‘Click’ D1 receptor agonists with a 5-HT1A receptor pharmacophore producing D2 receptor activity

Structural manipulation on the catecholic fragment of dopamine D1 receptor agonist 1-phenyl-N-methyl-benzazepines

“…Although the R-enantiomers of benzazepines 1e4 are generally more active than corresponding S-enantiomers, there is no significant difference between the racemates and their R-enantiomers at the DA receptor binding level [6,12,13]. Therefore, to quickly identify new compounds for further study, all compounds in current report were prepared and evaluated as racemates.…”

“…Reduction of nitrobenzene 11 with Pd/C gave 7-amino-8-hydroxybenzazepine 12 in 96% yield. Reductive amination [13] of 12 by treating with aryl aldehydes followed by NaBH 4 yielded corresponding benzylamines 13aee in 80e91% yields. Acylation of amine 12 led to benzazepine 14 in 41% yield, and diethylamino-substituted benzazepine 15 was prepared in 81% yield by treating 12 with acetaldehyde and NaBH(OAc) 3 .…”

“…Therefore, to quickly identify new compounds for further study, all compounds in current report were prepared and evaluated as racemates. As shown in Scheme 1, by following a literature procedure [12,13,22,23], 7-and 8-methoxy-N-methyl-1-benzazepines 7 and 8 were prepared from corresponding 3-or 4-methoxyphenyl ethanamine and 2-phenyloxirane in three steps [18,19]. Removal [23] of the Omethyl group by refluxing in 48% HBr aqueous solution led to monohydroxyl benzazepines 9 and 10 in 90% yield.…”

Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands

“…Therefore, a series of novel triazole-containing aporlogues were synthesized based on hit 4 through the widely used click reaction protocol 26 (Fig. 1).…”

The Use of Ligands in Copper-Catalyzed [3+2] Azide-Alkyne Cycloaddition: Clicker than Click Chemistry?

“…Unarguably, the most popular amine of this series is the Hünig's base, diisopropylethylamine (DIPEA). Not only it can be considered as the first ligand applied to this transformation -it was used in the groundbreaking work by Meldal et al- 6 but also it has become a well-established Click protocol not only in immobilization processes as in the original report, but also in the preparation of peptides 36 and other biomolecules 37,38 as well as macrocycles, 39,40 to name some examples. Additionally, DIPEA was also employed in a tandem CuACC/electrophilic addition to prepare a number of 4,5-functionalized triazolyl-nucleosides (Eq 1).…”