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CATHEPSIN CYSTEINE PROTEASE INHIBITORS

This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

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PROTECTED MONOMER AND METHOD OF FINAL DEPROTECTION FOR RNA SYNTHESIS

A nucleoside monomer that is protected by a thionocarbamate protecting group is provided, as well as a method for making a polynucleotide that uses the same. Also provided is a polynucleotide synthesis method that employs a diamine to deprotect a protected polynucleotide.

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Imidazopyridine CB2 agonists: Optimization of CB2/CB1 selectivity and implications for in vivo analgesic efficacy

A new series of imidazopyridine CB2 agonists is described. Structural optimization improved CB2/CB1 selectivity in this series and conferred physical properties that facilitated high in vivo exposure, both centrally and peripherally. Administration of a highly selective CB2 agonist in a rat model of analgesia was ineffective despite substantial CNS exposure, while administration of a moderately selective CB2/CB1 agonist exhibited significant analgesic effects.

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Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity

We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) ? Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.

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NOVEL COMPOUND USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES

A novel compound able to inhibit JAK is disclosed, this compound may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6.

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Rapid Access to a Broad Range of 6?-Substituted Firefly Luciferin Analogues Reveals Surprising Emitters and Inhibitors

Light-emitting firefly luciferin analogues contain electron-donating groups in the 6?-position, but the scope of known 6?-substitution remains narrow. A two-step route to a broad range of 6?-substituted luciferin analogues was developed to fill this void and enable more extensive study of the 6?-functionality. This chemistry allowed direct access to “caged” amide and bright azetidine analogues, but also revealed thioether inhibitors and unexpectedly luminogenic aryl amine derivatives.

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TRICYCLIC HETEROCYCLIC COMPOUNDS AND JAK INHIBITORS

Novel tricyclic pyrimidine compounds and tricyclic pyridine compounds having JAK inhibitory activities are provided. A tricyclic heterocyclic compound represented by the formula (Ia): wherein the rings Aa and Ba, Xa, ya, Rla, Rza, R3a, Lla, L2a, L3a and na are as defined in the description.

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NOVEL SOLID FORMS

The instant invention relates to novel solid forms of the compound of formula (I) as well as solvates, inclusion complexes with other suitable compounds, processes for their manufacture, pharmaceutical compositions containing these solid forms, and their use as pharmaceuticals.

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Benzoxazolamines and Benzothiazolamines: Potent, Enantioselective Inhibitors of Leukotriene Biosynthesis with a Novel Mechanism of Action

A series of benzoxazolamine and benzothiazolamine analogs that inhibit leukotriene (LT) biosynthesis are described.The initial lead, (S)-N-(benzothiazol-2-yl)phenylalanine ethyl ester (5a), was discovered in a screening program for inhibition of Ca-ionophore-A23187-induced LTB4 release in human polymorphonuclear leukocytes (IC50 0.23 muM).Through structural modification, it was determined that hydrophobic substituents in the 5-position and replacement of the phenyl ring of phenylalanine with a cyclohexyl group greatly enhance potency.Several ester bioisosteres that retain potency and enantiomeric selectivity are described.Lead optimization culminated in (S)-N-<2-cyclohexyl-1-(2-pyridinyl)ethyl>-5-methyl-2-benzoxazolamine (43b), IC50 0.001 muM.The compounds described are not inhibitors of 5-lipoxygenase but, rather, act at the level of arachidonic acid release.

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ANTIMICROBIAL COMPOUNDS AND METHODS OF MAKING AND USING THE SAME

The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, and reducing the risk of microbial infections in humans and animals.

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