Patent•
Compounds and methods for the treatment of cardiovascular, inflammatory and immune disorders
06 Jan 1995-
TL;DR: In this article, 2,5-Diaryl tetrahydrofurans, 1,3-diaryl cyclopentanes, and 2.5-dimethyltetrahydrothiophenes (2.5d) were shown to reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response.
Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. Also disclosed is a method to treat disorders mediated by PAF and/or leukotrienes that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, to a patient in need of such therapy.
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Patent•
24 Jul 1996TL;DR: In this article, 1,3dioxo-2-(2,6dioxopiperidin-3-yl)-5-aminoisoindoline is substituted with amino acid in the benzo ring.
Abstract: 1-Oxo- and 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl) isoindolines substituted with amino in the benzo ring reduce the levels of TNFα in a mammal. A typical embodiment is 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-aminoisoindoline.
274 citations
Patent•
22 Jul 1999
TL;DR: In this paper, the conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophiles, macrophages, and eosinophils.
Abstract: Conjugates containing as a ligand a chemokine receptor targeting agents, such as chemokines, and a targeted agent, such as a toxin are provided. These conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophiles, macrophages, and eosinophils. The conjugates provided herein are used to lessen or inhibit these processes to prevent or at least lessen the resulting secondary effects. In particular, the conjugates are used to target toxins to receptors on secondary tissue damage-promoting cells. The ligand moiety can be selected to deliver the cell toxin to such secondary tissue damage-promoting cells as mononuclear phagocytes, leukocytes, natural killer cells, dendritic cells, and T and B lymphocytes, thereby suppressing the proliferation, migration, or physiological activity of such cells. Among preferred conjugates are fusion proteins having a chemokine, or a biologically active fragment thereof, as the ligand moiety linked to a cell toxin via a peptide linker of from 2 to about 60 amino acid residues.
104 citations
Patent•
02 Aug 2001
TL;DR: In this paper, the effects of platelet activating factor (PAF) and the production and/or release of interleukin 8 (IL-8) are inhibited by a compound of formula (1) wherein R?1 and R2? are defined in the application, or a physiologically acceptable salt thereof.
Abstract: The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of formula (1) wherein R?1 and R2? are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.
83 citations
Patent•
14 May 2004
TL;DR: In this article, a method for treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines was proposed.
Abstract: The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.
52 citations
Patent•
08 Jun 2006
TL;DR: This article provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically acceptable aqueous carrier.
Abstract: There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier
40 citations
References
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TL;DR: In this article, a metal alkoxide is used as a catalyst, where the metal has a coordination number of at least four, and at least one, usually two, of the alkoxide groups bonded to the metal are bonded to asymmetric carbon atoms.
Abstract: OF THE DISCLOSURE Methods and compositions are provided for asymecrically donating an oxygen atom to a pair of electrons to produce an asymmetric product. Specifically, a metal alkoxide is used as a catalyst, where the metal has a coordination number of at least four, and at least one, usually two, of the alkoxide groups bonded to the metal are bonded to asymmetric carbon atoms. The metal catalyst is employed in conjunction with a hydroperoxide and an alkanol having a functionality with a pair of electrons capable of accepting an oxygen atom. The resulting product is enriched in one enantiomer due to the enantioselective introduction of an asymmetric center or an enhanced rate of reaction of one of the enantiomers of a chiral alkanol. Greatly enhanced yields of enantiomers are achieved as compared to prior enantioselective introduction of oxygen. This invention was made at least in part in the course of a grant from the U.S. National Institutes of Health (GM24551).
2,306 citations
Patent•
08 Jul 1982
TL;DR: In this article, the authors reported that serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of the muramyldeepthideptides.
Abstract: Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides.
1,621 citations
Patent•
Alza1
TL;DR: In this article, a method for delivering a drug substantially free of rapid precipitation from an osmotic device is described, which consists of imbibing fluid through the wall into the compartment at a rate determined by the permeability of the wall and the osmosis pressure gradient across the wall, forming in the compartment a basic solution containing drug and compound, which solution is delivered from the compartment through the passageway, and reacting the compound with the acid in the environment at the device-environment interface for evolving carbon dioxide, thereby, providing an effervescent suspension in the
Abstract: A method is disclosed for delivering a drug substantially free of rapid precipitation from an osmotic device. The osmotic device comprises a semipermeable wall surrounding a compartment, housing (1) a drug that exhibits limited solubility under neutral and acid conditions; and (2) a compound capable of evolving carbon dioxide in the presence of an acid in the environment of use. The method comprises, (a) imbibing fluid through the wall into the compartment at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, (b) forming in the compartment a basic solution containing drug and compound, which solution is delivered from the compartment through the passageway, (c) reacting the compound with the acid in the environment at the device-environment interface for evolving carbon dioxide, thereby, (d) providing an effervescent suspension in the environment that delivers the drug in a finely dispersed form to the environment of use over time. Also, a composition is disclosed comprising the drug and the compound.
658 citations
Patent•
Alza1
TL;DR: In this paper, an osmotic therapeutic system for delivering a drug is disclosed, which comprises a drug delivery module which module comprises a rate controlling laminated wall surrounding a reservoir and has a portal for delivering drug from the system.
Abstract: An osmotic therapeutic system for delivering a drug is disclosed. The system comprises a drug delivery module which module comprises a rate controlling laminated wall surrounding a reservoir and has a portal for delivering drug from the system. The laminated wall comprises a semipermeable lamina in laminar arrangement with a microporous lamina to provide a wall that is permeable to an external fluid, impermeable to drug and maintains its integrity during the delivery of drug. The reservoir contains a drug, or a mixture of drug and a solute which drug or solute is soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid. In operation, drug is released from the system by fluid being imbibed through the wall into the reservoir at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall thereby producing a solution of drug, or a solution of solute containing drug which solution is released through the portal at a controlled rate over a prolonged period of time.
580 citations
Journal Article•
TL;DR: The effectiveness of this compound for preventing LT formation in vitro, ex vivo and in vivo suggests its utility for preventing the pathophysiological effects of the LTs and other 5-lipoxygenase products in animals and in humans.
Abstract: Zileuton [N-(1-benzo[b]thien-2-ylethyl)-N-hydroxyure] inhibited 5-hydroxyeicosatetraenoic acid synthesis by rat basophilic leukemia cell 20,000 x g supernatant and rat polymorphonuclear leukocytes (PMNL) (IC50 = 0.5 and 0.3 microM) respectively. It also inhibited leukotriene (LT)B4 biosynthesis by rat PMNL (IC50 = 0.4 microM), human PMNL (IC50 = 0.4 microM) and human whole blood (IC50 = 0.9 microM). Inhibition of human PMNL LTB4 biosynthesis was removed readily by a simple wash procedure. At concentrations up to 100 microM, the compound produced little or no inhibition of several related enzymes, such as platelet 12-lipoxygenase, soybean and rabbit reticulocyte 15-lipoxygenase and sheep seminal vesicle cyclooxygenase. At p.o. doses from 0.5 to 5 mg/kg in the dog, zileuton produced a rapid and sustained inhibition of ex vivo blood LTB4 biosynthesis which correlated with the pharmacokinetic behavior of the compound. In a similar ex vivo study in the rat, the compound displayed an p.o. ED50 of 2 mg/kg. Zileuton was highly effective in preventing 6-sulfidopeptide LT formation in the rat peritoneal cavity triggered by an antigen-antibody reaction with an ED50 of 3 mg/kg. In experimental models of inflammation, zileuton significantly reduced arachidonic-acid induced mouse ear edema (ED50 = 31 mg/kg) and also attenuated inflammatory cell accumulation in the rat pleural Arthus reaction. The effectiveness of this compound for preventing LT formation in vitro, ex vivo and in vivo suggests its utility for preventing the pathophysiological effects of the LTs and other 5-lipoxygenase products in animals and in humans.
427 citations