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SGC STIMULATORS

The present patent application discloses at least the compounds according to Formula 1 shown below, or pharmaceutically acceptable salts thereof, wherein ringjB,n, JD, J,0, X, X1, J, RC, and W are as defined herein. These compounds are useful as simulators of soluble sGC.

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Development of thioquinazolinones, allosteric Chk1 kinase inhibitors

A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at Km for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site ?13 A from the ATP binding site. Preliminary data is presented for several of these compounds.

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Antimalarial Lead-Optimization Studies on a 2,6-Imidazopyridine Series within a Constrained Chemical Space to Circumvent Atypical Dose-Response Curves against Multidrug Resistant Parasite Strains

A lead-optimization program around a 2,6-imidazopyridine scaffold was initiated based on the two early lead compounds, 1 and 2, that were shown to be efficacious in an in vivo humanized Plasmodium falciparum NODscidIL2Rgammanull mouse malaria infection model. The observation of atypical dose-response curves when some compounds were tested against multidrug resistant malaria parasite strains guided the optimization process to define a chemical space that led to typical sigmoidal dose-response and complete kill of multidrug resistant parasites. After a structure and property analysis identified such a chemical space, compounds were prepared that displayed suitable activity, ADME, and safety profiles with respect to cytotoxicity and hERG inhibition.

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IMIDAZOPYRIDIN-2-ONE DERIVATIVES

The present invention is directed to imidazopyridin-2-one derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved

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AMINE DERIVATIVES OF LUPANES WITH HIV MATURATION INHIBITORY ACTIVITY

The present invention relates to compounds characterized by having a structure according to the following Formula I: (I) or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.

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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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SPIROINDOLINONE DERIVATIVES

The present invention relates to spiroindolinone derivatives of the formula and their enantiomers and pharmaceutically acceptable salts and esters thereof wherein R1, R2, R3, R4, R5, R6, R7 and R8, are as herein described.

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Fused ring compound and use thereof

The present invention provides a compound represented by the formula: wherein the symbols are as described in the specification, or a salt thereof, which is useful for preventing/treating eicosanoid-associated diseases such as atherosclerosis, diabetes, obesity, atherothrombosis, asthma, fever, pain, cancer, rheumatism, osteoarthritis and atopic dermatitis, and which has an excellent pharmacological action, physicochemical properties, etc.

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Compounds Which Modulate The CB2 Receptor

Compounds of formula (I) are disclosed. Compounds according to the and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

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QUINOLINONE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS

The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.

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