68 results about "Motilin" patented technology

Novel spatially-defined macrocyclic compounds containing specific conformational control elements are disclosed. Libraries of these macrocycles are then used to select one or more macrocycle species that exhibit a specific interaction with a particular biological target. In particular, compounds according to the invention are disclosed as agonists or antagonists of a mammalian motilin receptor and a mammalian ghrelin receptor.

A complex is provided for the treatment of neurogenic conditions having the formula:where R1 isM 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 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 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.

An isolated chimeric peptide consisting of one or two added peptides and an object peptide wherein the added peptide is bonded to the N-terminus, the C-terminus or both of the object peptide, wherein if the added peptides are bound to both terminals, the two added peptides may be the same or different; and physiological activity of the object peptide is still retained, wherein the object peptide is a natural physiologically active peptide selected from the group consisting of an atrial natriuretic peptide, a brain natriuretic peptide, a C-type natriuretic peptide, motilin, a glucagon-like peptide 1, parathyroid hormone, and calcitonin, or a derivative of any thereof, wherein the derivative has one or more amino acid(s) deleted from the amino acid sequence of a natural physiologically active peptide and has the desired physiological activity.

Compounds are provided which are useful in treating disorders of gastrointestinal motility and which have the structureor a pharmaceutically acceptable salt thereof, a prodrug ester thereof, and all stereoisomers thereof,wherein R1 and R2 are the same or different and are independently selected from hydrogen, alkyl, aryl, cycloalkyl, alkenyl, alkynyl, arylalkyl, heteroaryl, heteroarylalkyl or heterocycloalkyl;Z is selected from —CON(R4)R4a, —CO2R4, —SO2N(R4)R4a, —SO2R4, CN, andR4 and R4a are the same or different and are independently selected from hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl or R4 and R4a can be joined together to form a heterocycle.R4b is selected from hydrogen, halogen, hydroxyl, CN, OCF3, CF3, CONH2, SONH2, SO2CH3, NHCOCH3 or NHCO2CH3; andQ is a substituted bicyclic heterocycle.A method for using such compounds for treating disorders of gastrointestinal motility is also provided.

The present invention relates to novel substituted diamine derivatives for the formula wherein R1, R2, R3, R4, X1, X2, X3, X4, A, Y and n are as described in the specification, pharmaceutical compositions containing them and intermediates used in their manufacture. More particularly, the compounds of the invention are motilin receptor antagonists useful for the treatment of associated conditions and disorders such as gastrointestinal reflux disorders, eating disorders leading to obesity and irritable bowel syndrome.

The present invention aims at providing motilin-like peptide compounds that maintain the gastrointestinal motility stimulating activity of native motilin and which are adapted to have higher absorbability upon transmucosal administration. Motilin derivatives were designed and synthesized in consideration of the pathway for the degradation of motilin at a site of its transmucosal absorption and the maintenance of motilin's physiological activity and compounds characterized by substitutions for the amino acid at position 21 of native motilin have been found to show higher absorbability upon transmucosal administration and yet maintain the same activity as motilin.

The present invention provides conformationally-defined macrocyclic compounds that bind to and / or are functional modulators of the motilin receptor including subtypes, isoforms and / or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and / or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.