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image of Carboxamide: A Privileged Pharmacophore for the Development of 
Anti-infectious and Anti-cancer Drugs

Abstract

Carboxamide is a privileged scaffold that is often used in FDA-approved drugs. Unlike traditional amides, which exhibit properties similar to valence bonds, carboxamide has a more excellent binding mode and thus constructs rich pharmacological activities. According to the different working principles and -terminus substitution of its specific structures, carboxamide can be further divided into -unsubstituted carboxamide and -substituted carboxamide. Both kinds of carboxamides have been widely studied and used in drug design and development. This review starts from the binding style and thus summarizes the excellent carboxamide structures, current research progress, and future challenges in the fields of anti-infection and anti-cancer.

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2025-07-22
2026-01-20
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References

  1. Seidel T. Schuetz D.A. Garon A. Langer T The pharmacophore concept and its applications in computer-aided drug design. Prog Chem. Org Nat. Prod 2019 110 99 141 10.1007/978‑3‑030‑14632‑0_4
    [Google Scholar]
  2. Pautasso C. Troia R. Genuardi M. Palumbo A. Pharmacophore modeling technique applied for the discovery of proteasome inhibitors. Expert Opin. Drug Discov. 2014 9 8 931 943 10.1517/17460441.2014.923838 24877566
    [Google Scholar]
  3. Shrestha R. Fajardo J.E. Fiser A. Residue-based pharmacophore approaches to study protein–protein interactions. Curr. Opin. Struct. Biol. 2021 67 205 211 10.1016/j.sbi.2020.12.016 33486430
    [Google Scholar]
  4. Zhu H. Zhou R. Cao D. Tang J. Li M. A pharmacophore-guided deep learning approach for bioactive molecular generation. Nat. Commun. 2023 14 1 6234 10.1038/s41467‑023‑41454‑9 37803000
    [Google Scholar]
  5. Yang B. Vasbinder M.M. Hird A.W. Su Q. Wang H. Yu Y. Toader D. Lyne P.D. Read J.A. Breed J. Ioannidis S. Deng C. Grondine M. DeGrace N. Whitston D. Brassil P. Janetka J.W. Adventures in scaffold morphing: Discovery of fused ring heterocyclic checkpoint kinase 1 (CHK1) inhibitors. J. Med. Chem. 2018 61 3 1061 1073 10.1021/acs.jmedchem.7b01490 29301085
    [Google Scholar]
  6. Vara B.A. Levi S.M. Achab A. Candito D.A. Fradera X. Lesburg C.A. Kawamura S. Lacey B.M. Lim J. Methot J.L. Xu Z. Xu H. Smith D.M. Piesvaux J.A. Miller J.R. Bittinger M. Ranganath S.H. Bennett D.J. DiMauro E.F. Pasternak A. Discovery of diaminopyrimidine carboxamide hpk1 inhibitors as preclinical immunotherapy tool compounds. ACS Med. Chem. Lett. 2021 12 4 653 661 10.1021/acsmedchemlett.1c00096 33859804
    [Google Scholar]
  7. Brunner H. Ikeshita M. Tsuno T. Pyramidalization of the carboxamide sp 2 -center in peptide structures. J. Org. Chem. 2024 89 8 5511 5517 10.1021/acs.joc.3c02973 38592436
    [Google Scholar]
  8. Dhamodharan V. Harikrishna S. Bhasikuttan A.C. Pradeepkumar P.I. Topology specific stabilization of promoter over telomeric G-quadruplex DNAs by bisbenzimidazole carboxamide derivatives. ACS Chem. Biol. 2015 10 3 821 833 10.1021/cb5008597 25495750
    [Google Scholar]
  9. Wrobleski S.T. Moslin R. Lin S. Zhang Y. Spergel S. Kempson J. Tokarski J.S. Strnad J. Zupa-Fernandez A. Cheng L. Shuster D. Gillooly K. Yang X. Heimrich E. McIntyre K.W. Chaudhry C. Khan J. Ruzanov M. Tredup J. Mulligan D. Xie D. Sun H. Huang C. D’Arienzo C. Aranibar N. Chiney M. Chimalakonda A. Pitts W.J. Lombardo L. Carter P.H. Burke J.R. Weinstein D.S. Highly selective inhibition of tyrosine kinase 2 (TYK2) for the treatment of autoimmune diseases: Discovery of the allosteric inhibitor BMS-986165. J. Med. Chem. 2019 62 20 8973 8995 10.1021/acs.jmedchem.9b00444 31318208
    [Google Scholar]
  10. Luo B. Ning Y. Comprehensive overview of carboxamide derivatives as succinate dehydrogenase inhibitors. J. Agric. Food Chem. 2022 70 4 957 975 10.1021/acs.jafc.1c06654 35041423
    [Google Scholar]
  11. Ramesh V.V.E. Kale S.S. Kotmale A.S. Gawade R.L. Puranik V.G. Rajamohanan P.R. Sanjayan G.J. Carboxamide versus sulfonamide in peptide backbone folding: A case study with a hetero foldamer. Org. Lett. 2013 15 7 1504 1507 10.1021/ol4002762 23473041
    [Google Scholar]
  12. Vijayadas K.N. Davis H.C. Kotmale A.S. Gawade R.L. Puranik V.G. Rajamohanan P.R. Sanjayan G.J. An unusual conformational similarity of two peptide folds featuring sulfonamide and carboxamide on the backbone. Chem. Commun. (Camb.) 2012 48 78 9747 9749 10.1039/c2cc34533a 22914747
    [Google Scholar]
  13. Boros F. Vécsei L. Progress in the development of kynurenine and quinoline-3-carboxamide-derived drugs. Expert Opin. Investig. Drugs 2020 29 11 1223 1247 10.1080/13543784.2020.1813716 32819186
    [Google Scholar]
  14. Cronstein B.N. Aune T.M. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat. Rev. Rheumatol. 2020 16 3 145 154 10.1038/s41584‑020‑0373‑9 32066940
    [Google Scholar]
  15. Hawash M. Jaradat N. Sabobeh R. Abualhasan M. Qaoud M.T. New thiazole carboxamide derivatives as COX inhibitors: Design, synthesis, anticancer screening, in silico molecular docking, and ADME profile studies. ACS Omega 2023 8 32 29512 29526 10.1021/acsomega.3c03256 37599929
    [Google Scholar]
  16. Zeng L.F. Wang Y. Kazemi R. Xu S. Xu Z.L. Sanchez T.W. Yang L.M. Debnath B. Odde S. Xie H. Zheng Y.T. Ding J. Neamati N. Long Y.Q. Repositioning HIV-1 integrase inhibitors for cancer therapeutics: 1,6-naphthyridine-7-carboxamide as a promising scaffold with drug-like properties. J. Med. Chem. 2012 55 22 9492 9509 10.1021/jm300667v 23098137
    [Google Scholar]
  17. Singh Y.P. Kumar N. Chauhan B.S. Garg P. Carbamate as a potential anti‐Alzheimer’s pharmacophore: A review. Drug Dev. Res. 2023 84 8 1624 1651 10.1002/ddr.22113 37694498
    [Google Scholar]
  18. Li H. Gao M.Q. Chen Y. Wang Y.X. Zhu X.L. Yang G.F. Discovery of pyrazine-carboxamide-diphenyl-ethers as novel succinate dehydrogenase inhibitors via fragment recombination. J. Agric. Food Chem. 2020 68 47 14001 14008 10.1021/acs.jafc.0c05646 33185088
    [Google Scholar]
  19. Lizak C. Gerber S. Michaud G. Schubert M. Fan Y.Y. Bucher M. Darbre T. Aebi M. Reymond J.L. Locher K.P. Unexpected reactivity and mechanism of carboxamide activation in bacterial N-linked protein glycosylation. Nat. Commun. 2013 4 1 2627 10.1038/ncomms3627 24149797
    [Google Scholar]
  20. Schnute M.E. Benoit S.E. Buchler I.P. Caspers N. Grapperhaus M.L. Han S. Hotchandani R. Huang N. Hughes R.O. Juba B.M. Kim K.H. Liu E. McCarthy E. Messing D. Miyashiro J.S. Mohan S. O’Connell T.N. Ohren J.F. Parikh M.D. Schmidt M. Selness S.R. Springer J.R. Thanabal V. Trujillo J.I. Walker D.P. Wan Z.K. Withka J.M. Wittwer A.J. Wood N.L. Xing L. Zapf C.W. Douhan J. Aminopyrazole carboxamide bruton’s tyrosine kinase inhibitors. ACS Med. Chem. Lett. 2019 10 1 80 85 10.1021/acsmedchemlett.8b00461 30655951
    [Google Scholar]
  21. Zhang Y. Li X. Liu F. Bai X. Liu X. Sun H. Gao C. Lin Y. Xing P. Zhu J. Liu R. Wang Z. Dai J. Shi D. Design of selective PARP-1 inhibitors and antitumor studies. J. Med. Chem. 2024 67 11 8877 8901 10.1021/acs.jmedchem.3c02460 38776379
    [Google Scholar]
  22. Papeo G. Orsini P. Avanzi N.R. Borghi D. Casale E. Ciomei M. Cirla A. Desperati V. Donati D. Felder E.R. Galvani A. Guanci M. Isacchi A. Posteri H. Rainoldi S. Riccardi-Sirtori F. Scolaro A. Montagnoli A. Discovery of stereospecific PARP-1 inhibitor isoindolinone NMS-P515. ACS Med. Chem. Lett. 2019 10 4 534 538 10.1021/acsmedchemlett.8b00569 30996792
    [Google Scholar]
  23. Liu F. Chen J. Li X. Liu R. Zhang Y. Gao C. Shi D. Advances in development of selective antitumor inhibitors that target PARP-1. J. Med. Chem. 2023 66 24 16464 16483 10.1021/acs.jmedchem.3c00865 38088333
    [Google Scholar]
  24. Romero A.H. Fuentes G. Suescun L. Piro O. Echeverría G. Gotopo L. Pezaroglo H. Álvarez G. Cabrera G. Cerecetto H. Couto M. Tautomerism and rotamerism of favipiravir and halogenated analogues in solution and in the solid state. J. Org. Chem. 2023 88 15 10735 10752 10.1021/acs.joc.3c00777 37452781
    [Google Scholar]
  25. Sato T. Hashimoto N. Honma T. Bioisostere identification by determining the amino acid binding preferences of common chemical fragments. J. Chem. Inf. Model. 2017 57 12 2938 2947 10.1021/acs.jcim.7b00092 29111727
    [Google Scholar]
  26. Tran B. Pichling P. Tenney L. Connelly C.M. Moon M.H. Ferré-D’Amaré A.R. Schneekloth J.S. Jones C.P. Parallel discovery strategies provide a basis for riboswitch ligand design. Cell Chem. Biol. 2020 27 10 1241 1249.e4 10.1016/j.chembiol.2020.07.021 32795418
    [Google Scholar]
  27. Roy S. Bhattacharya S. Chemical information and computational modeling of targeting hybrid nucleic acid structures of PIM1 sequences by synthetic pyrrole-imidazole carboxamide drugs. J. Chem. Inf. Model. 2022 62 24 6411 6422 10.1021/acs.jcim.1c01500 35687766
    [Google Scholar]
  28. Guo Y. Liu Y. Hu N. Yu D. Zhou C. Shi G. Zhang B. Wei M. Liu J. Luo L. Tang Z. Song H. Guo Y. Liu X. Su D. Zhang S. Song X. Zhou X. Hong Y. Chen S. Cheng Z. Young S. Wei Q. Wang H. Wang Q. Lv L. Wang F. Xu H. Sun H. Xing H. Li N. Zhang W. Wang Z. Liu G. Sun Z. Zhou D. Li W. Liu L. Wang L. Wang Z. Discovery of zanubrutinib (BGB-3111), a novel, potent, and selective covalent inhibitor of bruton’s tyrosine kinase. J. Med. Chem. 2019 62 17 7923 7940 10.1021/acs.jmedchem.9b00687 31381333
    [Google Scholar]
  29. Huang W. Hulverson M.A. Choi R. Arnold S.L.M. Zhang Z. McCloskey M.C. Whitman G.R. Hackman R.C. Rivas K.L. Barrett L.K. Ojo K.K. Voorhis V.W.C. Fan E. Development of 5-aminopyrazole-4-carboxamide-based bumped-kinase inhibitors for cryptosporidiosis therapy. J. Med. Chem. 2019 62 6 3135 3146 10.1021/acs.jmedchem.9b00069 30830766
    [Google Scholar]
  30. Ma C. Li Q. Zhao M. Fan G. Zhao J. Zhang D. Yang S. Zhang S. Gao D. Mao L. Zhu L. Li W. Xu G. Jiang Y. Ding Q. Discovery of 1-Amino-1 H -imidazole-5-carboxamide Derivatives as Highly Selective, Covalent Bruton’s Tyrosine Kinase (BTK) Inhibitors. J. Med. Chem. 2021 64 21 16242 16270 10.1021/acs.jmedchem.1c01559 34672559
    [Google Scholar]
  31. Rana M. Faizan M.I. Dar S.H. Ahmad T. Rahisuddin, Correction to “design and synthesis of carbothioamide/carboxamide-based pyrazoline analogs as potential anticancer agents: Apoptosis, molecular docking, ADME assay, and DNA binding studies”. ACS Omega 2022 7 36 32827 32828 10.1021/acsomega.2c05261 36119987
    [Google Scholar]
  32. Chernov-Rogan T. Gianti E. Liu C. Villemure E. Cridland A.P. Hu X. Ballini E. Lange W. Deisemann H. Li T. Ward S.I. Hackos D.H. Magnuson S. Safina B. Klein M.L. Volgraf M. Carnevale V. Chen J. TRPA1 modulation by piperidine carboxamides suggests an evolutionarily conserved binding site and gating mechanism. Proc. Natl. Acad. Sci. USA 2019 116 51 26008 26019 10.1073/pnas.1913929116 31796582
    [Google Scholar]
  33. Hu X. Wan B. Liu Y. Shen J. Franzblau S.G. Zhang T. Ding K. Lu X. Identification of pyrazolo[1,5- a]pyridine-3-carboxamide diaryl derivatives as drug resistant antituberculosis agents. ACS Med. Chem. Lett. 2019 10 3 295 299 10.1021/acsmedchemlett.8b00410 30891129
    [Google Scholar]
  34. Kumari S. Carmona A.V. Tiwari A.K. Trippier P.C. Amide bond bioisosteres: Strategies, synthesis, and successes. J. Med. Chem. 2020 63 21 12290 12358 10.1021/acs.jmedchem.0c00530 32686940
    [Google Scholar]
  35. Hiesinger K. Dar’in D. Proschak E. Krasavin M. Spirocyclic scaffolds in medicinal chemistry. J. Med. Chem. 2021 64 1 150 183 10.1021/acs.jmedchem.0c01473 33381970
    [Google Scholar]
  36. Martinez-Ariza G. Ayaz M. Medda F. Hulme C. Synthesis of diverse nitrogen-enriched heterocyclic scaffolds using a suite of tunable one-pot multicomponent reactions. J. Org. Chem. 2014 79 11 5153 5162 10.1021/jo500723d 24788091
    [Google Scholar]
  37. Dick B.L. Cohen S.M. Metal-binding isosteres as new scaffolds for metalloenzyme inhibitors. Inorg. Chem. 2018 57 15 9538 9543 10.1021/acs.inorgchem.8b01632 30009599
    [Google Scholar]
  38. Lamberth C. Reversal of functional groups as a useful scaffold hopping tool in agrochemistry. J. Agric. Food Chem. 2022 70 36 11005 11010 10.1021/acs.jafc.1c08009 35380820
    [Google Scholar]
  39. Pihl R. Zheng Q. David Y. Nature-inspired protein ligation and its applications. Nat. Rev. Chem. 2023 7 4 234 255 10.1038/s41570‑023‑00468‑z 37117416
    [Google Scholar]
  40. Ghosh S. Tran P.N. McElheny D. Perez J.J. Nguyen A.I. Peptidic scaffolds enable rapid and multivariate secondary sphere evolution for an abiotic metallocatalyst. Inorg. Chem. 2022 61 17 6679 6687 10.1021/acs.inorgchem.2c00901 35446044
    [Google Scholar]
  41. Wang Y. Mitchell-Ryan S. Raghavan S. George C. Orr S. Hou Z. Matherly L.H. Gangjee A. Novel 5-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and as potential antitumor agents. J. Med. Chem. 2015 58 3 1479 1493 10.1021/jm501787c 25602637
    [Google Scholar]
  42. Tosh D.K. Phan K. Gao Z.G. Gakh A.A. Xu F. Deflorian F. Abagyan R. Stevens R.C. Jacobson K.A. Katritch V. Optimization of adenosine 5′-carboxamide derivatives as adenosine receptor agonists using structure-based ligand design and fragment screening. J. Med. Chem. 2012 55 9 4297 4308 10.1021/jm300095s 22486652
    [Google Scholar]
  43. Sasaki M. Yamamoto K. Ueda T. Irokawa H. Takeda K. Sekine R. Itoh F. Tanaka Y. Kuge S. Shibata N. One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression. Sci. Rep. 2023 13 1 13486 10.1038/s41598‑023‑38142‑5 37596270
    [Google Scholar]
  44. Zeida A. Trujillo M. Ferrer-Sueta G. Denicola A. Estrin D.A. Radi R. Catalysis of peroxide reduction by fast reacting protein thiols. Chem. Rev. 2019 119 19 10829 10855 10.1021/acs.chemrev.9b00371 31498605
    [Google Scholar]
  45. Dahal U.P. Joswig-Jones C. Jones J.P. Comparative study of the affinity and metabolism of type I and type II binding quinoline carboxamide analogues by cytochrome P450 3A4. J. Med. Chem. 2012 55 1 280 290 10.1021/jm201207h 22087535
    [Google Scholar]
  46. Cruciani G. Milani N. Benedetti P. Lepri S. Cesarini L. Baroni M. Spyrakis F. Tortorella S. Mosconi E. Goracci L. From experiments to a fast easy-to-use computational methodology to predict human aldehyde oxidase selectivity and metabolic reactions. J. Med. Chem. 2018 61 1 360 371 10.1021/acs.jmedchem.7b01552 29240409
    [Google Scholar]
  47. Xu Y. Li L. Wang Y. Xing J. Zhou L. Zhong D. Luo X. Jiang H. Chen K. Zheng M. Deng P. Chen X. Aldehyde oxidase mediated metabolism in drug-like molecules: A combined computational and experimental study. J. Med. Chem. 2017 60 7 2973 2982 10.1021/acs.jmedchem.7b00019 28263602
    [Google Scholar]
  48. Montefiori M. Jørgensen F.S. Olsen L. Aldehyde oxidase: Reaction mechanism and prediction of site of metabolism. ACS Omega 2017 2 8 4237 4244 10.1021/acsomega.7b00658 30023718
    [Google Scholar]
  49. Kiviranta P.H. Suuronen T. Wallén E.A.A. Leppänen J. Tervonen J. Kyrylenko S. Salminen A. Poso A. Jarho E.M.N. (epsilon)-thioacetyl-lysine-containing tri-, tetra-, and pentapeptides as SIRT1 and SIRT2 inhibitors. J. Med. Chem. 2009 52 7 2153 2156 10.1021/jm801401k 19296597
    [Google Scholar]
  50. Johannes J.W. Balazs A. Barratt D. Bista M. Chuba M.D. Cosulich S. Critchlow S.E. Degorce S.L. Fruscia D.P. Edmondson S.D. Embrey K. Fawell S. Ghosh A. Gill S.J. Gunnarsson A. Hande S.M. Heightman T.D. Hemsley P. Illuzzi G. Lane J. Larner C. Leo E. Liu L. Madin A. Martin S. McWilliams L. O’Connor M.J. Orme J.P. Pachl F. Packer M.J. Pei X. Pike A. Schimpl M. She H. Staniszewska A.D. Talbot V. Underwood E. Varnes J.G. Xue L. Yao T. Zhang K. Zhang A.X. Zheng X. Discovery of 5-4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl-N-methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA trapper with high selectivity for PARP1 over PARP2 and other PARPs. J. Med. Chem. 2021 64 14498 14512 10.1021/acs.jmedchem.1c01012 34570508
    [Google Scholar]
  51. Curreli F. Ahmed S. Victor B.S.M. Iusupov I.R. Belov D.S. Markov P.O. Kurkin A.V. Altieri A. Debnath A.K. Preclinical optimization of gp120 entry antagonists as anti-HIV-1 agents with improved cytotoxicity and ADME properties through rational design, synthesis, and antiviral evaluation. J. Med. Chem. 2020 63 4 1724 1749 10.1021/acs.jmedchem.9b02149 32031803
    [Google Scholar]
  52. Boldron C. Besse A. Bordes M.F. Tissandié S. Yvon X. Gau B. Badorc A. Rousseaux T. Barré G. Meneyrol J. Zech G. Nazare M. Fossey V. Pflieger A.M. Bonnet-Lignon S. Millet L. Briot C. Dol F. Hérault J.P. Savi P. Lassalle G. Delesque N. Herbert J.M. Bono F.N. -[6-(4-Butanoyl-5-methyl-1 H -pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1 H -indole-3-carboxamide (SAR216471), a novel intravenous and oral, reversible, and directly acting P2Y12 antagonist. J. Med. Chem. 2014 57 17 7293 7316 10.1021/jm500588w 25075638
    [Google Scholar]
  53. Ramalho M.J. Andrade S. Coelho M.Á.N. Loureiro J.A. Pereira M.C. Biophysical interaction of temozolomide and its active metabolite with biomembrane models: The relevance of drug-membrane interaction for Glioblastoma Multiforme therapy. Eur. J. Pharm. Biopharm. 2019 136 156 163 10.1016/j.ejpb.2019.01.015 30682492
    [Google Scholar]
  54. Ross C.L. Lawer A. Sircombe K.J. Pletzer D. Gamble A.B. Hook S. Site-specific antimicrobial activity of a dual-responsive ciprofloxacin prodrug. J. Med. Chem. 2024 67 11 9599 9612 10.1021/acs.jmedchem.4c00724 38780408
    [Google Scholar]
  55. Yu M. Zeng L. Xu G. Cui S. Multicomponent reactions for expeditious construction of β-indole carboxamide amino amides. J. Org. Chem. 2023 88 16 12150 12161 10.1021/acs.joc.3c01426 37498054
    [Google Scholar]
  56. Zeng L. Sajiki H. Cui S. Multicomponent ugi reaction of indole- n -carboxylic acids: Expeditious access to indole carboxamide amino amides. Org. Lett. 2019 21 13 5269 5272 10.1021/acs.orglett.9b01871 31247803
    [Google Scholar]
  57. Wang K. Herdtweck E. Dömling A. One-pot synthesis of 2-amino-indole-3-carboxamide and analogous. ACS Comb. Sci. 2011 13 2 140 146 10.1021/co100040z 21395342
    [Google Scholar]
  58. Wang Q. Wang D.X. Wang M.X. Zhu J. Still unconquered: Enantioselective passerini and ugi multicomponent reactions. Acc. Chem. Res. 2018 51 5 1290 1300 10.1021/acs.accounts.8b00105 29708723
    [Google Scholar]
  59. Qi J. Yin J. Li D. Chen S. Liu Z. Development of a one-step synthesis of 5-amino-1 H -imidazole-4-carboxamide. Org. Process Res. Dev. 2021 25 3 591 596 10.1021/acs.oprd.1c00013
    [Google Scholar]
  60. Zhu D. Xia L. Pan L. Li S. Chen R. Mou Y. Chen X. An asymmetric Ugi three-component reaction induced by chiral cyclic imines: Synthesis of morpholin- or piperazine-keto-carboxamide derivatives. J. Org. Chem. 2012 77 3 1386 1395 10.1021/jo2021967 22224946
    [Google Scholar]
  61. Guo W. Liao J. Liu D. Li J. Ji F. Wu W. Jiang H. A four‐component reaction strategy for pyrimidine carboxamide synthesis. Angew. Chem. Int. Ed. 2017 56 5 1289 1293 10.1002/anie.201608433 27966816
    [Google Scholar]
  62. Ito A. Choi J.H. Takemura H. Kotajima M. Wu J. Tokuyama S. Hirai H. Asakawa T. Ouchi H. Inai M. Kan T. Kawagishi H. Biosynthesis of the fairy chemicals, 2-azahypoxanthine and imidazole-4-carboxamide, in the fairy ring-forming fungus lepista sordida. J. Nat. Prod. 2020 83 8 2469 2476 10.1021/acs.jnatprod.0c00394 32786881
    [Google Scholar]
  63. Choi J.H. Matsuzaki N. Wu J. Kotajima M. Hirai H. Kondo M. Asakawa T. Inai M. Ouchi H. Kan T. Kawagishi H. Ribosides and ribotide of a fairy chemical, imidazole-4-carboxamide, as its metabolites in rice. Org. Lett. 2019 21 19 7841 7845 10.1021/acs.orglett.9b02833 31518147
    [Google Scholar]
  64. Takemura H. Choi J.H. Matsuzaki N. Taniguchi Y. Wu J. Hirai H. Motohashi R. Asakawa T. Ikeuchi K. Inai M. Kan T. Kawagishi H. A fairy chemical, imidazole-4-carboxamide, is produced on a novel purine metabolic pathway in rice. Sci. Rep. 2019 9 1 9899 10.1038/s41598‑019‑46312‑7 31289299
    [Google Scholar]
  65. Li L. Li Z. Yao W. Zhang X. Wang R. Li P. Yang K. Wang T. Liu K. Metabolic engineering of Pseudomonas chlororaphis QLU-1 for the enhanced production of phenazine-1-carboxamide. J. Agric. Food Chem. 2020 68 50 14832 14840 10.1021/acs.jafc.0c05746 33287542
    [Google Scholar]
  66. Jin Z.J. Zhou L. Sun S. Cui Y. Song K. Zhang X. He Y.W. Identification of a strong quorum sensing- and thermo-regulated promoter for the biosynthesis of a new metabolite pesticide phenazine-1-carboxamide in Pseudomonas strain PA1201. ACS Synth. Biol. 2020 9 7 1802 1812 10.1021/acssynbio.0c00161 32584550
    [Google Scholar]
  67. Jin X.J. Peng H.S. Hu H.B. Huang X.Q. Wang W. Zhang X.H. iTRAQ-based quantitative proteomic analysis reveals potential factors associated with the enhancement of phenazine-1-carboxamide production in Pseudomonas chlororaphis P3. Sci. Rep. 2016 6 1 27393 10.1038/srep27393 27273243
    [Google Scholar]
  68. Takagi H. Nogawa T. Futamura Y. Takahashi S. Osada H. Kinanthraquinone, a new anthraquinone carboxamide isolated from Streptomyces reveromyceticus SN-593-44. J. Antibiot. (Tokyo) 2018 71 4 480 482 10.1038/s41429‑017‑0020‑0 29410517
    [Google Scholar]
  69. Zhang Q. Chi H.T. Wu L. Deng Z. Yu Y. Two cryptic self‐resistance mechanisms in streptomyces tenebrarius reveal insights into the biosynthesis of apramycin. Angew. Chem. Int. Ed. 2021 60 16 8990 8996 10.1002/anie.202100687 33538390
    [Google Scholar]
  70. LaPlante K.L. Dhand A. Wright K. Lauterio M. Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance. Ann. Med. 2022 54 1 1686 1700 10.1080/07853890.2022.2085881 35723082
    [Google Scholar]
  71. Wang Z. Zhang Y. Bartual S.G. Luo J. Xu T. Du W. Xun Q. Tu Z. Brekken R.A. Ren X. Bullock A.N. Liang G. Lu X. Ding K. Tetrahydroisoquinoline-7-carboxamide derivatives as new selective discoidin domain receptor 1 (DDR1) inhibitors. ACS Med. Chem. Lett. 2017 8 3 327 332 10.1021/acsmedchemlett.6b00497 28337325
    [Google Scholar]
  72. Corte J.R. Pinto D.J.P. Fang T. Osuna H. Yang W. Wang Y. Lai A. Clark C.G. Sun J.H. Rampulla R. Mathur A. Kaspady M. Neithnadka P.R. Li Y.X.C. Rossi K.A. Myers J.E. Sheriff S. Lou Z. Harper T.W. Huang C. Zheng J.J. Bozarth J.M. Wu Y. Wong P.C. Crain E.J. Seiffert D.A. Luettgen J.M. Lam P.Y.S. Wexler R.R. Ewing W.R. Potent, orally bioavailable, and efficacious macrocyclic inhibitors of factor xia. discovery of pyridine-based macrocycles possessing phenylazole carboxamide P1 groups. J. Med. Chem. 2020 63 2 784 803 10.1021/acs.jmedchem.9b01768 31833761
    [Google Scholar]
  73. Naidu B.N. Sorenson M.E. Patel M. Ueda Y. Banville J. Beaulieu F. Bollini S. Dicker I.B. Higley H. Lin Z. Pajor L. Parker D.D. Terry B.J. Zheng M. Martel A. Meanwell N.A. Krystal M. Walker M.A. Synthesis and evaluation of C2-carbon-linked heterocyclic-5-hydroxy-6-oxo-dihydropyrimidine-4-carboxamides as HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 2015 25 3 717 720 10.1016/j.bmcl.2014.11.060 25529736
    [Google Scholar]
  74. Blair J.M.A. Webber M.A. Baylay A.J. Ogbolu D.O. Piddock L.J.V. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 2015 13 1 42 51 10.1038/nrmicro3380 25435309
    [Google Scholar]
  75. Hughes D. Andersson D.I. Evolutionary trajectories to antibiotic resistance. Annu. Rev. Microbiol. 2017 71 1 579 596 10.1146/annurev‑micro‑090816‑093813 28697667
    [Google Scholar]
  76. He T. Edwards T.C. Xie J. Aihara H. Geraghty R.J. Wang Z. 4,5-dihydroxypyrimidine methyl carboxylates, carboxylic acids, and carboxamides as inhibitors of human cytomegalovirus pul89 endonuclease. J. Med. Chem. 2022 65 7 5830 5849 10.1021/acs.jmedchem.2c00203 35377638
    [Google Scholar]
  77. Rizk O.H. Shaaban O.G. Wahab A.A.E. Synthesis of oxadiazolyl, pyrazolyl and thiazolyl derivatives of thiophene-2-carboxamide as antimicrobial and anti-HCV agents. Open Med. Chem. J. 2017 11 1 38 53 10.2174/1874104501711010038 28553409
    [Google Scholar]
  78. Sun X.P. Yu C.S. Min L.J. Cantrell C.L. Hua X. Sun N.B. Liu X.H. Discovery of highly efficient novel antifungal lead compounds targeting succinate dehydrogenase: Pyrazole-4-carboxamide derivatives with an N -phenyl substituted amide fragment. J. Agric. Food Chem. 2023 71 49 19312 19323 10.1021/acs.jafc.3c04842 38018356
    [Google Scholar]
  79. Wang X. Wang A. Qiu L. Chen M. Lu A. Li G. Yang C. Xue W. Expedient discovery for novel antifungal leads targeting succinate dehydrogenase: Pyrazole-4-formylhydrazide derivatives bearing a diphenyl ether fragment. J. Agric. Food Chem. 2020 68 49 14426 14437 10.1021/acs.jafc.0c03736 33216530
    [Google Scholar]
  80. Yin Y.M. Sun Z.Y. Wang D.W. Xi Z. Discovery of benzothiazolylpyrazole-4-carboxamides as potent succinate dehydrogenase inhibitors through active fragment exchange and link approach. J. Agric. Food Chem. 2023 71 40 14471 14482 10.1021/acs.jafc.3c03646 37775473
    [Google Scholar]
  81. Lu T. Yan Y. Zhang T. Zhang G. Xiao T. Cheng W. Jiang W. Wang J. Tang X. Design, synthesis, biological evaluation, and molecular modeling of novel 4 h -chromene analogs as potential succinate dehydrogenase inhibitors. J. Agric. Food Chem. 2021 69 36 10709 10721 10.1021/acs.jafc.1c03304 34476938
    [Google Scholar]
  82. Chen Y. Li T. Jin Z. Chi Y.R. New axially chiral molecular scaffolds with antibacterial activities against Xanthomonas oryzae pv. oryzae for protection of rice. J. Agric. Food Chem. 2022 70 20 6050 6058 10.1021/acs.jafc.2c01407 35544385
    [Google Scholar]
  83. Zhao Q. Xin L. Liu Y. Liang C. Li J. Jian Y. Li H. Shi Z. Liu H. Cao W. Current landscape and future perspective of oxazolidinone scaffolds containing antibacterial drugs. J. Med. Chem. 2021 64 15 10557 10580 10.1021/acs.jmedchem.1c00480 34260235
    [Google Scholar]
  84. Li S. Li D. Xiao T. Zhang S. Song Z. Ma H. Design, synthesis, fungicidal activity, and unexpected docking model of the first chiral boscalid analogues containing oxazolines. J. Agric. Food Chem. 2016 64 46 8927 8934 10.1021/acs.jafc.6b03464 27792876
    [Google Scholar]
  85. Wu Y.Y. Shao W.B. Zhu J.J. Long Z.Q. Liu L.W. Wang P.Y. Li Z. Yang S. Novel 1,3,4-Oxadiazole-2-carbohydrazides as Prospective Agricultural Antifungal Agents Potentially Targeting Succinate Dehydrogenase. J. Agric. Food Chem. 2019 67 50 13892 13903 10.1021/acs.jafc.9b05942 31774673
    [Google Scholar]
  86. Cheng X. Xu Z. Luo H. Chang X. Lv X. Design, synthesis, and biological evaluation of novel pyrazol-5-yl-benzamide derivatives containing oxazole group as potential succinate dehydrogenase inhibitors. J. Agric. Food Chem. 2022 70 43 13839 13848 10.1021/acs.jafc.2c04708 36270026
    [Google Scholar]
  87. Zhang L. Li W. Xiao T. Song Z. Csuk R. Li S. Design and discovery of novel chiral antifungal amides with 2-(2-oxazolinyl)aniline as a promising pharmacophore. J. Agric. Food Chem. 2018 66 34 8957 8965 10.1021/acs.jafc.8b02778 30092640
    [Google Scholar]
  88. Pang X. Han L. Zhou C. Li Y. Xu X. Shao X. Li Z. Design, synthesis, and insecticidal evaluation of n -pyridylpyrazole amide derivatives containing 4,5-dihydroisoxazole amide as potential ryanodine receptor activators. J. Agric. Food Chem. 2023 71 37 13688 13695 10.1021/acs.jafc.3c03199 37671936
    [Google Scholar]
  89. Zhang A. He H. Wang R. Shen Z. Wu Z. Song R. Song B. Synthesis, bioactivities, and antibacterial mechanism of 5-(thioether)- n -phenyl/benzyl-1,3,4-oxadiazole-2-carboxamide/amine derivatives. J. Agric. Food Chem. 2024 72 3 1444 1453 10.1021/acs.jafc.3c05816 38206812
    [Google Scholar]
  90. He B. Chen W. Ma Z. He X. Hu M. Hu Y. Zhang X. Yan W. Liu M. Zhang Z. Ye Y. Design and synthesis of novel diphenyl ether carboxamide derivatives to control the phytopathogenic fungus Sclerotinia sclerotiorum. J. Agric. Food Chem. 2024 72 6 2935 2942 10.1021/acs.jafc.3c04595 38317284
    [Google Scholar]
  91. Zhang A. Yue Y. Yang J. Shi J. Tao K. Jin H. Hou T. Design, synthesis, and antifungal activities of novel aromatic carboxamides containing a diphenylamine scaffold. J. Agric. Food Chem. 2019 67 17 5008 5016 10.1021/acs.jafc.9b00151 30977370
    [Google Scholar]
  92. Xiong L. Li H. Jiang L.N. Ge J.M. Yang W.C. Zhu X.L. Yang G.F. Structure-based discovery of potential fungicides as succinate ubiquinone oxidoreductase inhibitors. J. Agric. Food Chem. 2017 65 5 1021 1029 10.1021/acs.jafc.6b05134 28110534
    [Google Scholar]
  93. Wei G. Huang M.W. Wang W.J. Wu Y. Mei S.F. Zhou L.M. Mei L.C. Zhu X.L. Yang G.F. Expanding the chemical space of succinate dehydrogenase inhibitors via the carbon–silicon switch strategy. J. Agric. Food Chem. 2021 69 13 3965 3971 10.1021/acs.jafc.0c07322 33779164
    [Google Scholar]
  94. Li H. Wang Y.X. Zhu X.L. Yang G.F. Discovery of a fungicide candidate targeting succinate dehydrogenase via computational substitution optimization. J. Agric. Food Chem. 2021 69 44 13227 13234 10.1021/acs.jafc.1c04536 34709809
    [Google Scholar]
  95. He L. Cui K. Song Y. Mu W. Liu F. High-efficiency control of gray mold by the novel SDHI fungicide benzovindiflupyr combined with a reasonable application approach of dipping flower. J. Agric. Food Chem. 2018 66 26 6692 6698 10.1021/acs.jafc.8b01936 29889512
    [Google Scholar]
  96. Li K. Wang Y. Ge T. Larkin R.P. Smart A. Johnson S.B. Hao J. Risk evaluation of benzovindiflupyr resistance of Verticillium dahliae population in maine. Plant Dis. 2023 107 3 834 839 10.1094/PDIS‑06‑22‑1384‑RE 35997670
    [Google Scholar]
  97. Khodadadi F. González J.B. Martin P.L. Giroux E. Bilodeau G.J. Peter K.A. Doyle V.P. Aćimović S.G. Identification and characterization of colletotrichum species causing apple bitter rot in new york and description of C. noveboracense sp. nov. Sci. Rep. 2020 10 1 11043 10.1038/s41598‑020‑66761‑9 32632221
    [Google Scholar]
  98. Chen Y. Yu X. Yuan T. Wang F. Hu D. Lu P. Absolute configuration, enantioselective bioactivity, and mechanism study of the novel chiral fungicide benzovindiflupyr. J. Agric. Food Chem. 2023 71 23 8808 8815 10.1021/acs.jafc.3c00893 37260103
    [Google Scholar]
  99. Gosavi G. Jade D. Ponnambalam S. Harrison M.A. Zhou H. In-silico prediction, characterization, molecular docking and dynamic simulation studies for screening potential fungicides against leaf rust of Triticum aestivum. J. Biomol. Struct. Dyn. 2023 42 19 9993 10005 10.1080/07391102.2023.2254410 37668008
    [Google Scholar]
  100. Liu J. Wu J. Jin P. Hu J. Lamour K. Yang Z. Activity of the succinate dehydrogenase inhibitor fungicide benzovindiflupyr against Clarireedia spp. Plant Dis. 2023 107 12 3924 3932 10.1094/PDIS‑02‑23‑0201‑RE 37340553
    [Google Scholar]
  101. Lamberth C. Ring closure and ring opening as useful scaffold hopping tools in agrochemistry. J. Agric. Food Chem. 2023 71 47 18133 18140 10.1021/acs.jafc.3c01416 37223957
    [Google Scholar]
  102. Huang Y.H. Wei G. Wang W.J. Liu Z. Yin M.X. Guo W.M. Zhu X.L. Yang G.F. Structure-based discovery of new succinate dehydrogenase inhibitors via scaffold hopping strategy. J. Agric. Food Chem. 2023 71 47 18292 18300 10.1021/acs.jafc.3c02158 37738510
    [Google Scholar]
  103. Lamberth C. Latest research trends in agrochemical fungicides: Any learnings for pharmaceutical antifungals? ACS Med. Chem. Lett. 2022 13 6 895 903 10.1021/acsmedchemlett.2c00113 35707143
    [Google Scholar]
  104. Silvers M.A. Robertson G.T. Taylor C.M. Waldrop G.L. Design, synthesis, and antibacterial properties of dual-ligand inhibitors of acetyl-CoA carboxylase. J. Med. Chem. 2014 57 21 8947 8959 10.1021/jm501082n 25280369
    [Google Scholar]
  105. Kelvin D. Suess B. Tapping the potential of synthetic riboswitches: Reviewing the versatility of the tetracycline aptamer. RNA Biol. 2023 20 1 457 468 10.1080/15476286.2023.2234732 37459466
    [Google Scholar]
  106. Zhang J. Ponomareva L.V. Marchillo K. Zhou M. Andes D.R. Thorson J.S. Synthesis and antibacterial activity of doxycycline neoglycosides. J. Nat. Prod. 2013 76 9 1627 1636 10.1021/np4003096 23987662
    [Google Scholar]
  107. Clark R.B. Hunt D.K. He M. Achorn C. Chen C.L. Deng Y. Fyfe C. Grossman T.H. Hogan P.C. O’Brien W.J. Plamondon L. Rönn M. Sutcliffe J.A. Zhu Z. Xiao X.Y. Fluorocyclines. 2. Optimization of the C-9 side-chain for antibacterial activity and oral efficacy. J. Med. Chem. 2012 55 2 606 622 10.1021/jm201467r 22148555
    [Google Scholar]
  108. Xiao X.Y. Hunt D.K. Zhou J. Clark R.B. Dunwoody N. Fyfe C. Grossman T.H. O’Brien W.J. Plamondon L. Rönn M. Sun C. Zhang W.Y. Sutcliffe J.A. Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: A potent, broad spectrum antibacterial agent. J. Med. Chem. 2012 55 2 597 605 10.1021/jm201465w 22148514
    [Google Scholar]
  109. Clark R.B. He M. Deng Y. Sun C. Chen C.L. Hunt D.K. O’Brien W.J. Fyfe C. Grossman T.H. Sutcliffe J.A. Achorn C. Hogan P.C. Katz C.E. Niu J. Zhang W.Y. Zhu Z. Ronn M. Xiao X.Y. Synthesis and biological evaluation of 8-aminomethyltetracycline derivatives as novel antibacterial agents. J. Med. Chem. 2013 56 20 8112 8138 10.1021/jm401211t 24047201
    [Google Scholar]
  110. Deng Y. Sun C. Hunt D.K. Fyfe C. Chen C.L. Grossman T.H. Sutcliffe J.A. Xiao X.Y. Heterocyclyl tetracyclines. 1. 7-trifluoromethyl-8-pyrrolidinyltetracyclines: Potent, broad spectrum antibacterial agents with enhanced activity against Pseudomonas aeruginosa. J. Med. Chem. 2017 60 6 2498 2512 10.1021/acs.jmedchem.6b01903 28248499
    [Google Scholar]
  111. Sun C. Hunt D.K. Clark R.B. Lofland D. O’Brien W.J. Plamondon L. Xiao X.Y. Synthesis and antibacterial activity of pentacyclines: A novel class of tetracycline analogs. J. Med. Chem. 2011 54 11 3704 3731 10.1021/jm1015395 21500832
    [Google Scholar]
  112. Sun C. Hunt D.K. Chen C.L. Deng Y. He M. Clark R.B. Fyfe C. Grossman T.H. Sutcliffe J.A. Xiao X.Y. Design, synthesis, and biological evaluation of hexacyclic tetracyclines as potent, broad spectrum antibacterial agents. J. Med. Chem. 2015 58 11 4703 4712 10.1021/acs.jmedchem.5b00262 25927406
    [Google Scholar]
  113. Xu Z. Meshcheryakov V.A. Poce G. Chng S.S. MmpL3 is the flippase for mycolic acids in mycobacteria. Proc. Natl. Acad. Sci. USA 2017 114 30 7993 7998 10.1073/pnas.1700062114 28698380
    [Google Scholar]
  114. Su C.C. Klenotic P.A. Bolla J.R. Purdy G.E. Robinson C.V. Yu E.W. MmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine. Proc. Natl. Acad. Sci. USA 2019 116 23 11241 11246 10.1073/pnas.1901346116 31113875
    [Google Scholar]
  115. Su C.C. Klenotic P.A. Cui M. Lyu M. Morgan C.E. Yu E.W. Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport. PLoS Biol. 2021 19 8 e3001370 10.1371/journal.pbio.3001370 34383749
    [Google Scholar]
  116. Zhang B. Li J. Yang X. Wu L. Zhang J. Yang Y. Zhao Y. Zhang L. Yang X. Yang X. Cheng X. Liu Z. Jiang B. Jiang H. Guddat L.W. Yang H. Rao Z. Crystal structures of membrane transporter MMPL3, an anti-TB drug target. Cell 2019 176 3 636 648.e13 10.1016/j.cell.2019.01.003 30682372
    [Google Scholar]
  117. Stec J. Onajole O.K. Lun S. Guo H. Merenbloom B. Vistoli G. Bishai W.R. Kozikowski A.P. Indole-2-carboxamide-based MmpL3 inhibitors show exceptional antitubercular activity in an animal model of tuberculosis infection. J. Med. Chem. 2016 59 13 6232 6247 10.1021/acs.jmedchem.6b00415 27275668
    [Google Scholar]
  118. Libardo M.D.J. Duncombe C.J. Green S.R. Wyatt P.G. Thompson S. Ray P.C. Ioerger T.R. Oh S. Goodwin M.B. Boshoff H.I.M. Barry C.E. Resistance of Mycobacterium tuberculosis to indole 4-carboxamides occurs through alterations in drug metabolism and tryptophan biosynthesis. Cell Chem. Biol. 2021 28 8 1180 1191.e20 10.1016/j.chembiol.2021.02.023 33765439
    [Google Scholar]
  119. Ballell L. Bates R.H. Young R.J. Alvarez-Gomez D. Alvarez-Ruiz E. Barroso V. Blanco D. Crespo B. Escribano J. González R. Lozano S. Huss S. Santos-Villarejo A. Martín-Plaza J.J. Mendoza A. Rebollo-Lopez M.J. Remuiñan-Blanco M. Lavandera J.L. Pérez-Herran E. Gamo-Benito F.J. García-Bustos J.F. Barros D. Castro J.P. Cammack N. Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis. ChemMedChem 2013 8 2 313 321 10.1002/cmdc.201200428 23307663
    [Google Scholar]
  120. Tan Y.J. Li M. Gunawan G.A. Nyantakyi S.A. Dick T. Go M.L. Lam Y. Amide–Amine Replacement in Indole-2-carboxamides Yields Potent Mycobactericidal Agents with Improved Water Solubility. ACS Med. Chem. Lett. 2021 12 5 704 712 10.1021/acsmedchemlett.0c00588 34055215
    [Google Scholar]
  121. Kondreddi R.R. Jiricek J. Rao S.P.S. Lakshminarayana S.B. Camacho L.R. Rao R. Herve M. Bifani P. Ma N.L. Kuhen K. Goh A. Chatterjee A.K. Dick T. Diagana T.T. Manjunatha U.H. Smith P.W. Design, synthesis, and biological evaluation of indole-2-carboxamides: A promising class of antituberculosis agents. J. Med. Chem. 2013 56 21 8849 8859 10.1021/jm4012774 24090347
    [Google Scholar]
  122. Bhattarai P. Hegde P. Li W. Prathipati P.K. Stevens C.M. Yang L. Zhou H. Pandya A. Cunningham K. Grissom J. Sotelo R.M. Sowards M. Calisto L. Destache C.J. Rocha-Sanchez S. Gumbart J.C. Zgurskaya H.I. Jackson M. North E.J. Structural determinants of indole-2-carboxamides: Identification of lead acetamides with pan antimycobacterial activity. J. Med. Chem. 2023 66 1 170 187 10.1021/acs.jmedchem.2c00352 36563291
    [Google Scholar]
  123. Kozikowski A.P. Onajole O.K. Stec J. Dupont C. Viljoen A. Richard M. Chaira T. Lun S. Bishai W. Raj V.S. Ordway D. Kremer L. Targeting mycolic acid transport by indole-2-carboxamides for the treatment of Mycobacterium abscessus infections. J. Med. Chem. 2017 60 13 5876 5888 10.1021/acs.jmedchem.7b00582 28574259
    [Google Scholar]
  124. Raynaud C. Daher W. Roquet-Banères F. Johansen M.D. Stec J. Onajole O.K. Ordway D. Kozikowski A.P. Kremer L. Synergistic interactions of indole-2-carboxamides and β-lactam antibiotics against mycobacterium abscessus. Antimicrob. Agents Chemother. 2020 64 5 e02548 e19 10.1128/AAC.02548‑19 32041716
    [Google Scholar]
  125. Pandya A.N. Prathipati P.K. Hegde P. Li W. Graham K.F. Mandal S. Drescher K.M. Destache C.J. Ordway D. Jackson M. North E.J. Indole-2-carboxamides are active against Mycobacterium abscessus in a mouse model of acute infection. Antimicrob. Agents Chemother. 2019 63 3 e02245 e18 10.1128/AAC.02245‑18 30602519
    [Google Scholar]
  126. Patel H. Sengupta D. Antiviral drug target identification and ligand discovery. Methods Mol. Biol. 2024 2714 85 99 10.1007/978‑1‑0716‑3441‑7_4 37676593
    [Google Scholar]
  127. Delft V.A. Hall M.D. Kwong A.D. Purcell L.A. Saikatendu K.S. Schmitz U. Tallarico J.A. Lee A.A. Accelerating antiviral drug discovery: Lessons from COVID-19. Nat. Rev. Drug Discov. 2023 22 7 585 603 10.1038/s41573‑023‑00692‑8 37173515
    [Google Scholar]
  128. Ji X. Li Z. Medicinal chemistry strategies toward host targeting antiviral agents. Med. Res. Rev. 2020 40 5 1519 1557 10.1002/med.21664 32060956
    [Google Scholar]
  129. Patel R.V. Keum Y.S. Park S.W. Sketching the historical development of pyrimidones as the inhibitors of the HIV integrase. Eur. J. Med. Chem. 2015 97 649 663 10.1016/j.ejmech.2014.07.005 25084622
    [Google Scholar]
  130. Pala N. Stevaert A. Dallocchio R. Dessì A. Rogolino D. Carcelli M. Sanna V. Sechi M. Naesens L. Virtual screening and biological validation of novel influenza virus pa endonuclease inhibitors. ACS Med. Chem. Lett. 2015 6 8 866 871 10.1021/acsmedchemlett.5b00109 26288686
    [Google Scholar]
  131. Liu X. Liang J. Yu Y. Han X. Yu L. Chen F. Xu Z. Chen Q. Jin M. Dong C. Zhou H.B. Lan K. Wu S. Discovery of aryl benzoyl hydrazide derivatives as novel potent broad-spectrum inhibitors of influenza a virus RNA-dependent RNA polymerase (RdRp). J. Med. Chem. 2022 65 5 3814 3832 10.1021/acs.jmedchem.1c01257 35212527
    [Google Scholar]
  132. Ahidjo B.A. Loe M.W.C. Ng Y.L. Mok C.K. Chu J.J.H. Current perspective of antiviral strategies against COVID-19. ACS Infect. Dis. 2020 6 7 1624 1634 10.1021/acsinfecdis.0c00236 32485102
    [Google Scholar]
  133. Byléhn F. Menéndez C.A. Perez-Lemus G.R. Alvarado W. Pablo D.J.J. Modeling the binding mechanism of remdesivir, favilavir, and ribavirin to SARS-COV-2 RNA-dependent rna polymerase. ACS Cent. Sci. 2021 7 1 164 174 10.1021/acscentsci.0c01242 33527086
    [Google Scholar]
  134. Gonzalez S. Brzuska G. Ouarti A. Gallier F. Solarte C. Ferry A. Uziel J. Krol E. Lubin-Germain N. Anti-HCV and Zika activities of ribavirin C-nucleosides analogues. Bioorg. Med. Chem. 2022 68 116858 10.1016/j.bmc.2022.116858 35661850
    [Google Scholar]
  135. Huang B. Chen W. Zhao T. Li Z. Jiang X. Ginex T. Vílchez D. Luque F.J. Kang D. Gao P. Zhang J. Tian Y. Daelemans D. Clercq D.E. Pannecouque C. Zhan P. Liu X. Exploiting the tolerant region i of the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding pocket: Discovery of potent diarylpyrimidine-typed HIV-1 NNRTIs against wild-type and E138K mutant virus with significantly improved water solubility and favorable safety profiles. J. Med. Chem. 2019 62 4 2083 2098 10.1021/acs.jmedchem.8b01729 30721060
    [Google Scholar]
  136. Wang L. Sarafianos S.G. Wang Z. Cutting into the substrate dominance: Pharmacophore and structure-based approaches toward inhibiting human immunodeficiency virus reverse transcriptase-associated ribonuclease H. Acc. Chem. Res. 2020 53 1 218 230 10.1021/acs.accounts.9b00450 31880912
    [Google Scholar]
  137. Feng D. Lin H. Jiang L. Dai J. Zhang X. Zhou Z. Sun Y. Wang Z. Clercq E.D. Pannecouque C. Kang D. Zhan P. Liu X. Disubstituted pyrimidine-5-carboxamide derivatives as novel HIV-1 NNRTIs: Crystallographic overlay-based molecular design, synthesis, and biological evaluation. Eur. J. Med. Chem. 2023 246 114957 10.1016/j.ejmech.2022.114957 36446205
    [Google Scholar]
  138. Malancona S. Mori M. Fezzardi P. Santoriello M. Basta A. Nibbio M. Kovalenko L. Speziale R. Battista M.R. Cellucci A. Gennari N. Monteagudo E. Marco D.A. Giannini A. Sharma R. Pires M. Real E. Zazzi M. Lang D.M.C. Forni D.D. Saladini F. Mely Y. Summa V. Harper S. Botta M. 5,6-Dihydroxypyrimidine scaffold to target HIV-1 nucleocapsid protein. ACS Med. Chem. Lett. 2020 11 5 766 772 10.1021/acsmedchemlett.9b00608 32435383
    [Google Scholar]
  139. Zhang D. Debnath B. Yu S. Sanchez T.W. Christ F. Liu Y. Debyser Z. Neamati N. Zhao G. Design and discovery of 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide inhibitors of HIV-1 integrase. Bioorg. Med. Chem. 2014 22 19 5446 5453 10.1016/j.bmc.2014.07.036 25150089
    [Google Scholar]
  140. Massari S. Bertagnin C. Pismataro M.C. Donnadio A. Nannetti G. Felicetti T. Bona D.S. Nizi M.G. Tensi L. Manfroni G. Loza M.I. Sabatini S. Cecchetti V. Brea J. Goracci L. Loregian A. Tabarrini O. Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase. Eur. J. Med. Chem. 2021 209 112944 10.1016/j.ejmech.2020.112944 33328103
    [Google Scholar]
  141. Abu-Zaied M.A. Elgemeie G.H. Mahmoud N.M. Anti-covid-19 drug analogues: Synthesis of novel pyrimidine thioglycosides as antiviral agents against SARS-COV-2 and avian influenza H5N1 viruses. ACS Omega 2021 6 26 16890 16904 10.1021/acsomega.1c01501 34250348
    [Google Scholar]
  142. Beylkin D. Kumar G. Zhou W. Park J. Jeevan T. Lagisetti C. Harfoot R. Webby R.J. White S.W. Webb T.R. Protein-structure assisted optimization of 4,5-dihydroxypyrimidine-6-carboxamide inhibitors of influenza virus endonuclease. Sci. Rep. 2017 7 1 17139 10.1038/s41598‑017‑17419‑6 29215062
    [Google Scholar]
  143. Zhurilo N.I. Chudinov M.V. Matveev A.V. Smirnova O.S. Konstantinova I.D. Miroshnikov A.I. Prutkov A.N. Grebenkina L.E. Pulkova N.V. Shvets V.I. Isosteric ribavirin analogues: Synthesis and antiviral activities. Bioorg. Med. Chem. Lett. 2018 28 1 11 14 10.1016/j.bmcl.2017.11.029 29173944
    [Google Scholar]
  144. Okano Y. Saito-Tarashima N. Kurosawa M. Iwabu A. Ota M. Watanabe T. Kato F. Hishiki T. Fujimuro M. Minakawa N. Synthesis and biological evaluation of novel imidazole nucleosides as potential anti-dengue virus agents. Bioorg. Med. Chem. 2019 27 11 2181 2186 10.1016/j.bmc.2019.04.015 31003866
    [Google Scholar]
  145. Nakamura M. Uemura K. Saito-Tarashima N. Sato A. Orba Y. Sawa H. Matsuda A. Maenaka K. Minakawa N. Synthesis and anti-dengue virus activity of 5-ethynylimidazole-4-carboxamide (EICA) nucleotide prodrugs. Chem. Pharm. Bull. (Tokyo) 2022 70 3 220 225 10.1248/cpb.c21‑01038 34955490
    [Google Scholar]
  146. Tseng H.H. Huang W.R. Cheng C.Y. Chiu H.C. Liao T.L. Nielsen B.L. Liu H.J. Aspirin and 5-aminoimidazole-4-carboxamide riboside attenuate bovine ephemeral fever virus replication by inhibiting befv-induced autophagy. Front. Immunol. 2020 11 556838 10.3389/fimmu.2020.556838 33329515
    [Google Scholar]
  147. Aikawa A. Kozako T. Kato N. Ohsugi T. Honda S. Anti-tumor activity of 5-aminoimidazole-4-carboxamide riboside with AMPK-independent cell death in human adult T-cell leukemia/lymphoma. Eur. J. Pharmacol. 2023 961 176180 10.1016/j.ejphar.2023.176180 37956732
    [Google Scholar]
  148. Yuan W. Chen X. Liu N. Wen Y. Yang B. Andrei G. Snoeck R. Xiang Y. Wu Y. Jiang Z. Schols D. Zhang Z. Wu Q. Synthesis, anti-varicella-zoster virus and anti-cytomegalovirus activity of 4,5-disubstituted 1,2,3-(1H)-triazoles. Med. Chem. 2019 15 7 801 812 10.2174/1573406414666181109095239 30411688
    [Google Scholar]
  149. Wen Y.N. Zhang Z.F. Liu N.N. Andrei G. Snoeck R. Xiang Y.H. Schols D. Chen X. Zhang Z.Y. Zhang Q.S. Wu Q.P. Synthesis and ativiral activity of 5-(benzylthio)-4-carbamyl-1,2,3-triazoles against human cytomegalovirus (CMV) and varicella-zoster virus (VZV). Med. Chem. 2017 13 5 453 464 28290250
    [Google Scholar]
  150. Seliem I.A. Girgis A.S. Moatasim Y. Kandeil A. Mostafa A. Ali M.A. Bekheit M.S. Panda S.S. New pyrazine conjugates: Synthesis, computational studies, and antiviral properties against SARS‐CoV‐2. ChemMedChem 2021 16 22 3418 3427 10.1002/cmdc.202100476 34352160
    [Google Scholar]
  151. Lepri S. Nannetti G. Muratore G. Cruciani G. Ruzziconi R. Mercorelli B. Palù G. Loregian A. Goracci L. Optimization of small-molecule inhibitors of influenza virus polymerase: From thiophene-3-carboxamide to polyamido scaffolds. J. Med. Chem. 2014 57 10 4337 4350 10.1021/jm500300r 24785979
    [Google Scholar]
  152. Massari S. Nannetti G. Goracci L. Sancineto L. Muratore G. Sabatini S. Manfroni G. Mercorelli B. Cecchetti V. Facchini M. Palù G. Cruciani G. Loregian A. Tabarrini O. Structural investigation of cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly. J. Med. Chem. 2013 56 24 10118 10131 10.1021/jm401560v 24313730
    [Google Scholar]
  153. Desantis J. Nannetti G. Massari S. Barreca M.L. Manfroni G. Cecchetti V. Palù G. Goracci L. Loregian A. Tabarrini O. Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity. Eur. J. Med. Chem. 2017 138 128 139 10.1016/j.ejmech.2017.06.015 28666191
    [Google Scholar]
  154. Corona A. Desantis J. Massari S. Distinto S. Masaoka T. Sabatini S. Esposito F. Manfroni G. Maccioni E. Cecchetti V. Pannecouque C. Grice L.S.F.J. Tramontano E. Tabarrini O. Studies on Cycloheptathiophene‐3‐carboxamide Derivatives as Allosteric HIV‐1 Ribonuclease H Inhibitors. ChemMedChem 2016 11 16 1709 1720 10.1002/cmdc.201600015 26990134
    [Google Scholar]
  155. Pascual M.J. Merwaiss F. Leal E. Quintana M.E. Capozzo A.V. Cavasotto C.N. Bollini M. Alvarez D.E. Structure-based drug design for envelope protein E2 uncovers a new class of bovine viral diarrhea inhibitors that block virus entry. Antiviral Res. 2018 149 179 190 10.1016/j.antiviral.2017.10.010 29031833
    [Google Scholar]
  156. Li X.D. Liu L. Cheng L. Identification of thienopyridine carboxamides as selective binders of HIV-1 trans Activation Response (TAR) and Rev Response Element (RRE) RNAs. Org. Biomol. Chem. 2018 16 47 9191 9196 10.1039/C8OB02753F 30465585
    [Google Scholar]
  157. Berger M.F. Mardis E.R. The emerging clinical relevance of genomics in cancer medicine. Nat. Rev. Clin. Oncol. 2018 15 6 353 365 10.1038/s41571‑018‑0002‑6 29599476
    [Google Scholar]
  158. Waarts M.R. Stonestrom A.J. Park Y.C. Levine R.L. Targeting mutations in cancer. J. Clin. Invest. 2022 132 8 e154943 10.1172/JCI154943 35426374
    [Google Scholar]
  159. Hassan A.S. Moustafa G.O. Awad H.M. Nossier E.S. Mady M.F. Design, synthesis, anticancer evaluation, enzymatic assays, and a molecular modeling study of novel pyrazole–indole hybrids. ACS Omega 2021 6 18 12361 12374 10.1021/acsomega.1c01604 34056388
    [Google Scholar]
  160. Sabnis R.W. Tricyclic Carboxamide Derivatives as PRMT5 Inhibitors for Treating Cancer. ACS Med. Chem. Lett. 2022 13 8 1204 1205 10.1021/acsmedchemlett.2c00292 35978690
    [Google Scholar]
  161. Oh S. Kwon D.Y. Choi I. Kim Y.M. Lee J.Y. Ryu J. Jeong H. Kim M.J. Song R. Identification of piperidine-3-carboxamide derivatives inducing senescence-like phenotype with antimelanoma activities. ACS Med. Chem. Lett. 2021 12 4 563 571 10.1021/acsmedchemlett.0c00570 33859796
    [Google Scholar]
  162. Fales K.R. Njoroge F.G. Brooks H.B. Thibodeaux S. Torrado A. Si C. Toth J.L. Cowan M.J.R. Roth K.D. Thrasher K.J. Frimpong K. Lee M.R. Dally R.D. Shepherd T.A. Durham T.B. Margolis B.J. Wu Z. Wang Y. Atwell S. Wang J. Hui Y.H. Meier T.I. Konicek S.A. Geeganage S. Discovery of N -(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3 R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a potent and selective nonclassical antifolate aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT) inhibitor effective at tumor suppression in a cancer xenograft model. J. Med. Chem. 2017 60 23 9599 9616 10.1021/acs.jmedchem.7b01046 29072452
    [Google Scholar]
  163. Leblanc E. Ban F. Cavga A.D. Lawn S. Huang C.C.F. Mohan S. Chang M.E.K. Flory M.R. Ghaidi F. Lingadahalli S. Chen G. Yu I.P.L. Morin H. Lallous N. Gleave M.E. Mohammed H. Young R.N. Rennie P.S. Lack N.A. Cherkasov A. development of 2-(5,6,7-Trifluoro-1 H -Indol-3-yl)-quinoline-5-carboxamide as a potent, selective, and orally available inhibitor of human androgen receptor targeting its binding function-3 for the treatment of castration-resistant prostate cancer. J. Med. Chem. 2021 64 20 14968 14982 10.1021/acs.jmedchem.1c00681 34661404
    [Google Scholar]
  164. Patel M.R. Bhatt A. Steffen J.D. Chergui A. Murai J. Pommier Y. Pascal J.M. Trombetta L.D. Fronczek F.R. Talele T.T. Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors. J. Med. Chem. 2014 57 13 5579 5601 10.1021/jm5002502 24922587
    [Google Scholar]
  165. Huang A. Garraway L.A. Ashworth A. Weber B. Synthetic lethality as an engine for cancer drug target discovery. Nat. Rev. Drug Discov. 2020 19 1 23 38 10.1038/s41573‑019‑0046‑z 31712683
    [Google Scholar]
  166. Setton J. Zinda M. Riaz N. Durocher D. Zimmermann M. Koehler M. Reis-Filho J.S. Powell S.N. Synthetic lethality in cancer therapeutics: The next generation. Cancer Discov. 2021 11 7 1626 1635 10.1158/2159‑8290.CD‑20‑1503 33795234
    [Google Scholar]
  167. Zhang J. Gao Y. Zhang Z. Zhao J. Jia W. Xia C. Wang F. Liu T. Multi-therapies based on parp inhibition: Potential therapeutic approaches for cancer treatment. J. Med. Chem. 2022 65 24 16099 16127 10.1021/acs.jmedchem.2c01352 36512711
    [Google Scholar]
  168. Wang Y.Q. Wang P.Y. Wang Y.T. Yang G.F. Zhang A. Miao Z.H. An update on poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors: Opportunities and challenges in cancer therapy. J. Med. Chem. 2016 59 21 9575 9598 10.1021/acs.jmedchem.6b00055 27416328
    [Google Scholar]
  169. Papeo G. Posteri H. Borghi D. Busel A.A. Caprera F. Casale E. Ciomei M. Cirla A. Corti E. D’Anello M. Fasolini M. Forte B. Galvani A. Isacchi A. Khvat A. Krasavin M.Y. Lupi R. Orsini P. Perego R. Pesenti E. Pezzetta D. Rainoldi S. Riccardi-Sirtori F. Scolaro A. Sola F. Zuccotto F. Felder E.R. Donati D. Montagnoli A. Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1 H -isoindole-4-carboxamide (NMS-P118): A potent, orally available, and highly selective parp-1 inhibitor for cancer therapy. J. Med. Chem. 2015 58 17 6875 6898 10.1021/acs.jmedchem.5b00680 26222319
    [Google Scholar]
  170. Wang S.P. Li Y. Huang S.H. Wu S.Q. Gao L.L. Sun Q. Lin Q.W. Huang L. Meng L.Q. Zou Y. Zhu Q.H. Xu Y.G. Discovery of potent and novel dual PARP/BRD4 inhibitors for efficient treatment of pancreatic cancer. J. Med. Chem. 2021 64 23 17413 17435 10.1021/acs.jmedchem.1c01535 34813314
    [Google Scholar]
  171. Gu H. Yan W. Yang J. Liu B. Zhao X. Wang H. Xu W. Wang C. Chen Y. Dong Q. Zhu Q. Xu Y. Zou Y. Discovery of highly selective PARP7 inhibitors with a novel scaffold for cancer immunotherapy. J. Med. Chem. 2024 67 3 1932 1948 10.1021/acs.jmedchem.3c01764 38059836
    [Google Scholar]
  172. Wang J. Li H. He G. Chu Z. Peng K. Ge Y. Zhu Q. Xu Y. Discovery of novel dual poly(ADP-ribose)polymerase and phosphoinositide 3-kinase inhibitors as a promising strategy for cancer therapy. J. Med. Chem. 2020 63 1 122 139 10.1021/acs.jmedchem.9b00622 31846325
    [Google Scholar]
  173. Petropoulos M. Karamichali A. Rossetti G.G. Freudenmann A. Iacovino L.G. Dionellis V.S. Sotiriou S.K. Halazonetis T.D. Transcription–replication conflicts underlie sensitivity to PARP inhibitors. Nature 2024 628 8007 433 441 10.1038/s41586‑024‑07217‑2 38509368
    [Google Scholar]
  174. Lord C.J. Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science 2017 355 6330 1152 1158 10.1126/science.aam7344 28302823
    [Google Scholar]
  175. Li Y. DNA adducts in cancer chemotherapy. J. Med. Chem. 2024 67 7 5113 5143 10.1021/acs.jmedchem.3c02476 38552031
    [Google Scholar]
  176. Carbone A. Vaccher E. Gloghini A. Hematologic cancers in individuals infected by HIV. Blood 2022 139 7 995 1012 10.1182/blood.2020005469 34469512
    [Google Scholar]
  177. Noy A. Optimizing treatment of HIV-associated lymphoma. Blood 2019 134 17 1385 1394 10.1182/blood‑2018‑01‑791400 30992269
    [Google Scholar]
  178. Nogi Y. Saito-Tarashima N. Karanjit S. Minakawa N. Synthesis and behavior of DNA oligomers containing the ambiguous z-nucleobase 5-aminoimidazole-4-carboxamide. Molecules 2023 28 7 3265 10.3390/molecules28073265 37050028
    [Google Scholar]
  179. Räz M.H. Aloisi C.M.N. Gahlon H.L. Sturla S.J. DNA Adduct-Directed Synthetic Nucleosides. Acc. Chem. Res. 2019 52 5 1391 1399 10.1021/acs.accounts.9b00054 30964643
    [Google Scholar]
  180. Zimmer J. Tacconi E.M.C. Folio C. Badie S. Porru M. Klare K. Tumiati M. Markkanen E. Halder S. Ryan A. Jackson S.P. Ramadan K. Kuznetsov S.G. Biroccio A. Sale J.E. Tarsounas M. Targeting BRCA1 and BRCA2 deficiencies with g-quadruplex-interacting compounds. Mol. Cell 2016 61 3 449 460 10.1016/j.molcel.2015.12.004 26748828
    [Google Scholar]
  181. Edwards A.D. Marecki J.C. Byrd A.K. Gao J. Raney K.D. G-Quadruplex loops regulate PARP-1 enzymatic activation. Nucleic Acids Res. 2021 49 1 416 431 10.1093/nar/gkaa1172 33313902
    [Google Scholar]
  182. Awadasseid A. Ma X. Wu Y. Zhang W. G-quadruplex stabilization via small-molecules as a potential anti-cancer strategy. Biomed. Pharmacother. 2021 139 111550 10.1016/j.biopha.2021.111550 33831835
    [Google Scholar]
  183. Dallavalle S. Princiotto S. Mattio L.M. Artali R. Musso L. Aviñó A. Eritja R. Pisano C. Gargallo R. Mazzini S. Investigation of the complexes formed between PARP1 inhibitors and PARP1 g-quadruplex at the gene promoter region. Int. J. Mol. Sci. 2021 22 16 8737 10.3390/ijms22168737 34445442
    [Google Scholar]
  184. Xu H. Antonio D.M. McKinney S. Mathew V. Ho B. O’Neil N.J. Santos N.D. Silvester J. Wei V. Garcia J. Kabeer F. Lai D. Soriano P. Banáth J. Chiu D.S. Yap D. Le D.D. Ye F.B. Zhang A. Thu K. Soong J. Lin S. Tsai A.H.C. Osako T. Algara T. Saunders D.N. Wong J. Xian J. Bally M.B. Brenton J.D. Brown G.W. Shah S.P. Cescon D. Mak T.W. Caldas C. Stirling P.C. Hieter P. Balasubramanian S. Aparicio S. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours. Nat. Commun. 2017 8 1 14432 10.1038/ncomms14432 28211448
    [Google Scholar]
  185. Dallavalle S. Musso L. Artali R. Aviñó A. Scaglioni L. Eritja R. Gargallo R. Mazzini S. G-quadruplex binding properties of a potent PARP-1 inhibitor derived from 7-azaindole-1-carboxamide. Sci. Rep. 2021 11 1 3869 10.1038/s41598‑021‑83474‑9 33594142
    [Google Scholar]
  186. Rana M. Faizan M.I. Dar S.H. Ahmad T. Rahisuddin, Design and synthesis of carbothioamide/carboxamide-based pyrazoline analogs as potential anticancer agents: Apoptosis, molecular docking, ADME assay, and DNA binding studies. ACS Omega 2022 7 26 22639 22656 10.1021/acsomega.2c02033 35811873
    [Google Scholar]
  187. Ankers E.A. Evison B.J. Phillips D.R. Brownlee R.T.C. Cutts S.M. Design, synthesis, and DNA sequence selectivity of formaldehyde-mediated DNA-adducts of the novel N -(4-aminobutyl) acridine-4-carboxamide. Bioorg. Med. Chem. Lett. 2014 24 24 5710 5715 10.1016/j.bmcl.2014.10.062 25453806
    [Google Scholar]
  188. Baguley B.C. Drummond C.J. Chen Y.Y. Finlay G.J. DNA-binding anticancer drugs: One target, two actions. Molecules 2021 26 3 552 10.3390/molecules26030552 33494466
    [Google Scholar]
  189. Kostelansky F. Miletin M. Havlinova Z. Szotakova B. Libra A. Kucera R. Novakova V. Zimcik P. Thermal stabilisation of the short DNA duplexes by acridine-4-carboxamide derivatives. Nucleic Acids Res. 2022 50 18 10212 10229 10.1093/nar/gkac777 36156152
    [Google Scholar]
  190. Howell L.A. Bowater R.A. O’Connell M.A. Reszka A.P. Neidle S. Searcey M. Synthesis of small molecules targeting multiple DNA structures using click chemistry. ChemMedChem 2012 7 5 792 804 10.1002/cmdc.201200060 22378532
    [Google Scholar]
  191. Panda D. Debnath M. Mandal S. Bessi I. Schwalbe H. Dash J. A nucleus-imaging probe that selectively stabilizes a minor conformation of c-MYC G-quadruplex and down-regulates c-MYC transcription in human cancer cells. Sci. Rep. 2015 5 1 13183 10.1038/srep13183 26286633
    [Google Scholar]
  192. Duyar H. Portakal H.S. Yalçın E. Kanat B. Doluca O. Seferoğlu Z. Fluorene/fluorenone carboxamide derivatives as selective light-up fluorophores for c-myc G-quadruplex. Bioorg. Med. Chem. Lett. 2021 36 127824 10.1016/j.bmcl.2021.127824 33513388
    [Google Scholar]
  193. Ferreira R. Aviñó A. Mazzini S. Eritja R. Synthesis, DNA-binding and antiproliferative properties of acridine and 5-methylacridine derivatives. Molecules 2012 17 6 7067 7082 10.3390/molecules17067067 22683895
    [Google Scholar]
  194. Roy S. Ali A. Kamra M. Muniyappa K. Bhattacharya S. Specific stabilization of promoter G-Quadruplex DNA by 2,6-disubstituted amidoanthracene-9,10-dione based dimeric distamycin analogues and their selective cancer cell cytotoxicity. Eur. J. Med. Chem. 2020 195 112202 10.1016/j.ejmech.2020.112202 32302880
    [Google Scholar]
  195. Hager L.A. Mokesch S. Kieler C. Alonso-de Castro S. Baier D. Roller A. Kandioller W. Keppler B.K. Berger W. Salassa L. Terenzi A. Ruthenium–arene complexes bearing naphthyl-substituted 1,3-dioxoindan-2-carboxamides ligands for G-quadruplex DNA recognition. Dalton Trans. 2019 48 32 12040 12049 10.1039/C9DT02078K 31292575
    [Google Scholar]
  196. Kothiwale S. Borza C.M. Lowe E.W. Pozzi A. Meiler J. Discoidin domain receptor 1 (DDR1) kinase as target for structure-based drug discovery. Drug Discov. Today 2015 20 2 255 261 10.1016/j.drudis.2014.09.025 25284748
    [Google Scholar]
  197. Guo J. Zhang Z. Ding K. A patent review of discoidin domain receptor 1 (DDR1) modulators (2014-present). Expert Opin. Ther. Pat. 2020 30 5 341 350 10.1080/13543776.2020.1732925 32077340
    [Google Scholar]
  198. Liu M. Zhang J. Li X. Wang Y. Research progress of DDR1 inhibitors in the treatment of multiple human diseases. Eur. J. Med. Chem. 2024 268 116291 10.1016/j.ejmech.2024.116291 38452728
    [Google Scholar]
  199. Zhu D. Huang H. Pinkas D.M. Luo J. Ganguly D. Fox A.E. Arner E. Xiang Q. Tu Z.C. Bullock A.N. Brekken R.A. Ding K. Lu X. 2-Amino-2,3-dihydro-1 H -indene-5-carboxamide-based discoidin domain receptor 1 (DDR1) inhibitors: Design, synthesis, and in vivo antipancreatic cancer efficacy. J. Med. Chem. 2019 62 16 7431 7444 10.1021/acs.jmedchem.9b00365 31310125
    [Google Scholar]
  200. Murray C.W. Berdini V. Buck I.M. Carr M.E. Cleasby A. Coyle J.E. Curry J.E. Day J.E.H. Day P.J. Hearn K. Iqbal A. Lee L.Y.W. Martins V. Mortenson P.N. Munck J.M. Page L.W. Patel S. Roomans S. Smith K. Tamanini E. Saxty G. Fragment-based discovery of potent and selective DDR1/2 inhibitors. ACS Med. Chem. Lett. 2015 6 7 798 803 10.1021/acsmedchemlett.5b00143 26191369
    [Google Scholar]
  201. Tan X. Li C. Yang R. Zhao S. Li F. Li X. Chen L. Wan X. Liu X. Yang T. Tong X. Xu T. Cui R. Jiang H. Zhang S. Liu H. Zheng M. Discovery of pyrazolo[3,4- d]pyridazinone derivatives as selective DDR1 inhibitors via deep learning based design, synthesis, and biological evaluation. J. Med. Chem. 2022 65 1 103 119 10.1021/acs.jmedchem.1c01205 34821145
    [Google Scholar]
  202. Richter H. Satz A.L. Bedoucha M. Buettelmann B. Petersen A.C. Harmeier A. Hermosilla R. Hochstrasser R. Burger D. Gsell B. Gasser R. Huber S. Hug M.N. Kocer B. Kuhn B. Ritter M. Rudolph M.G. Weibel F. Molina-David J. Kim J.J. Santos J.V. Stihle M. Georges G.J. Bonfil R.D. Fridman R. Uhles S. Moll S. Faul C. Fornoni A. Prunotto M. DNA-encoded library-derived DDR1 inhibitor prevents fibrosis and renal function loss in a genetic mouse model of alport syndrome. ACS Chem. Biol. 2019 14 1 37 49 10.1021/acschembio.8b00866
    [Google Scholar]
  203. Wang Q. Tang B. Sun D. Dong Y. Ji Y. Shi H. Zhou L. Yang Y. Luo M. Tan Q. Chen L. Dong Y. Li C. Xie R. Zang Y. Shen J. Xiong B. Li J. Chen D. Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1H-pyrazol-4-yl) amino) quinazolin-6-yl)-N-(3-(trifluoromethyl) phenyl) benzamides as potent discoidin domain receptor inhibitors for the treatment of idiopathic pulmonary fibrosis. Acta Pharm. Sin. B 2022 12 4 1943 1962 10.1016/j.apsb.2021.11.012 35847490
    [Google Scholar]
  204. Wang Z. Zhang Y. Pinkas D.M. Fox A.E. Luo J. Huang H. Cui S. Xiang Q. Xu T. Xun Q. Zhu D. Tu Z. Ren X. Brekken R.A. Bullock A.N. Liang G. Ding K. Lu X. Design, synthesis, and biological evaluation of 3-(imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N -(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a dual inhibitor of discoidin domain receptors 1 and 2. J. Med. Chem. 2018 61 17 7977 7990 10.1021/acs.jmedchem.8b01045 30075624
    [Google Scholar]
  205. Liu L. Zhao L. Yang L. Chai M. Liu Z. Ma N. Wang Y. Wu Q. Guo J. Zhou F. Huang W. Ren X. Wang J. Ding M. Wang Z. Ding K. Discovery of LLC355 as an autophagy-tethering compound for the degradation of discoidin domain receptor 1. J. Med. Chem. 2024 67 10 8043 8059 10.1021/acs.jmedchem.4c00162 38730324
    [Google Scholar]
  206. Kasim M. Schulz M. Griebel A. Malhotra A. Müller B. Horsten V.H.H. Release of protein N-glycans by effectors of a Hofmann carboxamide rearrangement. Front. Mol. Biosci. 2022 9 983679 10.3389/fmolb.2022.983679 36172046
    [Google Scholar]
  207. Wiley J.L. Marusich J.A. Thomas B.F. Combination chemistry: Structure–activity relationships of novel psychoactive cannabinoids. Curr. Top. Behav. Neurosci. 2016 32 231 248 10.1007/7854_2016_17 27753007
    [Google Scholar]
  208. Ong C. Yang P. Minor-groove binding agents: Rational design of carboxamide bond isosteres. Curr. Top. Med. Chem. 2015 15 14 1359 1371 10.2174/1568026615666150413155251 25866277
    [Google Scholar]
  209. Sun J. Zhong H. Wang K. Li N. Chen L. Gains from no real PAINS: Where ‘Fair Trial Strategy’ stands in the development of multi-target ligands. Acta Pharm. Sin. B 2021 11 11 3417 3432 10.1016/j.apsb.2021.02.023 34900527
    [Google Scholar]
  210. Bajorath J. Evolution of assay interference concepts in drug discovery. Expert Opin. Drug Discov. 2021 16 7 719 721 10.1080/17460441.2021.1902983 33733961
    [Google Scholar]
  211. Baell J. Walters M.A. Chemistry: Chemical con artists foil drug discovery. Nature 2014 513 7519 481 483 10.1038/513481a 25254460
    [Google Scholar]
  212. Blagg J. Workman P. Choose and use your chemical probe wisely to explore cancer biology. Cancer Cell 2017 32 1 9 25 10.1016/j.ccell.2017.06.005 28697345
    [Google Scholar]
  213. Benek O. Korabecny J. Soukup O. A perspective on multi-target drugs for alzheimer’s disease. Trends Pharmacol. Sci. 2020 41 7 434 445 10.1016/j.tips.2020.04.008 32448557
    [Google Scholar]
  214. Quinn T.R. Giblin K.A. Thomson C. Boerth J.A. Bommakanti G. Braybrooke E. Chan C. Chinn A.J. Code E. Cui C. Fan Y. Grimster N.P. Kohara K. Lamb M.L. Ma L. Mfuh A.M. Robb G.R. Robbins K.J. Schimpl M. Tang H. Ware J. Wrigley G.L. Xue L. Zhang Y. Zhu H. Hughes S.J. Accelerated discovery of carbamate cbl-b inhibitors using generative ai models and structure-based drug design. J. Med. Chem. 2024 67 16 14210 14233 10.1021/acs.jmedchem.4c01034 39132828
    [Google Scholar]
  215. Gryniukova A. Kaiser F. Myziuk I. Alieksieieva D. Leberecht C. Heym P.P. Tarkhanova O.O. Moroz Y.S. Borysko P. Haupt V.J. AI-powered virtual screening of large compound libraries leads to the discovery of novel inhibitors of sirtuin-1. J. Med. Chem. 2023 66 15 10241 10251 10.1021/acs.jmedchem.3c00128 37499195
    [Google Scholar]
  216. Saramago L.C. Santana M.V. Gomes B.F. Dantas R.F. Senger M.R. Borges O.P.H. Ferreira V.N.S. dos Santos Rosa A. Tucci A.R. Miranda D.M. Lukacik P. Strain-Damerell C. Owen C.D. Walsh M.A. Ferreira S.B. Silva-Junior F.P. AI-driven discovery of sars-cov-2 main protease fragment-like inhibitors with antiviral activity in vitro. J. Chem. Inf. Model. 2023 63 9 2866 2880 10.1021/acs.jcim.3c00409 37058135
    [Google Scholar]
  217. Ishida S. Terayama K. Kojima R. Takasu K. Okuno Y. AI-driven synthetic route design incorporated with retrosynthesis knowledge. J. Chem. Inf. Model. 2022 62 6 1357 1367 10.1021/acs.jcim.1c01074 35258953
    [Google Scholar]
  218. Roggia M. Natale B. Amendola G. Grasso N. Maro D.S. Taliani S. Castellano S. Reina S.C.R. Salvati E. Amato J. Cosconati S. Discovering dually active anti-cancer compounds with a hybrid AI-structure-based approach. J. Chem. Inf. Model. 2024 64 21 8299 8309 10.1021/acs.jcim.4c01132 39276072
    [Google Scholar]
  219. Saadan N.M. Ahmed W.U. Kadi A.A. Al-Mutairi M.S. Al-Wabli R.I. Rahman A.F.M.M. Synthesis and evaluation of thiazolyl-indole-2-carboxamide derivatives as potent multitarget anticancer agents. ACS Omega 2024 9 40 41944 41967 10.1021/acsomega.4c06889 39398118
    [Google Scholar]
  220. Pippione A.C. Vigato C. Tucciarello C. Hussain S. Salladini E. Truong H.H. Henriksen N.M. Vanzetti G. Giordano G. Zonari D. Mirza O.A. Frydenvang K. Pignochino Y. Oliaro-Bosso S. Boschi D. Lolli M.L. AI based discovery of a new AKR1C3 inhibitor for anticancer applications. ACS Med. Chem. Lett. 2024 15 8 1269 1278 10.1021/acsmedchemlett.4c00150 39140045
    [Google Scholar]
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  • Article Type:
    Review Article
Keywords: N-terminus substitution ; anti-cancer ; binding mode ; Carboxamide ; anti-infection
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