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PYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS

The present invention relates to a compound of formula (VII)I, or a pharmaceutically acceptable salt or ester thereof, wherein: X is NR7; Y is O or N-(CH2)nR19; n is 1, 2 or 3; m is 1 or 2; R1 and R2 are each independently H, alkyl or cycloalkyl; R4 and R4′ are each independently H or alkyl; or R4 and R4′ together form a spiro cycloalkyl group; R19 is H, alkyl, aryl or a cycloalkyl group; R6 is OR8 or halogen; and R7 and R8 are each independently H or alkyl. Further aspects relate to pharmaceutical compositions comprising said compounds and use therefore in the treatment of proliferative disorders and the like

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Quinuclidine – Wikipedia,
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TRIAZINE DERIVATIVES, THEIR PREPARATION AND THERAPEUTIC APPLICATION THEREOF

The invention relates to triazine derivatives of general formula (I): Wherein R1, R2 and R3 are as defined herein. The invention also relates to a method for preparing these triazine derivatives and to the therapeutic application thereof.

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2-indolizine Carbamoyl amine compound and its preparation and use (by machine translation)

The invention discloses a novel 2-indolizine formylamine derivative. The general formula of the novel 2-indolizine formylamine derivative is as shown in a formula (I), wherein the definition of R is specified in the specification. In addition, the invention also discloses a preparation method and a medicine composition of the compound. The 2-indolizine formylamine derivative disclosed by the invention has an acetylcholine alpha 7 receptor exciting effect. The formula (I) is as shown in the specification.

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Glucosylceramide synthase inhibitors

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

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N-AZABICYCLO-AMIDE DERIVATIVES

Compounds of the general formula I wherein A represents: D represents oxygen, or sulfur and R1, R2 and R3 are as defined in the specification, enantiomers thereof, pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders

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Quinuclidine – Wikipedia,
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Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease

The invention provides compounds of Formula I: 1These compounds may be in the form of pharmaceutical salts or compositions, may be in pure enantiomeric form or racemic mixtures, and are useful in pharmaceuticals to treat conditions or diseases in which alpha7 is known to be involved.

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Quinuclidine – Wikipedia,
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IMMUNOMODULATING OXOPYRRAZOLOCINNOLINES AS CD 80 INHIBITORS

N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-4-(6,9-difluoro-3-oxo-1,3-dihydro-pyrazolo[4,3-c]cinnolin-2-yl)-benzamide is a CD80 antagonist, useful in the treatment of dieases which benefit from immuno-inhibition.

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Quinuclidine – Wikipedia,
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Anxiolytic-R-n(1-azabicyclo[2.2.2]oct-3-yl) benzamides and thiobenzamides

Compounds of general formula I STR1 wherein: X represents oxygen or sulphur; each of R1 and R3 independently represents hydrogen or a C1 -C4 alkyl group; Ar represents: a phenyl ring optionally substituted by one, two or three C1 -C4 alkoxy groups and/or by one or two halogen atoms; a phenyl ring of the general formula STR2 wherein R2 represents halogen, 4,5-benzo, C1 -C8 alkoxy, C1 -C4 alkylcarbonyl or Am, wherein Am represents amino, methylamino or dimethylamino, R4 represents C1 -C8 alkyl, n is 1 or 2; or a pyrimidinyl moiety of the general formula STR3 wherein R5 is C1 -C4 alkyl; and their N-oxides and pharmaceutically acceptable salts are useful as anxiolytic agents. A preferred compound is R-(+)-4-amino-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-2-methoxybenzamide.

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Design of alpha7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies

We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as alpha7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for alpha7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a phenyl ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furanes, benzothiophenes or benzofuranes. Among the 30 derivatives tested, the two derivatives 10 and 39 with Ki in the nanomolar range were identified (2.3 and 3 nM respectively). They exhibited a strict selectivity toward the alpha4beta2 nicotinic receptor (up to 1 muM) but interacted with the 5HT3 receptors with Ki around 3 nM. Synthesis, SAR studies and a full description of the derivatives are reported.

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Quinuclidine – Wikipedia,
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2-substituted benzamide and benzoate derivatives of 3-aminoquinuclidine and 3-quinuclidinol

This invention provides novel 3-quinuclidinyl benzamides and benzoates which have utility as therapeutical agents which exhibit anxiolytic, antipsychotic, cognition improvement, antiemetic and gastric prokinetic effects in warm blooded animals. The compounds useful in the methods and composition of this invention are represented by the formula: STR1 where X is oxygen or sulfur; Y is –NH or –O–; when Y is –O–, R1 is STR2 and when Y is –NH, R1 is STR3 and R2 is hydrogen, C1 -C4 alkyl or C1 -C4 alkenyl; the geometrical and optical isomers, or a pharmaceutically acceptable salt thereof.

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Reference£º
Quinuclidine – Wikipedia,
Quinuclidine | C7H110N | ChemSpider