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The structure-activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure-mutagenicity relationships for the released aromatic amine metabolites. Potent FAAH inhibitors were identified having heteroaryl amine leaving groups that were non-mutagenic in the Ames II assay.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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To identify novel glycine transporter 1(GlyT1) inhibitors with greater selectivity relative to GlyT2 and improved aqueous solubility, we synthesized a series of 4H-1,2,4-triazole derivatives with heteroaromatic rings at the 4-position and investigated their structure-activity relationships. Replacement of the 2-fluorophenyl group of lead compound 5 with various aromatic groups led to the identification of 5-(3-biphenyl-4-yl-5-ethyl-4H-1,2,4-triazol-4-yl) isoquinoline (15) with 38-fold selectivity between GlyT1 and GlyT2. 15 also showed improved aqueous solubility and in vivo efficacy on (+)-HA966-induced hyperlocomotion in mice over the lead compound.

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A compound represented by the following formula (1) or a salt thereof: 1 wherein R1 represents hydrogen atom, a halogen atom and the like; R2 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; and R3 represents ?O?X?C(A1)(A11)?C(A2)(A2l)?N(A3l)(A3)(X represents propylene group etc., A11 and A21 represent hydrogen atom, or a C1-6 alkyl group, A31 represents a C1-6 alkyl group substituted with hydroxyl group, or hydrogen atom, and A1, A2, and A3 represent hydrogen atom, a C1-6 alkyl group and the like) and the like, which has an inhibitory activity on the phosphorylation of myosin regulatory light chain, and is useful for treatment of diseases relating to contraction of various cells and the like.

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Isoquinoline – Wikipedia,
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A general and practical catalytic system for aryl amination of aryl chlorides with aqueous or gaseous ammonia has been developed, with CuI as the catalyst and bisaryl oxalic diamides as the ligands. The reaction proceeds at 105-120C to provide a diverse set of primary (hetero)aryl amines in high yields with various functional groups.

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Isoquinoline – Wikipedia,
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The S -benzyl thioester and methyl ester derivatives of a representative 4-pyridinone-based carboxylic acid were sufficiently activated to react efficiently in amide coupling reactions with the amide anion generated in situ from the N -trimethylsilyl derivative of different weakly nucleophilic heteroarylamines. In acetonitrile as solvent, the precipitated diheteroarylamide products were isolated in pure form by vacuum filtration. This simple amide bond forming protocol can be readily adapted to the parallel synthesis of compound libraries.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Investigation of structure-activity relationships of novel quinazolines has identified 4-(4-isoquinolylamino)-quinazoline and a 4-(trans-2-phenylcyclopropylamino)-quinazoline as potent inhibitors of EGF-receptor tyrosine kinase in vitro. Further modificatons of the latter compound have identified a derivative which shows anti-tumour activity against a tumour xenograft model when dosed orally once per day.

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Isoquinoline – Wikipedia,
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Starting from a single, commercially available bromoisoquinoline, convenient (multigram) syntheses of 4-substituted-1,2,3, 4-tetrahydroisoquinoline derivatives have been developed. The compounds thus prepared show suitable substitution patterns for further derivatization and constitute a new family of compounds of potential pharmacological interest.

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Isoquinoline – Wikipedia,
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Two new fluorescent probes of protein structure and dynamics have been prepared by concise asymmetric syntheses using the Schoellkopf chiral auxiliary. The site-specific incorporation of one probe into dihydrofolate reductase is reported. The utility of these tryptophan derivatives lies in their absorption and emission maxima which differ from those of tryptophan, as well as in their large Stokes shifts and high molar absorptivities.

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Isoquinoline – Wikipedia,
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Starting from a single, commercially available bromoisoquinoline, convenient (multigram) syntheses of 4-substituted-1,2,3, 4-tetrahydroisoquinoline derivatives have been developed. The compounds thus prepared show suitable substitution patterns for further derivatization and constitute a new family of compounds of potential pharmacological interest.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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The present invention provides compounds useful as inhibitors of Tec family kinases, compositions thereof, and methods of using the same.

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Isoquinoline – Wikipedia,
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