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Discovery of highly potent and selective type I B-Raf kinase inhibitors

A series of pyrazolo[1,5-alpha]pyrimidine analogs has been prepared and found to be potent and selective B-Raf inhibitors. Molecular modeling suggests they bind to the active conformation of the enzyme.

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INDOLONES USEFUL AS SEROTONERGIC AGENTS

This invention relates to compounds of the formula: STR1 which are useful as 5-HT 4 agonists or antagonists and 5-HT 3 antagonists.

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BRIDGED, BICYCLIC HETEROCYCLIC OR SPIRO BICYCLIC HETEROCYCLIC DERIVATIVES OF PYRAZOLO[1,5-A]PYRIMIDINES, METHODS FOR PREPARATION AND USES THEREOF

Compounds of formula A: Formula (1) pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by Raf kinases.

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BENZIMIDAZOLE COMPOUNDS

This invention relates to compounds useful in treating 5-HT. sub.4 and/or 5-HT 3 mediated conditions of the formula STR1 or a pharmaceutically acceptable salt thereof wherein R 1 and R 2 are independently selected from the group consisting of hydrogen, alkoxy, halogen, amino, monoalkylamino, dialkylamino, acylamino and alkylsulfonylamino; R 3 is selected from the group consisting of H, alkyl and cycloalkyl; X is NH or O; and Z is selected from the group consisting of STR2 pharmaceutical compositions including the compounds and a method for treating serotonin mediated conditions with the compositions which act as 5-HT 4 agonists or antagonists and/or 5-HT. sub.3 antagonists.

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CEPHEM COMPOUND HAVING PSEUDO-CATECHOL GROUP

A compound of the formula: wherein X is ?N?, ?CH?, or the like; W is ?CH2? or the like; U is ?S? or the like; R1 and R2 are each independently hydrogen, halogen, optionally substituted lower alkyl, or the like; Q is a single bond or the like; R3 is hydrogen or the like; Ring A is a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms; each R4 is independently hydrogen, halogen, or the like; m is an integer from 0 to 2; G is ?C(?O)? or the like; D is a single bond, ?NH?, or the like; and E is a cyclic quaternary ammonium group, or an ester, a protected compound at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.

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2 – Substituted cephem compound-containing pharmaceutical composition (by machine translation)

PROBLEM TO BE SOLVED: To provide a cephem compound which has a strong antimicrobial activity, in particular effective against various beta-lactamase producing Gram negative bacteria, and a composition comprising the compound.SOLUTION: The present invention provides a pharmaceutical composition comprising a compound represented by formula (I), an ester at a carboxyl group, an amino-protected compound when the amino is present on a ring in the 7-side chain, or a pharmaceutically acceptable salt thereof.

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5-HT3 RECEPTOR MODULATORS, METHODS OF MAKING, AND USE THEREOF

Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.

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THIAZOLYL COMPOUNDS USEFUL AS KINASE INHIBITORS

The invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula I thiazolyl compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer’s disease

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Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship

The structure-activity relationship (SAR) for a novel series of catechol conjugated siderophore cephalosporins is described with their in vitro activities against multi-drug resistant Gram-negative pathogens including Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacteriaceae. Cefiderocol (3) was one of the best molecules which displayed well-balanced and potent activities against multi-drug resistant Gram-negative pathogens including carbapenem resistant bacteria among the prepared compounds with the modified C-7 side chain and the modified C-3 side chain. Cefiderocol (3) is a highly promising parenteral cephalosporin for the treatment of multi-drug resistant Gram-negative infection.

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4-SUBSTITUTED QUINUCLIDINE DERIVATIVES, METHODS OF PRODUCTION, AND PHARMACEUTICAL USES THEREOF

The present invention relates to compounds and formulations capable of affecting nicotinic acetylcholine receptors (nAChRs), for example, as modulators of specific nicotinic receptor subtypes (specifically, the alpha7 nAChR subtype). The present invention also relates to methods for treating a wide variety of conditions and disorders, particularly those associated with dysfunction of the central and autonomic nervous systems.

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