Abstract: Dialkyl urea compounds are described which act as calcitonin mimetics. These compounds are useful in the treatment of diseases which are associated with bone resorption. The calcitonin mimetics of the present invention are also useful in assays for the determination of calcitonin receptor activity.

Abstract: The invention provides a novel amino acid, neo-tryptophan, as well as polypeptides containing this novel amino acid such as neurotensin analogs. In addition, the invention provides neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and polypeptides containing such derivatives. The invention also provides methods for making neo-tryptophan, neo-tryptophan derivatives, serotonin-like neo-tryptophan derivatives, and compositions containing these compounds. Further, the invention provides methods for inducing a neurotensin response in a mammal as well as methods for treating a mammal having a serotonin recognition molecule.

Abstract: Methods, compositions, and devices for alleviating the problems of toxic discharge of aldehydes present in waste streams are disclosed. The methods relate to reducing neutralized aldehydes wherein the neutalized aldehydes are formed by treating aldehydes with amino acids and thereinafter are reduced. These reduced, neutralized aldehydes do not revert back to toxic aldehydes, but form amino acids and thus allow waste containing aldehyde to be more environmentally safely disposed.

Abstract: Disclosed are compounds of formula (I) wherein W is CH or N; R is (mono- or di cabocyclic or heterocyclic aryl)-lower alkyl; R1 is hydrogen or lower alkyl; R2 and R3 are hydrogen, lower alkyl, lower alkoxy-lower alkyl or aryl-lower alkyl; or R2 and R3 joined together represent lower alkylene optionally interrupted by O, NH, N-lower alkyl or S so as to form a ring with the amide nitrogen; X is O, S, SO, S2 or a direct bond; X1 is O, S, SO, SO2 or a direct bond; Y is a direct bond, lower alkylene or lower alkylidene; and Z is carboxyl, 5-tetrazolyl,, hydroxymethyl or carboxyl derivatized in the form of a pharmaceutically acceptable ester, and pharmaceutically acceptable salts thereof; which arm useful as LTB-4 antagonists.

Abstract: A method for the crystallization of tryptophan, comprising storing a tryptophan solution at a pH of 8 to 13 and at a temperature of room temperature to 100° C. for 0.5 hour to 1 week and then, followed by crystallization.

Abstract: Use of a tryptophanyl-ester or an N-acyl derivative of a tryptophanyl-ester for the prophylaxis and therapy of oxidative pathologic processes in degenerative diseases and/or cancer diseases. Thereby, the tryptophanyl-ester or its N-acyl derivative is preferred to be tryptophanoctyl, N-oleoyl-tryptophanethyl-ester or N-dodecanoyl-tryptophanethyl-ester.

Abstract: The invention relates to novel, substituted N-benzyl-indol-3-ylglyoxylic acid derivatives of the following formula and their use for the treatment of oncoses 1

Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

Abstract: The invention relates to novel N-[2-(indol-3-yl)ethyl]-2-oxo-alkanarnides of the general formula (I) in which R1 represents optionally branched C1-C8-alkyl or C4-C8-cycloalkyl, R2 independently of R3 represents hydrogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-thioalkyl, phenyl or halogen, R3 represents hydrogen, C1 -C4-alkyl or halogen and R4 represents optionally branched C1-C6-alkyl, C4-C6-cycloalkyl, phenyl which is optionally mono- to trisubstituted by C1-C3-alkyl, C1-C3-alkoxy, C1-C3-thioalkyl, halogen, nitro or amino or benzyl which is optionally mono- to trisubstituted by C1-C3-alkyl, C1-C3-alkoxy, C1-C3-thioalkyl, halogen, nitro or amino, to processes for their preparation and to their use in antibacterial compositions.

Abstract: A class of novel 1H-indole-3-acetamides is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.

Abstract: A novel class of tripeptide &agr;-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M1—AA—AA—AA—CO—NR3R4.

Abstract: The present invention provides compounds having the formula: wherein n is 0 or 1; R is —NH2 or wherein R1 and R2 are independently selected from the group consisting of H, alkyl, aralkyl, heteroaralkyl, carboxy, carboxyalkyl, and carbamoyl; Q is R3C(O)— or wherein R5 is selected from the group consisting of H, alkyl, aralkyl, heteroaralkyl, and carbamoylalkyl, and R3 and R4 are selected from the group consisting of H, alkyl, alkoxy, arylalkoxy, aralkyl, heteroaralkyl, and carbamoylalkyl; the Q—NH—(CH2)n— and the —C(O)R substituents of the compound of formula I are independently positioned ortho, meta, orpara relative to the carbon atoms that form the bond between the two phenyl groups to which said substituents are bound, with the proviso that said substituents are not both positioned ortho; and the Q—NH—(CH2)n and the —C(O)R substituents of the compound of formula II are positioned meta orpara t

Abstract: Dialkyl urea compounds are described which act as calcitonin mimetics. These compounds are useful in the treatment of diseases which are associated with bone resorption. The calcitonin mimetics of the present invention are also useful in assays for the determination of calcitonin receptor activity.

Abstract: The present invention relates to small peptides that cause penile erections in male animals when injected into the paraventricular nucleus of the hypothalamus or when given systemically (intravenously or subcutaneously) to such animals. These peptides are useful in the treatment of erectile dysfunction.

Abstract: A compound of formula (I), in which: R1 is lower alkyl, cyclo(lower)alkyl, optionally substituted aryl, optionally substituted heterocyclic group, cyclo(lower)alkyl(lower)alkyl, or ar(lower)alkyl; R2 is hydrogen, hydroxy or protected hydroxy; R3 is lower alkyl, aryl, ar(lower)alkyl or optionally substituted heterocyclic(lower)alkyl; R4 is carboxy, protected carboxy or lower alkylsufonylcarbamoyl; R5 is hydrogen or lower alkyl; R6 is hydrogen or heterocyclic group; A is a single bond or lower alkylene, and Ar is optionally substituted aryl, or pharmaceutically acceptable salts thereof, having endothelin antagonistic activity.

Abstract: Compounds of general formula I ##STR1## wherein: R.sub.1 and R.sub.70 independently represent a hydrogen atom or an optionally substituted alkyl or acyl group; R.sub.2 represents a hydrogen atom or an optionally substituted alkyl or acyl group or is absent when R.sub.6 represents a group --CH.dbd. as hereinafter described; R.sub.73 represents a hydrogen atom or an optional substituent or is absent when R.sub.6 represents a methylene group or a group --CH.dbd. as hereinafter described; Y represents an optional substituent; n represents 0, 1, 2, 3, or 4; R.sub.3 represents a hydrogen atom, or an optionally substituted alkyl group; R.sub.74 represents a hydrogen atom, a hydroxy group or an optionally substituted alkyl or acyl group; R.sub.7 represents a hydrogen atom or an alkyl group; R.sub.75 represents an optionally substituted alkyl group; and i) R.sub.6 and R.sub.71 independently represent a hydrogen atom or an optionally substituted alkyl or acyl group; and R.sub.72 represents a hydrogen atom; or ii) R.

Abstract: Products of formula (I), wherein n is 0 or 1, R.sub.1 is particularly phenyl or biphenyl optionally substituted particularly by benzyloxy, dioxol or halogen, R.sub.2 is particularly hydrogen or methyl substituted particularly by indolyl, phenylthio or phenyl, which may in turn be substituted, and A is carboxy, tetrazolyl or substituted alkyl as well as all salts and isomers thereof, are disclosed.

Abstract: Disclosed is a method of preparing a compound represented by the following structural formula: ##STR1## and physiological salts thereof. R.sup.1 is --H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group.R.sup.2 is a substituted or unsubstituted 2-hydroxy-1-ethyl group.Ring A is a substituted or unsubstituted aryl group.Ring B is substituted or unsubstituted at position two.

Abstract: The invention involves a novel chemical compound, N-acetyl-5,6-dimethoxytryptamine (compound I), which can also be defined as a melatonin derivative. The molecular weight of compound I is 262 and the chemical structure is as follows. ##STR1## Compound I possesses potent in vitro and in vivo free radical scavenging capacity and exhibits protective effects against convulsions and brain damage induced by oxidative stress. It holds potential clinical usage for preventing and treating diseases which involve free radicals and oxidative stress.

Abstract: A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shiftwork sleep disturbance are provided.

Abstract: This invention relates to polyfluoroalkyl tryptophan tripeptides and to compositions containing them. The compounds are highly selective thrombin inhibitors which provide anticoagulant effects useful in the treatment of thrombin conditions and in preventing the coagulation of stored whole blood and blood products.

Abstract: Peptidomimetic compounds capable of inhibiting zinc-dependent metalloproteinases to treat pathological conditions associated with activation of endogenous metalloproteinases in mammals.

Abstract: The present invention comprises growth hormone releasing peptides/peptidomimetics (GHRP) capable of causing release of growth hormone from the pituitary. Compositions containing the GHRP's of this invention are used to promote growth in mammals either alone or in combination with other growth promoting compounds, especially IGF-1. In a method of this invention GHRP's in combination with IGF-1 are used to treat Type II diabetes. An exemplary compound of this invention is provided below.

Abstract: Compounds of formula (I), and their pharmaceutically acceptable derivatives, wherein R.sup.1 and R.sup.2 are optional substituents and independently represent C.sub.1-6 alkyl, C.sub.2-6 alkenyl [optionally substituted by CO.sub.2 H or CO.sub.2 (C.sub.1-6 alkyl)], C.sub.2-6 alkynyl, halogen, C.sub.1-3 perfluoroalkyl, (CH.sub.2).sub.m Ar.sup.1, (CH.sub.2).sub.m Het.sup.1, (CH.sub.2).sub.m CONR.sup.7 R.sup.8, (CH.sub.2).sub.m CO.sub.2 R.sup.8, O(CH.sub.2).sub.q CO.sub.2 R.sup.8, (CH.sub.2).sub.m COR.sup.8, (CH.sub.2).sub.m OR.sup.8, O(CH.sub.2).sub.p OR.sup.8, (CH.sub.2).sub.m NR.sup.7 R.sup.8, CO.sub.2 (CH.sub.2).sub.q NR.sup.7 R.sup.8, (CH.sub.2).sub.m CN, S(O).sub.n R.sup.8, SO.sub.2 NR.sup.7 R.sup.8, CONH(CH.sub.2).sub.m Ar.sup.1 or CONH(CH.sub.2).sub.m Het.sup.1 ; R.sup.3 represents H, C.sub.1-6, alkyl, (CH.sub.2).sub.p NR.sup.9 R.sup.10, SO.sub.2 R.sup.10, SO.sub.2 NR.sup.9 R.sup.10, (CH.sub.2).sub.m COR.sup.10, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.m CONR.sup.9 R.sup.10, (CH.sub.2).sub.

Abstract: A method for binding albumin by contacting an aqueous liquid containing an albumin with an albumin-binding compound is selected from albumin-binding compounds containing the scaffold --CO--NH--C(.dbd.C--)--CO--, and conjugates that are capable of binding albumin and exhibiting the scaffold --CO--NH--C(.dbd.C--)--CO--.

Abstract: The invention concerns tachykinin antagonists. The compounds are nonpeptides which have utility in treating disorders mediated by tachykinins. Such disorders are respiratory, inflammatory, gastrointestinal, ophthalmic, allergies, pain, vascular, diseases of the central nervous system, and migraine. Methods of preparing compounds and novel intermediates are also included. The compounds are expected to be especially useful in asthma and rheumatoid arthritis.

Abstract: An .alpha.-hydrazino acid derivative of general formula (I) is described, wherein R.sub.1, R.sub.2, R.sub.3 are hydrogen or a carbon radical, such that when R.sub.2 and R.sub.3 are different, C* is an asymmetric carbon of L, D or DL configuration, and R.sub.4 and R.sub.5 are a protecting group, characterized in that R.sub.4 is a benzyl ArCH.sub.2 radical of formula (a), wherein Ar is a phenyl radical or phenyl substituted by one or more X groups; X being hydrogen, halogen, a nitro or alkyl radical; and in that R.sub.5 is a Y--O--CO group, where Y is a carbon radical different from R.sub.4.

Abstract: Peptides containing in its amino acid chain a D-2-alkylTryptophan residue wherein the alkyl group has between one and three carbon atoms and having pharmacological activity equal to or greater than that of analogous peptides containing natural unsubstituted D-Tryptophan residues in place of the D-2-alkylTryptophan. These peptides are more resistant to oxidative degradation which usually takes place, for example, in the presence of reactive radicals or during high energy sterilization than unsubstituted Tryptophan containing peptides.

Abstract: A process for isolating substantially pure natural L-.beta.-3-indolylalanine (L-.beta.-3) from a mixture of amino acids, such as a protein hydrolysate, is described. A protein hydrolysate, for example of casein or soy protein, is passed over a polymeric resin attractive to aromatic amino acids but not attractive to aliphatic amino acids. The aromatic amino acids are retained on the resin while the aliphatic amino acids pass over the resin and are collected. The resin is then washed with water to displace any residual aliphatic acids which may be physically associated with but not bound to the resin. Thereafter, the resin is eluted with a dilute acid to displace L-phenylalanine and L-tyrosine and provide a solution thereof while allowing L-.beta.-3 to be retained on the resin. The resin is then further eluted with a dilute base to displace L-.beta.-3 from the resin and provide a solution of L-.beta.-3. Substantially pure natural L-.beta.-3 is recoverable from this solution.

Abstract: Synthetic immunomodulatory molecules having a .gamma.-L-glutamyl-, a .gamma.-D-glutamyl, a .beta.-L-aspartyl, or a .beta.-D-aspartyl moiety at the amino terminus are provided as illustrated by Formula A. In Formula A, "n" is 1 or 2, R is hydrogen, acyl or alkyl, and X is an aromatic or heterocyclic amino acid or its derivative. A particularly preferred embodiment is .gamma.-D-glutamyl-L-tryptophan, which has immunomodulatory activity.

Abstract: Novel cholecystokinin antagonists useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with use of nicotine, diazepam, alcohol, cocaine, coffee, or opioids. The compounds of the invention are also useful in treating and/or preventing panic. Also disclosed are pharmaceutical compositions and methods of treatment using the antagonists as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds in diagnostic compositions.

Abstract: A pharmaceutical preparation for the therapy of immune deficiency conditions comprising an active principle--a peptide of the structure: H--L--Glu--L--Trp--OH and a pharmaceutically acceptable vehicle.

Abstract: The present invention comprises growth hormone releasing peptides/peptidomimetics (GHRP) capable of causing release of growth hormone from the pituitary. Compositions containing the GHRP's of this invention are used to promote growth in mammals either alone or in combination with other growth promoting compounds, especially IGF-1. In a method of this invention GHRP's in combination with IGF-1 are used to treat Type II diabetes. An exemplary compound of this invention is provided below.

Abstract: A process for producing an alkoxycarbonylaminothiazoleacetic acid derivative, which comprises reacting an aminothiazoleacetic acid derivative ester with a dialkyl dicarbonate in the presence of a dialkyl carbonate to form an alkoxycarbonylaminothiazoleacetic acid derivative ester, then hydrolyzing the ester with a base, separating the carbonate formed as a by-product, and neutralizing the remaining base.The process can produce an alkoxycarbonylaminothiazoleacetic acid derivative in a simple operation and safely, at a high yield and at a high reactor yield.

Abstract: Tryptophan derivatives substituted by a hydrophobic group, e.g. carbobenzoxy, at the N-terminus, and a hydrophilic group, e.g. --COOH, --SO.sub.3 H or --PO.sub.3 H, at the C-terminus, were found to be cell-permeable blockers of protein tyrosine kinases (PTKs). These PTK blockers are useful in basic research and in the treatment of neoplastic diseases.

Abstract: Synthetic mammalian matrix metalloprotease inhibitors are disclosed that are useful for treating or preventing diseases wherein said diseases are caused by unwanted mammalian matrix metalloprotease activity and include skin disorders, keratoconus, restenosis, rheumatoid arthritis, wounds, cancer, angiogenesis and shock.

Abstract: Compounds of the formula A--B--C--D(--E).sub.p are used to stimulate the release of growth hormone from the pituitary.

Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.

Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.

Abstract: The new class of synthetic immunomodulatory molecules having a .gamma.-L-glutamyl- moiety at the amino terminus are provided as illustrated by Formula 1. ##STR1## In Formula 1, the Greek symbols designate the noted carbon atoms, R is hydrogen, acyl or alkyl, and X is an aromatic or heterocyclic amino acid or its derivative. Included as members of the new class (in addition to Bestim, .gamma.-L-glutamyl-L-tryptophan) are those compounds where R=hydrogen and X=L-tryptophan, such as .gamma.-L-glutamyl-N.sub.in -formyl-L-tryptophan, N-methyl-.gamma.-L-glutamyl-L-tryptophan, N-acetyl-.gamma.-L-glutamyl-L-tryptophan, and .gamma.-L-glutamyl-.beta.-thienyl-D-alanylamide. A preferred embodiment, termed "BESTIM," has the chemical structure of .gamma.-L-glutamyl-L-tryptophan.

Abstract: The invention relates to a compound selected from those of formula (I): ##STR1## in which A, R.sub.1, R'.sub.1, R.sub.2, R.sub.3 and n are as defined in the description, and medicinal product containing the same useful for treating a mammal afflicted with a disorder of the melatoninergic system.

Abstract: The present invention provides a cathepsin L inhibitor containing a compound of the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or an arylalkyl, heterocyclic-alkyl or lower alkyl group which may be substituted; R.sup.2 and R.sup.3 independently are a hydrogen atom or a hydrocarbon residue which may be substituted; R.sup.4 is an alkanoyl, sulfonyl, carbonyloxy, carbamoyl or thiocarbamoyl group which may be substituted; X is formula: --CHO or --CH.sub.2 OB (wherein B is a hydrogen atom or a protecting group of hydroxyl group); m and n independently are an integer of 0 or 1; provided that R.sup.4 is an alkanoyl group substituted by aryl, a sulfonyl group substituted by aryl having more than 9 carbon atoms or by lower alkyl, or a carbamoyl or thiocarbamoyl group which may be substituted when R.sup.1 is an unsubstituted lower alkyl, arylalkyl on methylthioethyl group, R.sup.2 and R.sup.3 independently are a lower alkyl or arylalkyl, X is --CHO, m is 1 and n is 0 or 1, or a salt thereof.

Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.

Abstract: An amino acid compound of the formula: R.sup.1 NH--CH(R.sup.2)--COHN--A--ONO.sub.2, wherein R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.7 alkanoyl group, a C.sub.1 -C.sub.6 alkoxycarbonyl group, a C.sub.6 -C.sub.10 arylcarbonyl group, a C.sub.7 -C.sub.13 aralkylcarbonyl group, a C.sub.7 -C.sub.13 aralkyloxycarbonyl group or a 5- or 6-membered aromatic heterocyclic carbonyl group; R.sup.2 represents a substituted C.sub.1 -C.sub.6 alkyl group; and A represents a C.sub.2 -C.sub.5 alkylene group; and pharmacologically acceptable salts thereof. The amino acid compound has an excellent vasodilator action for collateral vessels and is useful for treating angina pectoris.

Abstract: The present invention provides novel compounds having pharmacological properties represented by the general formula I ##STR1## processes for the manufacture, pharmaceutical compositions and the use of the compounds of formula I and salts thereof.

Abstract: A class of novel 1-indole-3-acetamides represented by the formula; ##STR1## is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids.

Abstract: The present invention relates to compounds of formula (I) and salts and prodrugs thereof, wherein Q.sup.1 represents a phenyl group substituted by one or more halo optionally substituted naphthyl, optionally substituted indolyl, optionally substituted benzthiophenyl, optionally substituted benzofuranyl, optionally substituted benzyl or optionally substituted fluorenyl; R.sup.1 represents H or C.sub.1-6 alkyl; R.sup.2 represents H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; Z.sup.1 represents a group selected from (a) or (b). The compounds are tachykinin antagonists useful for treating pain or inflammation, migraine or emesis.

Abstract: Esters or amides of a peptide, preferably a dipeptide, consisting essentially of natural or synthetic L-amino acids with hydrophobic side chains were found to have specific cellular toxicities. Preferable amino acids of the peptide are leucine, phenylalanine valine, isoleucine, alanine, proline, glycine or aspartic acid beta methyl ester. Preferable dipeptides are L leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-leucyl L-isoleucine, L-phenylalanyl L-phenylalanine, L-valyl L-leucine, L-leucyl L-alanine, L-valyl L-valine, L-phenylalanyl L leucine, L prolyl L-leucine, L-leucyl L-valine, L-phenylalanyl L-valine, L glycyl L-leucine, L-leucyl L-glycine, glycyl L-phenylalanine and L-aspartyl beta methyl ester L-phenylalanine. Most preferable dipeptides are L-leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-phenylalanyl L-leucine, L-leucyl L-isoleucine L-phenylalanyl L-phenylalanine and L-valyl L-leucine.

Abstract: Disclosed are the compounds of formula I ##STR1## wherein R represents hydrogen, lower alkyl, carbocyclic or heterocyclic aryl-lower alkyl or cycloalkyl-lower alkyl;R.sub.1 represents hydrogen, lower alkyl, cycloalkyl, carbocyclic aryl or heterocyclic aryl, or biaryl;R.sub.3 represents hydrogen or acyl;R.sub.4 represents hydrogen, lower alkyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, biaryl or biaryl-lower alkyl;R.sub.5 represents hydrogen or lower alkyl; or R.sub.4 and R.sub.

Abstract: Hydroxamate compounds of the following formula are disclosed:R--AA.sup.3 --AA.sup.4 --AA.sup.5 --AA.sup.6 --NH--OR.sup.2wherein AA.sup.3 --AA.sup.6 represent amino acid residues. The disclosed compounds are inhibitors of endothelin converting enzyme, and as such are useful for the treatment of disorders resulting from overproduction of endothelin, i.e., acute and chronic renal failure, cyclosporin-A induced nephrotoxicity, hypertension, myocardial infarction, metabolic, endocrinological, neurological disorders, congestire heart failure, endotoxic shock and hemorrhagic shock, septic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease, cerebral vasospasm, restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, ischemic bowel disease, and diabetes.