138112-84-2

Usage

InChI:InChI=1/C15H16BrNO2/c1-19-13-6-5-11-3-2-4-12(14(11)9-13)7-8-17-15(18)10-16/h2-6,9H,7-8,10H2,1H3,(H,17,18)

Upstream product

• 22118-09-8 2-bromoacetyl chloride 
• 139525-77-2 2-(7-methoxynaphthalen-1-yl)ethanamine hydrochloride 
• 598-21-0 2-Bromoacetyl bromide 

Downstream Products

• 138112-85-3 N-[2-(7-methoxynaphth-1-yl)ethyl]-2-morpholinoacetamide 
• 1363155-75-2 2-(benzylmethylamino)-N-[2-(-7-methoxy-naphthalen-1-yl)ethyl]acetamide 
• 138113-04-9 S 20319 

Relevant academic research and scientific papers

Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I)

As part of our ongoing interest in developing new melatoninergic ligands bearing the same pharmacological profile as agomelatine, we focused our attention on this compound as a lead. Several chemical modifications have been performed on positions C-3 and 8 of the naphthalene ring determined as primary targets for the agomelatine metabolism. Herein we report the modulation of the positions C-3 and 7 in addition of the amide side chain because of this later prominent role in the affinity profile of such ligands. Synthesized compounds were then biologically evaluated at human cloned melatoninergic and serotoninergic receptors and showed different binding affinity and intrinsic activity profiles. Compounds bearing fluoroacetamide group (compounds 4 and 5) showed a high melatoninergic binding affinity particularly towards MT 1 receptor subtype. Thus, the fluoroacetamide 4 exhibited a good melatoninergic (MT1/MT2) binding affinity (70 pM) higher than the lead. Moreover, other compounds (10a, 10e, 16, 17 and 18) issued from these modulations behaved as MT1 and MT2 agonists and exhibited a sub-nanomolar binding affinity towards these receptors. However, only compounds 10e, 17 and 18 showed a sub-nanomolar binding affinity at 5-HT2C higher than the agomelatine.

Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands

A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2- 125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the conclusion that naphthalene is a bioisostere of the indole moiety of melatonin. Moreover it appears that the affinity is strongly affected by the size of the substituent of the nitrogen of the amidic function. Many of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective ligand of the melatonin receptor and an agonist derivative, has been selected for clinical development.

Compounds having a naphthalene structure

Compounds of general formula: STR1 in which A and R are defined in the description.