Aminopeptidase P inhibitors and uses thereof

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

514 19, 514 18, 530328, 530329, 530330, 530332, 562567, A61K 3806, C07K 500, C07K 700, C07K 1600

Patent

active

056566034

ABSTRACT:
The present invention is directed to a compound of the formula: ##STR1## or a pharmaceutically acceptable addition salt thereof, wherein C.sup.3 and C.sup.2 in combination have the configuration S,R or R,S;

REFERENCES:
Ahmad, et al., "Depressor Action of Bradykinin Agonists Relative to Metabolism by Angiotensin-Converting Enzyme, Carboxypeptidase N, and Aminopeptidase P", P.S.E.B.M., 200: 115-121 (1992).
Allemann, et al., "Insulin Sensitivity In Normotensive Subjects During Angiotensin Converting Enzyme Inhibition With Fosinopril", Eur. J. Clin. Pharmacol 42: 275-280 (1992).
Ambrosioni, et al., "The Effect of the Angiotensin-Converting-Enzyme Inhibitor Zofenopril on Mortality And Morbidity After Anterior Myocardial Infarction," The New England Journal of Medicine, 332: 80-85 (Jan. 12, 1995).
Auch-Schwelk, et al., "Local Potentiation of Bradykinin-Induced Vasodilation by Converting-Enzyme Inhibition in Isolated Coronary Arteries," Journal of Cardiovascular Pharmacology, 20 (Suppl. 9): S62-S67 (1992).
Baker, Jr., et al., "Kinin Metabolism in the Perfused Ventilated Rat Lung. 1: Bradykinin Metabolism in a System Modeling The Normal, Uninjured Lung," Circulatory Shock 33: 37-47 (1991).
Baker, Jr., et al., "Kinin Metabolism in the Perfused Ventilated Rat Lung. II: Influence of Ventilation, Perfusion, and Perfusate Composition Variation on Bradykinin Metabolism in Uninjured Lung," Circulatory Shock 37: 280-290 (1992).
Bao, et al., "Chronic Kinin Receptor Blockade Attenuates the Antihypertensive Effect of Ramipril," Hypertension 20: 74-79 (1992).
Bao et al., "Role of Bradykinin in Chronic Antihypertensive Actions of Ramipril in Different Hypertension Models," Journal of Cardiovascular Pharmacology 20 (Suppl. 9): S96-S99 (1992).
Baumgarten, et al., "Ramiprilat Increases Bradykinin Outflow From Isolated Hearts of Rat," Br. J. Pharmacol. 108: 293-295 (1993).
Bhoola, et al., "Bioregulation of Kinins: Kallikreins, Kininogens, and Kininases" Pharmacological Review 44: 1-80 (1992).
Bonner, et al. "Hemodynamic Effects of Bradykinin on Systemic and Pulmonary Circulation in Healthy and Hypertensive Humans," Journal of Cardiovascular Pharmacology 15 (Suppl. 6) S46-S56 (1990).
Bonner, G., "Kinin-Related Effects of Angiotensin-Converting Enzyme Inhibition," Clinical Physiology and Biochemistry 9: 6-15 (1990).
Burley, et al., "Structure Determination and Refinement of Bovine Lens Leucine Aminopeptidase and its Complex with Bestatin," J. Mol. Biol. 224: 113-140 (1992).
Cachofeiro, et al., "Kinins, Nitric Oxide, and the Hypotensive Effect of Captopril and Ramiprilat in Hypertension," Hypertension 19: 138-145 (1992).
Carbonnell, et al., "Effect of a Kinin Antagonist on the Acute Antihypertensive Activity of Enalaprilat in Severe Hypertension," Hypertension 11: 239-243 (1988).
Carretero, et al., "Kinins as Regulators of Blood Flow and Blood Pressure," Hypertension: Pathophysiology, Diagnosis and Management, 805-817 (1990).
Castro, et al., "B.O.P.: A New Peptide Coupling Reagent Exemplified in the Synthesis of Somatostatin," in Peptides 1976 )Loffet, A., ed.) pp. 79-84, Univ. of Brussels (1976).
Cornish-Bowden, A., "A Simple Graphical Method for Determining the Inhibition Constants of Mixed, Uncompetitive and Non-Competitive Inhibitors," Biochem. J. 137: 143-144 (1974).
Dehm, et al., "The Cleavage of Prolyl Peptides by Kidney Peptidases," Eur. J. Biochem. 17: 364-371 (1970).
Dixon, M., "The Determination of Enzyme Inhibitor Constants," Biochem. J. 55: 170-171 (1953).
Dorer, et al., "Hydrolysis of Bradykinin by Angiotensin-Converting Enzyme," Cir. Res. 34: 824-827 (1974).
Dos Santos Medeiros, et al. "Processing and Metabolism of Peptide-YY: Pivotal Roles of Dipeptidylpeptidase-IV, Aminopeptidase-P, and Endopeptidase-24.11," Endocrinology 134: 2088-2094 (1994).
Farhy, et al., "Kinins Mediate The Antiproliferative Effect Of Ramipril In Rat Carotid Artery," Biochemical and Biophysical Research Communications, 182: 283-288 (1992).
Farhy, et al., "Role of Kinins and Nitric Oxide in the Effects of Angiotensin Converting Enzyme Inhibitors on Neointima Formation," Circulation Research 72: 1202-1210 (Jun. 1993).
Lasch, et al., FEBS Letters, "Enzymic Properties Of Intestinal Aminopeptidase P: A New Continuous Assay," 227: 171-174 (Jan., 1988).
Fleminger, et al., "Fluorogenic Substrates for Bacterial Aminopeptidase P And Its Analogs Detected In Human Serum and Calf Lung," Euro. J. Biochem 125: 609-615 (1982).
Gavras, H., "Angiotensin-Converting Enzyme Inhibition and the Heart," Hypertension 23: 813-818 (Jun. 1994).
Harada, et al., "High-performance Liquid Chromatographic Determination of Aminopeptidase P Activity in Fischer F344 Rat Serum and Kidney," Journal of Chromatography, 493: 176-181 (1989).
Harbeck, et al., "Aminopeptidase P From Rat Brain," Eur. J. Biochem. 198: 451-458 (1991).
Hartman, eta l., "Reduction of Myocardical Infarct Size in Rabbits by Ramiprilat: Reversal by the Bradykinin Antagonist HOE 140," J. Cardiovasc. Pharmacol. 21: 996-1003 (1993).
Hartman, et al., "Reduction of Myocardial Infarct Size by Ramiprilat Is Independent of Angiotensin II Synthesis Inhibition," European Journal of Pharmacology, 234: 229-236 (1993).
Hecker, et al., "Relaxation of Isolated Coronary Arteries by Angiotensin-converting Enzyme Inhibitors: Role of Endothelium-Derived Kinins," J. Vas. Res. 30: 257-262 (1993).
Hecker, et al., "Potentiation by ACE Inhibitors Of The Dilator Response To Bradykinin In The Coronary Microcirculation: Interaction At the Receptor Level," Br. J. Pharmcol. 111: 238-244 (1994).
Heller, et al., "The Effect of Kinin and Prostaglandin Inhibitors On The Renal Response To Angiotensin-Converting Enzyme Inhibition: A Micropuncture Study In The Dog," Pflugers Arch. 427: 219-224 (1994).
Hendriks, et al., "Aminopeptidase P And Dipeptidyl Peptidase IV Activity In Human Leukocytes And In Stimulated Lymphocytes," Clinica Chimica Acta. 196: 87-96 (1991).
Hooper, et al., "Purification and Characterization of Pig Kidney Aminopeptidase P," Biochem. J. 267: 509-515 (1990).
Hooper, et al., "Inhibition by Converting Enzyme Inhibitors of Pig Kidney Aminopeptidase P," Hypertension 19: 281-285 (1992).
Hooper, et al., "Ectoenzymes of the Kidney Microvillar Membrane," FEBS Letters 229: 340-344 (1988).
Ishida, et al., "Role of Angiotensin Converting Enzyme and Other Peptidases in In Vivo Metabolism of Kinins," Hypertension 14: 322-327 (1989).
Johnson, et al., "Neutral Metalloendopeptidase in Human Lung Tissue and Cultured Cells," Am. Rev. Respir. Dis. 132, 564-568 (1985).
Segel, I.H., Enzyme Kinetics, John Wiley and Sons, New York, (1975) pp. 64-71.
Kiowski, et al., "Coronary Vasodilatation and Improved Myocardial Lactate Metabolism After Angiotensin Converting Enzyme Inhibition With Cilazapril In Patients With Congestive Heart Failure," American Heart Journal, 1382-1388 (1991).
Kitamura, et al., "Inhibition of Aminopeptidase P Potentiates The Vassodepressor Response To Bradykinin," Hypertension 24: 396 (1994).
Kitamura, et al., "Potentiation By Aminopeptidase P Of Blood Pressure Response To Bradykinin," British Journal of Pharmacology, 114: 6-7 (1995).
Koelsch, et al., "Release of GPI-Anchored Membrane Aminopeptidase P By Enzymes And Detergents Has Some Peculiarities," Biochimica et Biophysica Acta 1190: 170-172 (1994).
Koida, et al., "Post-proline Cleaving Enzyme," The Journal of Biological Chemistry, 1221: 7593-7599 (1976).
Linder, et al., "ACE Inhibitors For The Treatment Of Myocardial Ischemia?," Cardiovascular Drugs and Therapy, 4: 1375-1384 (1990).
Linz, et al., "Bradykinin Prevents Left Ventricular Hypertrophy In Rats," Journal of Hypertension, 11 (Suppl. 5): S96-S97 (1993).
Linz, et al. "Cardiac Arrhythmias Are Ameliorated By Local Inhibition Of Angiotensin Formation And Bradykinin Degradation With The Converting-Enzyme Inhibitor Ramipril," Cardiovascular Drugs and Therapy, 3: 873-882 (1989).
Linz, et al., "Contribution of Bradykinin To The Cardiovascular Effects Of Ramipril," Journal of Cardiovascular Pharmacology, 22 (Suppl. 9): S1-S8 (1993).
Linz, et al., "Local Inhibition of Bradykinin Degradation in Ischem

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Aminopeptidase P inhibitors and uses thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Aminopeptidase P inhibitors and uses thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Aminopeptidase P inhibitors and uses thereof will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-160561

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.