Click chemistry reactions in medicinal chemistry: Applications of the 1,3-dipolar cycloaddition between azides and alkynes

Medicinal Research Reviews

Volumn 28, Issue 2, 2008, Pages 278-308

  Tron, Gian Cesare ^a   Pirali, Tracey ^a   Billington, Richard A ^a   Canonico, Pier Luigi ^a   Sorba, Giovanni ^a   Genazzani, Armando A ^a  

^a UNIVERSITY OF EASTERN PIEDMONT   (Italy)

Author keywords

1,3 dipolar cycloaddition; Alkyne; Azide; Bioconjugation; Click chemistry; Copper; Triazole

Indexed keywords

ALKYNE; ANTIINFECTIVE AGENT; AZIDE; BETA LACTAMASE INHIBITOR; BRADYKININ B1 RECEPTOR ANTAGONIST; CEPHALOSPORIN; CLAVULANIC ACID; CUPROUS ION; CYSTEINE PROTEINASE INHIBITOR; CYTOKINE RECEPTOR ANTAGONIST; FIPRONIL; HETERODIMER; HOMODIMER; KABIRAMIDE C; LIGAND; LIPID; LIPOSOME; MACROCYCLIC COMPOUND; MATRIX METALLOPROTEINASE INHIBITOR; NATURAL PRODUCT; NEPLANOCIN A; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; RESVERATROL; SUGAR; TAZOBACTAM; TRIAZOLE; TYROCIDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN; ZANAMIVIR;

BINDING SITE; BIOLOGICAL THERAPY; CATALYST; CHEMICAL REACTION; CONJUGATION; CYCLOADDITION; DRUG BINDING; DRUG DELIVERY SYSTEM; DRUG POTENCY; DRUG PURIFICATION; DRUG RESEARCH; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME IMMOBILIZATION; HUMAN; HYDROGEN BOND; IN SITU HYBRIDIZATION; LIPOGENESIS; MOLECULAR IMAGING; PROTEIN FUNCTION; REVIEW; STRUCTURE ACTIVITY RELATION;

ALKYNES; AZIDES; CATALYSIS; COMBINATORIAL CHEMISTRY TECHNIQUES; COPPER; CYCLIZATION; DIMERIZATION; DRUG DESIGN; HIV PROTEASE INHIBITORS; MACROCYCLIC COMPOUNDS; TRIAZOLES;

EID: 39549111477     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/med.20107     Document Type: Review

References (129)

1. Wender PH, Handy ST, Wright DL. Towards the ideal synthesis. Chem Ind 1997;19:765-768.
2. Kolb HC, Finn MG, Sharpless KB. Click chemistry: Diverse chemical function from a few good reactions. Angew Chem Int Ed Engl 2001;40:2004-2021.
3. Huisgen R, Guenter S, Leander M. 1,3-Dipolar cycloadditions. XXXII. Kinetics of the addition of organic azides to carbon-carbon multiple bonds. Chem Ber 1967;100:2494-2507.
4. Huisgen R. 1,3-Dipolar cycloadditions - Introduction, survey, mechanism. In: Padwa A, editor. 1,3-Dipolar cycloaddition chemistry. New York: Wiley; 1984. pp 1-176.
5. Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise Huisgen cycloaddition process: Copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. Angew Chem Int Ed 2002;41:2596-2599.
6. Tornøe CW, Christensen C, Meldal M. Peptidotriazoles on solid phase: [1,2,3]-Triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem 2002;67:3057-3 3064.
7. Bourne Y, Kolb HC, Radic Z, Sharpless KB, Taylor P, Marchot P. Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation. Proc Natl Acad Sci USA 2004;101:1449-1454.
8. (a) Whiting M, Muldoon J, Lin YC, Silverman SM, Lindstron W, Olson AJ, Kolb HC, Finn MG, Sharpless KB, Elder JH, Fokin VV, Inhibitors of HIV-1 protease by using in situ click chemistry. Angew Chem Int Ed 2006;45:1435-1439.
9. (b) Tornøe CW, Sanderson SJ, Mottram JC, Coombs GH, Meldal M, J Comb Chem 2004;6:312-324.
10. Bennet IS, Brooks G, Broom NJP, Calvert SH, Coleman K, Francois I. 6-(Substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. J Antibiotic 1991;44:969-977.
11. Bennett I, Broom NJP, Bruton G, Calvert S, Clarke BP, Coleman K, Edmondson R, Edwards P, Jones D, Osborne NF, Walker G. 6-(Substituted methylene)penenms, potent broad spectrum inhibitors of bacterial beta lactamase. J Antibiotics 1991;44:331-337.
12. Kume M, Kubota T, Kimura Y, Nakashimizu K, Motokawa M, Nakano M. Synthesis and structure-activity relationship of new 7-beta-[(Z)-2-(2- aminothiazol-4-yl)-2-hydroxyminoacetamido]-cephalosporins with 1,2,3-triazole in C-3 side chain. J Antibiotics 1993;46:177-192.
13. Makabe O, Suzuki H, Umezawa S. Synthesis of D-arabinofuranosyl and 2′-deoxy-D-ribofuranosyl 1,2,3-triazolecarboxamides. Bull Chem Soc Jpn 1977;50:2689-2693.
14. Alonso R, Camarasa MJ, Alonso G, De Las Heras FG. Synthesis and cytostatic activity of N-ribosyl-halomethyl-1,2,3 triazoles. Eur J Med Chem 1980;15:105-109.
15. Kauffmann T. The arenology principle. Angew Chem Int Ed Engl 1971;10:743-744.
16. Wadsworth HJ, Jenkins SM, Orlek BS, Cassidy F, Clark MSG, Brown F, Riley GJ, Graves D, Hawkins J, Naylor CB. Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem 1992;35:1280-1290.
17. Moltzen EK, Pedersen H, Bogeso KP, Meier E, Frederiksen K, Sanchez C, Lembol HL. Bioisostere of arecoline: 1,2,3,6-tetrahydro-5-pyridyl-substituted and 3-piperidyl-substituted derivatives of tetrazole and 1,2,3-triazole. Synthesis and muscarinic activity. J Med Chem 1994;37:4085-4099.
18. Dörner S, Westermann B. A short route for the synthesis of sweet macrocycles via a click-dimerization-Ring-closing metathesis approach. Chem Commun 2005:2852-2854.
19. Aucagne V, Leigh D. Chemoselective formation of successive triazole linkages in one pot: "click-click" chemistry. Org Lett 2006;8:4505-4507.
20. Peng W, Feldman AK, Nugent AK, Hawker CJ, Scheel A, Voit B, Pyun J, Fréchet JMJ, Sharpless KB, Fokin VV. Efficiency and fidelity in a click-chemistry route to triazole dendrimers by the copper(I)-catalyzed ligation of azides and alkynes. Angew Chem Int Ed 2004;43:3928-3932.
21. Malkoch M, Schleicher K, Drockenmuller E, Hawker CJ, Russell TP, Wu P, Fokin VV. Structurally diverse dendritic libraries: A highly efficient functionalization approach using click chemistry. Macromolecules 2005;38(9):3663-3678.
22. Lipshutz BH, Taft BR. Heterogeneous copper-in-charcoal-catalyzed click chemistry. Angew Chem Int Ed 2006;45:8235-8238.
23. Krasinski A, Fokin VV, Sharpless KB. Direct synthesis of 1,5-disubstituted-4-magnesio-1,2,3-triazoles, revisited. Org Lett 2004;6:1237-1240.
24. Liu D, Gao W, Dai Q, Zhang X. Triazole-based monophosphines for Suzuki-Miyaura coupling and amination reactions of aryl chlorides. Org Lett 2005;7:4907-4910.
25. Hlasta DJ, Ackerman J, James H. Steric effects on the regioselectivity of an azide-alkyne dipolar cycloaddition reaction: The synthesis of human leukocyte elastase inhibitors. J Org Chem 1994;59:6184-6189.
26. Coats SJ, Link JS, Gauthier D, Hlasta DJ. Trimethylsilyl-directed 1,3-dipolar cycloaddition reactions in the solid-phase synthesis of 1,2,3-triazoles. Org Lett 2005;7:1469-1472.
27. Zhang L, Chen X, Xue P, Sun HHY, Williams ID, Sharpless KB, Fokin VV, Jia G. Ruthenium-catalyzed cycloaddition of alkynes and organic azides. J Am Chem Soc 2005;127:15998-15999.
28. Majireck MM, Weinreb SM. A study of scope and regioselectivity of the ruthenium-catalyzed [3 + 2]-cycloaddition of azides with internal alkynes. J Org Chem 2006;71:8680-8683.
29. Chan TR, Hilgraf R, Sharpless KB, Fokin VV. Polytriazoles as copper(I)-stabilizing ligands in catalysis. Org Lett 2004;6:2853-2855.
30. Orgueira HA, Fokas D, Isome Y, Chan PCM, Baldino CM. Regioselective synthesis of [1,2,3]-triazoles catalyzed by Cu(I) generated in situ from Cu(0) nanosize activated powder and amine hydrochloride salts. Tetrahedron Lett 2005;46:2911-2914.
31. Gupta SS, Kuzelka J, Singh P, Lewis WG, Manchester M, Finn MG. Accelerated bioorthogonal conjugation: A practical method for the ligation of diverse functional molecules to a polyvalent virus scaffold. Bioconjug Chem 2005;16:1572-1579.
32. Kolb HC, Sharpless KB. The growing impact of click chemistry on drug discovery. Drug Discov Today 2003;8:1128-1137.
33. Bock VD, Hiemstra H, van Maarseveen JH. Cu(I)-catalyzed alkyne-azide click cycloadditions from a mechanistic and synthetic perspective. Eur J Org Chem 2006:51-68.
34. (a) Binder WH, Kluger C, Azide/alkyne-"click" reactions: Applications in material science and organic synthesis. Curr Org Chem 2006;10:1791-1815.
35. (b) Lutz JF. 1,3-Dipolar cycloadditions of azides and alkynes: A universal ligation tool in polymer and materials science. Angew Chem Int Ed 2007;46:1018-1025.
36. Brik A, Alexandratos J, Lin YC, Elder JH, Olson AJ, Wlodawer A, Goodsell DS, Wong CH. 1,2,3-Triazole as a peptide surrogate in the rapid synthesis of HIV-1 protease inhibitors. ChemBioChem 2005,6:1167-1169.
37. Oh K, Guan Z. A convergent synthesis of new β-turn mimics by click chemistry. Chem Commun 2006;29:3069-3071.
38. Horne WS, Yadav MK, Stout CD, Ghadiri MR. Heterocyclic peptide backbone modifications in an α-helical coiled coil. J Am Chem Soc 2004;126:15366-15367.
39. Angelo GN, Arora PS. Nonpeptidic foldamers from amino acids: Synthesis and characterization of 1,3-substituted triazole oligomers. J Am Chem Soc 2005;127:17134-17135.
40. Somu RV, Boshoff H, Qiao C, Bennett EM, Barry CE III, Aldrich CC. Rationally designed nucleoside antibiotics that inhibit siderophore biosynthesis of Mycobacterium tuberculosis. J Med Chem 2006;49:31-34.
41. Pagliai F, Pirali T, Del Grosso E, Di Brisco R, Tron GC, Sorba G, Genazzani AA. Rapid synthesis of triazole-modified resveratrol analogues via click chemistry. J Med Chem 2006;49:467-470.
42. Pirali T, Gatti S, Di Brisco R, Tacchi S, Zaninetti R, Brunelli E, Massarotti A, Sorba G, Canonico PL, Moro L, Genazzani AA, Tron GC, Billington RA. Estrogenic analogues synthesized via click chemistry. ChemMedChem 2007; DOI: 10.1002/cmdc.200600192.
43. Alam MS, Kajiki R, Hanatani H, Kong X, Ozoe F, Matsui Y, Matsumura F, Ozoe Y. Synthesis and structure-activity relationships of 1-phenyl-1H-1,2,3- triazoles as selective insect GABA receptor antagonists. J Agric Food Chem 2006;54:1361-1372.
44. Cho JH, Bernard DL, Sidwell RW, Kern ER, Chu CK. Synthesis of cyclopentenyl carbocyclic nucleosides as potential antiviral agents against orthopoxviruses and SARS. J Med Chem 2006;49:1140-1148.
45. Wermuth CG. The practice of medicinal chemistry. 2nd edition. New York: Academic Press; 2003.
46. Suh BC, Jeon H, Posner GH, Silverman SM. Vitamin D side chain triazole analogs via cycloaddition 'click' chemistry. Tetrahedron Lett 2004;45:4623-4625.
47. Zhang G, Fang L, Zhu L, Sun D, Wang PG. Syntheses and biological activity of bisdaunorubicins. Bioorg Med Chem 2006;14:426-434.
48. Wang D, Sutcliffe JA, Oyelere AK, Mcconnell TS, Ippolito JA, Abelson JN. Methods of preparation of bifunctional heterocyclic compounds for use as antiinfective, antiproliferative, antiinflammatory and prokinetic agents. 2004; WO 2004029066.
49. Fu X, Albermann C, Zhang C, Thorson JS. Diversifying vancomycin via chemoenzymatic strategies. Org Lett 2005;7:1513-1515.
50. Petchprayoon C, Suwanborirux K, Miller R, Sakata T, Marriott G. Synthesis and characterization of the 7-(4-aminomethyl-1H-1,2,3-triazol-1-yl) analogue of kabiramide C. J Nat Prod 2005;68:157-161.
51. Srinivasan R, Uttamchandani M, Yao SQ. Rapid assembly and in situ screening of bidentate inhibitors of protein tyrosine phosphatases. Org Lett 2006;8:713-716.
52. Wang J, Uttamchandani M, Li J, Hu M, Yao SQ. Rapid assembly of matrix metalloprotease inhibitors using click chemistry. Org Lett 2006;8:3821-3824.
53. Brik A, Muldoon J, Lin Y, Elder JH, Goodsell DS, Olson AJ, Fokin VV, Sharpless KB, Wong CH. Rapid diversity-oriented synthesis in microtiter plates for in situ screening of HIV protease inhibitors. ChemBioChem 2003;4:1246-1248.
54. Gopi HN, Tirupula KC, Baxter S, Ajith S, Chaiken IM. Click chemistry on azidoproline: High-affinity dual antagonist for HIV-1 envelope glycoprotein gp120. ChemMedChem 2006;1:54-57.
55. Lee LV, Mitchell ML, Huang SJ, Fokin VV, Sharpless KB, Wong CH. A potent and highly selective inhibitor of human alpha-1,3-fucosyltransferase via click chemistry. J Am Chem Soc 2003;125:9588-9589.
56. Musiol HJ, Dong S, Kaiser M, Bausinger R, Zumbusch A, Bertsch U, Moroder L. Toward semisynthetic lipoproteins by convergent strategies based on click and ligation chemistry. ChemBioChem 2005;6:625-628.
57. O'Neil EJ, Di Vittorio KM, Smith D. Phosphatidylcholine-derived bolaamphiphiles via click chemistry. Org Lett 2007;9:199-202.
58. Lin H, Walsh CT. A chemoenzymatic approach to glycopeptide antibiotics. J Am Chem Soc 2004;126:13998-14003.
59. Pérez-Balderas F, Ortega-Muñoz M, Morales-Sanfrutos J, Hernández-Mateo F, Calvo-Flores FG, Calvo-Asín JA, Isac-García J, Santoyo-González F. Multivalent neoglycoconjugates by regiospecific cycloaddition of alkynes and azides using organic-soluble copper catalysts. Org Lett 2003;5:1951-1954.
60. Yang F, Du Y. A practical synthesis of a (1 → 6)-linked-D- glucosamine nonasaccharide. Carbohydr Res 2003;338:495-502.
61. Chen Q, Yang F, Du Y. Synthesis of a C3-symmetric (1 → 6)-N-acetyl-beta-D-glucosamine octadecasaccharide using click chemistry. Carbohydr Res 2005;340:2476-2482.
62. Fu X, Albermann C, Jiang J, Liao J, Zhang C, Thorson JS. Antibiotic optimization via in vitro glycorandomization. Nat Biotechnol 2003;21:1467-1469.
63. Hotha S, Kashyap S. "Click chemistry" inspired synthesis of pseudo-oligosaccharides and amino acid glycoconjugates. J Org Chem 2006;71:852.
64. Wan Q, Chen J, Danishefsky SJ. A potentially valuable advance in the synthesis of carbohydrate-based anticancer vaccines through extended cycloaddition chemistry. J Org Chem 2006;71:8244-8249.
65. Casas-Solvas JM, Vargas-Berenguel A, Capitán-Vallvey LF, Gonzalez FS. Convenient methods for the synthesis of ferrocene-carbohydrate conjugates. Org Lett 2004;6:3687-3690.
66. Wilkinson BL, Bornaghi LF, Houston TA, Innocenti A, Supuran CT, Poulsen SA. A novel class of carbonic anhydrase inhibitors: Glycoconjugate benzene sulfonamides prepared by "click-tailing". J Med Chem 2006;49:6539-6548.
67. Wang Q, Chan TR, Hilgraf R, Fokin VV, Sharpless KB, Finn MG. Bioconjugation by copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition. J Am Chem Soc 2003;125:3192-3193.
68. Gierlich J, Burley GA, Gramlich PME, Hammond DM, Carell T. Click chemistry as a reliable method for the high-density postsynthetic functionalization of alkyne-modified DNA. Org Lett 2006;8:3639-3642.
69. Sivakumar K, Xie F, Cash BM, Long S, Barnhill HN, Wang Q. A fluorogenic 1,3-dipolar cycloaddition reaction of 3-azidocoumarins and acetylenes. Org Lett 2004;6:4603-4606.
70. Speers AE, Cravatt BF. Chemical strategies for activity-based proteomics. ChemBioChem 2004;5:41-47.
71. Adam GC, Vanderwal CD, Sorensen EJ, Cravatt BF. (-)-FR182877 is a potent and selective inhibitor of carboxylesterase-1. Angew Chem Int Ed 2003;42:5480-5484.
72. Speers AE, Adam GC, Cravatt BF. Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition. J Am Chem Soc 2003;125:4686-4687.
73. Speers AE, Cravatt BF. Profiling enzyme activities in vivo using click chemistry methods. Chem Biol 2004;11:535-546.
74. Hassane FS, Frisch B, Schuber F. Liposomes: Convenient coupling of ligands to preformed vesicles using "click chemistry". Bioconjugate Chem 2006;17:849-854.
75. Cavalli S, Tipton AR, Overhand M, Kros A. The chemical modification of liposomes surfaces via a copper-mediated [3 + 2] azide-alkyne cycloaddition monitored by a colorimetric assay. Chem Commun 2006:3193-3195.
76. Devaraj NK, Miller GP, Ebina W, Kakaradov B, Collman JP, Kool ET, Chidsey CED. Chemoselective covalent coupling of oligonucleotide probes to self-assembled monolayers. J Am Chem Soc 2005;127:8600-8601.
77. Sun XL, Stabler CL, Cazalis CS, Chaikof EL. Carbohydrate and protein immobilization onto solid surfaces by sequential Diels-Alder and azide-alkyne cycloadditions. Bioconjug Chem 2006;17:52-57.
78. Bryan MC, Lee LV, Wong CH. High-throughput identification of fucosyltransferase inhibitors using carbohydrate microarrays. Bioorg Med Chem Lett 2004;14:3185-3188.
79. Punna S, Kaltgrad E, Finn MG. "Clickable" agarose for affinity chromatography. Bioconjug Chem 2005;16:1536-1541.
80. Ortega-Munoz M, Lopez-Jaramillo J, Hernandez-Mateo F, Santoyo-Gonzales F. Synthesis of glyco-silica by Cu(I)-catalyzed "click chemistry" and their applications in affinity chromatography. Adv Synth Catal 2006;348:2410-2420.
81. Zhu J, Bienaymé H , editors. Multicomponent reaction. Weinheim: Wiley-VCH; 2005.
82. Ramachary DB, Barbas CF III. Towards organo-click chemistry: Development of organocatalytic multicomponent reactions through combinations of Aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen cycloaddition reactions. Chem Eur J 2004;10:5323-5331.
83. Akritopoulou-Zanze I, Gracias V, Djuric SW. A versatile synthesis of fused triazolo derivatives by sequential Ugi/alkyne-azide cycloaddition reactions. Tetrahedron Lett 2004;45:8439-8441.
84. Khanetskyy B, Dallinger D, Kappe CO. Combining Biginelli multicomponent and click chemistry: Generation of 6-(1,2,3-triazol-1-yl)-dihydropyrimidone libraries. J Comb Chem 2004;6:884-892.
85. Chandrasekhar S, Basu D, Rambabu C. Three-component coupling of alkynes, Baylis-Hillman adducts and sodium azide: A new synthesis of substituted triazoles. Tetrahedron Lett 2006;47:3059-3063.
86. Sreedhar B, Surendra RP, Sailendra Kumar N. Cu(I)-catalyzed one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles via nucleophilic displacement and 1,3-dipolar cycloaddition. Tetrahedron Lett 2006;47:3055-3058.
87. Horton DA, Bourne GT, Smythe ML. Exploring privileged structures: The combinatorial synthesis of cyclic peptides. J Comput-Aided Mol Des 2002;16:415-430.
88. Wessjohann LA, Ruijter E, Garcia-Rivera D, Brandt W. What can a chemist learn from nature's macrocycles? - A brief, conceptual view. Mol Diversity 2005;9:171-186.
89. Punna S, Kuzelka J, Wang Q, Finn MG. Head-to-tail peptide cyclodimerization by copper-catalyzed azide-alkyne cycloaddition. Angew Chem Int Ed 2005;44:2215-2220.
90. Angell Y, Burgess K. Ring closure to β-turn mimics via copper-catalyzed azide/alkyne cycloadditions. J Org Chem 2005;70:9595-9598.
91. Bock VD, Perciaccante R, Jansen TP, Hiemstra H, Van Maarseveen JH. Click chemistry as a route to cyclic tetrapeptide analogs: Synthesis of cyclo-[Pro-Val-ψ (triazolo)-Pro-Tyr]. Org. Lett 2006;8:919-922.
92. Bock VD, Speijer D, Hiemstra H, Van Maarseveen JH. 1,2,3-Triazoles as peptide bond isosters: Synthesis and biological evaluation of cyclotetrapeptide mimics. Org Biomol Chem 2007;5:971-975.
93. van Maarseveen JH, Horne WS, Ghadiri MR. Efficient route to C2 symmetric heterocyclic backbone modified cyclic peptides. Org Lett 2005;7:4503-4506.
94. Looper RE, Pizzirani D, Schreiber SL. Macrocycloadditions leading to conformationally restricted small molecules. Org Lett 2006;8:2063-2066.
95. Pirali T, Tron GC, Zhu J. One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3 + 2] cycloaddition. Org Lett 2006;8:4145-4148.
96. Billing JF, Nilsson UJ. C2-symmetric macrocyclic carbohydrate/amino acid hybrids through copper(I)-catalyzed formation of 1,2,3-triazoles. J Org Chem 2005;70:4847-4850.
97. Ray A, Mohan M, Bhadbhade M, Mukhopadhyay R, Bhattacharjya A. Cu(I)-catalyzed cycloaddition of constrained azido-alkynes: Access to 12- to 17-membered monomeric triazolophanes incorporating furanoside rings. Tetrahedron Lett 2006;47:2775-2778.
98. Lewis WG, Green LG, Grynszpan F, Radic Z, Carlier PR, Taylor P, Finn MG, Sharpless KB. Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew Chem Int Ed Engl 2002;41:1053-1057.
99. Manetsch R, Krasinski A, Radic Z, Raushel J, Taylor P, Sharpless KB, Kolb HC. In situ click chemistry: Enzyme inhibitors made to their own specifications. J Am Chem Soc 2004;126:12809-12818.
100. Krasinski A, Radic Z, Manetsch R, Raushel J, Taylor P, Sharpless KB, Kolb HC. In situ selection of lead compounds by click chemistry: Target-guided optimization of acetylcholinesterase inhibitors. J Am Chem Soc 2005;127:6686-6692.
101. Mocharla VP, Colasson B, Lee LV, Roper S, Sharpless KB, Wong CH, Kolb HC. In situ click chemistry: Enzyme-generated inhibitors of carbonic anhydrase II. Angew Chem Int Ed Engl 2004;44:116-120.
102. Manetsh R, Sharpless KB. In situ click chemistry: A powerful means for lead discovery. Exp Opin Drug Discovery 2006;1:525-538.
103. Loren JC, Krasinski A, Fokin VV, Sharpless KB. NH-1,2,3-triazoles from azidomethyl pivalate and carbamates: Base-labile N-protecting groups. Synlett 2005;18:2847-2850.
104. Yap AH, Weinreb SM. β-Tosylethylazide: A useful synthon for preparation of N-protected 1,2,3-triazoles via click chemistry. Tetrahedron Lett 2006;47:3035-3038.
105. Gerard B, Ryan J, Beeler AB, Porco JA, Jr. Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by copper-catalyzed cycloaddition-coupling of azide and terminal alkynes. Tetrahedron 2006;62:6405-6411.
106. Rees DC, Congreve M, Murray CW, Carr R. Fragment-based lead discovery. Nat Rev Drug Discov 2004;3:660-672.
107. Montagnat OD, Lessene G, Hughes AB. Synthesis of azide-alkyne fragments for "click"' chemical applications; formation of oligomers from orthogonally protected trialkylsilyl-propargyl azides and propargyl alcohols. Tetrahedron Lett 2006;47:6971-6974.
108. Preparation of 3-[4-(pyridin-3-yl)phenyl]-5-(1H-1,2,3- riazol-1-ylmethyl)oxazolidin-2-ones as antibacterial agents. 2005; WO 2005116023.
109. Preparation of 3-(1,2,3-triazol-1-yl)-1-thio-galactosides as antitumor and anti-inflammatory agents and for use as hydrolytically stable inhibitors of galectin-3. 2005; WO 2005113569.
110. Li J, Zheng M, Tang W, He PL, Zhu W, Li T, Zuo JP, Liu H, Jiang H. Synthesis of triazole-modified zanamivir analogues via click chemistry and anti-AIV activities Bioorg. Med Chem Lett 2006;16:5009-5013.
111. Preparation of triazolyl arylbenzamides as inhibitors of cytokines. 2005; WO 2005090333.
112. Preparation of novel triazoles as antibacterial agents. 2005; WO 2005082892.
113. Preparation of triazoles as bradykinin Bl receptor antagonists for treatment of inflammation-related disorders. 2006; WO 2006044355.
114. Kacprzak K, Migas M, Plutecka A, Rychlewska U, Gawronski J. The library of Cinchona alkaloidal 1,2,3-triazole derivatives: Structure and facile access by "click chemistry". Heterocycles 2005;65:1931-1938.
115. van der Peet P, Gannon CT, Walker I, Dinev Z, Angelin M, Tarn S, Ralton JE, McConville MJ, Williams SJ. Use of click chemistry to define the substrate specificity of Leishmania. ChemBioChem 2006;7:1384-1391.
116. Choi WJ, Shi ZD, Worthy KM, Bindu L, Karki RG, Nicklaus MC, Fisher RJ, Burke TR. Application of azide-alkyne cycloaddition ' click chemistry' for the synthesis of Grb2 SH2 domain-binding macrocycles. Bioorg Med Chem Lett 2006;16:5265-5269.
117. Chang KH, Lee L, Chen J, Li WS. Lithocholic acid analogues, new and potent a-2,3-sialyltransferase inhibitors. Chem Commun 2006(6):629-631.
118. Hasegawa T, Umeda M, Numata M, Li C, Bae AH, Fujisawa T, Haraguchi S, Sakurai K, Shinkai S. 'Click chemistry' on polysaccharides: A convenient, general, and monitorable approach to develop (1 → 3)-beta-D- glucans with various functional appendages. Carbohydr Res 2006;341:35-40.
119. Hotha S, Kashyap S. "Click chemistry" inspired synthesis of pseudo-oligosaccharides and amino acid glycoconjugates. J Org Chem 2006;71:852.
120. Kaval N, Ermolat'ev D, Appukkuttan P, Dehaen W, Kappe CO, Van der Eycken E. The application of "click chemistry" for the decoration of 2(1H)-pyrazinone scaffold: Generation of templates. J Comb Chem 2005;7:490-502.
121. Fang L, Zhang G, Li C, Zheng X, Zhu L, Xiao JJ, Szakacs G, Nadas J, Chan KK, Wang PG, Sun D. Discovery of a daunorubicin analogue that exhibits potent antitumor activity and overcomes P-gp-mediated drug resistance. J Med Chem 2006;49:932-941.
122. Rodriguez Loaiza P, Loeber S, Huebner H, Gmeiner P. Click chemistry on solid phase: Parallel synthesis of N-benzyltriazole carboxamides as super-potent G-protein coupled receptor ligands. J Comb Chem 2006;8:252-261.
123. Xie J, Seto CT. A two stage click-based library of protein tyrosine phosphatase inhibitors. Bioorg Med Chem 2007;15:458-473.
124. Cosyn L, Palaniappan KK, Kim SK, Duong HT, Gao ZG, Jacobson KA, Van Calenbergh S. 2-Triazole-substituted adenosines: A new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists. J Med Chem 2006;49:7373-7383.
125. Moorhouse AD, Santos AM, Gunaratnam M, Moore M, Neidle S, Moses JE. Stabilization of G-quadruplex DNA by highly selective ligands via click chemistry. J Am Chem Soc 2006;128:15972-15973.
126. Giguere D, Patnam R, Bellefleur MA, St-Pierre C, Sato S, Roy R. Carbohydrate triazoles and isoxazoles as inhibitors of galectins-1 and -3. Chem Commun 2006:2379-2381.
127. Jang H, Fafarman A, Holub JM, Kirshenbaum K. Click to fit: Versatile polyvalent display on a peptidomimetic scaffold. Org Lett 2005;7:1951-1954.
128. Lee T, Cho M, Ko SY, Youn HJ, Baek DJ, Cho WJ, Kang CY, Kim S. Synthesis and evaluation of 1,2,3-triazole containing analogues of the immunostimulant α-GalCer. J Med Chem 2007;50:585-589.
129. Ritschel J, Sasse F, Maier ME. Synthesis of a benzolactone collection using click chemistry. Eur J Org Chem 2007:78-87.