Synthesis and structure–activity relationship of novel cinnamamide derivatives as antidepressant agents

Han, Mei; Ma, Xiaojing; Jin, Ying‐Tai; Zhou, Wangyi; Cao, Jing; Wang, Yahu; Zhou, Shuiping; Wang, Guocheng; Yu, Zhu

doi:10.1016/j.bmcl.2014.09.050

Cited by 10 publications

(26 citation statements)

References 21 publications

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“…[33] The same test showed the beneficial impact of a5 '-halogenic substitution of 3',4'-methylenedioxycinnamamidesi nm ice. [33,35] Location of the substituent seemed to be equally important. [35,36] As imilare ffect was observed in the case of 4-substitutedh alocinnamoylaminoacetamide derivatives with a4 -chloro-substituted derivative (17)b eing the most potent in the standard test in both mice and rats.…”

Section: Modification Of Region Amentioning

confidence: 99%

“…The two isomersa ppear to differ in their pharmacological properties, with E isomerss howing depressant and Z isomers stimulatory activity in the CNS. [35,36] There have also been reports of highly modified derivatives exhibiting antidepressant activity in spite of their lacking ChemMedChem 2015, 10,1302 -1325 www.chemmedchem.org ad ouble bond. They are more likely to possess potent activity and are usually solids, while Z-isomers are liquids.…”

Section: Modification Of the Linkermentioning

confidence: 99%

“…Comparing 5'-substituted (E)-N-isobutyl-3',4'-methylenedioxycinnamamides (derivatives of 12), their activity in aT ST increased in the order:N O 2 < OCH 3 < H < I < Cl < CF 3 ,w ith the trifluoromethyl derivative being the most potent. So far,d erivatives containing methylenedioxy [35,36,40] or benzofuran [30] rings exhibited antidepressant activity.H owever, the possible benefits of such modifications in comparison with an unchanged phenyl ring are difficultt oe valuated ue to the use of different animal modelsa nd test conditions. [33,35] Location of the substituent seemed to be equally important.…”

Section: Modification Of Region Amentioning

confidence: 99%

“…As mentioned above,4 -substitutedd erivatives were the most potent. [35] Substitution of the benzofur- an ring needs separatee xamination, as it could interactw ith the electron effects of substituents.I nag roup of N-benzyl-or N-phenylpiperidine-substituted benzofurans (19)(20)(21), all kinds of 5'-benzofurans ubstitutions (including chloro) gave rise to derivatives with al ack of activity in aT BZ test in mice, apart from the methoxy-substituted compound. [33] However, al ack of substitution or di-or tri-substitution might not completely abolish antidepressant activity.…”

Section: Modification Of Region Amentioning

confidence: 99%

“…[41] Another issue is modificationo ft he phenylr ing. [35] However,e ven those unfavorable substituents are present in other potent cinnamamides. In somec ases, modification of the phenyl ring seemed to be necessary;cinnamoyl or chromene analogues of antidepressant benzofuran derivatives 19-21 (Table 2) were inactive in aT BZ test in mice.…”

Section: Modification Of Region Amentioning

confidence: 99%

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Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships

et al. 2015

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The cinnamamide scaffold has been incorporated in to the structure of numerous organic compounds with therapeutic potential. The scaffold enables multiple interactions, such as hydrophobic, dipolar, and hydrogen bonding, with important molecular targets. Additionally, the scaffold has multiple substitution options providing the opportunity to optimize and modify the pharmacological activity of the derivatives. In particular, cinnamamide derivatives have exhibited therapeutic potential in animal models of both central and peripheral nervous system disorders. Some have undergone clinical trials and were introduced on to the pharmaceutical market. The diverse activities observed in the nervous system included anticonvulsant, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle relaxant, and sedative properties. Over the last decade, research has focused on the molecular mechanisms of action of these derivatives, and the data reported in the literature include targeting the γ-aminobutyric acid type A (GABAA ) receptors, N-methyl-D-aspartate (NMDA) receptors, transient receptor potential (TRP) cation channels, voltage-gated potassium channels, histone deacetylases (HDACs), prostanoid receptors, opioid receptors, and histamine H3 receptors. Here, the literature data from reports evaluating cinnamic acid amide derivatives for activity in target-based or phenotypic assays, both in vivo and in vitro, relevant to disorders of the central and peripheral nervous systems are analyzed and structure-activity relationships discussed.

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Section: Modification Of Region Amentioning

confidence: 99%

Section: Modification Of the Linkermentioning

confidence: 99%

Section: Modification Of Region Amentioning

confidence: 99%

Section: Modification Of Region Amentioning

confidence: 99%

Section: Modification Of Region Amentioning

confidence: 99%

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Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships

et al. 2015

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Mild, Metal‐Free and Protection‐Free Transamidation of N‐Acyl‐2‐piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N‐Acyl‐2‐piperidones

Sundararaman

Kumar

2019

Eur J Org Chem

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Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N‐acyl‐2‐piperidones with a broad range of amines is demonstrated under exceedingly mild and metal‐free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal‐catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl‐N‐acyl‐2‐piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N‐acyl‐2‐piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X‐ray analysis of an N‐acyl‐2‐piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N‐acyl‐2‐piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.

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Novel 2-methyl-6-arylpyridines carrying active pharmacophore 4,5-dihydro 2-pyrazolines: synthesis, antidepressant, and anti-tuberculosis evaluation

et al. 2017

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Synthesis and structure–activity relationship of novel cinnamamide derivatives as antidepressant agents

Cited by 10 publications

References 21 publications

Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships

Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships

Mild, Metal‐Free and Protection‐Free Transamidation of N‐Acyl‐2‐piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N‐Acyl‐2‐piperidones

Novel 2-methyl-6-arylpyridines carrying active pharmacophore 4,5-dihydro 2-pyrazolines: synthesis, antidepressant, and anti-tuberculosis evaluation

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