38 results about "Lipoxygenase Inhibitors" patented technology

Pharmaceutical compositions comprising particles of lipoxygenase inhibitor compounds having an effective average size of from about 10 nm to about 50 microns are provided. More particularly, pharmaceutical compositions of particle of a 5-lipoxygenase inhibitor compound having an effective average size of from about 50 nm to about 5 microns are provided. The pharmaceutical compositions are in the form of aqueous suspensions with the particle of the 5-lipoxygenase inhibitor compound present in concentrations of from about 5 to about 200 mg / ml. In addition, methods for making such pharmaceutical compositions are provided. In particular, microprecipitation and direct homogenization in the presence of at least one surfactant are disclosed for making the pharmaceutical compositions.

This invention is in the field of a combination comprising a therapeutically-effective amount of a cyclooxygenase-2 inhibitor, a 5-lipoxygenase inhibitor and an immunosuppressive drug selected from antiproliferative agents, antiinflammatory-acting compounds and inhibitors of leukocyte activation. This combination may be used, for example, to suppress the immune response associated with organ transplantation, graft versus host disease, and conditions with underlying autoimmune or inflammatory reactivities or responses.

In accordance with the present invention, there are provided novel compounds that have a variety of properties, i.e., antioxidant, anti-inflammatory, antiviral, antibacterial, and antifungal properties. Invention compounds, therefore, have the ability to impart a variety of beneficial physiological effects, e.g., to protect neurons and / or to promote neuroregeneration and / or to promote memory formation and / or to act as protein phosphatase or kinase inhibitors and / or to act as lipoxygenase inhibitors. Such compounds are useful for treatment of a variety of indications, including neurodegenerative diseases and conditions, diabetes, ischemia associated with heart disease, and memory deficit. In another aspect of the present invention, there are also provided formulations containing one or more of the above-described compounds, optionally further containing additional neurologically active compound(s) and / or adjuvants to facilitate delivery thereof across the blood / brain barrier. In still another aspect of the present invention, there are further provided methods for treating a wide variety of neurological indications, e.g., acute neural injuries, chronic injuries, promoting memory formation, and the like.

The invention provides a 5-lipoxygenase inhibitor and a preparation method, a medical composite and an application thereof. More specifically, the invention provides a compound shown in general formula (I) or acceptable salt, solvate or hydrate thereof in pharmacy. The invention also relates to a preparation method, medical composite and application of the compound. The biological activity experiment shows that the compound of the invention is effective 5-LOX small molecule inhibitor with novel structure. Therefore the compound is expected to be developed to be new powerful chemical entity forcuring diseases related to leukotriene.

Methods for promoting osteogenesis to accelerate or enhance bone fracture healing, treat bone defects, and enhance bone formation are disclosed. The methods rely on in vivo or ex vivo modulation of an arachidonic acid metabolic or signaling pathway in general, and, in particular, utilize 5-lipoxygenase inhibitors, leukotriene A4 hydrolase inhibitors, and / or leukotriene B4 receptor antagonists. These molecules can be delivered alone or in combination with one or more agents that inhibit bone resorption, regulate calcium resorption from bone, enhance bone accumulation, enhance bone formation, induce bone formation, impair growth of microorganisms, reduce inflammation, and / or reduce pain.

A method may include treating pain, shock, and / or inflammatory conditions in a subject. A method may include using a therapeutically effective amount of an antibody, a lipoxygenase inhibitor, a cytochrome P-450 enzyme inhibitor, and / or an antioxidant configurable to at least partially treat pain, shock, and / or inflammatory conditions in a subject. A method of treating pain, shock, and / or inflammatory conditions in a subject may include inactivating or preventing at least one linoleic acid metabolite to treat certain conditions (e.g., pain, shock, and / or inflammation).

The use of compounds of the formula (I) Ar1-L1-Ar2-L2-C(R3)(R4)N(OR1)C(═Y)—R2 (I) where Y is selected from O or S; R1 is H, a salt or readily hydrolysable substituent; R2 is selected from H or CH3, CH2F, CF2H or CF3; R3 and R4 are selected independently from H, C 1-4 alkyl or alkenyl, CF3, CH2F, CF2H and F, with the proviso that if either R3 or R4 is H, then the other is not H; L1 is a linker group; L2 is a linker group comprising an optionally substituted or unsubstituted unsaturated branched or straight chain alkyl group; Ar1 is an optionally substituted or unsubstituted aryl or heterocyclic group; and Ar2 is an optionally substituted or unsubstituted aryl or heterocyclic group, in the treatment of 5-lipoxygenase mediated cancer provide improved therapies due to the effective inhibition of 5-lipoxygenase and long duration of activity in vivo after oral administration.

The present invention relates to 5-lipoxygenase inhibitors. Compounds disclosed herein can be useful in the treatment of bronchial asthma, chronic obstructive pulmonary disorder, arthritis, type I diabetes, multiple sclerosis, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, cancer, pruritis, urticaria, atopic dermatitis, allergic rhinitis, other inflammatory and autoimmune diseases. Processes for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds and their use as 5-lipoxygenase inhibitors are also provided.

The present invention provides oxazolyl and thiazolyl inhibitors of 15-LO, pharmaceutical compositions containing such inhibitors and methods for treating diseases related to the 15-LO cascade using such compounds and compositions.

The present invention relates generally to muscarinic receptor antagonist, which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds and the method for treating diseases mediated through muscarinic receptors. Also provided herein are pharmaceutical composition comprising one or more muscarinic receptor antagonists and at least one other active ingredients include, but are not limited to, corticosteroids, beta agonists, leukotriene antagonists, 5-lipoxygenase inhibitors, anti-histamines, antitussives, dopamine receptor antagonists, chemokine inhibitors, p38 MAP Kinase inhibitors, and PDE-IV inhibitors.

process is described for preparing a compound of Formula (1.3.0):comprising: establishing a reaction mixture consisting ofin an aprotic solvent; in the presence of a strong base in solid form selected from the group consisting of sodium hydroxide, NaOH; and potassium hydroxide, KOH;-and optionally-in the presence of a catalytic amount of cesium carbonate, Cs2CO3, or of a phase transfer catalyst, especially a quaternary ammonium salt or a phosphonium salt-followed by-heating said reaction mixture under a nitrogen atmosphere; whereby there is produced a compound of Formula (1.3.0); and in a preferred embodiment the aprotic solvent is DMSO, the strong base in solid form is NaOH in powder or pellet form, and the phase transfer catalyst is tetra-n-butylammonium chloride (TBAC), which is used to prepare a preferred compound, useful as a 5-lipoxygenase inhibitor, of the formula:especially the substantially pure methanesulfonate salt thereof.

The present invention relates to the use of derivatives of monosaccharides as 5-lipoxygenase inhibitor.

The present invention is directed to formulations of inclusion complexes of lipoxygenase inhibitors and cyclodextrins having a therapeutically effective concentration of the lipoxygenase inhibitor, methods of making the same and methods of treating disease states using the same. Forming cyclodextrin complexes permits the enhancement of the aqueous solubility of lipoxygenase inhibitors which allows higher concentrations of the lipoxygenase in solution. Aqueous formulations of lipoxygenase inhibitors-cyclodextrin complexes are suitable for parenteral or oral administration for treating and / or preventing inflammatory disease states. The aqueous formulations can be lyophilized to prolong storage stability, assist in oral administration and / or provide for convenient and economical packaging.

This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation.

The present invention relates to the identification of inhibitors of lipoxygenase enzymes. Methods are presented for using novel lipoxygenase inhibitors: LOXBlock-1 and LOXBlock-3, and other candidate lipoxygenase inhibitors identified by similar screening strategies, in therapy and diagnostics for neurodegenerative disorders.

There is provided compounds of formula (I) wherein W is an optionally substituted aryl or heteroaryl group, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15-lipoxygenase) is desired and / or required, and particularly in the treatment of inflammation.

A process is described for preparing a compound of Formula (1.3.0):comprising: establishing a reaction mixture consisting ofin an aprotic solvent; in the presence of NaOH or KOH; optionally in the presence of a phase transfer catalyst, especially a quaternary ammonium salt or a phosphonium salt; followed by heating said reaction mixture under a nitrogen atmosphere.

There is provided compounds of formula (I) wherein W is an optionally substituted aryl or heteroaryl group, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15- lipoxygenase) is desired and / or required, and particularly in the treatment of inflammation.

A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and / or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising a lipoxygenase inhibitor for the treatment of asthma, chronic obstructive pulmonary disease, or any other respiratory disease. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or any other respiratory disease.

The invention provides a pharmaceutical product comprising a first active ingredient which is N-[2-(Diethylamino)ethyl]-N-(2-{[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-naphthyl)ethoxy]propan amide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a CCR1 antagonist; achemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DP1 antagonist; an Histone Deacetylase Inducer; an IKK2 inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; an MPO inhibitor; a muscarinic antagonist which is Aclidinium bromide, Glycopyrrolate, Oxitropium bromide, Pirenzepine, telenzepine, Tiotropium bromide,3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide,3(R)-1-phenethyl-3-(9H-xanthene-9-carbonyloxy)-1-azoniabicyclo[2.2.2]octane bromide or (3R)-3-[(2S)-2-cyclopentyl-2-hydroxy-2-thien-2-ylacetoxy]-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]actane bromide; a p38 inhibitor; a PDE inhibitor; a PPARy agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

The invention belongs to the technical field of 5-lipoxygenase inhibitors, and particularly relates to application of liensinine as a 5-lipoxygenase inhibitor. Related researches in the prior art showthat 5-LOX plays an important role in inflammatory response of organisms. The 5-LOX inhibitor has a good treatment effect on inflammation, and chemical monomers with good 5-LOX inhibition activity are screened from traditional Chinese medicines with anti-inflammatory effects in the existing research. According to the present invention, the liensinine screened through the molecular interaction hasgood affinity with 5-LOX. Based on the research result, liensinine is expected to become a potent chemical entity for treating diseases related to 5-lipoxygenase. The liensinine can be used for preparing a 5-lipoxygenase inhibitor, an experimental model tool drug of the 5-lipoxygenase inhibitor or a drug for treating and preventing leukotriene-related diseases.

The present invention relates to 5-lipoxygenase inhibitors. Compounds disclosed herein can be useful in the treatment of bronchial asthma, chronic obstructive pulmonary disorder, arthritis, type I diabetes, multiple sclerosis, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, cancer, pruritis, urticaria, atopic dermatitis, allergic rhinitis, other inflammatory, and autoimmune diseases. Processes for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds and their use as 5-lipoxygenase inhibitors are also provided.

This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation.

A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and / or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising a lipoxygenase inhibitor for the treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases.

A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and / or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising a lipoxygenase inhibitor for the treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases.

A novel process intermediate, tetrahydro-4-[3-(4-fluorophenyl)thio]phenyl-2H-pyran-4-carboxamide, of the formula:is described, as well as its use in a process of preparing 5-lipoxygenase inhibitors of the formula:which comprises establishing a reaction mixture consisting of:andan electron deficient monocyclic or benzo-fused bicyclic N-heterocycle containing two nitrogen atoms of the formula: in an aprotic solvent; in the presence of a carbonate of the formula: (M)2-CO3, where M is an alkali metal, Group 1 / Ia element, selected from the group consisting of lithium, Li; sodium,Na; potassium, K; rubidium, Rb; and cesium, Cs; followed by heating of said reaction mixture under a nitrogen atmosphere; whereby there is produced the desired compound of the above-recited formula.

The present invention provides compounds of formula (I) wherein R, Z, Y, W, R5, V, and X are as defined in the description, and pharmaceutically acceptable salts thereof, which are useful for the treatment of diseases responsive to the inhibition of the enzyme 15-lipoxygenase. Thus, the compounds of formula (I) and their pharmaceutically acceptable salts are useful for treating diseases with an inflammatory component, including atherosclerosis, diseases involving chemotaxis of monocytes, inflammation, stroke, coronary artery disease, asthma, arthritis, colorectal cancer, and psoriasis.