Abstract: Provided is a process for efficiently producing N-glycyltyrosine of high purity represented by the following formula: a salt thereof, or a solvate thereof, which comprises adding dropwise to an aqueous suspension of tyrosine or a salt thereof 2 equivalents or more of a haloacetyl halide and an aqueous solution of an inorganic base simultaneously in the presence or absence of an organic solvent, and subjecting the resulting N-haloacetyltyrosine to a reaction with an ammonium ion. Also provided are N-glycyl-L-tyrosine dehydrate having the crystal structures showing specific diffraction patterns in X-ray powder diffraction and processes for producing the same which are characterized by comprising crystallizing the dihydrate from an ethanol-water mixed solvent or water.

Abstract: An amide compound of the formula (I): wherein R is amino and the like, A is alkylene and the like, X is O, S and the like, M is arylene and the like, R1, R2, R3 and R4 are H, hydroxy and the like, R5 is H, alkyl and the like, m is an integer of 0-6, R6 is an optionally substituted aryl and the like, and R7 is H, an optionally substituted alkyl and the like, a pharmaceutically acceptable acid addition salt thereof and a pharmaceutical containing same as an active ingredient. The amide compounds exhibit superior suppressive effects on cytokines directly or indirectly involved in inflammations, such as IL-8, IL-1, IL-6, TNF-&agr;, GM-CSF and the like, and are useful for the prophylaxis and treatment of rheumatic diseases, arthritis due to gout and the like.

Abstract: Compounds of formula 1 wherein R4 is an ester or thioester group, and R, R1, R2 and R3 are as defined in the specification are inhibitors of rapidly dividing tumour cells.

Abstract: The present invention is directed to novel dipeptides represented by the general Formula I: ##STR1## where R.sub.1 -R.sub.2 and AA are defined herein. The present invention relates to the discovery that compounds having Formula I are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.

Abstract: This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

Abstract: Compounds of the general formula I ##STR1## compositions containing them, and their use for treating medical disorders resulting from a deficiency in growth hormone are described.

Abstract: The invention includes selected novel optically active .alpha.-amino ketones which either are themselves useful or are intermediates for the preparation of known ketomethylene pseudopeptides useful as antibiotics, antibiotic enhancers, or enzyme inhibitors. Further, the present invention provides a method for dehydrogenation/asymmetrical hydrogenation to obtain essentially pure antipodes of ketomethylene pseudopeptides having two chiral centers.

Abstract: Amino acids are derivatized for use in peptide synthesis by conversion to N-carboxyanhydrides that are N-proected by either a trityl or a phenylfluorenyl group.

Abstract: With known methods of racemizing N-acetyl-D(L)-.alpha.-amino carboxylic acids in the non-aqueous state by heating them to temperatures above room temperatures, significant quantities of by-products are formed, especially acetyl dipeptides. By converting at least a proportion of the N-acetyl-D(L)-.alpha.-amino carboxylic acids to corresponding N-acetyl-D(L)-.alpha.-amino carboxylic acid salts before or during the heating, it is possible to increase the sojourn time of the educt which is to be racemized at higher temperatures without any evident increase in the quantity of by-product formed (in particular acetylated dipeptides). Also disclosed is the production of optically active amino acids by enzymatic splitting of racemic compounds.

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: The present invention provides compounds having the Formula I ##STR1## The present invention also provides methods of treating atherosclerosis, coronary heart disease, and restenosis using the compounds of Formula I, and pharmaceutical compositions comprising the compounds of Formula I.

Abstract: A process for the synthesis of hydroxyethylene dipeptide isosteres from .alpha.-N,N-di(protected)amino(alkyl or substituted alkyl) methyl ketones that can be efficiently carried out on an industrial scale. The process proceeds with excellent diastereoselectivity and chemical efficiency, and can be used to prepare a wide variety of hydroxyethylene dipeptide isosteres for a variety of uses, including as HIV-1 protease inhibitors and renin inhibitors.

Abstract: Disclosed is a compound represent by the following structural formula: ##STR1## X is --H or an amine protecting group; --OY is --OH, an activating group for a carboxylic acid or a protecting group for a carboxylic acid; Z is --H or a phenolic protecting group, with the proviso that Z is not a straight chained, unsaturated alkyl group such as, for example, methyl or ethyl, and at least one of X, Y or Z is not --H.Also disclosed is a photoreactive polypeptide having a polypeptide chain comprising a residue of the compound described above. Also disclosed is a method of labeling a target molecule which forms a complex with the photoreactive polypolypeptide by photolyzing the photoreactive polypeptide when complexed with the target molecule.

Abstract: The present invention provides an economically advantageous and efficient process for producing an optically active homophenylalanine derivative of the general formula (IV), and an intermediate therefor and a process for producing it. The present invention relates to a process for producing homophenylalanine derivative of the general formula (IV) which comprises reacting a .beta.-benzoylacrylic acid derivative of the general formula (II) with a 1-arylethylamine derivative of the general formula (III) and reducing the resultant .gamma.-oxo-homophenylalanine derivative of the general formula (I).

Abstract: The present invention relates to the compounds of formula (I) ##STR1## wherein R is carboxy, esterified carboxy, carbamoyl, N-(alkyl or aryl)-carbamoyl, cyano, 5-tetrazolyl or CONH--SO.sub.2 --R.sub.4 ; R.sub.1 is hydrogen, lower alkyl, aryl-lower alkyl or cycloalkyl-lower alkyl; R.sub.2 is hydrogen or lower alkyl, or R.sub.1 and R.sub.2 represent lower alkylene to form together with the carbon and nitrogen atoms to which they are attached an azacycloalkane ring; R.sub.3 is heterocyclic or carbocyclic (aryl or biaryl)-lower alkyl; Y is lower alkylidenyl, 3- to 10-membered cycloalkylidenyl which may be substituted by oxo, alkylenedioxy, hydroxy, acyloxy, lower alkoxy; or Y is 5- to 10-membered cycloalkylidenyl fused to a saturated or unsaturated carbocyclic 5- or 6-membered ring; or Y is 5- to 8-membered oxacycloalkylidenyl, 5- to 8-membered (thia-, oxothia- or dioxothia-) cycloalkylidenyl, or 5- to 8-membered azacycloalkylidenyl optionally N-substituted by lower alkyl or aryl-lower alkyl; R.sub.

Abstract: Peptidyl compounds have therapeutic utility via MMP and TNF inhibitory activity.

Abstract: Novel N-carboxyalkylpeptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. The matrix metalloendoproteinases are a family of zinc-containing proteinases including but not limited to stromelysin, collagenase, and gelatinase, that are capable of degrading the major components of articular cartilage and basement membranes. The inhibitors claimed herein may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to a permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation.

Abstract: Antagonists of endothelin are described, as well as methods of using them and pharmaceutical compositions containing them. These compounds are useful in controlling hypertension, myocardial infarction, pulmonary hypertension, angina, metabolic, endocrinological, and neurological disorders, congestive heart failure, septic or endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, acute and chronic renal failure, preeclampsia, and diabetes.

Abstract: A process for the preparation of disodium Z-L-aspartate from fumaric acid, in whicha) fumaric acid is reacted with ammonia in an inert diluent in the presence of aspartase or aspartase-producing microorganisms to give ammonium L-aspartate thenb) the ammonium L-aspartate-containing solution is treated with sodium hydroxide, forming, depending on the amount of sodium hydroxide used, the mono- or disodium L-aspartate or a mixture thereof, andc) the eliminated ammonia is returned to a fumaric acid suspension, which is used as starting solution for further enzymatic reactions, and thend) the residual mono and/or disodium L-aspartate-containing solution is reacted with benzyloxycarbonyl chloride at a pH of between 9 and 14, with the simultaneous addition of sodium hydroxide, to form disodium Z-L-aspartate.

Abstract: Tyrosine decarboxylase, or microorganisms of the genuses Enterococcus, Lactobacillus, Providencia, Fusarium, and Gibberella were reacted with a mixture of the enantiomers of threo-3-phenylserine or its halogen substitution products to produce (R)-2-amino-1-phenylethanol or its halogen substitution products. At the same time, one of the enantiomers of threo-3-phenylserine or its halogen substitution products were selectively left, and optically active threo-3-phenylserine or its halogen substitution products were produced. In addition, a novel material of 3-(3-chlorophenyl)serine, which is a substrate of the reaction in the present invention, was produced. (R)-2-amino-1-phenylethanol or its halogen substitution products, and optically active threo-3-phenylserine or its halogen substitution products can economically be produced on an industrial scale.

Abstract: Methods of use of compounds and compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds are those of formulae (I), (II) and (III): ##STR1## in which R.sub.1 is preferably 2-methyl propene, 2-butene, norleucine; R.sub.2, R.sub.4, and R.sub.8 are each independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; R.sub.5 is preferably iso-butyl; R.sub.6 is H or methyl; R.sub.7 --(Q).sub.n is preferably benzyloxycarbonyl or acetyl; Q is preferably --C(O)--; R.sub.8 is preferbly iso-butyl; R.sub.A =--(T).sub.m --(D).sub.m --R.sub.1, is which T is preferably oxygen or carbon, and D is preferably a mono-unsaturated C.sub.3-4 alkenyl being more preferred; and X is an alcohol, particularly a secondary alcohol.

Abstract: The invention concerns tachykinin antagonists. The compounds are neopeptides 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: Compounds of the formula I ##STR1## as well as methods for their preparation, their pharmaceutical preparations and their use in therapy, especially as analgesics and as immunosuppressive agents.

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: Process for the preparation of a threo-phenylserine amide of the general formula 2 in which glycine amide is contacted with the corresponding substituted benzaldehyde of formula 3 in an excess relative to the amount of glycine amide, this taking place at a pH between 9 and 14 in the presence of a suitable solvent. The resulting phenylserine amide can subsequently be hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently subjected to a stereoselective enzymatic hydrolysis yielding a (2S,3R) phenylserine. The non-hydrolyzed (2R,3S) phenylserine amide can be isolated as a Schiff base and be recirculated and simply racemized. The (2S,3R) phenylserine obtained can be used in the preparation of thiamphenicol or florfenicol. The threo-phenylserine amides of the general formula 1 or 2 are new intermediates in this commercially attractive process for the preparation of thiamphenicol and florfenicol.

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: The small compounds of the instant invention are tachykinin antagonists. The compounds are highly selective and functional NK.sub.3 antagonists expected to be useful in the treatment of pain, depression, anxiety, panic, schizophrenia, neuralgia, addiction disorders, inflammatory diseases, gastrointestinal disorders, vascular disorders, and neuropathological disorders.

Abstract: A process is disclosed for reducing amino acids and derivatives thereof Compounds of formula (I), in which n=0 or 1 and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 have the meanings given in the description, are reduced to the corresponding amino alcohols of formula (II): the formula (I) compounds are converted in a first step, in at least one alcohol and with the addition of acid and heat to an ester, this process producing a reaction mixture containing the ester; the ester is converted in a second reaction step with alkali or alkaline earth borohydride to compounds of formula II. By specifying that the second step be carried out without isolating the ester from the reaction mixture and by using alkali or alkaline earth borohydrides which are not activated, the invention facilitates the production from amino acids and their derivatives of the correponding alcohols in a simple "single vessel" process, with high yields and in such a way as to preserve a given centre of chirality.

Abstract: Fluorinated alkene compounds useful for and methods of controlling nematodes, insects, and acarids that prey on agricultural crops. Polar compounds, for example, 3,4,4-trifluoro-3-butene-1-amine or 3,4,4-trifluoro-3-butenoic acid, are particularly useful for systemic control of pests. Novel method and intermediates for the preparation of 3,4,4-trifluoro-3-butene-1-amine are also provided.

Abstract: Methods of making unnatural amino acids are provided which unnatural amino acids can be incorporated into peptides which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. These unnatural amino acids are useful in the synthesis of peptides and have the formula (a): ##STR1## where W is (CH.sub.2) or ##STR2## n is an integer from 1 to 6; j=1, 2 or 3, and preferably, Y is N--CN, X is NH and R.sub.2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pyridyl. Disclosed are peptides that are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions.

Abstract: Peptidyl derivatives of diesters of .alpha.-aminoalkylphosphonic acids with basic substitutents, their use in inhibiting serine proteases with trypsin-like specificity and their roles as anti-inflammatory agents, anticoagulants, and anti-tumor agents.

Abstract: A series of di- and tri-peptide mimetic dopamine prodrugs are synthesized in which D-phenylglycine or D-p-hydroxyphenylglycine is attached as tools for delivery of L-dopa through the intestine via the intestinal dipeptide-mediated carrier transport system. These compounds are found useful as an active ingredient for the treatment of Parkinson's disease.

Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Abstract: Diethylenetriaminepentaacetic acid monoamide derivatives, their complexes and complex salts, containing an element of atomic numbers 21-29, 31, 32, 39, 42-44, 49 or 57-83, pharmaceutical agents containing these compounds, their use as contrast media and process for their production.

Abstract: 4-substituted cyclohexylamine derivatives which are thrombin catalytic site inhibitors and which are useful as anticoagulants. These compounds show selectivity for thrombin over other trypsin-like enzymes and have oral bioavailability.

Abstract: A method for recovering an optically pure amino acid derivative from a waste liquor collected after a coupling reaction in peptide synthesis, comprising the steps of (a) adding into the waste liquor, in which an uncoupled amino acid derivative or an uncoupled small peptide fragment is contained, a compound selected from the group consisting of 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOObt) and N-hydroxy-5-norbornen-2,3-dicarboxylic acid imide(HONB); (b) concentrating the waste liquor obtained in step (a); (c) treating a residue obtained in step (b) with an acidic buffer solution containing a tertiary amine; and (d) extracting and purifying the uncoupled amino acid derivative or the uncoupled small peptide fragment under acidic conditions.

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 herein are compounds of the following formula: ##STR1## wherein R.sup.1 is a group of the formula ##STR2## "X" is CH.sub.2 or N, "Z" is O, S, or N--R.sup.6, "A" is an amino acid residue, and Y, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are substituent variables as defined herein.The compounds are antagonists of tachykinin, and as such are useful for alleviation of pain and for treatment of disorders including asthma, bronchitis, rhinitis, conjunctivitis, dermatitis, arthritis, and urticaria.

Abstract: The small compounds of the instant invention are tachykinin antagonists. The compounds are highly selective and functional NK.sub.3 antagonists expected to be useful in the treatment of pain, depression, anxiety, panic, schizophrenia, neuralgia, addiction disorders, inflammatory diseases, gastrointestinal disorders, vascular disorders, and neuropathological disorders.

Abstract: Therapeutic agents and methods for the treatment of immunologically mediated diseases and malignancies of myeloid cell or lymphoid cell origin. These particular methods utilize the characterization of particular activation mechanisms important to the progression of these pathologies in humans. Selective inhibition of cell types responsible for precipitating these disorders in humans are provided with therapeutic agents which include peptides capable of inhibiting dipeptidyl peptidase-I activation of proenzymes present primarily in cytotoxic T-cells and myeloid cells, such as Gly--Phe--CHN.sub.2. Antisense oligonucleotides are also characterized which are specific for human dipeptidyl peptidase-I gene which may be used in the treatment of the described disorders.

Abstract: Peptidomimetics of the formula C-AMBA-X where C is cysteine, X is, for example, methionine or phenylalanine and AMBA is a hydrophobic spacer, notably 3-aminomethylbenzoic acid. These compounds are effective inhibitors of p21 ras farnesyltransferase. Other modifications including alternative spacers for AMBA, and replacement of the A.sub.1 A.sub.2 X component of known CA.sub.1 A.sub.2 X tetrapeptides by a non-peptide aryl or heterocyclic component are also disclosed as are various phosphonylated and arylated derivatives of peptides and peptidomimetics. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also referred to.

Abstract: Compounds and methods are disclosed that are useful in inhibiting the TNF-.alpha. converting enzyme (TACE) responsible for cleavage of TNF-.alpha. precursor to provide biologically active TNF-.alpha.. The compounds employed in the invention are peptidyl derivatives having active groups capable of inhibiting TACE such as, hydroxamates, thiols, phosphoryls and carboxyls.

Abstract: A process for the synthesis of hydroxyethylene dipeptide isosteres from .alpha.-N,N-di(protected)-amino(alkyl or substituted alkyl)methyl ketones that can be efficiently carried out on an industrial scale. The process proceeds with excellent diastereoselectivity and chemical efficiency, and can be used to prepare a wide variety of hydroxyethylene dipeptide isosteres for a variety of uses, including as HIV-1 protease inhibitors and renin inhibitors.

Abstract: A process for improving the yield of crystallization of L-phenylalanine monomethyl sulfate from an aqueous solution containing L-phenylalanine and monomethyl sulfate, by adding an effective crystallization improving amount of a salt of an inorganic or organic acid with an alkali metal, an alkaline earth metal or ammonium, to the aqueous solution.

Abstract: The present invention provides methods and pharmaceutical preparations for inhibiting the growth of bacterial microorganisms.

Abstract: Methods of making unnatural amino acids are provided which unnatural amino acids can be incorporated into peptides which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. These unnatural amino acids are useful in the synthesis of peptides and have the formula (a): ##STR1## where W is (CH.sub.2).sub.n or ##STR2## n is an integer from 1 to 6; j=1, 2 or 3, and preferably, Y is N--CN, X is NH and R.sub.2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pyridyl. Disclosed are peptides that are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions.

Abstract: Novel antagonists of endothelin are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, metabolic, endocrinological, neurological disorders especially cerebral vasospasm, stroke, and head injury, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease, restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, and diabetes.

Abstract: The present invention is directed to the use of a cyclopropylmethyl derivative as a protecting group for compounds containing an amino group, carboxy group, amido group, mercapto group or hydroxy group and to the compounds formed having the cyclopropylmethyl moiety as the protecting group.

Abstract: Addition of a reaction mixture obtained by the mineral acid hydrolysis of at least one side flow generated from the production of .alpha.-L-aspartyl-L-phenylalanine methyl ester to a crystallization slurry containing L-phenylalanine while maintaining the pH of the slurry at 3-8 by adding aqueous alkali affords crystallized L-phenylalanine having a low water content in a high yield.