med Chem. 2011 Oct;11(12):1039-55. (PMID: 21861807) Immunol Rev. 1993 Dec;136:51-70. (PMID: 8132203) Arthritis Rheum. 2010 Sep;62(9):2569-81. (PMID: 20872595) J Med Chem. 2018 Jul 26;61(14):6034-6055. (PMID: 29939742) Biomed Res Int. 2019 Feb 11;2019:1473925. (PMID: 30886858) Cell Rep. 2018 Jun 19;23(12):3621-3634. (PMID: 29925003) Protein Cell. 2020 Oct;11(10):723-739. (PMID: 32754890) |
فهرسة مساهمة: | Keywords: AML, acute myeloid leukemia; Acrylamide derivatives; BPO, benzoyl peroxide; CIA, collagen-induced arthritis; DCE, 1,2-dichloroethane; DCM, dichloromethane; DHODH; DHODH inhibitors; DHODH, dihydroorotate dehydrogenase; DMAP, 4-dimethylaminopyridine; DMARDs, disease-modifying antirheumatic drugs; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; De novo pyrimidine biosynthesis; EA, ethyl acetate; FMN, flavin mononucleotide; HPLC, high performance liquid chromatography; HRMS, high-resolution mass spectrometry; IBD, inflammatory bowel disease; LAH, lithium aluminium hydride; LCMS, liquid chromatography mass spectrometry; MS, multiple sclerosis; MeOH, methanol; NBS, N-bromosuccinimide; NCS, N-chlorosuccinimide; NSAIDs, non-steroidal anti-inflammatory drugs; PDA, photodiode array detector; PE, petroleum ether; PK, pharmacokinetic; PhMe, toluene; RA, rheumatoid arthritis; Rheumatoid arthritis; SEL, systemic lupus erythematosus; TEA, triethylamine; TFA, trifluoroacetic acid; THF, tetrahydrofuran; TsCl, tosyl chloride |
تواريخ الأحداث: | Date Created: 20201020 Latest Revision: 20240222 |
رمز التحديث: | 20240223 |
مُعرف محوري في PubMed: | PMC7558257 |
DOI: | 10.1016/j.apsb.2020.10.008 |
PMID: | 33078092 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2211-3835 |
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DOI: | 10.1016/j.apsb.2020.10.008 |