• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.600-608
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• 2013

Amide analogs of tridecapeptide ${\alpha}$-factor (WHWLQLKPGQPMYCONH$_2$) of Saccharomyces cerevisiae, in which Trp at position 1 and 3 were replaced with other residues, were synthesized to ascertain whether cooperative interactions between two Trp residues occurred upon binding with its receptor. Analogs containing Ala or Aib at position 3 of the peptide $[Ala_3]{\alpha}$-factor amide (2) and $[Aib_3]{\alpha}$-factor amide (5) exhibited greater decreases in bioactivity than analogs with same residue at position one $[Ala^1]{\alpha}$-factor amide (1) and $[Aib^1]{\alpha}$-factor amide (4), reflecting that $Trp^3$ may plays more important role than $Trp^1$ for agonist activity. Analogs containing Ala or Aib in both position one and three 3, 6 exhibited complete loss of bioactivity, emphasizing both the essential role and the combined role of two indole rings for triggering cell signaling. In contrast, double substituted analog with D-Trp in both positions 9 exhibited greater activity than single substituted analog with D-Trp 8 or deleted analog 7, reflecting the combined contribution of two tryptophane residues of ${\alpha}$-factor ligand to activation of Ste2p through interaction with residue $Tyr^{266}$ and importance of the proper parallel orientation of two indole rings for efficient triggering of signal G protein coupled activation. Among ten amide analogs, $[Ala^{1,3}]{\alpha}$-factor amide (3), $[Aib^{1,3}]{\alpha}$-factor amide (6), [D-$Trp^3]{\alpha}$-factor amide (8) and [des-$Trp^1,Phe^3]{\alpha}$-factor amide (10) were found to have antagonistic activity. Analogs 3 and 6 showed greater antagonistic activity than analogs 8 and 10.

• Bulletin of the Korean Chemical Society
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• v.18 no.1
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• pp.50-56
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• 1997

The mode of action of mastoparan B, an antimicrobial cationic tetradecapeptide amide isolated from the hornet Vespa basalis, toward phospholipid bilayers was studied with synthetic mastoparan B and its analogs with individual Ala instead of hydrophobic amino acids (1-Ile, 3-Leu, 6-Leu, 7-Val, 9-Trp, 13-Val, 14-Leu) in mastoparan B. Mastoparan B and its analogs were synthesized by the solid-phase method. Circular dichroism spectra showed that mastoparan B and its analogs adopted an unordered structure in buffer solution. In the presence of neutral and acidic liposomes, most of the peptides took an α-helical structure. The calcein leakage experiment indicated that mastoparan B interacted strongly with neutral and acidic lipid bilayers than its analogs. Mastoparan B also showed a more or less highly antimicrobial activity and hemolytic activity for human erythrocytes than its analogs. These results indicate that the hydrophobic face in the amphipathic α-helix of mastoparan B critically affect biological activity and helical contents.

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.985-989
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• 2004

A functional divergency oriented synthetic approach to the azoninone (9-membered lactams), key intermediate for the indolizidine alkaloids library, using amide enolate induced aza-Claisen rearrangement has been achieved.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.246-247
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• 1996

In the previous reports (Park et al., 1991, and 1993), we described the synthesis and analgesic effects of various homovanillic amides as analogs of capsaicin. In the study, we tried to enhance the analgesic actvity of capsaicin by structural modification. Our study has been performed in three directions. First, the amide bond of capsaicin was transposed. Second, a phenyl ring was introduced to replace a double bond of capsaicin. Finally, aminoethylation was performed on 4-hydroxy group of capsaicin to improve oral bioavailability. These studies have led to N-(3-phenylpropyl)homovanillic amide 2 which has high analgesic activity. Our continuing efforts in this area have focused on the introduction of various substituents on the phenyl ring of 2 as well as their pharmacological studies. We report herein the synthesis of homovanillic amide derivatives and their analgesic activity.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3318-3326
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• 2010

Five new series of 3,4-ethylenedioxythiophene derivatives carrying important pharamacophores, viz., amide, ester, ether and active secondary aryl moieties have been designed and synthesized through multistep reactions starting from thiodiglycolic ester and diethyl oxalate. They have been characterized by elemental and spectral data. All the target compounds have been screened for their anticonvulsant activity at three different models viz. maximal electroshock (MES), subcutaneous metrazole (scMET), and 6 Hz screen and evaluated for their neurotoxicity in rotorod model. Compound 6a emerged as lead with no neurotoxicity. All the five series of compounds are safe in the toxicity studies at the maximum dose of 300 mg/kg of body weight. Amongst the tested compounds, the ester pharmacophore with thioamide fragment has showed better activity than the other analogs.

• Journal of Photoscience
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• v.12 no.2
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• pp.63-66
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• 2005

The azomethine ylide forming photoreaction has been explored by probing the excited state chemistry of several N-trimethylsilylmethyl substituted cyclic and acyclic imides and amide analogs. N-[(Trimethylsilyl)methyl]-N-mesylbenzamide (5) undergoes the excited state C to O silyl migration reaction to produce azomethine ylide intermediate 13. This ylide undergoes electrocyclization to form transient aziridine intermediate 14 which react further by ring opening to generate N-phenacylamine product 10. On the other hand, photolysis of N-[N-mesyl-N-(trimethylsilyl)methyl]aminoethyl-N-mesylbenzamide (8) brings about desilylation resulting in the production of dimer 17.

• Bulletin of the Korean Chemical Society
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• v.32 no.6
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• pp.1891-1896
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• 2011

On the basis of potent HDAC-inhibitory activity and anticancer activity of SAHA, novel SAHA derivatives 3a-d and 7 with a bulky cap such as p-dimethylaminophenyl, 4-phenylaminophenyl, 4-phenyloxyphenyl, 9H-fluorenyl or naphthalenyl ring were synthesized starting from the corresponding aryl amines or naphthalenyl acetic acid using an EDC-mediated amide coupling reaction in the presence of HOBt followed by a nucleophilic addition-elimination reaction with hydroxylamine. Compounds 3b, 3c and 3d showed more potent inhibitory activity on total HDACs (14~27-fold), HDAC1 (8~15-fold), HDAC2 (1.3~25-fold) and HDAC7 (1~3-fold) and more potent anticancer activity (2~22-fold) against MCF-7, MDA-MB-231, MCF-7/Dox, MCF-7/Tam, SK-OV-3, LNCaP and PC3 human cancer cell lines than SAHA.

• BMB Reports
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• v.36 no.6
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• pp.552-557
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• 2003

Oligomers with $\alpha$-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a $CDCl_3$ solution. In order to design an $\alpha$-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on $\alpha$-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-$d_6$ contain a stable 7-membered-ring structure that is similar to a $\gamma$-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.