Disclosed are a compound as represented by general formula (I), a cis-trans isomer thereof, an enantiomer thereof, a diastereoisomer thereof, a racemate thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof or a prodrug thereof, a preparation method therefor, a pharmaceutical composition comprising the compound and the use of the compound as an Lp-PLA.sub.2 inhibitor

##STR00001##

Disclosed is a compound of formula (I)

##STR00001## or a stereoisomer thereof, or a salt of any of the foregoing and to processes for its preparation. The compounds of formula (I) are useful in the treatment TRPML1-mediated disorders or diseases.

The invention relates to a derivative of a GLP-1 analogue of a general Formula I, which derivative comprises a side chain attached to a Lys residue at position 34, 35, 36, 37, or 38 of the GLP-1 analogue, which side chain comprises a Branched linker, a 1.sup.st and a 2.sup.nd Protractor selected from C18 diacid, C20 diacid, and sulfonic acid C16, and at least one Linker element-1 incorporating ethylene glycol units. Linker element-1 may be incorporated in an optional Pre-linker, and/or in a 1.sup.st or 2.sup.nd Post-linker. The invention also relates to novel GLP-1 analogues, novel side chain intermediate products and their manufacture and use to prepare derivatives of biologically active peptides and proteins, as well as pharmaceutical compositions and medical uses of the analogues and derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Sodium channel, voltage-gated, alpha subunit (SCNA), in particular, by targeting natural antisense polynucleotides of Sodium channel, voltage-gated, alpha subunit (SCNA). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of SCNA.

A method for treating conditions associated with thalamocortical dysrhythmia. The method includes applying transcranial low voltage electrical stimulation (TLVES) therapy or transcranial magnetic stimulation (TMS) therapy to a patient in need thereof, and administering to the patient a dissociative anesthetic during the TLVES therapy or the TMS therapy. A number of conditions including tinnitus, depression and pain can be treated with TLVES or TMS in combination with the dissociative anesthetic, such as an NMADR inhibitor, including ketamine.

The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands of the NR2B receptor and may be useful for the treatment of various disorders of the central nervous system.

##STR00001##

Provided herein are methods of treating multiple sclerosis with a fumarate, wherein the fumarate is a dialkyl fumarate, a monoalkyl fumarate, a combination of a dialkyl fumarate and a monoalkyl fumarate, a prodrug of monoalkyl fumarate, a deuterated form of any of the foregoing, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, or stereoisomer of any of the foregoing, or a combination of any of the foregoing. The methods provided herein improve the safety of treatment by informing and monitoring patients undergoing treatment regarding progressive multifocal leukoencephalopathy, and/or by monitoring lymphocyte count.

Disclosed herein are polymorphic and amorphous forms of anhydrate, hydrate, and solvates of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide and methods of using such compositions for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. Further disclosed are methods of making such polymorphic and amorphous forms.

Disclosed is the use of O-(3-piperidino-2-hydroxy-1-propyl)-nicotinic amidoxime (BGP15), its tautomers, enantiomers and pharmaceutically acceptable salts thereof for the treatment of Familial Dysaustonomia.