892413-77-3

Upstream product

• 636-93-1 5-nitroguaiacol 
• 83948-53-2 3-bromopropylamine tert-butylcarbamate 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 892413-78-4 [3-(5-amino-2-methoxyphenoxy)propyl]-carbamic acid 1,1-dimethylethyl ester 

Relevant academic research and scientific papers

Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors

Glutamyl cyclase (QC) is a promising therapeutic target because of its involvement in the pathogenesis of Alzheimer's disease. In this study, we developed novel QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore. Several potent inhibitors were identified, showing IC50 values in a low nanomolar range, and were further studied for in vitro toxicity and in vivo activity. Among these, inhibitors 51 and 53 displayed the most potent AβN3pE?40-lowering effects in in vivo acute model with reasonable BBB penetration, without showing cytotoxicity and hERG inhibition. The molecular modeling analysis of 53 indicated that the salt bridge interaction and the hydrogen bonding in the active site provided a high potency. Given the potent activity and favorable BBB penetration with low cytotoxicity, we believe that compound 53 may serve as a potential candidate for anti-Alzheimer's agents.

2,4 (4,6) PYRIMIDINE DERIVATIVES

The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z1 and Z2 represent NH; Y represents -C3-9alkyl-, -C3-9alkenyl-, -C1-5alkyl-NR6-C1-5alkyl-, -C1-5alkyl-NR7-CO-C1 -5alkyl-, -C1-6alkyl-CO-NH-, -C1-6alkyl-NH-CO-, -C1-2alkyl-CO-Het10-CO-, -C1-3alkyl-NH-CO-Het3-, -Het4-C1-3alkyl-CO-NH-C1-3alkyl-, -C1-2alkyl-NH-CO-L1-NH-, -NH-CO-L2-NH-, -C1-2alkyl-CO-NH-L3-CO-, -C1-2alkyl-NH-CO-L1-NH-CO-C1-3alkyl-, -C1-2alkyl-CO-NH-L3-CO-NH-C1-3alkyl-, -C1-2alkyl-NR11-CH2-CO-NH-C1-3alkyl-, Het5-CO-C1-2alkyl-, -C1-5alkyl-CO-NH-C1-3alkyl-CO-NH-, -C1-5alkyl-NR13-CO-C1-3alkyl-NH-, -C1-3alkyl-NH-CO-Het27-CO-, or -C1-3alkyl-CO-Het28-CO-NH-; X1 represents a direct bond, O, -O-C1-2alkyl-, -CO-C1-2alkyl-, -NR16-C1-2alkyl-, -CO-NR17-, Het23-C1-2alkyl- or C1-2alkyl; X2 represents a direct bond, O, -O-C1-2alkyl-, -CO-C1-2alkyl-, -NR18-C1-2alkyl-, -CO-NR19-, Het24-C1-2alkyl- or C1-2alkyl; R1 and R5 each independently represent hydrogen, halo, C1-6alkyloxy- or C1-6alkyloxy- substituted with Het1 or C1-4alkyloxy-; R2 and R4 each independently represent hydrogen or halo; R3 represents hydrogen or cyano; R6, R7, R13, R17 and R19represent hydrogen; R11 represents hydrogen or C1-4alkyl; R16and R18 represent hydrogen, C1-4alkyl or Het17-C1-4alkyl-; L1, L2 and L3each independently represents C1-8alkyl optionally substituted with one or where possible two or more substituents selected from phenyl, methylsulfide, cyano, polyhaloC1-4alkyl-phenyl-, C1-4alkyloxy, pyridinyl, mono- or di(C1-4alkyl)-amino- or C3-6cycloalkyl; Het1 , Het2, Het17 each independently represent morpholinyl, oxazolyl, isoxazolyl, or piperazinyl; Het3, Het4, Het5 each independently represent morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl; Het10 represents piperazinyl, piperidinyl, pyrrolidinyl or azetidinyl; Het22 represents morpholinyl, oxazolyl, isoxazolyl or piperazinyl wherein said Het22 is optionally substituted with C1-4alkyl; Het23 and Het24 each independently represent a heterocycle selected from pyrrolidinyl, piperazinyl or piperidinyl wherein said Het23 or Het24 are optionally substituted with Het22-carbonyl; Het27 and Het28 each independently represent a heterocycle selected from morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl.