04095nas a2201153   4500000000100000008004100001260003600042653002400078653001400102653001900116653001400135653002200149653004000171653003900211100001400250700001100264700001600275700001300291700001100304700002100315700001400336700002200350700001500372700001400387700001700401700001200418700001700430700001500447700001500462700001400477700001500491700001200506700001900518700001000537700001700547700001300564700001500577700001200592700001200604700001500616700001700631700001100648700001100659700001000670700001300680700001400693700001300707700001000720700001300730700001600743700001300759700001300772700001300785700001300798700001200811700001400823700001400837700001300851700001400864700001200878700001100890700001200901700001100913700001500924700001500939700001400954700002200968700001500990700001501005700001301020700001101033700001501044700001401059700001201073700001601085700001301101700001201114700001501126700001501141700001201156700001301168700001801181700001301199700001201212700001401224700001501238700001201253700001201265700001201277700001401289700001201303700001201315700001701327245017301344856008101517300000901598520130901607022002502916       2025                            d  bAmerican Chemical Society (ACS)10aInfectious diseases10aParasites10aDrug Discovery10aEducation10aTrypanosoma cruzi10a structure−activity relationships10aNeglected tropical diseases (NTDs)1 aAbdulai Z1 aAgbo N1 aAnderson JI1 aAstley F1 aChan B1 aAtkinson-Evans O1 aAvelar JL1 aAparecida-Silva C1 aBhardwaj K1 aBowley WJ1 aBreitkreuz N1 aCanby R1 aCartwright E1 aClifford C1 aCordell SA1 aDonker WJ1 aDriscoll J1 aGrady M1 aHigginbotham L1 aHsu D1 aHutchinson J1 aImberg L1 aJackson HF1 aJohns F1 aJones E1 aKalinin DV1 aKardeşler C1 aKeal A1 aKeel L1 aKim S1 aKnight P1 aKödel JF1 aKumeta L1 aLee H1 aLe Roy S1 aMaccarone R1 aMahmud M1 aMartin M1 aNguyen I1 aNolan CJ1 aNoyes L1 aNtuwa ANW1 aObarska W1 aOldham O1 aOnyiuke E1 aOtter J1 aPage H1 aPatel D1 aReid K1 aSamaddar K1 aShabbir SM1 aShevlin P1 aSinclair-Wright C1 aSmithies A1 aThomson AS1 aTinker J1 aUner A1 aVan Pelt N1 aWaddell E1 aWagwa H1 aWalthorne C1 aWarner S1 aWinge T1 aSum Wong N1 aWysocki LJ1 aYong CA1 aZaheen Z1 aMatheeussen A1 aCaljon G1 aAmewu R1 aBertram A1 aBiersack B1 aFriel C1 aLima LM1 aSmith C1 aWünsch B1 aPerry B1 aCruz LR1 aNortcliffe A00aCollaborative Synthesis for Neglected Diseases through the Open Synthesis Network: Structure–Activity Relationships of Arylaminopyrazoles as Chagas Disease Treatments  uhttps://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00481?ref=article_openPDF  a1-143 a<p>Neglected tropical diseases (NTDs) make up a diverse group of debilitating illnesses disproportionately affecting impoverished communities in tropical and subtropical regions. Despite their significant global health burden, they are often overshadowed by more prominent diseases, resulting in a critical lack of investment in the research and development of new treatments. A renewed focus on NTDs is, therefore, urgently needed, particularly in terms of novel therapeutic strategies. The Open Synthesis Network, launched by DNDi and partner institutions in 2016, is an innovation powerhouse that taps into the potential of students to help drive the discovery of new drugs for patients living with NTDs. We present the results of student-led work into the development of a series of aminopyrazoles for Chagas disease, a multisystemic disease caused by the Trypanosoma cruzi parasite. Seventy-four compounds were synthesized by undergraduate and postgraduate students from six universities from Brazil, Ghana, Germany, USA, and UK, illustrating that open innovation and collaboration for education can drive drug discovery forward. Early evaluation of the structure−activity relationships identified a range of potent hit compounds with selectivity for T. cruzi and no observable cytotoxicity.</p>
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