Conformational restriction: An effective tactic in 'follow-on'-based drug discovery

Future Medicinal Chemistry

Volumn 6, Issue 8, 2014, Pages 885-901

  Fang, Zengjun ^a   Song, Yu'Ning ^a   Zhan, Peng ^a   Zhang, Qingzhu ^a   Liu, Xinyong ^a  

^a SHANDONG UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOHEXENE DERIVATIVE; CYCLOPENTANE DERIVATIVE; CYCLOPROPANE DERIVATIVE; FLUCONAZOLE; IMIDAZO[1,2 A]PYRIDINE DERIVATIVE; MARAVIROC; MEMANTINE; N (4 FLUOROBENZYL) 8 HYDROXY 5 (TETRAHYDRO 2H 1,2 THIAZIN 2 YL) 1,6 NAPHTHYRIDINE 7 CARBOXAMIDE S,S DIOXIDE; OSELTAMIVIR; PERAMIVIR; PLERIXAFOR; PYRROLIDINE DERIVATIVE; RIVASTIGMINE; SIALIDASE INHIBITOR; SULFONAMIDE; THIOUREA; TRIAZOLE DERIVATIVE; ZANAMIVIR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CHEMOKINE RECEPTOR CXCR; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; NEUROPROTECTIVE AGENT; SECRETASE;

ALZHEIMER DISEASE; CONFORMATION; CONFORMATION RESTRICTION; CRYSTAL STRUCTURE; DRUG BINDING; DRUG DESIGN; DRUG METABOLISM; DRUG SELECTIVITY; DRUG TARGETING; GENOTYPE; HIGH THROUGHPUT SCREENING; HUMAN; IC 50; MINIMUM INHIBITORY CONCENTRATION; PHARMACOLOGICAL PROCEDURES; PRIORITY JOURNAL; REVIEW; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DEVELOPMENT; HIV INFECTIONS; METABOLISM;

ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN SECRETASES; ANTI-HIV AGENTS; DRUG DESIGN; DRUG DISCOVERY; HIV INFECTIONS; HIV PROTEASE; HUMANS; MOLECULAR CONFORMATION; NEUROPROTECTIVE AGENTS; RECEPTORS, CXCR;

EID: 84903318804     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.14.50     Document Type: Review

References (99)

1. Raju TN. The Nobel chronicles. 1988: James Whyte Black, (b 1924), Gertrude Elion (19189-9), and George H Hitchings (19059-8). Lancet 355, 1022 (2000).
2. Zhao H, Guo Z. Medicinal chemistry strategies in followon drug discovery. Drug Discov. Today 14, 5165-5122 (2009).
3. Fischer J, Ganellin CR. Analogue-based Drug Discovery. Wiley VCH, Weinheim, Germany (2006).
4. Fischer J, Ganellin CR. Analogue-Based Drug Discovery II. Wiley VCH, Weinheim, Germany (2010).
5. Fischer J, Ganellin CR, Rotella DP. Analogue-Based Drug Discovery III. Wiley VCH, Weinheim, Germany (2012).
6. Valle G, Kazmierski WM, Crisma M. Constrained phenylalanine analogues. Preferred conformation of the 1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid (Tic) residue. Int. J. Pept. Protein Res. 40(3-4), 222-232 (1992).
7. Kümmerle AE, Vieira MM, Schmitt M et al. Design, synthesis and analgesic properties of novel conformationally-restricted N-acylhydrazones (NAH). Bioorg. Med. Chem. Lett. 19(17), 4963-4966 (2009).
8. Hanessian S, Auzzas L. The practice of ring constraint in peptidomimetics using bicyclic and polycyclic amino acids. Acc. Chem. Res. 41(10), 1241-1251 (2008).
9. Chang CE, Chen W, Gilson MK. Ligand configurational entropy and protein binding. Proc. Natl Acad. Sci. USA 104(5), 1534-1539 (2007). (Pubitemid 46214625)
10. Tiwari RK, Parang K. Conformationally constrained peptides as protein tyrosine kinase inhibitors. Curr. Pharm. Des. 18(20), 2852-2566 (2012).
11. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J. Clin. 55, 74-108 (2005).
12. Doody RS, Ferris SH, Salloway S et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebocontrolled trial. Neurology 72(18), 1555-1561 (2009).
13. van Marum RJ. Update on the use of memantine in Alzheimer's disease. Neuropsychiatr. Dis. Treat. 5, 237-247 (2009).
14. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer's disease. Am. J. Med. 120(5), 388-397 (2007). (Pubitemid 46627453)
15. Bolognesi ML, Bartolini M, Cavalli A et al. Design, synthesis, and biological evaluation of conformationally restricted rivastigmine analogues. J. Med. Chem. 47(24), 5945-5952 (2004). (Pubitemid 39507336)
16. Boy KM, Guernon JM, Shi J et al. Monosubstituted γ-lactam and conformationally constrained 1, 3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE). Bioorg. Med. Chem. Lett. 21(22), 6916-6924 (2011).
17. Al-Tel TH, Semreen MH, Al-Qawasmeh RA et al. Design, synthesis, and qualitative structure-activity evaluations of novel β-secretase inhibitors as potential Alzheimer's drug leads. J. Med. Chem. 54(24), 8373-8385 (2011).
18. Stachel SJ, Steele TG, Petrocchi A et al. Discovery of pyrrolidine-based β-secretase inhibitors: lead advancement through conformational design for maintenance of ligand binding efficiency. Bioorg. Med. Chem. Lett. 22(1), 240-244 (2012).
19. Mandal M, Zhu Z, Cumming JN et al. Design and validation of bicyclic iminopyrimidinones as beta amyloid cleaving enzyme-1 (BACE1) inhibitors: conformational constraint to favor a bioactive conformation. J. Med. Chem. 55(21), 9331-9345 (2012).
20. Yonezawa S, Yamamoto T, Yamakawa H et al. Conformational restriction approach to β-secretase (BACE1) inhibitors: effect of a cyclopropane ring to induce an alternative binding mode. J. Med. Chem. 55(20), 8838-8858 (2012).
21. Yonezawa S, Yamakawa H, Muto C et al. Conformational restriction approach to BACE1 inhibitors II: SAR study of the isocytosine derivatives fixed with a cis-cyclopropane ring. Bioorg. Med. Chem. Lett. 23(10), 2912-2915 (2013).
22. Bischoff F, Berthelot D, De Cleyn M et al. Design and synthesis of a novel series of bicyclic heterocycles as potent γ-secretase modulators. J. Med. Chem. 55(21), 9089-9106 (2012).
23. Maher-Edwards G, Zvartau-Hind M, Hunter AJ et al. Double-blind, controlled Phase II study of a 5-HT6 receptor antagonist, SB-742457, in Alzheimer's disease. Curr. Alzheimer Res. 7(5), 374-385 (2010).
24. Ivachtchenko AV, Golovina ES, Kadieva MG et al. Antagonists of 5-HT6 receptors. Substituted 3-(phenylsulfonyl)pyrazolo[1, 5-a]pyrido[3, 4-e]pyrimidines and 3-(phenylsulfonyl)pyrazolo[1, 5-a]pyrido[4, 3-d] pyrimidines-synthesis and 'structure-activity' relationship. Bioorg. Med. Chem. Lett. 22(13), 4273-4280 (2012).
25. Nirogi R, Shinde A, Daulatabad A et al. Design, synthesis, and pharmacological evaluation of piperidin-4-yl amino aryl sulfonamides: novel, potent, selective, orally active, and brain penetrant 5-HT(6) receptor antagonists. J. Med. Chem. 55(21), 9255-9269 (2012).
26. De Clercq E. A 40-year journey in search of selective antiviral chemotherapy. Annu. Rev. Pharmacol. Toxicol. 51, 1-24 (2011).
27. Steen A, Schwartz TW, Rosenkilde MM. Targeting CXCR4 in HIV cell-entry inhibition. Mini Rev. Med. Chem. 9(14), 1605-1621 (2009).
28. Valks GC, McRobbie G, Lewis EA et al. Configurationally restricted bismacrocyclic CXCR4 receptor antagonists. J. Med. Chem. 49(21), 6162-6165 (2006). (Pubitemid 44595193)
29. Fujii N, Oishi S, Hiramatsu K et al. Molecular-size reduction of a potent CXCR4-chemokine antagonist using orthogonal combination of conformation-and sequence-based libraries. Angew. Chem. Int. Ed. Engl. 42(28), 3251-3253 (2003). (Pubitemid 36917168)
30. Ueda S, Oishi S, Wang ZX et al. Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. J. Med. Chem. 50(2), 192-198 (2007). (Pubitemid 46147700)
31. Mungalpara J, Thiele S, Eriksen O et al. Rational design of conformationally constrained cyclopentapeptide antagonists for C-X-C chemokine receptor 4 (CXCR4). J. Med. Chem. 55(22), 10287-10291 (2012).
32. Demmer O, Frank AO, Hagn F et al. A conformationally frozen peptoid boosts CXCR4 affinity and anti-HIV activity. Angew. Chem. Int. Ed. Engl. 51(32), 8110-8113 (2012).
33. Chen W, Zhan P, De Clercq E, Liu X. Recent progress in small molecule CCR5 antagonists as potential HIV-1 entry inhibitors. Curr. Pharm. Des. 18(1), 100-112 (2012).
34. Metz M, Bourque E, Labrecque J et al. Prospective CCR5 small molecule antagonist compound design using a combined mutagenesis/modeling approach. J. Am. Chem. Soc. 133(41), 16477-16485 (2011).
35. Rotstein DM, Gabriel SD, Manser N et al. Synthesis, SAR and evaluation of [1, 4́]-bipiperidinyl-4-yl-imidazolidin-2-one derivatives as novel CCR5 antagonists. Bioorg. Med. Chem. Lett. 20(11), 3219-3222 (2010).
36. Duan M, Kazmierski WM, Tallant M et al. Discovery of a novel series of cyclic urea as potent CCR5 antagonists. Bioorg. Med. Chem. Lett. 21(21), 6381-6385 (2011).
37. Castonguay LA, Weng Y, Adolfsen W et al. Binding of 2-aryl-4-(piperidin- 1-yl)butanamines and 1, 3, 4-trisubstituted pyrrolidines to human CCR5: a molecular modeling-guided mutagenesis study of the binding pocket. Biochemistry 42(6), 1544-1550 (2003). (Pubitemid 36205961)
38. Barber CG, Blakemore DC, Chiva JY et al. 1-amido-1-phenyl-3- piperidinylbutanes-CCR5 antagonists for the treatment of HIV: part 2. Bioorg. Med. Chem. Lett. 19(5), 1499-1503 (2009).
39. Egbertson MS. HIV integrase inhibitors: from diketoacids to heterocyclic templates: a history of HIV integrase medicinal chemistry at Merck West Point and Merck Rome (IRBM). Curr. Top Med. Chem. 7(13), 1251-1272 (2007). (Pubitemid 47317046)
40. Fardis M, Jin H, Chen X et al. Conformationally constrained tricyclic HIV integrase inhibitors. In: HIV-1 Integrase: Mechanism and Inhibitor Design (First Edition). Neamati N (Ed.). John Wiley & Sons Inc., NY, USA, 239-254 (2011).
41. Zhao XZ, Maddali K, Smith SJ et al. 6, 7-dihydroxy-1-oxoisoindoline-4- sulfonamide-containing HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 22(24), 7309-7313 (2012).
42. Fisher TE, Kim B, Staas DD et al. 8-hydroxy-3, 4-dihydropyrrolo[1, 2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 17(23), 6511-6515 (2007). (Pubitemid 350026333)
43. Thuring JWJ, Bonfanti J-F, Fortin JMC: WO2011045330 A1 (2011).
44. Li X, Vince R. Conformationally restrained carbazolonecontaining alpha, gamma-diketo acids as inhibitors of HIV integrase. Bioorg. Med. Chem. 14(9), 2942-2955 (2006).
45. Artico M, Di Santo R, Costi R et al. Geometrically and conformationally restrained cinnamoyl compounds as inhibitors of HIV-1 integrase: synthesis, biological evaluation, and molecular modeling. J. Med. Chem. 41(21), 3948-3960 (1998). (Pubitemid 28483472)
46. Buolamwini JK, Assefa H. CoMFA and CoMSIA 3D QSAR and docking studies on conformationally-restrained cinnamoyl HIV-1 integrase inhibitors: exploration of a binding mode at the active site. J. Med. Chem. 45(4), 841-852 (2002). (Pubitemid 34173934)
47. Kawasuji T, Johns BA, Yoshida H et al. Carbamoyl pyridone HIV-1 integrase inhibitors. 2. Bi-and tricyclic derivatives result in superior antiviral and pharmacokinetic profiles. J. Med. Chem. 56(3), 1124-1135 (2013).
48. Johnson TW, Tanis SP, Butler SL et al. N-hydroxydihydronaphthyridinones as potent and orally bioavailable HIV-1 integrase inhibitors. J. Med. Chem. 54(9), 3393-3417 (2011).
49. Pryde DC, Webster R, Butler SL et al. Discovery of an HIV integrase inhibitor with an excellent resistance profile. Med. Chem. Commun. 4, 709-719 (2013).
50. Biswas D, Samp L, Ganguly AK. Synthesis of conformationally restricted sulfonamides via radical cyclisation. Tetrahedron Lett. 51, 2681-2684 (2010).
51. Ganguly AK, Alluri SS, Caroccia D et al. Design, synthesis, and X-ray crystallographic analysis of a novel class of HIV-1 protease inhibitors. J. Med. Chem. 54(20), 7176-7183 (2011).
52. Mathé C, Périgaud C. Recent approaches in the synthesis of conformationally restricted nucleoside analogues. Eur. J. Org. Chem. 2008(9), 1489-1505 (2008).
53. Díaz-Rodríguez A, Sanghvi YS, Fernández S et al. Synthesis and anti-HIV activity of conformationally restricted bicyclic hexahydroisobenzofuran nucleoside analogs. Org. Biomol. Chem. 7(7), 1415-1423 (2009).
54. Figueras A, Miralles-Llumà R, Flores R et al. Synthesis, anti-HIV activity studies, and in silico rationalization of cyclobutane-fused nucleosides. Chem. Med. Chem. 7(6), 1044-1056 (2012).
55. Zhan P, Chen X, Li D et al. HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design. Med. Res. Rev. 33(1), E1-E72 (2013).
56. Zhan P, Liu X. Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent review (2005-2010). Expert Opin. Ther. Pat. 21(5), 717-796 (2011).
57. Zhan P, Liu X, Li Z, Pannecouque C, De Clercq E. Design strategies of novel NNRTIs to overcome drug resistance. Curr. Med. Chem. 16(29), 3903-3917 (2009).
58. Zhan P, Liu X, Li Z. Recent advances in the discovery and development of novel HIV-1 NNRTI platforms: 20062-008 update. Curr. Med. Chem. 16(22), 2876-2889 (2009).
59. Song YN, Fang Z, Zhan P, Liu X. Recent advances in the discovery and development of novel HIV-1 NNRTI platforms (Part II): 2009-2013 update. Curr. Med. Chem. 21(3), 329-355 (2014).
60. Pauwels R, Andries K, Desmyter J et al. Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343, 470-474 (1990). (Pubitemid 120028562)
61. Schafer JJ, Short WR. Rilpivirine, a novel non-nucleoside reverse transcriptase inhibitor for the management of HIV-1 infection: a systematic review. Antivir. Ther. 17(8), 1495-1502 (2012).
62. Klibanov OM, Kaczor RL. IDX-899, an aryl phosphinateindole non-nucleoside reverse transcriptase inhibitor for the potential treatment of HIV infection. Curr. Opin. Invest. Drugs 11(2), 237-245 (2010).
63. Moyle G, Boffito M, Stoehr A et al. Phase 2a randomized controlled trial of short-term activity, safety, and pharmacokinetics of a novel nonnucleoside reverse transcriptase inhibitor, RDEA806, in HIV-1-positive, antiretroviral-naive subjects. Antimicrob. Agents Chemother. 54(8), 3170-3178 (2010).
64. Wu B, Nguyen TN, Ellis DA et al. US20080287516 A1 (2008).
65. Gomez R, Jolly SJ, Williams T et al. Design and synthesis of conformationally constrained inhibitors of non-nucleoside reverse transcriptase. J. Med. Chem. 54(22), 7920-7933 (2011).
66. Cantrell AS, Engelhardt P, Högberg M et al. Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs. J. Med. Chem. 39(21), 4261-4274 (1996). (Pubitemid 26339837)
67. Zhang H, Oberg B, Bottiger D et al. MIV-150 in a vaginal microbicide with superior anti-HIV activities. Presented at: The XV International AIDS Conference. Bangkok, Thailand, 12-16 July 2004.
68. Barreca ML, Rao A, De Luca L et al. Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains. Bioorg. Med. Chem. Lett. 17, 1956-1960 (2007). (Pubitemid 46367661)
69. Venkatachalam TK, Mao C, Uckun FM. Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives. Biochem. Pharmacol. 67, 1933-1946 (2004). (Pubitemid 38591382)
70. Salaun, J. Cyclopropane derivatives and their diverse biological activities. In: Small Ring Compounds in Organic Synthesis VI. Springer-Verlag, Berlin, Germany, 240 (1999).
71. Högberg M, Sahlberg C, Engelhardt P et al. Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues. J. Med. Chem. 42, 4150-4160 (1999). (Pubitemid 29483032)
72. Dmitry A, Christian S, Stefan L, Christer S. WO2004021969 A2 (2004).
73. Ren J, Diprose J, Warren J et al. Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases. Structural and biochemical analyses. J. Biol. Chem. 275(8), 5633-5639 (2000). (Pubitemid 30115202)
74. Su DS, Lim JJ, Tinney E et al. Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants. Bioorg. Med. Chem. Lett. 19, 5119-5123 (2009).
75. Radi M, Maga G, Alongi M et al. Discovery of chiral cyclopropyl dihydro-alkylthio-benzyl-oxopyrimidine (S-DABO) derivatives as potent HIV-1 reverse transcriptase inhibitors with high activity against clinically relevant mutants. J. Med. Chem. 52, 840-851 (2009).
76. Jiang T, Kuhen KL, Wolff K et al. Design, synthesis and biological evaluations of novel oxindoles as HIV-1 nonnucleoside reverse transcriptase inhibitors. Part I. Bioorg. Med. Chem. Lett. 16, 2105-2108 (2006). (Pubitemid 43351059)
77. Jiang T, Kuhen KL, Wolff K et al. Design, synthesis, and biological evaluations of novel oxindoles as HIV-1 nonnucleoside reverse transcriptase inhibitors. Part 2. Bioorg. Med. Chem. Lett. 16(8), 2109-2112 (2006). (Pubitemid 43351060)
78. Ellis D, Kuhen KL, Anaclerio B et al. Design, synthesis, and biological evaluations of novel quinolones as HIV-1 nonnucleoside reverse transcriptase inhibitors. Bioorg. Med. Chem. Lett. 16, 4246-4251 (2006).
79. Hassam M, Basson AE, Liotta DC et al. Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors. ACS Med. Chem. Lett. 3(6), 470-475 (2012).
80. Mai A, Sbardella G, Artico M et al. Structure-based design, synthesis, and biological evaluation of conformationally restricted novel 2-alkylthio-6-[1-(2, 6-difluorophenyl)alkyl]-3, 4-dihydro-5-alkylpyrimidin-4(3H) -ones as non-nucleoside inhibitors of HIV-1 reverse transcriptase. J. Med. Chem. 44(16), 2544-2554 (2001). (Pubitemid 32852144)
81. Ragno R, Mai A, Sbardella G et al. Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[1-(2, 6-difluorophenyl)alkyl]-3, 4-dihydro-5-alkylpyrimidin-4(3H)-ones as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. J. Med. Chem. 47(4), 928-934 (2004). (Pubitemid 38176795)
82. Rotili D, Samuele A, Tarantino D et al. 2-(alkyl/aryl)amino-6- benzylpyrimidin-4(3H)-ones as Inhibitors of wild-type and mutant HIV-1: enantioselectivity studies. J. Med. Chem. 55(7), 3558-3562 (2012).
83. Alexandre FR, Amador A, Bot S et al. Synthesis and biological evaluation of aryl-phospho-indole as novel HIV-1 nonnucleoside reverse transcriptase inhibitors. J. Med. Chem. 54(1), 392-395 (2011).
84. Gu SX, Li ZM, Ma XD et al. Chiral resolution, absolute configuration assignment and biological activity of racemic diarylpyrimidine CH(OH)-DAPY as potent nonnucleoside HIV-1 reverse transcriptase inhibitors. Eur. J. Med. Chem. 53, 229-234 (2012).
85. Kang IJ, Wang LW, Lee CC et al. Design, synthesis, and anti-HCV activity of thiourea compounds. Bioorg. Med. Chem. Lett. 19(7), 1950-1955 (2009).
86. Kang IJ, Wang LW, Hsu SJ et al. Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors. Bioorg. Med. Chem. Lett. 19(21), 6063-6068 (2009).
87. Kang IJ, Wang LW, Yeh TK et al. Synthesis, activity, and pharmacokinetic properties of a series of conformationallyrestricted thiourea analogs as novel hepatitis C virus inhibitors. Bioorg. Med. Chem. 18(17), 6414-6421 (2010).
88. McGowan D, Vendeville S, Lin TI et al. Fingerloop inhibitors of the HCV NS5b polymerase. Part 1: Discovery and optimization of novel 1, 6-and 2, 6-macrocyclic indole series. Bioorg. Med. Chem. Lett. 22(13), 4431-4436 (2012).
89. Vendeville S, Lin TI, Hu L et al. Finger loop inhibitors of the HCV NS5b polymerase. Part II. Optimization of tetracyclic indole-based macrocycle leading to the discovery of TMC647055. Bioorg. Med. Chem. Lett. 22(13), 4437-4443 (2012).
90. Rudd MT, McIntyre CJ, Romano JJ et al. Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers. Bioorg. Med. Chem. Lett. 22(23), 7207-7213 (2012).
91. Brant MG, Wulff JE. A rigid bicyclic platform for the generation of conformationally locked neuraminidase inhibitors. Org. Lett. 14(23), 5876-5879 (2012).
92. Bastida A, Hidalgo A, Chiara JL et al. Exploring the use of conformationally locked aminoglycosides as a new strategy to overcome bacterial resistance. J. Am. Chem. Soc. 128(1), 100-116 (2006). (Pubitemid 43102730)
93. Wang W, Wang S, Liu Y et al. Novel conformationally restricted triazole derivatives with potent antifungal activity. Eur. J. Med. Chem. 45(12), 6020-6026 (2010).
94. De Wachter R, de Graaf C, Keresztes A et al. Synthesis, biological evaluation, and automated docking of constrained analogues of the opioid peptide H-Dmt-DAla-Phe-Gly-NH2 using the 4-or 5-methyl substituted 4-amino-1, 2, 4, 5-tetrahydro-2-benzazepin-3-one scaffold. J. Med. Chem. 54(19), 6538-6547 (2011).
95. Palomo C, Aizpurua JM, Benito A et al. Development of a new family of conformationally restricted peptides as potent nucleators of beta-turns. Design, synthesis, structure, and biological evaluation of a beta-lactam peptide analogue of melanostatin. J. Am. Chem. Soc. 125(52), 16243-16260 (2003). (Pubitemid 38028559)
96. Iwata T, Tanaka K, Tahara T et al. A conformationally fixed analog of the peptide mimic Grb2-SH2 domain: synthesis and evaluation against the A431 cancer cell. Mol. Biosyst. 9(5), 1019-1025 (2013).
97. Meijler MM, Matsushita M, Altobell LJ 3rd, Wirsching P, Janda KD. A new strategy for improved nicotine vaccines using conformationally constrained haptens. J. Am. Chem. Soc. 125(24), 7164-7165 (2003). (Pubitemid 36798951)
98. Zhao PL, Wang L, Zhu XL et al. Subnanomolar inhibitor of cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues. J. Am. Chem. Soc. 132(1), 185-194 (2010).
99. PyMOL0.99. www.pymol.org