144 results about "AVP - Arginine vasopressin" patented technology

A complex is provided for the treatment of neurogenic conditions having the formula: where R1 is M is a metal ion Ca(II), Mg(II), Cu(II) or Ni(II); n is an integer 1 or 2; R is BBB peptide, transferrin, membrane transporter peptide, TAT peptide, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, L-lactate, L-leucine, L-tryptophan, and L-glutamate; and R is coupled to M through a carboxylate moiety. Magnesium (II) represents the preferred metal ion as magnesium is known to have neuroprotective effects. The metal ion is in part chelated by a non-steroidal anti-inflammatory drug that does not inhibit platelet activity and includes salicylate and ibuprofenate. The complex also includes a ligand operative in transport across the blood brain barrier. A process for making an inventive complex includes the stoichiometric addition of ligands containing carboxylate groups to a solution of the metal ion. In instances where the metal ion is magnesium (II), a stoichiometric ratio of 1:1:1 is found between the non-steroidal anti-inflammatory ligand:magnesium (II):transporter ligand.

A compound is provided that has the formula NH2CH2CH2CH2C(O)N—R   (I) where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidetransferrin, glucosylamnine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

The disclosed invention is a composition agonists and / or antagonists of V.sub.2, V.sub.1a or both receptors, in a host, including animals, and especially humans, using a small molecule or its pharmaceutically acceptable salt or prodrug.

4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivatives, which have excellent arginine vasopressin V2 activity and are useful for a drug for the treatment of central diabetes insipidus and / or nocturia.

Compounds according to general formulae (1 and 2), wherein G<1 >is an azepine derivative and G<2 >is a group according to general formulae (9-11) are new. Compounds according to the invention are vasopressin V2 receptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents.

This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V1 and V2 are both H, OMe or F, or one of V1 and V2 is Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N3, NH2, NHBn or NH-acyl and the other is H, or V1 and V2 together are =O, -O(CH2)pO- or -S(CH2)pS-; W1 is either O or S; X1 and X2 are both H, or together are =O or =S; Y is OR5 or NR6R7; R1, R2, R3 and R4 are independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; R5 is selected from H and lower alkyl; R6 and R7 are independently selected from H and lower alkyl, or together are -(CH2)n; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V1 and V2 are both H, OMe or F, or one of V1 and V2 is Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N3, NH2, NHBn or NH-acyl and the other is H, or V1 and V2 together are ═O, —O(CH2)pO— or —S(CH2)pS—; W1 is either O or S; X1 and X2 are both H, or together are ═O or ═S; Y is OR5 or NR6R7; R1, R2, R3 and R4 are independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; R5 is selected from H and lower alkyl; R6 and R7 are independently selected from H and lower alkyl, or together are —(CH2)n—; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

A compound is provided that has the formula NH2CH2CH2CHR1C(O)N—R  (I) where R1 is p-chlorophenyl, R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

Compounds according to general formula (1), and pharmaceutically acceptable salts thereof, wherein V is a covalent bond or NH, X is selected from CH2, O and N-alkyl, Z is either S or -CH=CH-, R<1 >and R<2 >are independently selected from H, F, Cl, Br and alkyl, R<3 >is selected from OH, O-alkyl and NR<4>R<5>, R<4 >and R<5 >are each independently H or alkyl, or together are -(CH2)q-, p is 0, 1, 2, 3 or 4, and q is 4 or 5, are new. They are agonists at the asopressin V2 receptor and are useful as antidiuretics and pro-coagulants.

The invention provides methods, nucleic acids, compositions and kits for predicting a subject's response to treatment with one or more vasopressin receptor agonists to identify subjects having a greater benefit from treatment with vasopressin receptor agonist(s). The method generally comprises determining a vasopressin pathway associated gene polymorphism genotype(s) of a subject for one or more polymorphisms in the these genes, comparing the determined genotype with known genotypes for the polymorphism that correspond with an improved response genotype to identify potential subjects having an inflammatory condition who are more likely to benefit from treatment with a vasopressin receptor agonist and subsequent to treatment recover from the inflammatory condition. The invention also provides for methods of treating such subjects with vasopressin receptor agonists based on the subject's genotype.

Provided herein are peptide formulations comprising polymers as stabilizing agents. The peptide formulations can be more stable for prolonged periods of time at temperatures higher than room temperature when formulated with the polymers. The polymers used in the present invention can decrease the degradation of the constituent peptides of the peptide formulations.

A compound is provided that has the formulaNH2CH2CH2CH2C(O)N—R  (I)where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidetransferrin, glucosylamnine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

A compound is provided that has the formulaNH2CH2CH2CHR1C(O)N—R   (I)where R1 is p-chlorophenyl, R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.

The invention discloses a method for preparing vasopressin tannate. The preparation method of the vasopressin comprises the following step: sequentially carrying out reverse-phase purification and reverse-phase desalination on a vasopressin crude product solution by a high performance liquid chromatography, so as to obtain the vasopressin tannate, wherein packing of the high performance liquid chromatography, is a polystyrene-divinylbenzene (PS-DVB) copolymer. By combination of reverse-phase purification and reverse-phase desalination, the latest application of the polymer packing polystyrene-divinylbenzene is designed; and the vasopressin tannate can be prepared on a large scale.

The present invention relates to a method for reducing infarction comprising administering to a patient ion need thereof a therapeutically effective amount of a composition comprising as an active ingredient a vasopressin antagonist compound and to a composition useful therefor. The present invention also relates to a method for reducing infarction comprising administering to a patient in need thereof a therapeutically effective amount of a combination of a vasopressin antagonist compound and a beta-blocker and to combinations useful therefor. The methods, compositions and combinations of the present invention can be used for reducing infarction in the heart (myocardial infarction) and the brain (stroke). The methods, compositions and combinations of the present invention can also be used for the treatment and / or prevention of hypertension, edema, ascites, heart failure, renal function disorder, vasopressin inappropriate secretion syndrome (SIADH), hepatocirrhosis, hyponatremia, hypokalemia, polycystic kidney disease, diabetes, or circulation disorder.

A compound of the formulawhere R1 is H, C1–C4 alkyl and OH; R2 in is H, C1–C4 alkyl and OH; R3 is H and C1–C4 alkyl; R4 is H and C1–C4 alkyl; n is an integer between 0 and 2 inclusive; R5 is a nullity, NHR7C(O)—, C6H4—, C6H4—O—; R7 is C2–C6 alkyl; and R6 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, transferrin, glucosylamine, amino saccharin, saccharin ester, lactylamine, leucine, tryptophan, amino glutamate and amino cholines.

A pharmaceutical composition has a therapeutically effective amount of at least one of: a pharmaceutically active nasal peptide, its pharmaceutically acceptable salt and its peptidic fragment. The composition also contains an absorbefacient effective amount of THAM in a pharmaceutically acceptable, aqueous liquid diluent or carrier. The composition is provided in a convenient form for nasal administration. In one embodiment, the peptidic fragment may be selected physiologically active lymphokines and monokines, peptidic enzymes, proteic vaccines, peptidic toxoids and personalized proteins derived from genoma. In another embodiment, the peptidic fragment may be selected from the peptide hormones and hormone antagonists buserelin, desmopressin, vasopressin, angiotensin, felypressin, octreotide, somatropin, thyrotropin (TSH), somatostatin, gosereline, thryptorelin and insulin selected from the group consisting of cow and pig, synthetic and recombinant.

Novel compounds of Formula (I)and pharmaceutically acceptable salts thereof, and pharmaceutical formulations containing such compounds which are useful as anti-aquaretic agents in the treatment of nocturnal urinary enuresis, nocturnal urinary urgency, and / or similar conditions.

A compound of the formula where R1 is H, C1-C4 alkyl and OH; R2 in is H, C1-C4 alkyl and OH; R3 is H and C1-C4 alkyl; R4 is H and C1-C4 alkyl; n is an integer between 0 and 2 inclusive; R5 is a nullity, NHR7C(O)—, C6H4—, C6H4—O—; R7 is C2-C6 alkyl; and R6 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidegluconate, transferrin, glucosylamine, amino saccharin, saccharin ester, lactylamine, leucine, tryptophan, amino glutamate and amino cholines.

The present invention relates to a compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one O-methy19243-yloxime, and / or an active metabolite thereof having antagonist action at the oxytocin receptor and / or vasopressin V1a receptor, to processes for their preparation, pharmaceutical compositions containing them and their use.

Provided herein are peptide formulations comprising polymers as stabilizing agents. The peptide formulations can be more stable for prolonged periods of time at temperatures higher than room temperature when formulated with the polymers. The polymers used in the present invention can decrease the degradation of the constituent peptides of the peptide formulations.

The present invention is concerned with spiro-dihydrotetraazabenzoazulenes, i.e. spiro-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes of formula I wherein R1, R2, R3, X, Y, Z, m and n are as described herein. The compounds according to the invention act as V1a receptor modulators and are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.

The present invention relates to heterobiaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula Iwherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.

The present invention is concerned with aryl- / heteroaryl-cyclohexenyl-tetraazabenzo[e]azulenes of formula Iwherein R1, R2 and R3 are as described herein. The invention further provides methods for the manufacture of such compounds and pharmaceutical compositions containing them. The compounds according to the invention act as V1 a receptor modulators, and in particular as V1 a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.

The disclosure provides methods for processing a biological samples and determining the presence or an amount of a polypeptide in a biological sample, such as when the polypeptide is oxytocin or vasopressin.

The invention relates to tangerine peel buccal tablets, oral disintegrating tablets and application thereof. 1,000 tangerine peel buccal tablets or 1,000 oral disintegrating tablets are prepared fromthe following components and pharmaceutically acceptable additives: 120 to 220 grams of tangerine peel and 380 to 480 grams of fresh ginger. The tangerine peel has bidirectional regulation function ongastrointestinal smooth muscles so as to influence the gastrointestinal motility; the ginger can inhibit the central nervous system to release vasopressin so as to relive electrogastric hypsarrhythmia in motion sickness and symptoms such as nausea, vomit and the like; and when the tangerine peel and the ginger are combined, the effect of the combination is superior to that of dimenhydrinate, andthe combination has no adverse reaction such as drowsiness, dizziness, headache, thirst, nausea, vomit, epigastric region discomfort and the like.

The present invention is concerned with heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula Iwherein R1, R2 and R3 are as described herein.The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.

The invention relates to 3-pyrrole carboxylic acid derivatives, and a preparing method and an application thereof, and particularly relates to the 3-pyrrole carboxylic acid derivatives having a structure represented by formula I and pharmaceutically acceptable salts thereof and the preparing method of the derivatives, pharmaceutical compositions with the 3-pyrrole carboxylic acid derivatives having the structure represented by the formula I and the pharmaceutically acceptable salts of the 3-pyrrole carboxylic acid derivatives as active ingredients, and applications of the pharmaceutical compositions in prevention or treatment of diseases related with an arginine vasopressin V1a receptor, an arginine vasopressin V1b receptor, an arginine vasopressin V2 receptor, a sympathetic nervous system or a renin-angiotensin-aldosterone system.