Recent progress on the discovery of non-peptidic direct renin inhibitors for the clinical management of hypertension

Bibliography

• Amin Zaman M, Oparil S, Calhoun DA. Drugs targeting the renin–angiotensin–aldosterone system. Nat Rev Drug Discov 2002;1(8):621-36
   PubMed Web of Science ®Google Scholar
• Ma MK, Kam KK, Yan BP, et al. Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. Br J Pharmacol 2010;160(6):1273-92
   PubMed Web of Science ®Google Scholar
• Abassi Z, Winaver J, Feuerstein GZ. The biochemical pharmacology of renin inhibitors: implications for translational medicine in hypertension, diabetic nephropathy and heart failure: expectations and reality. Biochem Pharmacol 2009;78:933-40
   PubMed Web of Science ®Google Scholar
• Shafiq MM, Menon DV, Victor RG. Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug. Am J Med 2008;121:265-71
   PubMed Web of Science ®Google Scholar
• Westermann D, Schmieder R, Schultheiss HP, et al. J Mol Med 2008;86:691-5
   PubMed Web of Science ®Google Scholar
• Azizi M, Webb R, Nussberger J, et al. Renin inhibition with aliskiren: where are we now, and where are we going? J Hypertens 2006;24:243-56
   PubMed Web of Science ®Google Scholar
• Raddatz P. Recent developments in renin inhibitors: part I. Expert Opin Ther Patents 1994;4:489-504
   Google Scholar
• Raddatz P. Recent developments in renin inhibitors: part II. Expert Opin Ther Patents 1994;4:1347-59
   Google Scholar
• Maibaum J, Feldman DL. Renin inhibitors as novel treatments for cardiovascular diseases. Expert Opin Ther Patents 2003;13:589-603
   Web of Science ®Google Scholar
• Jensen CH, Herold P, Brunner HR. Aliskiren, the first renin inhibitor for clinical treatment. Nat Rev Drug Discov 2008;7(5):399-410
   PubMed Web of Science ®Google Scholar
• Maibaum J, Feldman DL. Case history on Tekturna/Rasilez (aliskiren), a highly efficacious direct oral renin inhibitor as a new therapy for hypertension. Annu Rev Drug Discov 2009;44:105-27
   Google Scholar
• Wood JM, Maibaum J. Discovery and development of aliskiren, the first-in-class direct renin inhibitor for the treatment of hypertension. In: Ghosh AK, Mannhold R, Kubinyi H, Folkers G, editors. Aspartic acid proteases as therapeutic targets methods and principles in medicinal chemistry. volume 45 Wiley-VCH, Weinheim, Germany. 2010; p. 265-96
   Google Scholar
• Vieira E, Binggeli A, Breu V, et al. Substituted piperidines - highly potent renin inhibitors due to induced fit adaptation of the active site. Bioorg Med Chem Lett 1999;9:1397-402
   PubMed Web of Science ®Google Scholar
• Güller R, Binggeli A, Breu V, et al. Piperidine-renin inhibitors compounds with improved physicochemical properties. Bioorg Med Chem Lett 1999;9:1403-8
   PubMed Web of Science ®Google Scholar
• Oefner C, Binggeli A, Breu V, et al. Renin inhibition by substituted piperidines: a novel paradigm for the inhibition of monomeric aspartic proteinases? Chem Biol 1999;6:127-31
   PubMed Web of Science ®Google Scholar
• Märki HP, Binggeli A, Bittner B, et al. Piperidine renin inhibitors: from lead to drug candidates. Farmaco 2001;56:21-7
   PubMedGoogle Scholar
• Mervaala E, Müller DN, Schmidt F, et al. Blood pressure-independent effects in rats with human renin and angiotensinogen. Hypertension 2000;35:587-94
   PubMed Web of Science ®Google Scholar
• Bittner B, Chou R, Schleimer M, et al. Preformulation approaches to improve the oral bioavailability of two novel piperidine renin inhibitors in dog. Arzneimittelforschung 2002;52:593-6
   PubMed Web of Science ®Google Scholar
• Bursavich MG, Rich DH. Designing non-peptide peptidomimetics in the 21st century: inhibitors targeting conformational ensembles. J Med Chem 2002;45:541-58
   PubMed Web of Science ®Google Scholar
• Yokokawa F, Maibaum J. Recent advances in the discovery of non-peptidic direct renin inhibitors as antihypertensives. Expert Opin Ther Patents 2008;18:581-602
   Web of Science ®Google Scholar
• Tice CM. Renin inhibitors. Annu Rev Drug Discov 2006;41:155-67
   Google Scholar
• Kasai A, Subedi R, Stier M, et al. Cardiovascular agents: renin inhibitors and factor Xa inhibitors. Heterocycles 2007;73:47-85
   Web of Science ®Google Scholar
• Webb RL, Schiering N, Sedrani R, et al. Direct renin inhibitors as a new therapy for hypertension. J Med Chem 2010;53:7490-520
   PubMed Web of Science ®Google Scholar
• Tice CM, Singh SB. Evolution of diverse classes of renin inhibitors through the years. In: Ghosh AK, Mannhold R, Kubinyi H, Folkers G, editors. Aspartic acid proteases as therapeutic targets. Methods and principles in medicinal chemistry. volume 45 Wiley-VCH; Weinheim, Germany; 2010. p. 297-324
   Google Scholar
• Tice CM, Xu Z, Yuan J, et al. Design and optimization of renin inhibitors: orally bioavailable alkyl amines. Bioorg Med Chem Lett 2009;19:3541-5
   PubMed Web of Science ®Google Scholar
• Xu Z, Cacatian S, Yuan J, et al. Optimization of orally bioavailable alkyl amine renin inhibitors. Bioorg Med Chem Lett 2010;20:694-9
   PubMed Web of Science ®Google Scholar
• Yuan J, Simpson RD, Zhao W, et al. Biphenyl/diphenyl ether renin inhibitors: filling the S1 pocket of renin via the S3 pocket. Bioorg Med Chem Lett 2011;21:4836-43
   PubMed Web of Science ®Google Scholar
• Jia L, Simpson RD, Yuan J, et al. Discovery of VTP-27999, an alkyl amine renin inhibitor with potential for clinical utility. ACS Med Chem Lett 2011;2:747-51
   PubMed Web of Science ®Google Scholar
• Ishchenko A, Liu Z, Lindblom P, et al. Structure-based design technology Contour and its application to the design of renin inhibitors. J Chem Inf Model 2012;52:2089-97
   PubMed Web of Science ®Google Scholar
• Gregg R, McGeehan G, Bryson C, et al. VTP-27999: A novel renin inhibitor with potential for superior nephroprotection. J Hypertension 2011;29(Suppl A):Abstract 6D08
   Google Scholar
• Braun L, Sood V, Hogue S, et al. High burden and unmet patient needs in chronic kidney disease. Int J Nephrol Renovasc Dis 2012;5:151-63
   PubMedGoogle Scholar
• Nakamura Y, Sugita C, Meguro M, et al. Design and optimization of novel (2S,4S,5S)-5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxy-2-isopropylhexanamides as renin inhibitors. Bioorg Med Chem Lett 2012;22:4561-6
   PubMed Web of Science ®Google Scholar
• Nakamura Y, Fujimoto T, Ogawa Y, et al. Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: discovery of DS-8108b, an orally active renin inhibitor. Bioorg Med Chem 2013; In press. Available online on 26 March 2013
   Google Scholar
• Liu J, Obando D, Liao V, et al. The many faces of the adamantyl group in drug design. Eur J Med Chem 2011;46:1949-63
   PubMed Web of Science ®Google Scholar
• Mori Y, Ogawa Y, Mochizuki A, et al. Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors. Bioorg Med Chem Lett 2012;22:7677-82
   PubMed Web of Science ®Google Scholar
• Scheiper B, Matter H, Steinhagen H, et al. Discovery and optimization of a new class of potent and non-chiral indole-3-carboxamide-based renin inhibitors. Bioorg Med Chem Lett 2010;20:6268-72
   PubMed Web of Science ®Google Scholar
• Scheiper B, Matter H, Steinhagen H, et al. Structure-based optimization of potent 4- and 6-azaindole-3-carboxamides as renin inhibitors. Bioorg Med Chem Lett 2011;21:5480-6
   PubMed Web of Science ®Google Scholar
• Matter H, Scheiper B, Steinhagen H, et al. Structure-based design and optimization of potent renin inhibitors on 5- or 7-azaindole-scaffolds. Bioorg Med Chem Lett 2011;21:5487-92
   PubMed Web of Science ®Google Scholar
• Ostermann N, Ruedisser S, Ehrhardt C, et al. A novel class of oral direct renin inhibitors: highly potent 3,5-disubstituted piperidines bearing a tricyclic P3-P1 pharmacophore. J Med Chem articles ASAP 2013;56:2196-206
   PubMed Web of Science ®Google Scholar
• Lorthiois E, Breitenstein W, Cumin F, et al. The discovery of novel potent trans-3,4-disubstituted pyrrolidine inhibitors of the human aspartic protease renin from in silico three dimensional (3D) pharmacophore searches. J Med Chem articles ASAP 2013;56:2207-17
   PubMed Web of Science ®Google Scholar
• Bezençon O, Bur D, Weller T, et al. Design and properties of potent, nonpeptidic, bioavailable renin inhibitors. J Med Chem 2009;52:3689-702
   PubMed Web of Science ®Google Scholar
• Jones-Burton C, Rubino J, Roy S, et al. Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension. J Am Soc Hypertens 2010;4:219-26
   PubMed Web of Science ®Google Scholar
• Nicolas L, Gutierrez MM, Binkert C, et al. Entry-into-humans study with a new direct renin inhibitor. Eur J Clin Pharmacol 2012;68:1257-66
   PubMed Web of Science ®Google Scholar
• Nicolas LB, Gutierrez MM, Binkert C, et al. Pharmacokinetics, pharmacodynamics, and tolerability of ACT-077825, a new direct renin inhibitor after multiple-ascending doses in healthy subjects. J Cardiovasc Pharmacol 2013;61:42-50
   PubMed Web of Science ®Google Scholar
• Remeñ Ĺ, Bezençon O, Richard-Bildstein S, et al. New classes of potent and bioavailable human renin inhibitors. Bioorg Med Chem Lett 2009;19:6762-5
   PubMed Web of Science ®Google Scholar
• Corminboeuf O, Bezençon O, Grisostomi C, et al. Design and optimization of new piperidines as renin inhibitors. Bioorg Med Chem Lett 2010;20:6286-90
   PubMed Web of Science ®Google Scholar
• Corminboeuf O, Bezençon O, Remeñ Ĺ, et al. Piperidine-based renin inhibitors: upper chain optimization. Bioorg Med Chem Lett 2010;20:6291-6
   PubMed Web of Science ®Google Scholar
• Nicolas LB, Behm MO, Denney W, et al. Pharmacokinetic interactions between ACT-178882/MK-1597, a new renin inhibitor, and atorvastatin and simvastatin in healthy male subjects. Clin Pharmacol Ther 2010;87(Suppl 1):Abstract PII-51
   Google Scholar
• Nicolas LB, Treiber A, Behm MO, et al. Sex and age effect on the pharmacokinetics of ACT-178882/MK-1597, a new renin inhibitor. Clin Pharmacol Ther 2010;87(Suppl 1):Abstract PII-52
   Google Scholar
• Thomson Reuters. MK-1597. Drug Data Rep 2010;32:1067
   Google Scholar
• Aspiotis R, Chen A, Cauchon E, et al. The discovery and synthesis of potent zwitterionic inhibitors of renin. Bioorg Med Chem Lett 2011;21:2430-6
   PubMed Web of Science ®Google Scholar
• Ekroos M, Sjögren T. Structural basis for ligand promiscuity in cytochrome P450 3A4. PNAS 2006;103:13682-7
   PubMed Web of Science ®Google Scholar
• Jamieson C, Moir EM, Rankovic Z, et al. Medicinal chemistry of hERG optimizations: highlights and hang-ups. J Med Chem 2006;49:5029-46
   PubMed Web of Science ®Google Scholar
• Chen A, Dubé D, Dubé L, et al. Addressing time-dependent CYP3A4 inhibition observed in a novel series of substituted amino propanamide renin inhibitors, a case study. Bioorg Med Chem Lett 2010;20:5074-9
   PubMed Web of Science ®Google Scholar
• Aspiotis R, Chen A, Cauchon E, et al. The discovery and synthesis of potent zwitterionic inhibitors of renin. Bioorg Med Chem Lett 2011;21:2430-6
   PubMed Web of Science ®Google Scholar
• Chen A, Campeau LC, Cauchon E, et al. Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of pyridone-substituted piperidines. Bioorg Med Chem Lett 2011;21:3970-5
   PubMed Web of Science ®Google Scholar
• Lévesque JF, Bleasby K, Chefson A, et al. Impact of passive permeability and gut efflux transport on the oral bioavailability of novel series of piperidine-based renin inhibitors in rodents. Bioorg Med Chem Lett 2011;21:5547-51
   PubMed Web of Science ®Google Scholar
• Chen A, Cauchon E, Chefson A, et al. Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of tertiary alcohol-bearing piperidines. Bioorg Med Chem Lett 2011;21:3976-81
   PubMed Web of Science ®Google Scholar
• Chen A, Aspitois R, Campeau LC, et al. Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of spirocyclic piperidines. Bioorg Med Chem Lett 2011;21:7399-404
   PubMed Web of Science ®Google Scholar
• Chen A, Bayly C, Bezençon O, et al. Design and optimization of a substituted amino propanamide series of renin inhibitors for the treatment of hypertension. Bioorg Med Chem Lett 2010;20:2204-9
   PubMed Web of Science ®Google Scholar
• Lacombe P, Aspiotis R, Bayly C, et al. Identification of a new biaryl scaffold generating potent renin inhibitors. Bioorg Med Chem Lett 2010;20:5822-6
   PubMed Web of Science ®Google Scholar
• Lacombe P, Arbour M, Aspiotis R, et al. 3,4-Diarylpiperidines as potent renin inhibitors. Bioorg Med Chem Lett 2012;22:1953-7
   PubMed Web of Science ®Google Scholar
• Fournier PA, Arbour M, Cauchon E, et al. Design and synthesis of potent, isoxazole-containing renin inhibitors. Bioorg Med Chem Lett 2012;22:2670-4
   PubMed Web of Science ®Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. Amide derivative. WO2008093737; 2008
   Google Scholar
• Speedel Experimenta AG. 2,5-Disubstituted piperidines. WO2007141318; 2007
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. Nitrogen-containing aromatic derivative. WO2008136457; 2008
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. Naphthalene derivative. WO2008153135; 2008
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. Quinolone derivative. WO2009005002; 2009
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. Bicyclic pyrrole derivative. WO2009014217; 2009
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. 4-Arylphenyl derivative. WO2009072649; 2009
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. Bicyclic heterocyclic derivative. WO2009078481; 2009
   Google Scholar
• Dainippon Sumitomo Pharma Co., Ltd. N-Substituted-cyclic amino derivative. WO2010150840; 2010
   Google Scholar
• Mitsubishi Tanabe Pharma Co., Ltd. Morpholine derivative. WO2008153182
   Google Scholar
• Mitsubishi Tanabe Pharma Co., Ltd. Nitrogen-containing saturated heterocyclic compound. WO2012124775; 2012
   Google Scholar
• Takeda Pharm Co., Ltd. Amide compound and use of the same. WO2009051112; 2009
   Google Scholar
• Takeda Pharm Co., Ltd. Heterocyclic compound and use thereof. WO2009154300; 2009
   Google Scholar
• Takeda Pharm Co., Ltd. Crystal of amide compound. WO2011158880; 2011
   Google Scholar
• Plexxikon, Inc. Compounds and methods for inhibition of renin, and indications therefore. WO2010129467; 2010
   Google Scholar
• Cadila Healthcare Ltd. Compounds as inhibitors of renin. WO2012085935; 2012
   Google Scholar
• Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217-23
   PubMed Web of Science ®Google Scholar
• Ong KL, Cheung BMY, Man YB, et al. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999-2004. Hypertension 2007;49:69-75
   PubMed Web of Science ®Google Scholar
• Edwards MP, Price DA. Role of physicochemical properties and ligand efficiency in addressing drug safety risks. Annu Rep Med Chem 2010;45;381-91
   Web of Science ®Google Scholar
• Hann MM. Molecular obesity, potency and other addictions in drug discovery. Med Chem Commun 2011;2:349-55
   Web of Science ®Google Scholar
• Tarcsay A, Keserű GM. Contributions of molecular properties to drug promiscuity. J Med Chem ASAP 2013;56:1789-95
   PubMed Web of Science ®Google Scholar
• Hughes JD, Blagg J, Price DA, et al. Physicochemical properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett 2008;18:4872-5
   PubMed Web of Science ®Google Scholar
• Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 2007;6:881-90
   PubMed Web of Science ®Google Scholar
• Parving HH, Brenner BM, McMurray JJV, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012;367:2204-13
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Böhm M, Greene SJ, et al. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure. J Am Med Assoc 2013;309:1125-35
   PubMed Web of Science ®Google Scholar
• Therapeutic Area Partnerships, Top Projects to Watch. Available from: http://www.tapartnerships.com/TA/TA12-top10.html [Last accessed 13 February 2013]
   Google Scholar
• Wang RF, Podos SM, Serle JB, et al. Effect of SPP635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes. Exp Eye Res 2012;94:146-9
   PubMed Web of Science ®Google Scholar
• Leo AJ, Hoekman D. Calculating log P (oct) with no missing fragments; The problem of estimating new interaction parameters. Perspect Drug Discov Des 2000;18:19-38
   Google Scholar
• Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 2000;43:3714-17
   PubMed Web of Science ®Google Scholar