925239-58-3

Upstream product

• 937248-15-2 (R)-tert-butyl 1-(4-(4-methoxybenzyl)-5-phenylethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethylcarbamate 
• 103-25-3 3-phenylpropanoic acid methyl ester 
• 3538-68-9 3-phenylpropanehydrazide 
• 501-52-0 3-Phenylpropionic acid 
• 2393-23-9 4-methoxy-benzylamine 
• 5241-64-5 Boc-D-Trp-OH 
• 937247-85-3 (R)-tert-butyl 1-(4-methoxybenzylamino)-3-(1H-indol-3-yl)-1-thioxopropan-2-ylcarbamate 
• 956489-58-0 (R)-tert-butyl 1-(4-methoxybenzylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-ylcarbamate 

Downstream Products

• 1187364-81-3 (2R)-N-((R)-1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)piperazine-2-carboxamide 

Relevant academic research and scientific papers

NOVEL 1,2,4-TRIAZOLE DERIVATIVES AND PROCESS OF MANUFACTURING THEREOF

The invention provides 1,2,4-triazole compounds, compositions containing those compounds, methods of treating diseases and/or disorders with those compounds and processes of manufacturing 1,2,4-triazole compounds.

Novel triazole derivatives as ligands of G-protein coupled receptors

The present invention provides novel triazole derivatives according to formula (I) as ligands of G-protein coupled receptors (GPCR), which are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, which are mediated by GPCR. The present invention further provides GPCR antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular adipogenesis, adiposity, cachexia, diabetes, diabetes type I, diabetes type II, energy balance, energy homeostasis, food intake, hyperlipidemia, hyperphagia, obesity, short-, medium- and/or long-term regulation of energy balance, short-, medium- and/or long-term regulation (stimulation and/or inhibition) of food intake.

Trisubstituted 1,2,4-triazoles as ligands for the ghrelin receptor: On the significance of the orientation and substitution at position 3

The synthesis and structure-activity relationships concerning 3,4,5-trisubstituted 1,2,4-triazoles as ghrelin receptor ligands are described. The importance of the starting aminoacid material as well as its configuration was explored and the (d) Trp resid

New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations

Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the α- aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.

Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1

A new series of growth hormone secretagogue (GHS) analogues based on the 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and their ability to stimulate intracellular calcium release to the cloned hGHS-1a ghrelin receptor expressed in LLC PK-1 cells. We have synthesized potent ligands of this receptor, some of them behaving as agonists, partial agonists, or antagonists. Some compounds among the most potent, i.e., agonist 29c (JMV2873), partial agonists including 21b (JMV2810), antagonists 19b (JMV2866) and 19c (JMV2844), were evaluated for their in vivo activity on food intake, after sc injection in rodents. Some compounds were found to stimulate food intake like hexarelin; some others were identified as potent hexarelin antagonists in this assay. Among the tested compounds, 21b was identified as an in vitro ghrelin receptor partial agonist, as well as a potent in vivo antagonist of hexarelin-stimulated food intake in rodents. Compound 21b was without effect on GH release from rat. However, in this series of compounds, it was not possible to find a clear correlation between in vitro and in vivo results.

Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations

A series of ghrelin receptor ligands based on the trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the significance of the aminoisobutyryl (Aib) moiety, a common feature in numerous growth hormone secretagogues described in the literature. Potent agonist and antagonist ligands of the growth hormone secretagogue receptor type 1a (GHS-R1a) were obtained, i.e., compounds 41 (JMV2894) and 17 (JMV3031). The best compounds were evaluated for their in vivo activity on food intake, after sc injection in rodents. Among the tested compounds, few of them were able to stimulate food intake and some others, i.e., compounds 4 (JMV2959), 17, and 52 (JMV3021), acted as potent in vivo antagonist of hexarelin-stimulated food intake. These compounds did not stimulate growth hormone secretion in rats and furthermore did not antagonize growth hormone secretion induced by hexarelin, revealing that it is possible to modulate food intake without altering growth hormone secretion.