Skip to main content
SpringerLink
Log in

Renin Inhibitors

  • Chapter
Pharmacology of Antihypertensive Therapeutics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 93 / 1))

  • 164 Accesses

Abstract

The very high utility of inhibitors of angiotensin converting enzyme (ACE) for the amelioration of all forms of hypertension has made them drugs of choice for basic treatment. Many researchers have now focussed their interest on renin inhibitors with the hope that interference with the renin-angiotensin system at the level of this highly specific enzyme will give rise to antihypertensive agents with a low incidence of side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akahane K, Nakagawa S, Umeyama H (1985a) Three-dimensional structure of human renin and renin inhibitors. New approach to drug design. J Pharmacobiodyn 8: S174

    Google Scholar 

  • Akahane K, Umeyama H, Nakagawa S, Moriguchi I, Hirose S, Iizuka K, Murakami K (1985b) Three-dimensional structure of human renin. Hypertension 7: 3–12

    PubMed  CAS  Google Scholar 

  • Andreeva NS, Zdanov AS, Gustchina AE, Fedorov AA (1984) Structure of ethanolinhibited porcine pepsin at 2-Ă‚ resolution and binding of the methyl ester of phenylalanyl-diiodotyrosin to the enzyme. J Biol Chem 259: 11353–11365

    PubMed  CAS  Google Scholar 

  • Antonaccio MJ, Cushman DW (1981) Drugs inhibiting the renin-angiotensin system. Fed Proc 40: 2275–2284

    PubMed  CAS  Google Scholar 

  • Antonaccio MJ, Wright JJ (1987) Enzyme inhibitors of the renin-angiotensin system. Prog Drug Res 31: 161–191

    PubMed  CAS  Google Scholar 

  • Arrowsmith R, Carter K, Dann JG, Davies DE, Harris J, Morton JA, Lister P, et al. (1986) Novel renin inhibitors: synthesis of aminostatine and comparison with statine-containing analogues. J Chem Commun:755–757

    Google Scholar 

  • Blaine EH, Schorn TW, Boger J (1984) Statine-containing renin inhibitor. Dissociation of blood pressure lowering and renin inhibition in sodium-deficient dogs. Hypertension [Suppl 1] 6: 111–118

    Google Scholar 

  • Blaine EH, Nelson BJ, Seymour AA, Schorn TW, Sweet CS, Slater EE, Nussberger J, Boger J (1985) Comparison of renin and converting enzyme inhibition in sodiumdeficient dogs. Hypertension [Suppl 1] 7: 166–171

    Google Scholar 

  • Blundell T, Sibanda BL, Pearl L (1983) Three-dimensional structure, specificity and catalytic mechanism of renin. Nature 304: 273–275

    Article  PubMed  CAS  Google Scholar 

  • Blundell TL, Cooper J, Foundling SI, Jones DM, Atrash B, Szelke M (1987) On the rational design of renin inhibitors: X-ray studies of aspartic proteinases complexed with transition-state analogues. Biochemistry 26: 5585–5590

    Article  PubMed  CAS  Google Scholar 

  • Bock MG, DiPardo RM, Evans BE, Rittle KE, Boger JS, Freidinger RM, Veber DF (1985) Dipeptide analogues. Synthesis of a potent renin inhibitor. J Chem Soc Chem Commun 109–110

    Google Scholar 

  • Bock MG, DiPardo RM, Evans BF, Rittle KE, Boger J, Poe M, LaMont BI, et al. (1987) Renin inhibitors. Statine-containing tetrapeptides with varied hydrophobic carboxy termini. J Med Chem 30: 1853–1857

    Article  PubMed  CAS  Google Scholar 

  • Boger J (1985a) Renin inhibitors. Design of angiotensin transition-state analogs containing statine. In: Kostka V (ed) Aspartic proteinases and their inhibitors. Springer, Berlin Heidelberg New York, pp 401–420

    Google Scholar 

  • Boger J (1985b) Renin inhibition. Annu Rep Med Chem 20: 257–266

    Article  CAS  Google Scholar 

  • Boger J (1986) Renin inhibitors: Drug design and molecular modelling. In: Lambert BW (ed) Third SCI-RSC medicinal chemistry symposium, Cambridge, Sept 15–18. Royal Society of chemistry, London, pp 271–292

    Google Scholar 

  • Boger J (1987) Clinical goal in sight for small molecule renin inhibitors. Trends Pharm Sci 8: 370–372

    Article  CAS  Google Scholar 

  • Boger J, Lohr N, Ulm EH, Poe M, Blaine EM, Fanelli GM, Lin T-Y, et al. (1983) Novel renin inhibitors containing the amino acid statine. Nature 303: 81–84

    Article  PubMed  CAS  Google Scholar 

  • Boger J, Payne LS, Perlow DS, Lohr NS, Poe M, Blaine EH, Ulm EH, et al. (1985a) Renin inhibitors. Synthesis of subnanomolar, competitive, transition-state analogue inhibitors containing a novel analogue of statine. J Med Chem 28: 1779–1790

    Article  PubMed  CAS  Google Scholar 

  • Boger J, Bennett CD, Payne LS, Ulm EH, Blaine EH, Homnick CF, Schorn TW, et al. (1985b) Design of proteolytically-stable, peptidal renin inhibitors and determination of their fate in vivo. Regul Pept 11: 8–13

    Article  Google Scholar 

  • Bolis G, Fung AKL, Greer J, Kleinert HD, Marcotte PA, Perun TJ, Plattner JJ, Stein HH (1987) Renin inhibitors. Dipeptide analogues of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond. J Med Chem 30: 1729–1737

    Google Scholar 

  • Bott R, Subramanian E, Davies DR (1982) Three-dimensional structure of the complex of the Rhizopus chinensis carboxyl proteinase and pepstatin at 2.5 A resolution. Biochemistry 21: 6956–6962

    Article  PubMed  CAS  Google Scholar 

  • Breipohl G, Geiger R, Henke S, Kleemann H-W, Knolle J, Ruppert D, Scholkens BA, et al. (1987) Studies on renin inhibitors. Top Med Chem 4: 101–127

    Google Scholar 

  • Brunner HR, Nussberger J, Waeber B (1988) ACE inhibition and renin inhibition. Symposium: Renin inhibitors-present and future, Osaka, May 28

    Google Scholar 

  • BĂĽhlmayer P, Caselli A, Fuhrer W, Goschke R, Rasetti V, RĂĽeger H, Stanton JL, et al. (1988) Synthesis and biological activity of some transition-state inhibitors of human renin. J Med Chem 31: 1839–1846

    Article  PubMed  Google Scholar 

  • Burton J, Cody RJ Jr, Herd A, Haber E (1980) Specific inhibition of renin by an angiotensinogen analog: studies in sodium depletion and renin-dependent hypertension. Proc Natl Acad Sci USA 77: 5476–5479

    Article  PubMed  CAS  Google Scholar 

  • Burton J, Slater EE, Corvol P, MĂ©nard J, Hartley LH (1982a) Use of anti-human renin antisera to inhibit renin in primates. Clin Exp Hypertens [A], 4: 322–324

    Google Scholar 

  • Burton J, Cody R Jr, Poulsen K, Hartley LH, Slater EE, Haber E (1982b) The design of specific inhibitors of renin which are active in vivo. In: Yashida Y, Hagihara Y, Ebashi S (eds) Advances in pharmacology and therapeutics, vol 2. Pergamon, London, pp 231–241

    Google Scholar 

  • Burton J, Hyun H, TenBrink RE (1983) The design of substrate analog renin inhibitors. In: Hruby VB, Rich DH (eds) Peptides: structure and function. Pierce, Rockford, IL, pp 559–567

    Google Scholar 

  • Campbell DJ (1985) The site of angiotensin production. J Hypertens 3: 199–207

    Article  PubMed  CAS  Google Scholar 

  • Campbell DJ (1987) Circulating and tissue angiotensin systems. J Clin Invest 79: 1–6

    Article  PubMed  CAS  Google Scholar 

  • Carlson W, Handschumacher M, Haber E (1984) Studies of the three-dimensional structure of human renin and its inhibitors. J Hypertens [Suppl 3] 2: S281–S284

    CAS  Google Scholar 

  • Carlson W, Karplus M, Haber E (1985) Construction of a model for the threedimensional structure of human renal renin. Hypertension 7: 199–207

    Google Scholar 

  • Carlson WD, Handschumacher M, Summers M, et al. (1987) Models for the threedimensional structure of renin inhibitors bound in the active site of human renin: an analysis of the properties that produce tight binding. J Cardiovasc Pharmacol [Suppl 7] 10: S91–S93

    Article  CAS  Google Scholar 

  • Cody RJ, Burton J, Evin G, Poulsen K, Herd JA, Haber E (1980) A substrate analog inhibitor of renin that is effective in vivo. Biochem Biophys Res Commun 97: 230–235

    Article  PubMed  CAS  Google Scholar 

  • Corvol P, Menard J (1986) From the renin gene to renin inhibitors. Ann Endocrinol (Paris) 47: 156–166

    CAS  Google Scholar 

  • Corvol P, Michel JB, Evin G, et al. (1983) Inhibition of the renin system at the level of the renin-substrate reaction. Ann Endocrinol (Paris) 44: 339–342

    CAS  Google Scholar 

  • Cumin F, Evin G, Fehrentz J-A, Seyer R, Castro B, M6nard J, Corvol P (1985) Inhibition of human renin by synthetic peptides derived from its prosegment. J Biol Chem 260: 9154–9157

    PubMed  CAS  Google Scholar 

  • Cumin F, Nisato D, Gagnol J-P, Corvol P (1987a) A potent radiolabeled human renin inhibitor, 3H-SR42128: Enzymatic, kinetic, and binding studies to renin and other aspartic proteases. Biochemistry 26: 7615–7621

    Google Scholar 

  • Cumin F, Nisato D, Gagnol J-P, Corvol P (1987b) Binding of a tritiated pepstatin analog to human renin. J Cardiovasc Pharmacol [Suppl 7] 10: S102–S104

    Article  CAS  Google Scholar 

  • Dann JG, Stammer DK, Harris CJ, Arrowsmith RJ, Davies DE, Hardy GW, Morton JA (1986) Human renin: A new class of inhibitors. Biochem Biophys Res Commun 134: 71–77

    Google Scholar 

  • De Clavtere M, Fourment P, Richaud JP, Vukovic J, Gagnol J-P, Mague G (1985a) Haemodynamic effects of the renin inhibitor SR 42128 in conscious baboons. J Hypertens [Suppl 3] 3: S271–S273

    Google Scholar 

  • De Clavifcre M, Cazaubon C, Lacoure C, Nisato D, Gagnol JP, Evin G, Corvol P (1985b) In vitro and in vivo inhibition of human and primate renin by a new potent renin inhibitor: SR 42128. J Cardiovasc Pharmacol [Suppl 4] 7: S58–S61

    Article  Google Scholar 

  • DeForrest JM, Waldron TL, Oehl RS, Scalese RJ, Free CA, Weller HN, Ryono DE (1988) Pharmacology of novel imidazole alcohol inhibitors of primate renin. Symposium: Renin Inhibitors—Present and Future, May 28, Osaka

    Google Scholar 

  • Dellaria JF, Maki RG, Bopp BA, Cohen J, Kleinert HD, Luly JR, Mevits I, et al. (1987) Optimization and in vivo evaluation of a series of small, potent, and specific renin inhibitors containing a novel Leu-Val replacement. J Med Chem 30: 2137–2144

    Article  PubMed  CAS  Google Scholar 

  • Diaz, J (1987) Pepstatin analogs:promising antihypertensive compounds. Drugs Fut 12: 1133–1144

    Google Scholar 

  • Dzau VJ (1985) In vivo inhibition of renin by antirenin antibodies: Potential experimental and clinical applications. J Cardiovasc Pharmacol [Suppl 4] 7: S53–S57

    Article  Google Scholar 

  • Dzau VJ (1986) Significance of the vascular renin-angiotensin system. Hypertension 8: 553–559

    PubMed  CAS  Google Scholar 

  • Dzau VJ, Kopelman RI, Barger AC, Haber E (1980) Renin-specific antibody for study of cardiovascular homeostasis. Science 207: 1091–1093

    Article  PubMed  CAS  Google Scholar 

  • Dzau VJ, Brenner A, Wolfsohn S, Haber E (1982) Characterization of antibodies to canine renal renin. Studies of interspecies homology of renin using antibodies as probe. Hypertension 4: 341–343

    Google Scholar 

  • Dzau VJ, Devine D, Mudgett-Hunter M, Kopelman RI, Barger AC, Haber E (1983) Antibodies as specific renin inhibitors: Studies with polyclonal and monoclonal antibodies and Fab fragments. Clin Exp Hypertens [A] 5: 1207–1220

    Google Scholar 

  • Dzau VJ, Kopelman RI, Barger AC, Haber E (1984) A comparison of renin specific IgG and Fab in studies of blood pressure regulation. Am J Physiol 246: H404–H409

    PubMed  CAS  Google Scholar 

  • Eid M, Evin G, Castro B, MĂ©nard J, Corvol P (1981) New renin inhibitors homologous with pepstatin. Biochem J 197: 465–471

    PubMed  CAS  Google Scholar 

  • Epps DE, Mao B, Staples DJ, Sawyer TK (1988) Structure-conformation relationships of synthetic peptide inhibitors of human renin studied by resonance energy transfer and molecular modeling. Int J Pept Protein Res 31: 22–34

    Article  PubMed  CAS  Google Scholar 

  • Evans BE, Rittle KE, Bock MG, Bennett CD, DiPardo RM, Boger J, Poe M, et al. (1985) A uniquely potent renin inhibitor and its unanticipated plasma binding component. J Med Chem 28: 1755–1756

    Article  PubMed  CAS  Google Scholar 

  • Fearon K, Spaltenstein A, Hopkins PB, Gelb MH (1987) Fluoroketones containing peptides as inhibitors of human renin. J Med Chem 30: 1617–1622

    Article  PubMed  CAS  Google Scholar 

  • Fehrentz JA, Heitz A, Castro B (1986) Synthesis of aldehydic peptides inhibiting renin. Int J Pept Protein Res 26 (3): 236–241

    Article  Google Scholar 

  • Fix JA, Engle K, Dorter PA, Leppert PS, Selk SJ, Gardner CR, Alexander J (1986) Acylcarnitins: drug absorbtion-enhancing agents in the gastrointestinal tract. Am J Physiol 251. G332–G340

    PubMed  CAS  Google Scholar 

  • Foundling SI, Cooper J, Watson FE, Cleasby A, Pearl LH, Sibanda BL, Hemmings AM, et al. (1987a) Crystallographic studies of reduced bond inhibitors complexed with an aspartic proteinase. J Cardiovasc Pharmacol [Suppl 7] 10: S59–S68

    Article  CAS  Google Scholar 

  • Foundling SI, Cooper J, Watson FE, Cleasby A, Peral LH, Sibanda BL, Hemmings A, et al. (1987b) High resolution X-ray analyses of renin inhibitor-aspartic proteinase complexes. Nature 327: 349–352

    Article  PubMed  CAS  Google Scholar 

  • Free CA, Ryono DE, Samaniego SG, Neubeck R, Petrillo EW Jr (1985) Potent and selective renin inhibitors based upon substrate analogs containing an aminoalcohol function. Fed Proc 44 (5964): 1431

    Google Scholar 

  • Galen FX, Devaux C, Atlas S, Guyenne T, MĂ©nard J, Corvol P, Simon D, et al. (1984) New monoclonal antibodies directed against human renin. J Clin Invest 74: 732–735

    Article  Google Scholar 

  • Ganten D, Unger T, Lang RE (1984) Pharmacological interferences with the reninangiotensin system. Arzneimittelforschung 34 (10B): 1391–1398

    PubMed  CAS  Google Scholar 

  • Gardes J, Evin G, Castro B, Corvol P, MĂ©nard J (1980) Synthesis and renin inhibitory properties of a new soluble pepstatin derivative. J Cardiovasc Pharmacol 2: 687–698

    Article  PubMed  CAS  Google Scholar 

  • Greenlee WJ (1988) Renin inhibitors. Pharm Res 4: 364–373

    Article  Google Scholar 

  • GuĂ©gan R, Diaz J, Cazamba C, Beaumont M, Carlet C, ClĂ©ment J, Demorne H, et al. (1986) Pepstatin analogues as novel renin inhibitors. J Med Chem 29: 1152–1159

    Article  PubMed  Google Scholar 

  • Haber E, Burtonz (1979) Inhibitors of renin and their utility in physiological studies. Fed Proc 338: 2768–2773

    Google Scholar 

  • Haber E (1980) The fifth Volhard lecture. Specific inhibitors of renin. Clin Sci 59: 7s–19s

    PubMed  CAS  Google Scholar 

  • Haber E (1983a) Peptide inhibitors of renin in cardiovascular studies. Fed Proc 42: 3155–3161

    PubMed  CAS  Google Scholar 

  • Haber E (1983b) Inhibitors of renin: Present and future. Clin Exp Hypertens 5: 1193–1205

    Article  CAS  Google Scholar 

  • Haber E (1984a) Renin inhibitors. N Engl J Med 311: 1631–1633

    Article  PubMed  CAS  Google Scholar 

  • Haber E (1984b) Potential tools for determing the role of renin in human essential hypertension. J Hypertens [Suppl 1] 2: 95–103

    CAS  Google Scholar 

  • Haber E (1984c) The first Sir George Pickering memorial lecture. Which inhibitors will give us true insight into what renin really does? J Hypertens 2: 223–230

    Article  PubMed  CAS  Google Scholar 

  • Haber E (1985a) Defining the physiologic and pathophysiologic roles of renin: the role of specific inhibitors. Am J Kidney Dis 5: A14–A22

    PubMed  CAS  Google Scholar 

  • Haber E (1985b) Will renin inhibitors influence decision-making in antihypertensive therapy? J Hypertens [Suppl 2] 3: S71–S80

    CAS  Google Scholar 

  • Haber E (1986) Renin inhibitors. Hypertension 8: 1093–1095

    PubMed  CAS  Google Scholar 

  • Haber E, Zusman R, Burton J, Dzau VJ, Barger AC (1983) Is renin a factor in the etiology of essential hypertension? Hypertension 5: V8–V15

    PubMed  CAS  Google Scholar 

  • Haber E, Hui KY, Carlson WD, Bernatowicz MS (1987) Renin inhibitors: a search for principles of design. J Cardiovasc Pharmacol [Suppl 7] 10: S54–S58

    Article  CAS  Google Scholar 

  • Hallett A, Jones DM, Atrash B, Szelke M, Leckie BJ, Beattie S, Dunn BM, et al. (1985) Inhibition of aspartic proteinases by transition state substrate analogs. In: Kostka V (ed) Aspartic proteinases and their inhibitors. Springer, Berlin Heidelberg New York, pp 467–478

    Google Scholar 

  • Hanson GJ, Baran JS, Lindberg T, Walsh GM, Papaioannou SE, Babler M, Bittner SE, et al. (1985) Dipeptide glycols: A new class of renin inhibitors. Biochem Biophys Res Commun 132: 155–161

    Google Scholar 

  • Hanson GJ, Baran JS, Lowrie HS, Sarussi SJ, Yang PC, Babler M, Bittner SE, et al. (1987) Enhanced potency dipeptide glycol renin inhibitors: studies in vitro and in the conscious rhesus. Biochem Biophys Res Commun 146: 959–963

    Article  PubMed  CAS  Google Scholar 

  • Hiwada K, Kokubu T, Murakami E, Muneta S, Morisawa Y, Yabe Y, Koike H, Iijima Y (1988) A highly potent and long-acting oral inhibitor of human renin. Hypertension 11: 708–712

    PubMed  CAS  Google Scholar 

  • Hofbauer KG, Wood JM (1984) Inhibition of renin: recent developments. Contrib Nephrol 43: 144–152

    PubMed  CAS  Google Scholar 

  • Hofbauer KG, Wood JM (1985) Inhibition of renin, recent immunological and pharmacological advances. Trends Pharm Sci 6: 173–177

    Article  CAS  Google Scholar 

  • Hofbauer KG, Fuhrer W, Heusser C, Wood JM (1985) Comparison of different drug interference with the renin-angiotensin system. J Cardiovasc Pharmacol [Suppl 4] 7: S62–S68

    Article  CAS  Google Scholar 

  • Hui KY, Carlson WD, Bernatowicz MS, Haber E (1987) Analysis of structure-activity relationships in renin substrate analogue inhibitory peptides. J Med Chem 30: 1287–1298

    Article  PubMed  CAS  Google Scholar 

  • Iizuka K, Kamiya T, Kubota T, Akahane K, Umeyama H, Kiso Y (1988a) New human renin inhibitors containing an unnatural amino acid, norstatine. J Med Chem 31: 701–704

    Article  PubMed  CAS  Google Scholar 

  • Iizuka K, Kamijo T, Kubota T, Akahane K, Harada H, Shimaoka I, Umeyama H, Kiso Y (1988b) New potent renin inhibitors. In: Shiba T, Sakakibara S (eds) Peptide chemistry 1987. Protein Research Foundation, Osaka, pp 649–652

    Google Scholar 

  • James MNG, Sielecki AR (1983) Stereochemical analysis of peptide bond hydrolysis catalyzed by the aspartic proteinase penicillopepsin. Biochemistry 24: 3701–3713

    Article  Google Scholar 

  • James MNG, Sielecki AN, Fujinaga M, Muir AK, Murphy MEP, Carilli CT, Shine J (1988) The molecular structure of recombinant human renin. 18th Linderstr0m-Lang Conference on Aspartic Proteinases, July 4–8, Elsinore

    Google Scholar 

  • Johnson RL (1984) Inhibition of renin by substrate analogue inhibitors containing the oleĂĽnic amino acid 5(S)-amino-7-methyl-3(E)-octenoic Acid. J Med Chem 27: 1351–1354

    Article  PubMed  CAS  Google Scholar 

  • Kati WM, Pals DT, Thaisrivongs S (1987) Kinetics of the inhibition of human renin by an inhibitor containing a hydroxyethylene dipeptide isostere. Biochemistry 16: 7621–7626

    Article  Google Scholar 

  • Kay J (1985) Structure and activity of aspartic proteinases. Aspartic proteinases and their inhibitors. Biochem Soc Trans 13: 1027–1029

    PubMed  CAS  Google Scholar 

  • Kempf DJ de Lara E, Stein RH, Cohen J, Plattner JJ (1987) Renin inhibitors based on novel dipeptide analogues. Incorporation of the dehydrohydroxyethylene isostere at the scissile bond. J Med Chem 30: 1978–1983

    Google Scholar 

  • Kleinert HD, Luly JR, Marcotte PA, Perun TJ, Plattner JJ, Stein H (1988a) Renin inhibitors: Improvements in the stability and biological activity of small peptides containing novel Leu-Val replacements. FEBS Lett 230: 38–42

    Google Scholar 

  • Kleinert HD, Martin D, Chekal MA, Kadam J, Luly JR, Plattner JJ, Perun TJ, Luther RR (1988b) Effects of the renin inhibitor A-64662 in monkeys and rats with varying baseline plasma renin activity. Hypertension 11: 613–619

    PubMed  CAS  Google Scholar 

  • Kokubu T, Hiwada K (1987) Human renin inhibitors. Drugs Today 23: 101–108

    CAS  Google Scholar 

  • Kokubu T, Hiwada K, Ito T, Ueda E, Yamamura Y, Mitoguchi T, Shigezane K (1973) Peptide inhibitors of renin-angiotensin reaction system. Biochem Pharmacol 22: 3217–3223

    Article  PubMed  CAS  Google Scholar 

  • Kokubu T, Hiwada K, Sato Y, Iwata T, Imamura Y, Matsueda R, Yabe Y, et al. (1984) Highly potent and specific inhibitors of human renin. Biochem Biophys Res Commun 118: 929–933

    Article  PubMed  CAS  Google Scholar 

  • Kokubu T, Hiwada K, Murakami E, Imamura Y, Matsueda R, Yabe Y, Koike H, Iijima Y (1985) Highly potent and specific inhibitors of human renin. Hypertension [Suppl 1] 7: 8–11

    CAS  Google Scholar 

  • Kokubu T, Hiwada K, Nague A, Murakami E, Morisawa Y, Yabe Y, Koike H, Iijima Y (1986) Statine-containing dipeptide and tripeptide inhibitors of human renin. Hypertension [Suppl 2] 8: 111–115

    Google Scholar 

  • Kokubu T, Hiwada K, Murakami E, et al. (1987) In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES-1005). J Cardiovasc Pharmacol [Suppl 7] 10: S88–R90

    Article  CAS  Google Scholar 

  • Kokubu T, Hiwada K, Murakami E, Muneta S, Morisawa Y, Yabe Y, Koike H, Iijima Y (1988) A highly potent and long-acting inhibitor of human renin-derivative of thiazolylalanine cyclostatine. Clin Exp Hypertens [A] 10: 512

    Google Scholar 

  • Leckie BJ, Szelke M, Hallett A, Hughes M, Lever AF, Mclntyre G, Merthen JJ, Tree M (1983) Peptide inhibitors of renin. Clin Exp Hypertens [A] 5: 1221–1236

    Article  CAS  Google Scholar 

  • Leckie BJ, Szelke M, Atrash B, Beattie SR, Hallett A, Jones DM, Mclntyre GD, et al. (1985) Human renin inhibitors. Biochem Soc Trans 13: 1029–1032

    PubMed  CAS  Google Scholar 

  • Lee VHL (1986) Enzymic barriers to peptide and protein absorption and the use of penetration enhancers to modify absorption. NATO ASI Ser [A] 125: 87–104

    CAS  Google Scholar 

  • Liepina I, Nikiforovich GV, Paira ACM (1984) Conformational aspects of angiotensinogen analogues with renin inhibitory activity. Biochem Biophys Res Commun 122: 700–705

    Article  PubMed  CAS  Google Scholar 

  • Luly JR, Plattner JJ, Stein H, Yi N, Soderquist J, Marcotte PA, Kleinert HD, Perun TJ (1987) Modified peptides which display potent and specific inhibition of human renin. Biochem Biophys Res Commun 143: 44–51

    Article  PubMed  CAS  Google Scholar 

  • Luly JR, Bolis G, Ba Maung N, Soderquist J, Dellaria JF, Stein H, Cohen J, et al. (1988) New inhibitors of human renin that contain novel Leu-Val replacements. Examination of the PI site. J Med Chem 31: 532–539

    Article  PubMed  CAS  Google Scholar 

  • Marciniszyn J, Hartsuck JA, Tang J (1976) Mode of inhibition of acid proteases by pepstatin. J Biol Chem 251: 7088–7094

    PubMed  CAS  Google Scholar 

  • Michel J-B, Wood J, Hofbauer K, Corvol P, MĂ©nard J (1984) Blood pressure effects of renin inhibition by human renin antiserum in normotensive marmosets. Am J Physiol 246: F309–F316

    PubMed  CAS  Google Scholar 

  • Morris BJ (1988) Renin gene and protein structure; sites for renin blockade. Symposium: Renin Inhibitors-Present and Future, May 28, Osaka Neisius D, Wood JM (1987) Antihypertensive effect of a renin inhibitor in marmosets with a segmental renal infarction. J Hypertens 5: 721–725

    Google Scholar 

  • Nisato D, Lacacer C, Roccon A, Gayvaud R, Cazaubon C, Carlet C, Plouzauc C, et al. (1987a) Discovery and pharmacological characterization of highly potent, picomolarrange, renin inhibitors. J Hypertens [Suppl 5] 5: S23–S25

    CAS  Google Scholar 

  • Nisato D, Wagnon J, Callet G, Mettefeu D, Assens J-L, Plouzauc C, Tonnere B, et al. (1987b) Renin inhibitors. Free-Wilson and correlation analysis of the inhibitory potency of a series of pepstatin analogues on plasma renin. J Med Chem 30: 2287–2291

    Google Scholar 

  • Oldham AA, Arnstein MJA, Major JS, Crough DP (1984) In vivo comparison of the renin inhibitor H 77 with the angiotensin-converting enzyme inhibitor captopril. J Cardiovasc Pharmacol 6: 672–677

    Article  PubMed  CAS  Google Scholar 

  • Omura S, Imamura N, Kawakita K, Yamazaki Y, Masuma R, Takahashi Y, Tamaha H, et al. (1986) Ahpatinins, new acid protease inhibitors containing 4-amino-3-hydroxy-5-phenylpentanoic acid. J Antibiot (Tokyo) 39: 1079–1085

    CAS  Google Scholar 

  • Ondetti MB, Cushman DW (1982) Enzymes of the renin-angiotensin system and their inhibitors. Annu Rev Biochem 51: 283–308

    Article  PubMed  CAS  Google Scholar 

  • Pals DT, de Graaf GL, Kati WM, Lawson JA (1985) Cardiovascular effects of a renin inhibitor in relation to posture in nonhuman primates. Clin Exp Hypertens [A] 7: 105–121

    CAS  Google Scholar 

  • Pals DT, Thaisrivongs S, Lawson JA, Kati WM, Turner SR, de Graaf GL, Harris DW, Johnson GA (1986) An orally active inhibitor of renin. Hypertension 8: 1105–1112

    CAS  Google Scholar 

  • Papaioannou S, Hanson D Jr, Babler M, Yang P-C, Bittner S, Miller A, Clare M (1985a) New class of inhibitors specific for human renin. Clin Exp Hypertens [A] 7: 1243–1257

    Article  CAS  Google Scholar 

  • Papaioannou S, Hanson D Jr, Babler M, Yang P-C, Bittner S, Clare M (1985b) New inhibitors specific for human renin. Fed Proc 44 (6487): 1520

    Google Scholar 

  • Pearl L, Blundell T (1984) The active site of aspartic proteinases. FEBS Lett 174: 96–101

    Article  PubMed  CAS  Google Scholar 

  • Plattner JJ, Creer J, Flung AKL, Stein H, Kleinert MD, Skan HL, Smital JR, Perun TJ (1986) Peptide analogues of angiotensinogen. Effect of peptide chain length on renin inhibition. Biochem Biophys Res Commun 139: 982–990

    Google Scholar 

  • Poulsen K, Burton J, Haber E (1973) Competitive inhibitors of renin. Biochemistry 12: 3877–3882

    Article  PubMed  CAS  Google Scholar 

  • Rich DH (1986) Inhibitors of aspartic proteinases. In: Barrett AJ, Salvesen G (eds) Proteinase inhibitors. Elsevier, Amsterdam, pp 129–217

    Google Scholar 

  • Rosenberg S, Plattner JJ, Wood KJ, Skin HK, Marcotte PM, Cohen J, Perun TJ (1987) Novel renin inhibitors containing analogues of statine retro-inverted at the Ctermini: specificity at the P2 histidine site. J Med Chem 30: 1224–1228

    Article  PubMed  CAS  Google Scholar 

  • Roy P, Delepierre M, Wagnon J, Nisato D, Roques BP (1987) Conformational analysis of pepstatin and related renin inhibitors by 400 MHz *H N.M.R. spectroscopy. Int J Pept Protein Res 30: 44–53

    Article  PubMed  CAS  Google Scholar 

  • Samani NJ, Swales JD, Brammar WJ (1988) Expression of the renin gene in extrarenal tissues of the rat. Biochem J 253: 907–910

    PubMed  CAS  Google Scholar 

  • Sawyer TK, Pals DT, Mao B, Maggiora LL, Staples DJ,, de Vaux AE, Schostarez H et al. (1988a) Structure-conformation-activity relationships of renin inhibitory peptides having P1-P1XAA(CH2NH)YAA substitutions: molecular modeling and crystallography studies. Tetrahedron 44: 661–673

    Article  CAS  Google Scholar 

  • Sawyer TK, Pals DT, Mao B, Staples DJ, deVaux AE, Maggiora LL, Affholter JA, et al. (1988b) Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal N(In)-For-Trp (Ftr): angiotensinogen congeners modified by Pl-P1, Phe-Phe, Sta, Lem Ăź(CH(OH)CH2)Val or Lem (CH2NH) Val substitutions. J Med Chem 31: 18 - 30

    Article  PubMed  CAS  Google Scholar 

  • Scholkens BA, Jung W (1974) Renin inhibition by pepstatin in experimental hypertension. Arch Int Pharmacodyn Ther 208: 24–34

    PubMed  CAS  Google Scholar 

  • Serre M, Galindo G, Marion A, et al. (1987) Hemodynamic response to SR 42128A in normal and sodium-depleted baboons. J Cardiovasc Pharmacol [Suppl 7] 10: S99–S101

    Article  CAS  Google Scholar 

  • Sham HL, Rempel C, Plattner JJ, Stein H, Cohen J, Perun TJ (1986) Renin inhibitors: Tripeptides incorporating 2-substituted statine analogs which display potent and specific inhibition of human renin (Abstr 8). 191th American Chemical Society Meeting, New York

    Google Scholar 

  • Sham HL, Stein H, Rempel CA, Cohen J, Plattner JJ (1987) Highly potent and specific inhibitors of human renin. FEBS Lett 220: 299–301

    Article  PubMed  CAS  Google Scholar 

  • Sham HL, Bolis G, Stein HH, Fesik SW, Marcotte PA, Plattner JJ, Rempel CA, Greer J (1988) Renin inhibitors. Design and synthesis of a new class of conformationally restricted analogues of angiotensinogen. J Med Chem 31: 284–295

    Google Scholar 

  • Skeggs LT, Lentz KE, Kahn JR, Hochstrasser H (1968) Kinetics of the reaction of renin with nine synthetic peptide substrates. J Exp Med 128: 13–34

    Article  PubMed  CAS  Google Scholar 

  • Smith CW, Saneii TK, Pals DT, Scahill TA, Kamdar BV, Lawson JA (1988) Synthesis and renin inhibitory activity of angiotensinogen analogues having dehydrostatine, Lem [CH2S]Val or Lem [CH2SO]Val at the PrPi’ cleavge site. J Med Chem 31: 1377–1382

    Article  PubMed  CAS  Google Scholar 

  • Smith SG, Seymour AA, Mazack EK, Boger J, Blaine EH (1987) Comparison of a new renin inhibitor and enalaprilat in renal hypertensive dogs. Hypertension 9: 150–156

    PubMed  CAS  Google Scholar 

  • Szelke M, Leckie BJ, Hallett A, Jones DM, Sueiras-Diaz J, Atrash B, Lever AF (1982) Potent new inhibitors of renin. Nature 299: 555–557

    Article  PubMed  CAS  Google Scholar 

  • Szelke M, Jones DM, Atrash B, Hallett A, Leckie BJ (1983) Novel transition state analog inhibitors of renin. In: Hruby VJ, Rich DH (eds) Peptides: structure and function. Pierce, Rockford, IL, pp 579–582

    Google Scholar 

  • Szelke M, Tree M, Leckie BJ, Jones MD, Atrash B, Beattie S, Donovan B, et al. (1985) A transition-state analogue inhibitor of human renin (H 261): test in vitro and a comparison with Captopril in the anaesthetized baboon. J Hypertens 3: 13–18

    Article  PubMed  CAS  Google Scholar 

  • Takaori K, Donowitz M, Burton J (1984) Intact jejunal absorption of a synthetic nonapeptide renin inhibitor. Fed Proc 43 (943): 446

    Google Scholar 

  • Takaori K, Hartley LH, Burton J (1987) Hypotensive effects of the renin inhibitor (RI-78) and the converting enzyme inhibitor (teprotide) in conscious monkeys. Clin Exp Hypertens [A] 9: 387–390

    Article  CAS  Google Scholar 

  • TenBrink RE, Pals DT, Harris DW, Johnson GA (1988) Renin inhibitors containing Psi(CH20)pseudopeptide inserts. J Med Chem 31: 671–677

    Google Scholar 

  • Thaisrivongs S, Pals DT, Kati WM, Turner SR, Thomasco LM (1985) Difluorostatineand difluorostatone-containing peptides as potent and specific renin inhibitors. J Med Chem 28: 1553–1555

    Article  PubMed  CAS  Google Scholar 

  • Thaisrivongs S, Pals DT, Harris DW, Kati WM, Turner SR (1986a) Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo. J Med Chem 29: 2088–2093

    Article  PubMed  CAS  Google Scholar 

  • Thaisrivongs S, Pals DT, Kati WM, Turner SR, Thomasco LM, Watt W (1986b) Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone, and related analogues. J Med Chem 29: 2080–2087

    Article  PubMed  CAS  Google Scholar 

  • Thaisrivongs S, Pals DT, Kroll DT, Turner SR, Han F-S (1987b) Renin inhibitors. Design of angiotensinogen transition-state analogues containing novel (2R, 3R, 4R, 5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid. J Med Chem 30: 976–982

    Article  PubMed  CAS  Google Scholar 

  • Thaisrivongs S, Pals DT, Turner SR, Krol LT (1988) Conformationally constrained renin inhibitory peptides: ylactam-bridged isosteres as conformational restriction. J Med Chem 31: 1369–1376

    Article  PubMed  CAS  Google Scholar 

  • Tree M, Atrash B, Donovan B, Gamble J, Hallett A, Hughes M, Jones DM, et al. (1983) New inhibitors of human renin tested in vitro and in vivo in the anaesthetized baboon. J Hypertens 1: 399–403

    Article  PubMed  CAS  Google Scholar 

  • Tree M, Szelke M, Leckie B, Atrash B, Donovan B, Hallett A, Jones DM, et al. (1985) Renin inhibitors: their use in understanding the role of angiotensin II as a pressor hormone. J Cardiovasc Pharmacol [Suppl 4] 7: S49–S52

    Article  CAS  Google Scholar 

  • Umezawa H, Aoyagi T, Morishima M, Matsuzaki M, Hamada M, Takeuchi T (1970) Pepstatin, a new pepsin inhibitor produced by actinomycetes. J Antibiot (Tokyo) 23: 259–262

    CAS  Google Scholar 

  • Waeber B, Nussberger J, Brunner HR (1986) What have we learned about inhibitors of renin angiotensin system? Ann Endocrinol (Paris) 47: 167–177

    CAS  Google Scholar 

  • Webb DJ, Cumming AMM, Leckie BJ, Level AF, Morton JJ, Robertson JIS, Szelke M, Donovan B (1983) Reduction of blood pressure in man with H-142, a potent new renin inhibitor. Lancet 2: 1486–1487

    Article  PubMed  CAS  Google Scholar 

  • Webb DJ, Manhem PJO, Ball SG, Inglis GI, Leckie BJ, Lever AF, Morton LJ, et al. (1985) A study of the renin inhibitor H142 in man. J Hypertens 3: 653–658

    Article  PubMed  CAS  Google Scholar 

  • Webb DJ, Manhem PJO, Ball SG, Inglis GI, Leckie BJ, Lever AF, Morton LJ, et al. (1987) Clinical and biochemical effects of the renin inhibitor H142 in humans. J Cardiovasc Pharmacol [Suppl 7] 10: S69–S74

    Article  CAS  Google Scholar 

  • Wolfenden R (1976) Transition state analog inhibitors and enzyme catalysis. Annu Rev Biophys Bioeng 5: 271–306

    Article  PubMed  CAS  Google Scholar 

  • Wood JM, Gulati N, Forgiarini P, FĂĽhrer W, Hofbauer KG (1985) Effects of a specific and long-acting renin inhibitor in the marmoset. Hypertension 7: 797–803

    PubMed  CAS  Google Scholar 

  • Wood JM, Heusser C, Gulati N, Forgiarini P, Hofbauer KG (1986) Monoclonal antibodies against human renin. Blood pressure effects in the marmoset. Hypertension 8: 600–605

    PubMed  CAS  Google Scholar 

  • Wood JM, Baum H-P, Jobber RA, Neisius D (1987a) Sustained reduction in blood pressure during chronic administration of a renin inhibitor to normotensive marmosets. J Cardiovasc Pharmacol [Suppl 7] 10: S96–S98

    Article  CAS  Google Scholar 

  • Wood JM, Jobber RA, Baum H-P, Hofbauer KG (1987b) Comparison of chronic inhibition of renin and converting enzyme in the marmoset. Clin. Exp Hypertens [A] 9: 337–343

    Article  CAS  Google Scholar 

  • Wood JM, Stanton JL, Hofbauer KG (1987c) Inhibitors of renin as potential therapeutic agents. J Enzyme Inhib 1: 169–185

    Article  PubMed  CAS  Google Scholar 

  • Wood JM, Whitfield SL, Baum H-P, Jobber RA (1988) Effects of chronic administration of a renin inhibitor on renin-like activity in marmoset tissues (Abstr 1313). 12th Scientific Meeting of the International Society of Hypertension, May 22–26, Kyoto

    Google Scholar 

Download references

Authors
  1. R. Henning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. A. Schölkens
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. German Institute for High Blood Pressure Research and Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-6900, Heidelberg, Germany

    Detlev Ganten M.D, Ph.D.

  2. Medical College of Ohio, CS10008, 300 Arlington Avenue, Toledo, OH, 43699, USA

    Patrick J. Mulrow M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Henning, R., Wagner, A., Schölkens, B.A. (1990). Renin Inhibitors. In: Ganten, D., Mulrow, P.J. (eds) Pharmacology of Antihypertensive Therapeutics. Handbook of Experimental Pharmacology, vol 93 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74209-5_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74209-5_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74211-8

  • Online ISBN: 978-3-642-74209-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation