Abstract: Compounds which directly inhibit IRE-1? activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.

Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.

Abstract: Analogs related to oleamide are employed for potentiating the 5-HT2A and 5-HT1A responses to serotonin (5-HT). With respect to the potentiation of the 5-HT2A receptor response, it is disclosed that, of the naturally occurring fatty acids, the primary amide of oleic acid (oleamide) is the most effective potentiating agent of serotonin and that the potentiating activity of oleamide analogs is highly dependent upon their structural features. In particular, the presence, position, and stereochemistry of the 9-cis double bond is required and even subtle structural variations reduce or eliminate activity. Secondary or tertiary amides may replace the primary amide but follow a well-defined relationship requiring small amide substituents suggesting that the carboxamide serves as a hydrogen bond acceptor but not donor. Alternative modifications at the carboxamide as well as modifications of the methyl terminus or the hydrocarbon region spanning the carboxamide and double bond typically eliminate activity.

Abstract: The present invention describes a novel treatment for neuropsychiatric disorders, including anxiety disorders, mood disorders, psychotic disorders, somatoform disorders, and neuropsychiatric symptoms resulting from movement disorders. The treatment of the present invention utilizes any agent that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate (calcium N-acetylhomotaurinate). Alternatively, separate agents having these activities can be combined as a compound or mixture and thereby administered together. The invention also provides for a third agent that acts as a non-competitive NMDA-receptor blocking agent or ion channel blocker, that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium.

Abstract: Disclosed are multibinding compounds which are &bgr;2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma and bronchitis. They are also useful in the treatment of nervous system injury and premature labor.

Abstract: The present invention describes a novel treatment for neuropsychiatric disorders, including anxiety disorders, mood disorders, psychotic disorders, somatoform disorders, and neuropsychiatric symptoms resulting from movement disorders. The treatment of the present invention utilizes any agent that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate (calcium N-acetylhomotaurinate). Alternatively, separate agents having these activities can be combined as a compound or mixture and thereby administered together. The invention also provides for a third agent that acts as a non-competitive NMDA-receptor blocking agent or ion channel blocker, that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium.

Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.

Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.

Abstract: The invention relates to a drug, which contains one or more inhibitors for the cGMP-stimulated phosphodiesterase (PDE II) together with conventional substrates and/or diluents. Preferably the drug contains erythro-9-(2-hydroxy-3-nonyl)-adenine or 2-o-propoxyphenyl-8-azapurine-6-one, optionally together with one or more activators of guanyl cyclase. The invention also relates to the application of inhibitors of cGMP-stimulated phosphodiesterase (PDE II) for the control and prophylaxis of cardiovascular diseases and for the manufacture of drugs for cardiovascular diseases. Preferably erythro-9-(2-hydroxy-3-nonyl)-adenine or 2-o-propoxyphenyl-8-azapurine-6-one is used, optionally together with one or more activators of guanyl cyclase.

Abstract: This invention provides a disinfectant composition which is suited to the disinfection of confined spaces such as the interior of an ambulance or the like. It is prepared extemporaneously by blending a highly concentrated alcohol with glutaraldehyde and a buffer solution such as an aqueous solution of diethanolamine. This composition containing 65 to 80% of alcohol and 2 to 4% of glutaraldehyde exhibits a strong and lasting disinfectant effect. The invention further provides a method for space disinfection which comprises atomizing and spraying this disinfectant composition by means of a high-pressure gas such as pressurized carbon dioxide gas.

Abstract: Use of at least one aminothiol ester derivative for the preparation of a pharmaceutical composition intended to increase the inhibition of a character resistant to the induction of apoptosis of transformed cells, this character being due to the bc12 gene present in these cells. The pharmaceutical composition is more particularly intended to treat pathologies chosen from breast cancers, B cell lymphomas, leukaemias, neuroblastomas, adenocarcinomas of the prostate, prolactinomas and other pituitary adenomas.

Abstract: The instant invention is concerned with acetylphenols which are useful as antiobesity and antidiabetic compounds. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering or modulating triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility or for treating atherosclerosis are also disclosed.

Abstract: The present invention is directed to novel ketomethylene group-containing aldehyde inhibitors of cysteine or serine proteases. Methods for the use of the protease inhibitors are also described.

Abstract: A composition suitable for topical application to mammalian skin or hair for inducing, maintaining or increasing hair growth comprises:(i) a special protein tyrosine kinase inhibitor; and(ii) a cosmetically acceptable vehicle for the inhibitor.