The present disclosure relates to novel sulfonylurea and sulfonyl thiourea compounds and related compounds and their use in treating a disease or condition responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.

In one aspect, described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains an intronic REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises an intronic REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising an intronic REMS, and uses of those artificial gene constructs to modulate protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise an intronic REMS, and the use of a compound described herein to modulate protein produced from such altered endogenous genes.

The present invention provides a therapeutic drug that is useful for levodopa induced dyskinesia in Parkinson's disease. In particular, the present invention provides a composition and method for treating, improving, delaying the progression, or preventing motor complications associated with levodopa therapy for Parkinson's disease, especially levodopa induced dyskinesia (PD-LID), comprising tandospirone or a pharmaceutically acceptable salt or prodrug thereof, wherein the tandospirone or a pharmaceutically acceptable salt or prodrug thereof is parenterally administered.

According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A.sub.1-A.sub.2b or, particularly, the A.sub.2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy.sup.1 or Het.sup.A; Cy.sup.1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy.sup.1 group is optionally substituted by one or more R.sup.4a substituents; Het.sup.A represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more hetermatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy.sup.2 or Het.sup.B; Cy.sup.2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, which Cy.sup.2 group is optionally substituted by one or more R.sup.4c substituents; Het.sup.B represents a 3- to 10-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one or two rings and which Het.sup.B group is optionally substituted by one or more R.sup.4d substituents.

##STR00001##

Disclosed herein are tricyclic compounds, including pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-4-amine, and pyrimido[4′,5′:4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M.sub.4 (mAChR M.sub.4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

The present invention aims to provide a novel compound having a high mPTP-opening inhibitory activity and/or a useful therapeutic effect on various diseases. An aspect of the present invention relates to a mitochondrial permeability transition pore (mPTP)-opening inhibitor, a medicament or a pharmaceutical composition comprising a compound represented by formula (I), wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are the same as defined in the specification and the claims, a stereoisomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, as an active ingredient. Another aspect of the present invention relates to a compound represented by formula (Ia), wherein R.sup.1a, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are the same as defined in the specification and the claims, a stereoisomer thereof, a prodrug thereof, or a salt thereof, or a solvate thereof.

An 8-substituted styryl xanthine derivatives and uses thereof, specifically, relates to a novel 8-substituted styryl xanthine derivative and a pharmaceutical composition containing this compound, which can be selective adenosine A.sub.2A receptor antagonist, and also relates to methods of preparing this compound and pharmaceutical composition, and uses thereof in the manufacture of a medicament for treating an adenosine A.sub.2A receptor-related disease, especially Parkinson's Disease.

During clinical trials on patients suffering from neurological disorders, it has been observed that some patients obtain dramatic improvements in motor control and/or higher mental functioning, when they receive a combination of dextromethorphan and quinidine, at suitable dosages. Improved motor control has been exemplified to date by improved ability to swallow and/or speak, among victims of stroke, head injury, or ALS. Improved higher mental functioning has been exemplified in better job performance, increased ability to analyze and solve problems, and increased ability to have successful and satisfying interactions with other people. These types of effects can be seen in a relatively brief time period, such as within several days to a week.

Herein is reported an anti-transferrin receptor antibody that specifically binds to human transferrin receptor and cynomolgus transferrin receptor, which comprises i) a humanized heavy chain variable domain derived from the heavy chain variable domain of SEQ ID NO: 01, and ii) a humanized light chain variable domain derived from the light chain variable domain of SEQ ID NO: 26, wherein the antibody has an off-rate for the human transferrin receptor that is equal to or less than (i.e. at most) the off-rate of the anti-transferrin receptor antibody 128.1 for the cynomolgus transferrin receptor, whereby the off-rates are determined by surface plasmon resonance, and whereby the anti-transferrin receptor antibody 128.1 has a heavy chain variable domain of SEQ ID NO: 64 and a light chain variable domain of SEQ ID NO: 65.

The present disclosure relates to combinations of a β-lactam compound or a pharmaceutically acceptable salt thereof and probenecid or a pharmaceutically acceptable salt thereof. The present disclosure also relates to methods of treating or preventing a disease via administering to subjects in need thereof a β-lactam compound or a pharmaceutically acceptable salt thereof and probenecid or a pharmaceutically acceptable salt thereof.