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PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF

Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and prevention of CCR4-related diseases.

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Heterocyclic core analogs of a direct thrombin inhibitor

Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin.

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INHIBITORS OF HEPATITIS C VIRUS

The present application includes novel inhibitors of HCV, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

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Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1- tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K v7.1 (KCNQ1) potassium channel activator

A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (>100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel.

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Discovery of 4-(tert-Butoxycarbonyl)thiomorpholine-3-carboxylic acid

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Compounds, compositions, and methods for stimulating neuronal growth and elongation

The present invention concerns methods, pharmaceutical compounds, and compositions for stimulating neuroite outgrowth in nerve cells leading to nerve regeneration. These methods, compounds and compositions inhibit rotamase enzyme activity associated with binding proteins.

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THROMBIN INHIBITORS

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: (I) or a pharmaceutically acceptable salt thereof, wherein Q is CH2, NR4, O, S, S(O) or S (02), wherein R4 is H, C1-6 alkyl, aryl, or C 3-8 cycloalkyl; R1 is a heterocycle or -(CR5R6)1-2NH2, wherein R5 and R6, each time in which they occur, are independently H, C1-6 alkyl, -CH2F,-CHF2, CF3 or -CH2OH; R2 is OH, NH2or NHS02CH3; and R3 is C1-6 alkyl

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NOVEL COMPOUNDS

This invention relates to novel compounds useful in the treatment of diseases associated with TRPV4 channel receptor. More specifically, this invention relates to certain substituted piperidines, according to Formula I. Specifically, the invention is directed to compounds according to Formula (I). Wherein R1 is optionally substituted aryl; X is CH2, S, or SO2, and n = 1 or 2.

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INHIBITORS OF HEPATITIS C VIRUS

The present application includes novel inhibitors of HCV, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

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THROMBIN INHIBITORS

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: (I) or a pharmaceutically acceptable salt thereof, wherein Q is CH2, NR4, O, S, S(O) or S (02), wherein R4 is H, C1-6 alkyl, aryl, or C 3-8 cycloalkyl; R1 is a heterocycle or -(CR5R6)1-2NH2, wherein R5 and R6, each time in which they occur, are independently H, C1-6 alkyl, -CH2F,-CHF2, CF3 or -CH2OH; R2 is OH, NH2or NHS02CH3; and R3 is C1-6 alkyl

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Thiomorpholine – Wikipedia,
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Optically active thiomorpholine derivatives

Optically active carboxamide derivatives having analgesic activity and being useful as an analgesic agent. The compounds have a general formula: STR1 (in the above formula, R1 represents a hydrogen or halogen atom; R2 represents a halogen atom; R3 represents a pyrrolidino or piperidino group; Y represents a methylene or carbonyl group; and n is an integer of 1 or 2) and pharmacologically acceptable salts thereof.

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