Cyclization-activated prodrugs

Molecules

Volumn 12, Issue 11, 2007, Pages 2484-2506

  Gomes, Paula ^a,c   Vale, Nuno ^a   Moreira, Rui ^b  

^a UNIVERSITY OF PORTO   (Portugal)

^b RESEARCH INSTITUTE FOR MEDICINES IMED ULISBOA   (Portugal)

^c NONE   (Portugal)

Author keywords

Cyclization, prodrugs, peptides, intramoleculary activated prodrugs; Two step activation

Indexed keywords

AMIDE; AMINE; PEPTIDE; PRODRUG;

ANIMAL; BIOAVAILABILITY; CHEMICAL STRUCTURE; CHEMISTRY; CYCLIZATION; DRUG DESIGN; HUMAN; METABOLISM; REVIEW;

AMIDES; AMINES; ANIMALS; BIOLOGICAL AVAILABILITY; CYCLIZATION; DRUG DESIGN; HUMANS; MOLECULAR STRUCTURE; PEPTIDES; PRODRUGS;

EID: 36849072605     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/12112484     Document Type: Review

References (97)

1. Salama, N.N.; Fasano, A.; Thakar, M.; Eddington, N.D. The impact of ΔG on the oral bioavailability of low bioavailable therapeutic agents. J. Pharmacol. Exp. Ther. 2005, 312, 199-205.
2. Lin, J.H.; Lu, A.Y.H. Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol. Rev. 1997, 49, 403-449.
3. Han, H.K.; Amidon, G.L. Targeted prodrug design to optimize drug delivery. AAPS PharmSci. 2000, 2, E6.
4. Sinkula, A.A.; Yalkowsky, S.H. Rationale for design of biologically reversible drug derivatives: prodrugs. J. Pharm. Sci. 1975, 64, 181-210.
5. Yu, L.X.; Straughn, A.B.; Faustion, P.J.; Yang, Y.; Parekh, A.; Ciavarella, A.B.; Asafu-Adjaye, E.; Mehta, M.U.; Conner, D.P.; Lesko, L.J.; Hussain, A.S. The effect of food on the relative bioavailability of rapidly dissolving immediate-release solid oral products containing highly soluble drugs. Mol. Pharm. 2004, 1, 357-362.
6. Shan, D.; Nicolaou, M.G.; Borchardt, R.T.; Wang, B. Prodrug strategies based on intramolecular cyclization reactions. J. Pharm. Sci. 1997, 86, 765-767.
7. Testa, B.; Mayer, J.M. Design of intramolecularly activated prodrugs. Drug Metab. Rev.1998, 30, 787-807.
8. Wang, W.; Jiang, J.; Ballard, C.E.; Wang, B. Prodrug approaches to the improved delivery of peptide drugs. Curr. Pharm. Des. 1999, 5, 265-287.
9. Vinšová, J.; Imramovský, A. Intramolekulá rní cycklizace využívané k uvolňová ní účinných látek z proléčiv. Chem. Listy 2005, 99, 21-29.
10. Papot, S.; Tranoy, I.; Tillequin, F.; Florent, J.-C-; Gesson, J.-P. Design of selectively activated anticancer prodrugs: elimination and cyclization strategies. Curr. Med. Chem. - Anti-Cancer Agents 2002, 2, 155-185.
11. Testa, B. Prodrug research: futile or fertile? Biochem. Pharmacol. 2004, 68, 2097-2106.
12. Stella, Borchardt, Hageman, Oliyai, Maag and Tilley (eds.). Prodrugs: challenges and rewards. Part 1 and 2, Springer-AAPS Press: New York, 2007 (the initial sections of Part 2 are particularly relevant in the present context).
13. Bundgaard, H.; Falch, E.; Larsen, C.; Mesher, G.L.; Mikkelson, T. Pilocarpic acid esters as novel sequentially labile pilocarpine prodrugs for improved ocular delivery. J. Med. Chem. 1985, 28, 979-981.
14. Song, L.; Bevins, R.; Anderson, B.D. Kinetics and mechanisms of activation of α-amino acid ester prodrugs of camptothecins. J. Med. Chem. 2006, 49, 4344-4355.
15. Bom, D.; Curran, D.P.; Kruszewski, S.; Zimmer, S.G.; Strode, J.T.; Kohlhagen, G.; Du, W.; Chavan, A.J.; Fradey, K.A.; Bingcang, A.L.; Latus, L.J.; Pommier, Y.; Burke, T.G. The novel silatecan 7-tert-butyldimethylsilyl- 10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity. J. Med. Chem. 2000, 43, 3970-3980.
16. Vigroux, A.; Bergon, M.; Zedde, C. Cyclization-activated prodrugs: N-(substituted 2 hydroxyphenyl and 2-hydroxypropyl)carbamates based on ring-opened derivatives of active benzoxazolones and oxazolidinones as mutual prodrugs of acetaminophen. J. Med. Chem. 1995, 38, 3983-3994.
17. Fredholt, K.; Mork, N.; Begtrup, M. Hemiesters of aliphatic dicarboxylic acids as cyclizationactivated prodrug forms for protecting phenols against first-pass metabolism. Int. J. Pharm. 1995, 123, 209-216.
18. Bruice, T.C.; Pandit, U.K. The effect of germinal substitution, ring size and rotamer distribution on the intramolecular nucleophilic catalysis of the hydrolysis of monophenyl esters of dibasic acids and the solvolysis of the intermediate anhydrides. J. Am. Chem. Soc. 1960, 82, 5858-5865.
19. Thomsen, K.F.; Bundgaard, H. Cyclization-activated phenyl carbamate prodrug forms for protecting phenols against first-pass metabolism. Int. J. Pharm. 1993, 91, 39-49.
20. Matsumoto, H.; Sohma, Y.; Kimura, T.; Hayashi, Y.; Kiso, Y. Controlled drug release: new watersoluble prodrugs of an HIV protease inhibitor. Bioorg. Med. Chem. Lett. 2001, 11, 605-609.
21. Sohma, Y.; Hayashi, Y.; Ito, T.; Matsumoto, H.; Kimura, T.; Kiso, Y. Development of water-soluble prodrugs of HIV-1 protease inhibitor KNI-727: importance of the conversion time for higher gastrointestinal absorption of prodrugs based on spontaneous chemical cleavage. J. Med. Chem. 2003, 46, 4124-4135.
22. Matsumoto, H.; Kimura, T.; Hamawaki, T.; Kumagai, A.; Goto, T.; Sano, K.; Hayashi, Y.; Kiso, Y. Design, synthesis, and biological evaluation of anti-HIV double-drugs: conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor through spontaneously cleavable linkers. Bioorg. Med. Chem. 2001, 9, 1589-1600.
23. Santos, C.; Mateus, M.L.; Santos, A.P.; Moreira, R.; Oliveira, E.; Gomes, P. Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamol. Bioorg. Med. Chem. Lett. 2005, 15, 1595-1598.
24. Gomes, P.; Gomes, J.R.B.; Rodrigues, M.; Moreira, R. Amino acids as selective sulfonamide acylating agents. Tetrahedron 2003, 59, 7473-7480.
25. Saari, W.S.; Schwering, J.E.; Lyle, P.A.; Smith, S.J.; Engelhardt, E.L. Cyclization-activated prodrugs. Basic carbamates of 4-hydroxyanisole. J. Med. Chem. 1990, 33, 97-101.
26. Saari, W.S.; Schwering, J.E.; Lyle, P.A.; Smith, S.J.; Engelhardt, E.L. Cyclization-activated prodrugs. Basic esters of 5-bromo-2'-deoxyuridine. J. Med. Chem. 1990, 33, 2590-2595.
27. Nam, N.H.; Kim, Y.; You, Y.J.; Hong, D.H.; Kim, H.M.; Ahn, B.Z. Water soluble prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5- trimethoxyphenyl)cyclopent-2-ene-1-one. Bioorg. Med. Chem. 2003, 11, 1021-1029.
28. Besser, D.; Müller, B.; Agricola, I.; Reissmann, S. Synthesis of differentially protected N-acylated reduced pseudodipeptides as building units for backbone cyclic peptides. J. Peptide Sci. 2000, 6, 130-138.
29. Besser, D.; Müller, B.; Kleinwächter, P.; Greiner, G.; Seyfarth, L.; Steinmetzer, T.; Arad, O.; Reissmann, S. Synthesis and characterization of octapeptide somatostatin analogues with backbone cyclization: comparison of different strategies, biological activities and enzymatic stabilities. J. Prakt. Chem. 2000, 342, 537-545.
30. Kaul, R.; Surprenant, S.; Lubell, W.D. Systematic study of the synthesis of macrocyclic dipeptide β-turn mimics possessing 8-, 9-, and 10- membered rings by ring-closing metathesis. J. Org. Chem. 2005, 70, 3838-3844.
31. Poteau, R.; Trinquier, G. All-cis cyclic peptides. J. Am. Chem. Soc. 2005, 127, 13875-13889.
32. Nielsen, T.E.; Quement, S.L.; Meldal, M. Solid-phase synthesis of bicyclic dipeptide mimetics by intramolecular cyclization of alcohols, thiols, amines, and amides with N-acyliminium intermediates. Org. Lett. 2005, 7, 3601-3604.
33. Liederer, B.M.; Fuchs, T.; Velde, D.V.; Siahaan, T.J.; Borchardt, R.T. Effects of amino acid chirality and the chemical linker on the cell permeation characteristics of cyclic prodrugs of opioid peptides. J. Med. Chem. 2006, 49, 1261-1270.
34. 9]GnRH: stimulation of gonadotropin gene expression. J. Med. Chem. 2006, 49, 105-110.
35. Flora, D.; Mo, H.; Mayer, J.P.; Khan, M.A.; Yan, L.Z. Detection and control of aspartimide formation in the synthesis of cyclic peptides. Bioorg. Med. Chem. Lett. 2005, 15, 1065-1068.
36. Che, Y.; Marshall, G.R. Engineering cyclic tetrapeptides containing chimeric amino acids as preferred reverse-turn scaffolds. J. Med. Chem. 2006, 49, 111-124.
37. Arnott, G.; Clayden, J.; Hamilton, S.D. Azabicyclic amino acids by stereoselective dearomatizing cyclization of the enolates of N-nicotinoyl glycine derivatives. Org. Lett. 2006, 8, 5325-5328.
38. 2-aminoacids in the design of conformationally homogeneous cyclo-peptide scaffolds. J. Org. Chem. 2006, 71, 6814-6821.
39. Gilon, C.; Halle, D.; Chorev, M.; Selinger, Z.; Byk, G. Backbone cyclization: a new conformational constraint on peptides. Biopolymers 1991, 31,745-750.
40. Al-Obeidi, F.; Castrucci, A.M.L.; Hadley, M.E.; Hruby, V.J. Potent and prolonged acting cyclic lactam analogues off α-melanotropin: design based on molecular dynamics. J. Med. Chem. 1989, 32, 2555-2561.
41. Charpentier, B.; Dor, A.; Roy, P.; England, P.; Pham, H.; Durieux, C.; Roques, B.P. Synthesis and binding affinities of cyclic and related linear analogues of CCK8 selective for central receptors. J. Med. Chem. 1989, 32, 1184-1190.
42. Reissmann, S.; Imhof, D. Development of conformationally restricted analogues of bradykinin and somatostain using constrained amino acids and different types of cyclization. Curr. Med. Chem. 2004, 11, 2823-2844.
43. Davies, J.S. The cyclization of peptides and depsipeptides. J. Peptide Sci. 2003, 9, 471-501.
44. Bray, A.M.; Maeji, N.J.; Valerio, R.M.; Campbell, R.A.; Geysen, H.M. Direct cleavage of peptides from a solid support into aqueous buffer. Applications in simultaneous multiple peptide synthesis. J. Org. Chem. 1991, 56, 6659-6666.
45. Capasso, S.; Vergara, A.; Mozzarella, l. Mechanism of 2,5-dioxopiperazine formation. J. Am. Chem. Soc. 1998, 120, 1990-1995.
46. Besada, P.; Mamedova, L.; Thomas, C.J.; Costanzi, S.; Jacobson, K.A. Design and synthesis of new bicyclic diketopiperazines as scaffolds for receptor probes of structurally diverse functionality. Org. Biomol. Chem. 2005, 3, 2016-2025.
47. Moyroud, J.; Gelin, J.; Chêne, A.; Mortier, J. Synthèse d'analogues structuraux de Thaxtomines, phytotoxines responsables de la gale de la pomme de terre. Tetrahedron 1996, 52, 8525-8534.
48. Szardenings, A.K.; Burkoth, T.S.; A simple procedure for the solid phase synthesis of diketopiperazine and diketomorpholine derivatives. Tetrahedron 1997, 53, 6573-6593.
49. Sollis, S.L. Short and novel stereospecific synthesis of trisubstituted 2,5-diketopiperazines. J. Org. Chem. 2005, 70, 4735-4740.
50. Niida, A.; Tanigaki, H.; Inokuchi, E.; Sasaki, Y.; Oishi, S.; Ohno, H.; Tamamura, H.; Wang, Z.; Peiper, S.C.; Kitaura, K.; Otaka, A.; Fujii, N. Stereoselective synthesis of 3,6-disubstituted-3,6-dihydropyridun-2-ones as potential diketopiperazine mimetics using organocopper-mediated anti-SN2' reactions and their use in the preparation of low-molecule CXCR4 antagonists. J. Org. Chem. 2006, 71, 3942-3951.
51. Kanoh, K.; Kohno, S.; Katada, J.; Takahashi, J.; Uno, I.; Hayashi, Y. Synthesis and biological activies of phenylahistin derivatives. Bioorg. Med. Chem. 1999, 7, 1451-1457.
52. Donkor, I.O.; Sanders, M.L. Synthesis of a reported calpain inhibitor isolated from Streptomyces griseus. Bioorg. Med. Chem. Lett. 2001, 11, 2647-2649.
53. Nam, N.H.; Ye, G.; Sun, G.; Parang, K. Conformationally constrained peptide analogues of pTyr-Glu-Glu-Ile as inhibitors of the Src SH2 domain binding. J. Med. Chem. 2004, 47, 3131-3141.
54. Borthwick, A.D.; Davies, D.E.; Exall, A.M.; Livermore, D.G.; Sollis, S.L.; Nerozzi, F.; Allen, M.J.; Perren, M.; Shabbir, S.S.; Woollard, P.M.; Wyatt, P.G. 2,5-Diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 2. Synthesis, chirality, and pharmacokinetics. J. Med. Chem. 2005, 48, 6956-6969.
55. Gomes, P.; Gomes, J.R.B.; Rodrigues, M.; Moreira, R. Amino acids as selective sulfonamide acylating agents. Tetrahedron 2003, 59, 7473-7480.
56. Santos, C.; Moreira, R.; Gomes, P. Cyclization-activated prodrugs: dipeptide esters of paracetamol. In Peptides 2004, M. Flegel, M. Fridkin, C. Gilon e J. Slaninova (eds.), Kenes International: Tel A'viv, 2005.
57. Brady, S.F.; Pawluczyk, J.M.; Lumma, P.K.; Feng, D.M.; Wai, J.M.; Jones, R.; DeFeo-Jones, D.; Wong, B.K.; Miller-Stein, C.; lin, J.H.; Oliff, A.; Freidinger, R.M.; Garsky, V.M. Design and synsthesis of a pro-drug of vinblastine targeted at treatment of prostate cancer with enhanced efficacy and reduced systemic toxicity. J. Med. Chem. 2002, 45, 4706-4715.
58. Purdie, J. E.; Benoiton, N. L. Piperazinedione formation from esters of dipeptides containing glycine, alanine, and sarcosine: the kinetics in aqueous solution. J. Chem. Soc. Perkin II 1973, 13, 1845-1852.
59. Meresaar, U.; Ågren, A. Hydrolysis of protolytic esters VI. Alkaline hydrolysis and ring closure of glycylglycine ethyl ester. Acta Pharm. Suec. 1968, 5, 85-94.
60. Jensen, E.; Bundgaard, H. Peptide esters as water-soluble prodrugs for hydroxyl containing agents: chemical stability and enzymatic hydrolysis of benzyl esters of glycine, diglycine and triglycine. Int. J. Pharm. 1991, 71, 117-125.
61. Larsen, S.W.; Ankersen, M.; Larsen, C. Kinetics of degradation and oil solubility of ester prodrug of a model dipeptide (Gly-Phe). Eur. J. Pharm. Sci. 2004, 22, 399-408.
62. Goolcharran, C.; Borchardt, R. T. Kinetics of diketopiperazine formation using model peptides. J. Pharm. Sci. 1998, 87, 283-288.
63. Shan, D.; Nicolaou, M.G.; Borchardt, R.T.; Wang, B. Prodrug strategies based on intramolecular cyclization reactions. J. Pharm. Sci., 1997, 86, 765.
64. Bertoloni, A.; Ferrari, A.; Ottani, A.; Guerzoni, S.; Tacchi, R.; Leone, S. Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006, 12, 250-275.
65. Lloyd-Williams, P.; Albericio, F.; Giralt, E. Chemical Approaches to the Synthesis of Peptides and Proteins. CRC Press: Boca Raton, 1997, p. 60.
66. Wipf, P.; Li, W.L.; Adeyeye, C.M.; Rusnak, J.M.; Lazo, J.S. Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity. Bioorg. Med. Chem. 1996, 4, 1585-1596.
67. Hamel, A.R.; Hubler, F.; Carrupt, A.; Wenger, R.M.; Mutter, M. Cyclosporin A prodrugs: design, synthesis and biophysical properties. J. Peptide Res. 2004, 63, 147-154.
68. Wei, Y.; Pei, D. Activation of antibacterial prodrugs by peptide deformylase. Bioorg, Med. Chem. Lett. 2000, 10, 1073-1076.
69. Jackson, D.Y.; Burnier, J.P.; Wells, J.A. Enzymatic cyclization of linear peptide esters using subtiligase. J. Am. Chem. Soc. 1995, 117, 819-820.
70. Kohchi, Y.; Hattori, K.; Oikawa, N.; Mizuguchi, E.; Isshiki, Y.; Aso, K.; Yoshinari, K.; Shirai, H.; Miwa, M.; Inagaki, Y.; Ura, M.; Ogawa, K.; Okabe, H.; Ishitsuka, H.; Shimma, N. Design and synthesis of novel prodrugs of 2′-deoxy-2′-methylidenecytidine activated by membrane dipeptidase overexpressed in tumor tissues. Bioorg. Med. Chem. Lett. 2007, 17, 2241-2245.
71. Atwell, G.; Sykes, B.M.; O'Connor, C.J.; Denny, W.A. Relationships between structure and kinetics of cyclization of 2-aminoaryl amides: potential prodrugs of cyclization-activated aromatic mustards. J. Med. Chem. 1994, 37, 371-380.
72. Sykes, B.M.; Atwell, G.J.; Hogg, A.; Wilson, W.R.; O'Connor, C.J.; Denny, W.A. N-substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization. J. Med. Chem. 1999, 4, 346-355.
73. Kirk, K.L.; Cohen, L.A. Intramolecular aminolysis of amides. Effects of electronic variation in the attacking and leaving groups. J. Am. Chem. Soc. 1972, 94, 8142-8147.
74. Liu, B.; Hu, L. 5′-(2-nitrophenylalkanoyl)-2′-deoxy-5- fluorouridines as prodrugs of FUDR for reductive activation. Bioorg. Med. Chem. 2003, 11, 3889-3899.
75. Milstien, S.; Cohen, L.A. Stereopopulation control. I. Rate enhancement in the lactonizations of o-hydroxyhydrocinnamic acids. J. Am. Chem. Soc. 1972, 94, 9158-9165.
76. Amsberry, K.L.; Borchardt, R.T. Amine prodrugs which utilize hydroxy amide lactonization. I. A potential redox-sensitive amide prodrug. Pharm. Res. 1991, 8, 323-330.
77. Wolfe, J.L.; Vander Velde, D.G.; Borchardt, R.T. Facilitated intramolecular conjugate addition of N-(p- methoxypheny1)-3-(3′,6′- dioxo-2′,4′-dimethylcyclohexa-1′,4′-dienyl)-3, 3-dimethylpropionamide. 1. Product characterization. J. Org. Chem. 1992, 57, 6138-6142.
78. Nicolaou, M.G.; Wolfe, J.L.; Schowen, R.L.; Borchardt, R.T. Facilitated intramolecular conjugate addition of amides of 3-(3′,6′-dioxo- 2′,4′-dimethyl-1′,4′-cyclohexadienyl)-3, 3-dimethylpropionic acid. 2. Kinetics of degradation. J. Org. Chem. 1996, 61, 6633-6638.
79. Amsberry, K.L.; Gerstenberger, E.; Borchardt, R.T. Amine prodrugs which utilize hydroxy amide lactonization. II. A potential esterase-sensitive amide prodrug. Pharm. Res. 1991, 8, 455-461.
80. Wang, B.; Gangwar, S.; Pauletti, G.M.; Siahaan, T.J.; Borchardt, R.T. Synthesis of a novel esterase-sensitive cyclic prodrug system for peptides that utilizes a "trimethyl lock"-facilitated lactonization reaction. J. Org. Chem. 1997, 62, 1363-1367.
81. Pauletti, G.M.; Gangwar, S.; Wang, B.; Borchardt, R.T. Esterase-sensitive cyclic prodrugs of peptides: evaluation of a phenylpropionic acid promoiety in a model hexapeptide. Pharm. Res. 1997, 14, 11-17.
82. Nicolaou, M.G.; Yuan, C.-S.; Borchardt, R.T. Phosphate prodrugs for amines utilizing a fast intramolecular hydroxy amide lactonization. J. Org. Chem. 1996, 61, 8636-8641.
83. Hershfield, R.; Schmir, G.L. Lactonization of coumarinic acids. Kinetic evidence for three species of the tetrahedral intermediate. J. Am. Chem. Soc. 1973, 95, 8032-8040.
84. Wang, B.; Zhang, H.; Wang, W. Chemical feasibility studies of a potential coumarin-based prodrug system. Bioorg. Med. Chem. Lett. 1996, 6, 945-950.
85. Wang, B.; Wang, W.; Zhang, H.; Shan, D.; Smith, T.D. Coumarin-based prodrugs 2. Synthesis and bioreversibility studies of an esterase-sensitive cyclic prodrug of dadle, an opioid peptide. Bioorg. Med. Chem. Lett. 1996, 6, 2823-2826.
86. Ouyang, H.; Borchardt, R.T.; Siahaan, T.J.; Vander Velde, D.G. Synthesis and conformational analysis of a coumarinic acid-based cyclic prodrug of an opioid peptide with modified sensitivity to esterase-catalyzed bioconversion. J. Peptide Res. 2002, 59, 183-195.
87. Tang, F.; Borchardt, R.T. Characterization of the efflux transporter(s) responsible for restricting intestinal mucosa permeation of an acyloxyalkoxy-based cyclic prodrug of the opioid peptide DADLE. Pharm. Res. 2002, 19, 780-786.
88. Tang, F.; Borchardt, R.T. Characterization of the efflux transporter(s) responsible for restricting intestinal mucosa permeation of a coumarinic acid-based cyclic prodrug of the opioid peptide DADLE. Pharm. Res. 2002, 19, 787-793.
89. Yang, J.Z.; Chen, W.; Borchardt, R.T. In vitro stability and in vivo pharmacokinetic studies of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs. J. Pharmacol. Exper. Ther. 2002, 303, 840-848.
90. Chen, W.; Yang, J.Z.; Andersen, R.; Nielsen, L.H.; Borchardt, R.T. Evaluation of the permeation characteristics of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs across the blood-brain barrier using an in situ perfused rat brain model. J. Pharmacol. Exper. Ther. 2002, 303, 849-857.
91. Liederer, B.M.; Borchardt, R.T. Stability of oxymethyl-modified coumarinic acid cyclic prodrugs of diastereomeric opioid peptides in biological media from various animal species including human. J. Pharm. Sci. 2005, 94, 2198-2206.
92. Camenish, G.P.; Wang, W.; Wang, B.; Borchardt, R.T. A comparison of the bioconverstion rates and the Caco-2 cell permeation characteristics of coumarin-based cyclic prodrugs and methylester-based linear prodrugs of RGD peptidomimetics. Pharm. Res. 1998, 15, 1174-1181.
93. Dillon, M.P.; Cai, H.; Maag, H. Application of the "trimethyl lock" to ganciclovir, a pro-prodrug with increased oral bioavailability. Bioorg. Med. Chem. Lett. 1996, 6, 1653-1656.
94. Greenwald, R.B.; Choe, Y.H.; Conover, C.D.; Shum, K.; Wu, D.; Royzen, M. Drug delivery systems based on trimethyl lock lactonization: poly(ethyleneglycol) prodrugs of amino-containing compounds. J. Med. Chem. 2000, 43, 475-487.
95. Chandran, S.S.; Dickson, K.A.; Raines, R.T. Latent fluorophore based on the trimethyl lock. J. Am. Chem. Soc. 2005, 127, 1652-1653.
96. Lavis, L.D.; Chao, T.-Y.; Raines, R.T. Latent blue and red fluorophores based on trimethyl lock. ChemBioChem. 2006, 7, 1151-1154.
97. Weerapreeyakul, N.; Anorach, R.; Khuansawad, T.; Yenjai, C.; Isaka, M. Synthesis of bioreductive esters from fungal compounds. Chem. Pharm. Bull. 2007, 55, 930-935.