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Synthesis 2025; 57(15): 2261-2277
DOI: 10.1055/a-2603-0471
review

Stereoselectivity Seems To Be the Hardest Word: Tracking the Evolution of Asymmetric API Syntheses from Medicinal Chemistry to Process Development

José María Álvarez-Calero
,
Matthew A. Horwitz∗
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Abstract

While medicinal chemistry campaigns are frequently carried out using non-stereoselective syntheses, the goal of most small molecule drug discovery programs involving chiral drug substances is to nominate and subsequently develop a single, unichiral entity. One of the consequences of this is that fit-for-purpose solutions like chiral SFC and HPLC, which are routinely employed during the discovery phase, must be replaced with more efficient approaches to obtaining the stereoisomer of interest as the program enters development. In this review, we examine twenty case studies from the last two decades of R&D in the pharmaceutical industry where non-stereoselective routes identified during medicinal chemistry campaigns were revised and new solutions for the stereoselective API candidate syntheses were identified during process development.

1 Introduction

2 Case Studies

3 Conclusion and Outlook

Key words

drug discovery - discovery chemistry - process development - route scouting - asymmetric synthesis


Publication History

Received: 14 March 2025

Accepted after revision: 08 May 2025

Accepted Manuscript online:
08 May 2025

Article published online:
11 June 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Ariens EJ, Wuis EW. Clin Pharmacol. Ther. 1987; 42: 361
    Search in Google Scholar
  • 2 Gal J. Chiral Drugs from a Historical Point of View . In Chirality in Drug Research . Francotte E, Lindner W. Wiley; Weinheim: 2006: 3-26
    Search in Google Scholar
    • 4a Cabrera DG, Smith DA, Basarab GS, Duffy J, Spangenberg T, Chibale K. ACS Med. Chem. Lett. 2023; 14: 875
      Search in Google Scholar
    • 4b McVicker RU, O’Boyle NM. J. Med. Chem. 2024; 67: 2305
      Search in Google Scholar
  • 5 Cornwall P, Diorazio LJ, Monks N. Bioorg. Med. Chem. 2018; 26: 4336
    Search in Google Scholar
  • 6 Hulshof LA. Right First Time in Fine-Chemical Process Scale-up. Scientific Update; Crowborough: 2013
    Search in Google Scholar
  • 7 Anderson NG. Practical Process Research & Development, 2nd ed. Elsevier; Amsterdam: 2012
    Search in Google Scholar
  • 8 FDA, Guidance Document: Development of New Stereoisomeric Drugs 1992 (accessed May 23, 2025): https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-new-stereoisomeric-drugs
  • 9 ICH Harmonized Tripartite Guideline: Impurities in New Drug Substances Q3A(R2), 2006 (accessed May 23, 2025): https://www.ema.europa.eu/en/ich-q3a-r2-impurities-new-drug-substances-scientific-guideline
  • 10 Mangin D, Puel F, Veesler S. Org. Process Res. Dev. 2009; 13: 1241
    Search in Google Scholar
  • 11 Owen DR, Allerton CM. N, Anderson AS, Aschenbrenner L, Avery M, Berritt S, Boras B, Cardin RD, Carlo A, Coffman KJ, Dantonio A, Di L, Eng H, Ferre R, Gajiwala KS, Gibson SA, Greasley SE, Hurst BL, Kadar EP, Kalgutkar AS, Lee JC, Lee J, Liu W, Mason SW, Noell S, Novak JJ, Obach RS, Ogilvie K, Patel NC, Pettersson M, Rai DK, Reese MR, Sammons MF, Sathish JG, Singh RR. P, Steppan CM, Stewart AE, Tuttle JB, Updyke L, Verhoest PR, Wei L, Yang Q, Zhu Y. Science 2021; 374: 1586
    Search in Google Scholar
  • 12 Algera RF, Allais C, Baldwin AF, Becirovic H, Bowles P, Brown AR, Buske JM, Clarke HJ, Do NM, Doyle K, Fifer J, Gray K, Happe A, Hardink M, Hubbell AK, James C, Khadamkar HP, Magano J, McInturff EL, Mustakis J, Ozbuyukkaya G, Piper JL, Place DW, Ragan JA, Rauschenberger B, Reyes G, Shehadeh R, Stanchina C, Stanley M, Weekly RM, Weinstein E, Weisenburger GA, Wood E, Yayla HG, Yu S. Org. Process Res. Dev. 2023; 27: 2240
    Search in Google Scholar
  • 13 Algera RF, Allais C, Baldwin AF, Busch T, Colombo F, Colombo M, Depretz C, Dumond YR, Quintero AR. F, Heredia M, Jung J, Lall A, Lee T, Liu Y, Mandelli S, Mantel M, Morris R, Mustakis J, Nguyen B, Pearson R, Piper JL, Ragan JA, Ruffin B, Talicska C, Tcyrulnikov S, Uyeda C, Weekly RM, Zeng M. Org. Process Res. Dev. 2023; 27: 2260
    Search in Google Scholar
  • 14 Zhang R, Mamai A, Madalengoitia JS. J. Org. Chem. 1999; 64: 547
    Search in Google Scholar
  • 15 Zhang Z, Madalengoitia JS. J. Org. Chem. 1999; 64: 330
    Search in Google Scholar
  • 16 Park J, Sudhakar A, Wong G, Chen M, Weber J, Yang X, Kwok D.-i, Jeon I, Raghavan RR, Tamarez M, Tong W, Vater EJ. WO 2004113295A1, 2004
  • 17 Wu G, Chen FX, Rashatasakhon P, Eckert JM, Wong GS, Lee H.-C, Erickson NC, Vance JA, Nirchio PC, Weber J, Tsai DJ.-S, Nanfei Z. WO 2007075790A1, 2007
  • 18 Li T, Liang J, Ambrogelly A, Brennan T, Gloor G, Huisman G, Lalonde J, Lekhal A, Mijts B, Muley S, Newman L, Tobin M, Wong G, Zaks A, Zhang X. J. Am. Chem. Soc. 2012; 134: 6467
    Search in Google Scholar
  • 19 Werth J, Uyeda C. Angew. Chem. Int. Ed. 2018; 57: 13902
    Search in Google Scholar
  • 20 Chen CH, Dong H. WO 2023009521A1, 2023
  • 21 Avery S, Buske JM, Chen D, Chen H, Chen X, Davidson AR, Desrosiers J.-N, Dong H, Fellah N, Fernández DF, Grosso J, Han L, Hochdorfer T, Johnson AM, Jones BP, Kalinowski M, Launer-Felty KD, Lopez J, Makowski T, Mastriano C, Nguyen TN, Patel ND, Peng Z, Potter T, Pritchard RP, Rane AM, Reeve M, Richins MC, Salazar CA, Salisbury JJ, Simpson R, Tabshey L, Tweed EJ, Wahome PG, Walsh-Sayles N, Willie JA, Wood E. Org. Process Res. Dev. 2024; 28: 4079
    Search in Google Scholar
  • 22 Bernhardson DJ, Lara-Boykin S, McWilliams JC, Nieves-Quinones Y, Sharninghausen LS, Singer RA, Wang Z, Girvin ZC. Org. Process Res. Dev. 2024; 28: 4420
    Search in Google Scholar
  • 23 Reck F, Alm RA, Brassil P, Newman JV, Ciaccio P, McNulty J, Barthlow H, Goteti K, Breen J, Comita-Prevoir J, Cronin M, Ehmann DE, Geng B, Godfrey AA, Fisher SL. J. Med. Chem. 2012; 55: 6916
    Search in Google Scholar
  • 24 Benson H, Bones K, Churchill G, Ford G, Frodsham L, Janbon S, Millington F, Powell L, Raw SA, Reid J, Stark A, Steven A. Org. Process Res. Dev. 2020; 24: 588
    Search in Google Scholar
  • 25 Bender JA, Ding M, Gentles RG, Hewawasan P. US 20070270405A1, 2007
  • 26 Bien J, Davulcu A, DelMonte AJ, Fraunhoffer KJ, Gao Z, Hang C, Hsiao Y, Hu W, Katipally K, Littke A, Pedro A, Qiu Y, Sandoval M, Schild R, Soltani M, Tedesco A, Vanyo D, Vemishetti P, Waltermire RE. Org. Process Res. Dev. 2018; 22: 1393
    Search in Google Scholar
  • 27 DeGoey DA, DeAnda FJr, Dombrowski AW, Dubovyk I, Greszler SN, Khrakovsky D, Lee C.-H, Newton JN, Noey EL, Okano A, Sippy KB, Souers AJ, Wang L, Wilson NS, Zablocki JA. WO 2022132997A1, 2022
  • 28 Brady PB, Harper KC, Sorensen BK, Greszler SN, Lai C, Florjancic AS, Zhao G, Shelat BH, Storer GE, Henry RF, Hansen TM. Org. Process Res. Dev. 2024; 28: 3152
    Search in Google Scholar
  • 29 DeGoey DA, DeAnda FJr, Dombrowski AW, Dubovyk I, Greszler SN, Khrakovsky D, Lee C.-H, Newton JN, Noey EL, Okano A, Sippy KB, Souers AJ, Wang L, Wilson NS, Zablocki JA. US 20220213092A1, 2022
  • 30 Terrett JA, Chen H, Constantineau-Forget L, Larouche-Gauthier R, Lépissier L, Beaumier F, Déry M, Grand-Maître C, Sturino C, Volgraf M, Villemure E. US 20190284179A1, 2019
  • 31 Terrett JA, Chen H, Shore DG, Villemure E, Larouche-Gauthier R, Déry M, Beaumier F, Constantineau-Forget L, Grand-Maître C, Lépissier L, Ciblat S, Sturino C, Chen Y, Hu B, Lu A, Wang Y, Cridland AP, Ward SI, Hackos DH, Reese RM, Shields SD, Chen J, Balestrini A, Riol-Blanco L, Lee WP, Liu J, Suto E, Wu X, Zhang J, Ly JQ, La H, Johnson K, Baumgardner M, Chou K.-J, Rohou A, Rougé L, Safina BS, Magnuson S, Volgraf M. J. Med. Chem. 2021; 64: 3843
    Search in Google Scholar
  • 32 Terrett JA, Ly JQ, Katavolos P, Hasselgren C, Laing S, Zhong F, Villemure E, Déry M, Larouche-Gauthier R, Chen H, Shore DG, Lee WP, Suto E, Johnson K, Brooks M, Stablein A, Beaumier F, Constantineau-Forget L, Grand-Maître C, Lépissier L, Ciblat S, Sturino C, Chen Y, Hu B, Elstrott J, Gandham V, Joseph V, Booler H, Cain G, Chou C, Fullerton A, Lepherd M, Stainton S, Torres E, Urban K, Yu L, Zhong Y, Bao L, Chou K.-J, Lin J, Zhang W, La H, Liu L, Mulder T, Chen J, Chernov-Rogan T, Johnson AR, Hackos DH, Leahey R, Shields SD, Balestrini A, Riol-Blanco L, Safina BS, Volgraf M, Magnuson S, Kakiuchi-Kiyota S. J. Med. Chem. 2024; 67: 3287
    Search in Google Scholar
  • 33 Hong AY, Piechowicz KA, Timmerman JC, Zhang H, Molinaro C, Gosselin F. Org. Process Res. Dev. 2024; 28: 2325
    Search in Google Scholar
  • 34 Hecker S, Reddy RK, Glinka T, Rodny O. WO 2018005662A1, 2018
  • 35 Hecker SJ, Reddy KR, Lomovskaya O, Griffith DC, Rubio-Aparicio D, Nelson K, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Parkinson J, Totrov M, Boyer SH, Glinka TW, Pemberton OA, Chen Y, Dudley MN. J. Med. Chem. 2020; 63: 7491
    Search in Google Scholar
  • 36 Boyer SH, Gonzalez-de-Castro A, Hubertus-Dielemans JA, Lefort L, Zhu Z, Gnahn M, Schörghuber J, Steinhofer S, de Vries AH. M, Hecker SJ. Org. Process Res. Dev. 2022; 26: 925
    Search in Google Scholar
  • 37 Goossen K, Kuhn O, Berwe M, Krüger J, Militzer H.-C. WO 2006133822A1, 2006
  • 38 Humphrey GR, Dalby SM, Andreani T, Xiang B, Luzung MR, Song ZJ, Shevlin M, Christensen M, Belyk KM, Tschaen DM. Org. Process Res. Dev. 2016; 20: 1097
    Search in Google Scholar
  • 39 Broeker J, Abbott J, Cui J, Fesik SW, Gollner A, Hodges T, Little A, Mantoulidis A, Phan J, Sarkar D. WO 2023099592A1, 2023
  • 40 Leung JC, Xu Y, Radomkit S, Lee J, Kim WS, Reeves JT, Dong W, Jang H, Hou X, Lorenz JC, Shao X, Byrne D, Johnson J, Brundage A, Valentin C, Beyer P, DiMeo SV, Qu B, Li R, Sarvestani M, Song JJ. Org. Process Res. Dev. 2024; 28: 67
    Search in Google Scholar
  • 41 Tan Z, Ju X, Wu H, Dong W, Leung JC, Hou X, Lee H, Granger A, Paolillo JM, DiMeo SV, Chen C, Wu L, Lorenz JC, Sarvestani M, Buono F, Frutos R, Tampone TG, Huang X, Zhang G, Wang Y, Spinelli E, Lei Z, Song JJ. Org. Process Res. Dev. 2024; 28: 78
    Search in Google Scholar
  • 42 Kuvshinov AM, Gulevskaya VI, Rozhkov VV, Shevelev SA. Synthesis 2000; 1474
  • 43 Jones P, Ontoria JM, Scarpelli R, Schultz-Fademrecht C. WO 2008084261A1, 2008
  • 44 Wallace DJ, Baxter CA, Brands KJ. M, Bremeyer N, Brewer SE, Desmond R, Emerson KM, Foley J, Fernandez P, Hu W, Keen SP, Mullens P, Muzzio D, Sajonz P, Tan L, Wilson RD, Zhou G, Zhou G. Org. Process Res. Dev. 2011; 15: 831
    Search in Google Scholar
  • 45 Chung CK, Bulger PG, Kosjek B, Belyk KM, Rivera N, Scott ME, Humphrey GR, Limanto J, Bachert DC, Emerson KM. Org. Process Res. Dev. 2014; 18: 215
    Search in Google Scholar
  • 46 Sherer BA. WO 2016037026A1, 2016
  • 47 Crescenzi C, Fuchss T, Ippoliti D, Langella A, Di Mola A, Massa A, Rozzi D. Org. Process Res. Dev. 2020; 24: 1018
    Search in Google Scholar
  • 48 Campbell BT, Chang W, Hartingh TJ, Hurzy DM, Kelly MJ. III, Klinger F.-M, Layton ME, McCauley JA, Nawrat CC, Parish CA, Perkins JJ, Roecker AJ, de Lera Ruiz M, Schreier JD, Shurtleff VW, Su J, Truong QT.
  • 49 Peng F, Qi J, Zhang J, Wang E, Cao X, Chen L, Fan C, Fan W, Feng C, Lin M, Liu M, Nawrat CC, Schultz DM, Song C, Wang F, Yin J, Zhang Y. Org. Process Res. Dev. 2024; 28: 2150
    Search in Google Scholar
  • 50 Zhong W, Zhu X, Feng S, Sun X, Yang M. WO 2021000855A1, 2021
  • 51 Feng S, Zhang H, Tang Z, Peng X, Yang M, Wei X, Zhong W. Org. Process Res. Dev. 2022; 26: 3089
    Search in Google Scholar
  • 52 EMA, ICH guideline Q3D (R2) on elemental impurities (accessed May 23, 2025): https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-q3d-elemental-impurities-step-5-revision-2_en.pdf
  • 53 Cadieux J.-J, Chafeev M, Chowdhury S, Fu J, Jia Q, Abel S, El-Sayed E, Huthmann E, Isarno T. US 8742109B2, 2014
  • 54 Sclafani JA, Chen J, Levy DV, Reese H, Dimitri M, Mudipalli P, Christie M, Neville CJ, Olsen M, Bakale RP. Org. Process Res. Dev. 2017; 21: 1616
    Search in Google Scholar
  • 55 Dixon DD, Grina J, Josey JA, Rizzi JP, Schlachter ST, Wallace EM, Wang B, Wehn P, Xu R, Yang H. WO 2015035223A1, 2015
  • 56 Wehn PM, Rizzi JP, Dixon DD, Grina JA, Schlachter ST, Wang B, Xu R, Yang H, Du X, Han G, Wang K, Cao Z, Cheng T, Czerwinski RM, Goggin BS, Huang H, Halfmann MM, Maddie MA, Morton EL, Olive SR, Tan H, Xie S, Wong T, Josey JA, Wallace EM. J. Med. Chem. 2018; 61: 9691
    Search in Google Scholar
  • 57 Xu R, Wang K, Rizzi JP, Huang H, Grina JA, Schlachter ST, Wang B, Wehn PM, Yang H, Dixon DD, Czerwinski RM, Du X, Ged EL, Han G, Tan H, Wong T, Xie S, Josey JA, Wallace EM. J. Med. Chem. 2019; 62: 6876
    Search in Google Scholar
  • 58 Peng F, Tan L, Chen L, Dalby SM, DiRocco DA, Duan J, Feng M, Gong G, Guo H, Hethcox JC, Jin L, Johnson HC, Kim J, Le D, Lin Y, Liu W, Shen J, Wan Y, Xiao C, Xiang B, Xiang Q, Xu J, Yan L, Yang W, Ye H, Yu Y, Zhang J. Org. Process Res. Dev. 2022; 26: 508
    Search in Google Scholar
  • 59 Bottecchia C, Lévesque F, McMullen JP, Ji Y, Reibarkh M, Peng F, Tan L, Spencer G, Nappi J, Lehnherr D, Narsimhan K, Wismer MK, Chen L, Lin Y, Dalby SM. Org. Process Res. Dev. 2022; 26: 516
    Search in Google Scholar
  • 60 Chen Z, Marzijarani NS, Quirie S, Pirrone GF, Dalby SM, Wang T, Kim J, Peng F, Fine AJ. Org. Process Res. Dev. 2022; 26: 525
    Search in Google Scholar
  • 61 Marzijarani NS, Fine AJ, Dalby SM, Gangam R, Poudyal S, Behre T, Ekkati AR, Armstrong BM, Schultz CS, Dance ZE. X. Org. Process Res. Dev. 2022; 26: 533
    Search in Google Scholar
  • 62 Wang T, Phillips EM, Dalby SM, Sirota E, Axnanda S, Schultz CS, Patel P, Waldman JH, Alwedi E, Wang X, Zawatzky K, Chow M, Padivitage N, Weisel M, Whittington M, Duan J, Lu T. Org. Process Res. Dev. 2022; 26: 543
    Search in Google Scholar
  • 63 Pirnot M, Stone K, Wright TJ, Lamberto DJ, Schoell J, Lam Y.-h, Zawatzky K, Wang X, Dalby SM, Fine AJ, McMullen JP. Org. Process Res. Dev. 2022; 26: 551
    Search in Google Scholar
  • 64 DiRocco DA, Zhong Y.-L, Le DN, McCann SD, Hethcox JC, Kim J, Koley JN, Kosjek B, Dalby SM, McMullen JP, Gangam R, Morris WJ. Org. Process Res. Dev. 2024; 28: 404
    Search in Google Scholar
  • 65 Hethcox JC, Kim J, Johnson HC, Ji Y, Chow M, Newman JA, DiRocco DA, McMullen JP. Org. Process Res. Dev. 2024; 28: 413
    Search in Google Scholar
  • 66 Kim J, Zhang V, Abe K, Qin Y, DiRocco DA, McMullen JP, Sun A, Gangam R, Chow M, Pitts-McCoy A, Malkani AS. Org. Process Res. Dev. 2024; 28: 422
    Search in Google Scholar
  • 67 McCann SD, Dubina SH, Kosjek B, Alwedi E, Behre T, Burgess SA, Poggetto GD, DiRocco DA, Hartmanshenn C, McMullen JP, Padivitage N, Sun AC. Org. Process Res. Dev. 2024; 28: 441
    Search in Google Scholar
  • 68 Le DN, Wright TJ, Alwedi E, Hartmanshenn C, Li H, McMullen JP, DiRocco DA. Org. Process Res. Dev. 2024; 28: 451
    Search in Google Scholar
  • 69 Silverman RB, Andruszkiewicz R, Yuen P.-W, Sobieray DM, Franklin LC, Schwindt MA. WO 9323383, 1993
  • 70 Hoekstra MS, Sobieray DM, Schwindt MA, Mulhern TA, Grote TM, Huckabee BK, Hendrickson VS, Franklin LC, Granger EJ, Karrick GL. Org. Process Res. Dev. 1997; 1: 26
    Search in Google Scholar
  • 71 Burk MJ, de Koning PD, Grote TM, Hoekstra MS, Hoge G, Jennings RA, Kissel WS, Le TV, Lennon IC, Mulhern TA, Ramsden JA, Wade RA. J. Org. Chem. 2003; 68: 5731
    Search in Google Scholar
  • 72 Martinez CA, Hu S, Dumond Y, Tao J, Kelleher P, Tully L. Org. Process Res. Dev. 2008; 12: 392
    Search in Google Scholar
  • 73 Debarge S, McDaid P, O’Neill P, Frahill J, Wong JW, Carr D, Burrell A, Davies S, Karmilowicz M, Steflik J. Org. Process Res. Dev. 2014; 18: 109
    Search in Google Scholar
  • 74 Moccia M, Cortigiani M, Monasterolo C, Torri F, Del Fiandra C, Fuller G, Kelly B, Adamo MF. A. Org. Process Res. Dev. 2015; 19: 1274
    Search in Google Scholar
  • 75 Suzuki Y, Lehmann I, Bichsel HU, Bader T, Thamapipol S. WO 2015189068A1, 2015
  • 76 Carlone A, Bernardi L, McCormack P, Warr T, Oruganti S, Cobley CJ. Org. Process Res. Dev. 2021; 25: 2795
    Search in Google Scholar
  • 77 Giovannini R, Bertani B, Ferrara M, Lingard I, Mazzaferro R, Rosenbrock H. WO 2013017657A1, 2013
  • 78 Frutos R, Tampone TG, Mulder J, Gao J, Sieber JD, Rodriguez S, Haddad N, Baer K, Brown J, Yang B.-S, Giovannini R, Song JJ, Grinberg N, Lee H, Senanayake CH. Org. Process Res. Dev. 2023; 27: 505
    Search in Google Scholar
  • 79 Sieber JD, Rodriguez S, Frutos R, Buono F, Zhang Y, Li N, Qu B, Premasiri A, Li Z, Han ZS, Xu Y, Byrne D, Haddad N, Lorenz J, Grinberg N, Kurouski D, Lee H, Narayanan B, Nummy L, Mulder J, Brown JD, Granger A, Gao J, Krawiec M, Williams Z, Pennino S, Song JJ, Hossain A, Yee NK, Busacca C, Roschangar F, Xin Y, Mao Z, Zhang X, Hong Y, Senanayake CH. J. Org. Chem. 2018; 83: 1448
    Search in Google Scholar
  • 80 Barlaam B, Cosulich S, Degorce S, Fitzek M, Green S, Hancox U, Lambert-van der Brempt C, Lohmann J.-J, Maudet M, Morgentin R, Pasquet M.-J, Péru A, Plé P, Saleh T, Vautier M, Walker M, Ward L, Warin N. J. Med. Chem. 2015; 58: 943
    Search in Google Scholar
  • 81 Moore PR, Muir JC, Dubiez J, Leslie KW, Tomlin P, McCormick M, Janbon SL, Cornwall P, Ryberg P, Berg R. Org. Process Res. Dev. 2021; 25: 1889
    Search in Google Scholar
  • 82 Bartkovitz DJ, Chu X.-J, Ding Q, Jiang N, Liu J.-J, Ross TM, Zhang J, Zhang Z. US 20100152190A1, 2010
  • 83 Rimmler G, Alker A, Bosco M, Diodone R, Fishlock D, Hildbrand S, Kuhn B, Moessner C, Peters C, Rege PD, Schantz M. Org. Process Res. Dev. 2016; 20: 2057
    Search in Google Scholar
  • 84 Shu L, Gu C, Fishlock D, Li Z. Org. Process Res. Dev. 2016; 20: 2050
    Search in Google Scholar
  • 85 Batt DG, Bertrand MB, Delucca G, Galella MA, Ko SS, Langevine CM, Liu Q, Shi Q, Srivastava AS, Tino JA, Watterson SH. US 20140378475A1, 2014
  • 86 Conaghan PG, Nowak M, Du S, Luo Y, Landis J, Pachai C, Fura A, Catlett IM, Grasela DM, Østergaard M. Lancet Rheumatol. 2023; 5: e263
    Search in Google Scholar
  • 87 Wisniewski SR, Carrasquillo-Flores R, Lora-Gonzalez F, Ramirez A, Casey M, Soumeillant M, Razler TM, Mack B. Org. Process Res. Dev. 2018; 22: 1426
    Search in Google Scholar
  • 88 Beutner G, Carrasquillo R, Geng P, Hsiao Y, Huang EC, Janey J, Katipally K, Kolotuchin S, La Porte T, Lee A, Lobben P, Lora-Gonzalez F, Mack B, Mudryk B, Qiu Y, Qian X, Ramirez A, Razler TM, Rosner T, Shi Z, Simmons E, Stevens J, Wang J, Wei C, Wisniewski SR, Zhu Y. Org. Lett. 2018; 20: 3736
    Search in Google Scholar