The application of bioisosteres in drug design for novel drug discovery: focusing on acid protease inhibitors

Bibliography

• Fischer E. Einfluss der configuration auf die Wirkung der Enzyme. Ber Dt Chem Ges 1894;27:2985-93
   Google Scholar
• Friedman HL. Influence of isosteric replacements upon biological activity. NASNRS 1951;206:295-358
   Google Scholar
• Thornber CW. Isosterism and molecular modification in drug design. Chem Soc Rev 1979;8:563-80
   Web of Science ®Google Scholar
• Lipinski CA. Bioisosterism in drug design. Annu Rep Med Chem 1986;21:283-91
   Google Scholar
• Burger A. Isosterism and Bioisosterism in drug design. Prog Drug Res 1991;37:287-371
   PubMedGoogle Scholar
• Patani GA, LaVoie EJ. Bioisosterism” A rational approach in drug design. Chem Rev 1996;96:3147-76
   PubMed Web of Science ®Google Scholar
• Lima LM, Barreiro EJ. Bioisosterism: a useful strategy for molecular modification and drug design. Curr Med Chem 2005;12:23-49
   PubMed Web of Science ®Google Scholar
• Patani GA, LaVoie EJ. Bioisosterism: a rational approach in drug design. Chem ReV 1996;96:3147-76
   PubMed Web of Science ®Google Scholar
• Thornber CW. Isosterism and molecular modification in drug design. Chem Soc ReV 1979;8:563-80
   Web of Science ®Google Scholar
• Sheridan RP. The most common chemical replacements in druglike compounds. J Chem Inf Comput Sci 2002;42:103-8
   PubMedGoogle Scholar
• Wagener M, Lommerse JPM. The quest for bioisosteric replacements. J Chem Inf Model 2006;46:677-85
   PubMed Web of Science ®Google Scholar
• Meanwell NA. Synopis of some recent tactical application of bioisosteres in drug design. J Med Chem 2011;54:2529-91
   PubMed Web of Science ®Google Scholar
• Leung D, Abbenante G, Fairlie D. Protease inhibitors: current status and future prospects. J Med Chem 2000;43:305-41
   PubMed Web of Science ®Google Scholar
• Greenlee WJ. Renin inhibitors. Pharm Res 1987;4:364-74
   PubMed Web of Science ®Google Scholar
• Nguyen J.-T, Hamada Y, Kimura T, Kiso Y. Design of potent aspartic protease inhibitors to treat various diseases. Arch Pharm Chem Life Sci 2008;341:523-35
   PubMed Web of Science ®Google Scholar
• Boger J, Lohr NS, Ulm EH, Novel renin inhibitors containing the amino acid statine. Nature 1983;303:81-4
   PubMed Web of Science ®Google Scholar
• Iizuka K, Kamijo T, Akahane K, KRI-1314: Orally potent human renin inhibitors derived from angiotensinogen transition state: design, synthesis, and mode of interaction. J Med Chem 1990;10:2707-14
   Google Scholar
• Kiso Y. Design and synthesis of HIV proteaswe inhibitors containing allophenylnorstatine as a transition-state mimic. In: Takahashi K, editor. Aspartic proteases: function, biology and biomedical implications. Olenum Press; New York: 1995. p. 413-23
   Google Scholar
• Mimoto T, Kato R, Takaku H, Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine. J Med Chem 1999;42:1789-802
   PubMed Web of Science ®Google Scholar
• Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 1999;399:A23-31
   PubMed Web of Science ®Google Scholar
• Sinha S, Lieberburg I. Cellular mechanism of β-amyloid production and secretion. Proc Natl Acad Sci USA 1999;96:11049-53
   PubMed Web of Science ®Google Scholar
• Hamada Y, Kiso Y. Recent progress in the drug discovery of non-peptidic BACE1 inhibitors. Expert opin Drug Discov 2009;4:391-416
   PubMed Web of Science ®Google Scholar
• Sinha S, Ander4son JP, Barbour R, Purification and cloning of amyloid precursor protein β−secretase from human brain. Nature 1999;402:637-40
   Google Scholar
• Ghosh AK, Shin D, Downs D, Design of potent inhibitors for human brain memapsin 2 (β−secretase). J Am Chem Soc 2000;122:3522-3
   PubMed Web of Science ®Google Scholar
• Hong L, Koelsch G, Lin X, Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor. Science 2000;290:150-3
   PubMed Web of Science ®Google Scholar
• Ghosh AK, Bilcer G, Harwood C, Structure-based design: potent inhibitors of human brain memapsin 2 (β-secretase). J Med Chem 2001;44:2865-8
   PubMed Web of Science ®Google Scholar
• Tang J, Hong L, Ghosh AK. Inhibitors of memapsin 2 and use thereof. PCT Int Appl. WO 2001000665; 2001
   Google Scholar
• Ghosh AK, Devasamudram T, Hong L, Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (β-secretase). Bioorg Med Chem Lett 2005;15:15-20
   PubMed Web of Science ®Google Scholar
• Boyd SA, Fung AKL, Baker WR, Nonpeptide renin inhibitors with good intraduodenal bioavailability and efficacy in dog. J Med Chem 1994;37:2991-3007
   PubMed Web of Science ®Google Scholar
• Andersen KE, Jørgensen AS, Braestrup C. Oxadiazoles as bioisosteric transformations of carboxylic functionalities. Part I. Eur J Med Chem 1994;29:393-9
   Web of Science ®Google Scholar
• Carroll FI, Gray JL, Abraham P, 3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane Analogues of Cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters. J Med Chem 1993;36:2886-90
   PubMed Web of Science ®Google Scholar
• Street LJ, Baker R, Castro JL, Synthesis and serotonergic activity of 5-(oxadiazolyl)tryptamines: potent agonists for 5-HT1D receptors. J Med Chem 1993;36:1529-38
   PubMed Web of Science ®Google Scholar
• Dunbar PG, Durant GJ, Fang Z, Design, synthesis, and neurochemical evaluation of 5-(3-Alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem 1993;36:842-7
   PubMed Web of Science ®Google Scholar
• Adelstein GW, Yen CH, Dajani EZ, 3,3-Diphenyl-3-(2-alkyl-1,3,4-oxadiazol-5-yl)propylcycloalkylamines, A novel series of antidiarrheal agents. J Med Chem 1976;19:1221-5
   PubMed Web of Science ®Google Scholar
• Tully WR, Gardner CR, Gillespie RJ, 2-(Oxadiazolyl)- and 2-(Thiazolyl)imidazo[1,2-a]pyrimidines as agonists and inverse agonists at benzodiazepine receptors. J Med Chem 1991;34:2060-7
   PubMed Web of Science ®Google Scholar
• Orlek BS, Blaney FE, Brown F, Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor. J Med Chem 1991;34:2726-35
   PubMed Web of Science ®Google Scholar
• Thompson SK, Eppley AM, Frazee JS, Synthesis and antiviral activity of a novel class of HIV-1 protease inhibitors containing heterocyclic P1'-P2' amide bond isosteres. Bioorg Med Chem Lett 1994;4:2441-6
   Web of Science ®Google Scholar
• Kim BH, Chung YJ, Keum G, A New peptide bond surrogate: 2-isoxazoline in pseudodipeptide chemistry. Tetrahedron Lett 1992;33:6811-14
   Web of Science ®Google Scholar
• Jones CFR, Ward GJ. Amide bond isosteres: imidazolines in pseudopeptide chemistry. Tetrahedron Lett 1988;29:3853-6
   Web of Science ®Google Scholar
• Clercq ED. Toward improved anti-HIV chemotherapy: therapeutic strategies for intervention with HIV infections. J Med Chem 1995;38:2491-517
   PubMed Web of Science ®Google Scholar
• Rajapakse HA, Nantermet PG, Selnick HG. Discovery of oxadiazoyl tertialy carbinamine inhibitors of β-secretase (BACE1). J Med Chem 2006;49:7270-3
   PubMed Web of Science ®Google Scholar
• Sankaranarayanan S, Holahan MA, Colussi D, First demonstration of cerebrospinal fluid and plasma Aβ Lowering with oral administration of a β-Site amyloid precursor protein-cleaving enzyme 1. Inhibitor in nonhuman primates. J Phamacol Exp Ther 2009;328:131-40
   PubMed Web of Science ®Google Scholar
• Maurya SK, Gollapalli DR, Kirubakaran A, Triazole inhibitors of cryptosporidium parvum inosine 5'-monophosphate dehydrogenase. J Med Chem 2009;52:4623-30
   PubMed Web of Science ®Google Scholar
• Narumi T, Hayashi R, Tomita K, Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres. Org Biomol Chem 2010;8:616-21
   PubMed Web of Science ®Google Scholar
• Shuto D, Kasai S, Kimura T, KMI-008, a Novel β−secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic: design and synthesis of substrate-based octapeptides. Bioorg Med Chem Lett 2003;13:4273-6
   PubMed Web of Science ®Google Scholar
• Kimura T, Shuto D, Kasai S, KMI-358 and KMI-370, highly potent and small-sized BACE1 inhibitors containing phenylnorstatine. Bioorg Med Chem Lett 2004;14:1527-31
   PubMed Web of Science ®Google Scholar
• Kimura T, Shuto D, Hamada Y, Design and synthesis of highly active Alzheimer's β-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability. Bioorg Med Chem Lett 2005;15:211-15
   PubMed Web of Science ®Google Scholar
• Asai M, Hattori C, Iwata N, The novel β−secretase inhibitor KMI-429 reduces amyloid β prptide production in amyloid precursor protein transgenic and wild-type mice. J Neurochem 2006;96:533-40
   PubMed Web of Science ®Google Scholar
• Kimura T, Hamada Y, Stochaj M, Design and synthesis of potent β-secretase (BACE1) inhibitors with P1' carboxylic acid bioisostere. Bioorg Med Chem Lett 2006;16:2380-6
   PubMed Web of Science ®Google Scholar
• Hamada Y, Igawa N, Ikari H, β-Secretase inhibitors: Modification at the P4 position and improvement of inhibitory activity in cultured cells. Bioorg Med Chem Lett 2006;16:4354-9
   PubMed Web of Science ®Google Scholar
• Hamada Y, Abdel-Rahman H, Yamani A, BACE1 inhibitors: optimization by replacing the P1' residue with non-acidic moiety. Bioorg Med Chem Lett 2008;18:1649-53
   PubMed Web of Science ®Google Scholar
• Tagad HD, Hamada Y, Nguyen J-T, Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1' and P4 positions. Bioorg Med Chem 2010;18:3175-86
   PubMed Web of Science ®Google Scholar
• Tagad HD, Hamada Y, Nguyen J-T, Structure-guided design and synthesis of P1' position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors. Bioorg Med Chem 2011;19:5238-46
   PubMed Web of Science ®Google Scholar
• Hamada Y, Ohta H, Miyamoto N, Novel non-peptidic and small-sized BACE1 inhibitors. Bioorg Med Chem Lett 2008;18:1654-8
   Web of Science ®Google Scholar
• Hamada Y, Ohta H, Miyamoto N, Significance of interaction of BACE1-Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold. Bioorg Med Chem Lett 2009;19:2435-9
   PubMed Web of Science ®Google Scholar
• Satchell JF, Smith BJ. Calculation of aqueous dissociation constants of 1,2,4-triazole and tetrazole: a comparison of salvation models. Phys Chem Chem Phys 2002;4:4314-18
   Web of Science ®Google Scholar
• Kohara Y, Kubo K, Imamiya E, Synthesis and angiotensin II receptor antagonistic activities of benzimidazole derivatives bearing acidic heterocycles as novel tetrazole bioisosteres. J Med Chem 1996;39:5228-35
   PubMed Web of Science ®Google Scholar
• Ballatore C, Soper JH, Piscitelli F, Cyclopentane-1,3-dione: a novel isostere for the carboxylic acid functional group. application to the design of potent thromboxane (A2) receptor antagonists. J Med Chem 2011;54:6969-83
   PubMed Web of Science ®Google Scholar
• Boothe J, Wilkinson R, Kushner S, Synthesis of aureomycin degradation products. II J Am Chem Soc 1953;75:1732-3
   Web of Science ®Google Scholar
• Hiraga K. Structures of cyclopentanepolyones. Chem Pharm Bull 1965;13:1300
   PubMed Web of Science ®Google Scholar
• Katrusiak A. Structure of 1, 3-cyclopentanedione. Acta Crystallogr C 1990;46:1289-93
   Web of Science ®Google Scholar
• Katrusiak A. Structure of 2-methyl-1, 3-cyclopentanedione. Acta Crystallogr C 1989;45:1897-9
   Web of Science ®Google Scholar
• Dickinson RP, Dack KN, Long CJ, Thromboxane modulating agents. 3. 1H-Imidazol-1-ylalkyl- and 3-pyridinylalkylsubstituted 3-[2-[(arylsulfonyl)amino]ethyl]benzenepropanoic acid derivatives as dual thromboxane synthase inhibitor/thromboxane receptor antagonists. J Med Chem 1997;40:3442-52
   PubMed Web of Science ®Google Scholar
• Carini DJ, Christ DD, Duncia JV, The discovery and development of angiotensin II agonists. Pharm Biotechnol 1998;11:29-56
   PubMedGoogle Scholar
• Soll RM, Kinney WA, Primeau J, 3-Hydroxy-cyclobutene-1,2-dione: application of a novel carboxylic acid bioisostere to an in vivo active non-tetrazole angiotensin II antagonist. Bioorg Med Chem Lett 1993;3:4720-6
   Google Scholar
• Kortum SW, Benson TE, Bienkowski MJ, Potent and selective isophthalamide S2 hydroxyethylamine inhibitors of BACE1. Bioorg Med Chem Lett 2007;17:3378-83
   PubMed Web of Science ®Google Scholar
• Imai YN, Inoue Y, Nakanishi I, Cl–π interactions in protein–ligand complexes. Protein Sci 2008;17:1129-37
   PubMed Web of Science ®Google Scholar
• Stubbs MT, Reyda S, Dullweber F, pH-Dependent binding modes observed in trypsin crystals: lessons for structure-based drug design. Chem Bio Chem 2002;3:246-9
   Google Scholar
• Adler M, Kochanny MJ, Ye B, Crystal structures of two potent nonamidine inhibitors bound to factor Xa. Biochemistry 2002;41:15514-23
   PubMed Web of Science ®Google Scholar
• Choi-Sledeski YM, Kearney R, Poli G, Discovery of an orally efficacious inhibitor of coagulation factor Xa which incorporates a neutral P1 ligand. J Med Chem 2003;46:681-4
   PubMed Web of Science ®Google Scholar
• Maignan S, Guilloteau JP, Choi-Sledeski YM, Molecular structures of human factor Xa complexed with ketopiperazine inhibitors: preference for a neutral group in the S1 pocket. J Med Chem 2003;46:685-90
   PubMed Web of Science ®Google Scholar
• Nazare M, Will DW, Matter H, Probing the subpockets of factor Xa reveals two binding modes for inhibitors based on a 2-carboxyindole scaffold: a study combining structure–activity relationship and X-ray crystallography. J Med Chem 2005;48:4511-25
   PubMed Web of Science ®Google Scholar
• Roehrig S, Straub A, Pohlmann J, Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY59-7939): an oral, direct factor Xa inhibitor. J Med Chem 2005;48:5900-8
   PubMed Web of Science ®Google Scholar
• Tucker TJ, Brady SF, Lumma WC, Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position. J Med Chem 1998;41:3210-19
   PubMed Web of Science ®Google Scholar
• Hamada Y, Ishiura S, Kiso Y. BACE1 Inhibitor peptides: can an infinitely small kcat value turn the substrate of an enzyme into its inhibitor? ACS Med Chem Lett 2012;3:193-7
   PubMed Web of Science ®Google Scholar
• Hamada Y, Tagad HD, Nishimura Y, Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design. Bioorg Med Chem Lett 2012;22:1130-5
   PubMed Web of Science ®Google Scholar
• Mimoto T, Hattori N, Takaku H, Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere. Chem Pharm Bull 2000;48:1310-26
   PubMed Web of Science ®Google Scholar
• Kageyama S, Mimoto T, Murakawa Y, In vitro anti-HIV activity of transition-state mimetic HIV protease inhibitors containing allophenylnorstatine. Antimicrob Agent Chemother 1993;37:810-17
   PubMed Web of Science ®Google Scholar
• Mimoto T, Imai J, Kisanuki S, Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine. Chem Pharm Bull 1992;40:2251-3
   PubMed Web of Science ®Google Scholar
• Kiso Y, Matsumoto H, Mizumoto S, Small dipeptide-based HIV protease inhibitors containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic. Biopolymers 1999;51:59-68
   PubMed Web of Science ®Google Scholar
• Kiso Y, Matsumoto H, Yamaguchi S, Design of small peptidomimetic HIV-1 protease inhibitors and prodrug forms. Lett Pept Sci 1999;6:275-81
   Google Scholar
• Mimoto T, Imai J, Tanaka S, Rational design and synthesis of a novel class of active site-targeted HIV protease inhibitors containing a hydroxymethylcarbonyl isostere. Use of phenylnorstatine or allophenylnorstatine as a transition-state mimic. Chem Pharm Bull 1991;39:2465-7
   PubMed Web of Science ®Google Scholar
• Mimoto T, Imai J, Tanaka S, KNI-102, a novel tripeptide HIV protease inhibitor containing allophenylnorstatine as a transition-state mimic. Chem Pharm Bull 1991;39:3088-90
   PubMed Web of Science ®Google Scholar
• Kiso Y, Yamaguchi S, Matsumoto H, KNI-577, a potent small-sized HIV protease inhibitor based on the dipeptide containing the hydroxymethylcarbonyl isostere as an ideal transition-state mimic. Arch Pharm Pharm Med Chem 1998;331:87-9
   PubMed Web of Science ®Google Scholar
• Doi M, Ishida T, Katsuya Y, KNI-272, a highly selective and potent peptidic HIV protease inhibitor. Acta Crystallogr 2001;C 57:1333-5
   Web of Science ®Google Scholar
• Rajesh S, Ami E, Kimura T, An expedient synthesis of Na-protected-L-tetrahydrofuranylglycine and its application in the synthesis of novel substrate based inhibitors of HIV-1 protease. Bioorg Med Chem Lett 2002;12:3615-17
   PubMed Web of Science ®Google Scholar
• Hamada Y, Ohtake J, Sohma Y, New water-soluble prodrugs of HIV protease inhibitors based on O→N intramolecular acyl migration. Bioorg Med Chem 2002;10:4155-67
   PubMed Web of Science ®Google Scholar
• Hamada Y, Matsumoto H, Kimura T, Effect of the acyl groups on O→N acyl migration in the water-soluble prodrugs of HIV-1 protease inhibitor. Bioorg Med Chem Lett 2003;13:2727-30
   PubMed Web of Science ®Google Scholar
• Hamada Y, Matsumoto H, Yamaguchi S, Water-soluble prodrugs of dipeptide HIV protease inhibitors based on O-N intramolelcular acyl migration: design, synthesis and kinetic study. Bioorg Med Chem 2004;12:159-70
   PubMed Web of Science ®Google Scholar
• Doi M, Kimura T, Ishida T, Rigid backbone moiety of KNI-272, a highly selective HIV protease inhibitor: methanol, acetone and dimethylsulfoxide solvated forms of 3-[3-benzyl-2-hydroxy-9-(isoquinolin-5-yloxy)-6-methylsulfanylmethyl-5,8-dioxo-4,7-diazanonanoyl]-N-tert-butyl-1,3-thiazolidine-4-carboxamide. Acta Crystallogr B 2004;B60:433-7
   Google Scholar
• Vega S, Kang L-W, Velazquez-Campoy A, A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV-1 protease. Proteins Struct Funct Bioinformatics 2004;55:594-602
   PubMed Web of Science ®Google Scholar
• Adachi M, Ohhara T, Kurihara K, Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography. Proc Natl Acad Sci USA 2009;106:4641-6
   PubMed Web of Science ®Google Scholar
• Ami E, Nakahara K, Sato A, Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties. Bioorg Med Chem Lett 2007;17:4213-17
   PubMed Web of Science ®Google Scholar
• Matsumura H, Adachi M, Sugiyama S, Crystallization and preliminary neutron diffraction studies of HIV-1 protease cocrystallized with inhibitor KNI-272. Acta Crystallographica 2008;F64:1003-6
   Google Scholar
• Nakatani K, Hidaka K, Ami E, Combination of Non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficacy in mutant HIV. J Med Chem 2008;51:2992-3004
   PubMed Web of Science ®Google Scholar
• Velazquez-Campoy A, Luque I, Todd MJ, Thermodynamic dissection of the binding energetics of KNI-272, a potent HIV-1 protease inhibitor. Protein Sci 2000;9(9):1801-9
   PubMed Web of Science ®Google Scholar
• Satoh T, Li M, Nguyen J-T, Crystal structures of inhibitor complexes of human T-cell leukemia virus (HTLV-1) protease. J Mol Biol 2010;401:626-41
   PubMed Web of Science ®Google Scholar
• Zhang M, Nguyen J-T, Kumada H-O, Locking the two ends of tetrapeptidic HTLV-I protease inhibitors inside the enzyme. Bioorg Med Chem 2008;16:6880-90
   PubMed Web of Science ®Google Scholar
• Zhang M, Nguyen J-T, Kumada H-O, Synthesis and activity of tetrapeptidic HTLV-1 protease inhibitors possessing different P3-cap moieties. Bioorg Med Chem 2008;16:5795-802
   PubMed Web of Science ®Google Scholar
• Nguyen J-T, Zhang M, Kumada H-O, Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors. Bioorg Med Chem Lett 2008;18:366-70
   PubMed Web of Science ®Google Scholar
• Kimura T, Nguyen J-T, Maegawa H, Chipping at large, potent human T-cell leukemia virus type 1 protease inhibitors to uncover smaller, equipotent inhibitors. Bioorg Med Chem Lett 2007;17:3276-80
   PubMed Web of Science ®Google Scholar
• Maegawa H, Kimura T, Arii Y, Identification of peptidomimetic HTLV-1 protease inhibitors containing hydroxymethylcarbonyl (HMC) isostere as the transition state mimic. Bioorg Med Chem Lett 2004;14:5925-9
   PubMed Web of Science ®Google Scholar
• Available from: http://www.cresset-group.com/products/fieldstere/
   Google Scholar
• Available from: http://syrris.com/batch-products/bioisostere-software
   Google Scholar
• Available from: http://www.eyesopen.com/brood
   Google Scholar
• Devereux M, Popelier PLA, McLay IM. Quantum Isostere Database: a Web-Based Tool Quantum Chemical Bioisosteric Replacements for Drug Design. J Chem Inf Model 2009;49:1497-513
   PubMed Web of Science ®Google Scholar