Aminothiazole Derivatives as Neuropeptide Y5 Receptor Ligands: Finding the Balance between Affinity and Physicochemical Properties

Nettekoven, Matthias; Guba, Wolfgang; Neidhart, Werner; Mattei, Patrizio; Pflieger, Philippe; Plancher, Jean‐Marc; Taylor, Sven

doi:10.1002/cmdc.200500022

Cited by 13 publications

(11 citation statements)

References 15 publications

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“…Further SAR studies around the lead led to subnanomolar compounds such as (27), while additional derivatives with improved pysiochemical properties have also been prepared [121,122]. Affinities of the diverse and potent Y5 antagonists are shown in Table 3.…”

Section: Y5 Antagonistsmentioning

confidence: 98%

NPY Y1 and Y5 Receptor Selective Antagonists as Anti-Obesity Drugs

MacNeil¹

2007

CTMC

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A combination of pharmacological and genetic studies in mice confirmed that the Y1 and Y5 receptors mediate the potent orexigenic actions of exogenous NPY. Although the physiological role of NPY in causing obesity is less clear, potent and selective antagonists of both Y1 and Y5 have been developed. Some of the NPY antagonists have suitable pharmacokinetic (PK) properties that allowed them to be evaluated in various rodent models of obesity. Several different Y1 and Y5 antagonists cause weight loss in rodent models, though confirmation that these effects are mechanism based has been limited. One Y5 antagonist, MK-0557 was evaluated in a 1-yr clinical trial and found to cause modest weight loss. Optimal NPY antagonist therapeutics for obesity may require blockade of both the Y1 and Y5 receptors.

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Section: Y5 Antagonistsmentioning

confidence: 98%

NPY Y1 and Y5 Receptor Selective Antagonists as Anti-Obesity Drugs

MacNeil¹

2007

CTMC

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“…In this synthesis, the mixture of thiourea derivative ( 354 ) containing a protecting group (Boc: tert ‐butoxycarbonyl) and DMF‐DMA was refluxed in DMF. The enamine compound ( 355 ) obtained as a result of this reaction was reacted with α‐bromoketone ( 356 ) and the molecules ( 357 ) containing thiazole ring were synthesized [83] . In addition, Koca et al.…”

Section: Formation Of Heterocycle Structures By Dmf‐dma Reactionsmentioning

confidence: 99%

Enamines and Dimethylamino Imines as Building Blocks in Heterocyclic Synthesis: Reactions of DMF‐DMA Reagent with Different Functional Groups

Gümüş

Koca

2020

ChemistrySelect

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N,N‐Dimethylformamide dimethyl acetal (DMF‐DMA) reagent can react with different functional groups of organic compounds. Enamines and dimethylamino imines are obtained, when the DMF‐DMA reagent is reacted with methylene, methyl and amino groups. These products are formed in the intermediate step in the synthesis of many hetero rings. These compounds are especially used as a starting material in the synthesis of heterostructures such as pyrimidine, pyridine, pyrazole, etc. Therefore, DMF‐DMA has been particularly prominent as a reagent in targeted synthesis and designs of many heterocyclic compounds. Herein, the reactions of DMF‐DMA reagent with different functional groups are categorized in four classes (methylene, methyl, amino, other groups) and the reactions of obtained enamine and dimethylamino imine compounds are investigated in detail such as nucleophilic addition, intramolecular cyclization or condensation reactions. The synthesis and continuation reactions of the enamine and dimethylamino imine compounds are also examined in terms of experimental conditions and reagents used.

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“…[13] These are also known to be ligands of estrogen receptors, [14] adenosine receptor antagonists, [15] and neuropeptide Y5 receptor. [16] The most commonly adopted method for the synthesis of 2-amino thiazoles is the reaction of thiourea or thioamide with a-bromo ketones. [17] These reactions have been further improved using catalysts such as ammonium-I2-molybdophosphate (AMP) [18] and b-cyclodextrin in water, [19] conventional heating, and the use of microwaves in an alcoholic media [20] at ambient temperature or in an aqueous medium.…”

Section: One-pot Preparation Of Cyanamide and Thiazole 793mentioning

confidence: 99%