Jeewoo Lee

Summary

Affiliation: Seoul National University
Country: Korea

Publications

  1. ncbi request reprint N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues: novel potent and high affinity antagonists and partial antagonists of the vanilloid receptor
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 46:3116-26. 2003
  2. ncbi request reprint 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 14:2022-31. 2006
  3. ncbi request reprint Protein kinase C ligands based on tetrahydrofuran templates containing a new set of phorbol ester pharmacophores
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 42:4129-39. 1999
  4. ncbi request reprint Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: discovery of an N-hydroxythiourea analogue with potent analgesic acti
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 14:2291-7. 2004
  5. ncbi request reprint Analysis of structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as TRPV1 antagonists
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:4136-42. 2005
  6. ncbi request reprint Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:4143-50. 2005
  7. ncbi request reprint N-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: analysis of structure-activity relationships for the "C-Region"
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:371-85. 2004
  8. ncbi request reprint Structure-activity relationships of simplified resiniferatoxin analogues with potent VR1 agonism elucidates an active conformation of RTX for VR1 binding
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:1055-69. 2004
  9. ncbi request reprint Conformationally constrained diacylglycerol (DAG) analogs: 4-C-hydroxyethyl-5-O-acyl-2,3-dideoxy-D-glyceropentono-1,4-lactone analogs as protein kinase C (PKC) ligands
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Eur J Med Chem 39:69-77. 2004
  10. ncbi request reprint Analysis of structure-activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:3411-20. 2004

Collaborators

Detail Information

Publications70

  1. ncbi request reprint N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues: novel potent and high affinity antagonists and partial antagonists of the vanilloid receptor
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 46:3116-26. 2003
    ....
  2. ncbi request reprint 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 14:2022-31. 2006
    ..7 microM. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study of 13c was carried out...
  3. ncbi request reprint Protein kinase C ligands based on tetrahydrofuran templates containing a new set of phorbol ester pharmacophores
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 42:4129-39. 1999
    ....
  4. ncbi request reprint Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: discovery of an N-hydroxythiourea analogue with potent analgesic acti
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 14:2291-7. 2004
    ..The N(C)-hydroxy thiourea analogues (12, 13) showed excellent analgesic activities in the acetic acid writhing assay compared to the parent thiourea analogues...
  5. ncbi request reprint Analysis of structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as TRPV1 antagonists
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:4136-42. 2005
    ..The 2-halogen analogues showed enhanced antagonism compared to the prototype antagonist...
  6. ncbi request reprint Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:4143-50. 2005
    ..A docking model of potent antagonist 2 with the sensor region of TRPV1 is proposed...
  7. ncbi request reprint N-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: analysis of structure-activity relationships for the "C-Region"
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:371-85. 2004
    ..Our findings indicate that 4-t-butylbenzyl is one of the most favorable groups for high receptor binding and potent antagonism to VR1 in this structural series...
  8. ncbi request reprint Structure-activity relationships of simplified resiniferatoxin analogues with potent VR1 agonism elucidates an active conformation of RTX for VR1 binding
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:1055-69. 2004
    ..92), predicting a model of the active conformation of RTX and related vanilloids for binding to VR1. Poorer correlation was obtained between any of the conformations and the EC(50) values for calcium influx...
  9. ncbi request reprint Conformationally constrained diacylglycerol (DAG) analogs: 4-C-hydroxyethyl-5-O-acyl-2,3-dideoxy-D-glyceropentono-1,4-lactone analogs as protein kinase C (PKC) ligands
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Eur J Med Chem 39:69-77. 2004
    ....
  10. ncbi request reprint Analysis of structure-activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism
    Jeewoo Lee
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 12:3411-20. 2004
    ..The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand...
  11. ncbi request reprint Branched diacylglycerol-lactones as potent protein kinase C ligands and alpha-secretase activators
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy and Department of Biochemistry and Cancer Research Institute, Seoul National University, Seoul 151 742, Korea
    J Med Chem 49:2028-36. 2006
    ..Further investigation indicated that 2 exhibited a modestly higher level of sAPPalpha secretion than did phorbol 12,13-dibutyrate (PDBu)...
  12. ncbi request reprint N-(3-acyloxy-2-benzylpropyl)-N'-dihydroxytetrahydrobenzazepine and tetrahydroisoquinoline thiourea analogues as vanilloid receptor ligands
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 9:1713-20. 2001
    ..We report here the rationale for the design, the synthesis, and the in vitro characterization of activity in assays for [(3)H]resiniferatoxin binding and (45)Ca influx using heterologously expressed rat VR1...
  13. ncbi request reprint N-(3-Acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, South Korea
    Bioorg Med Chem 9:19-32. 2001
    ..The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency...
  14. ncbi request reprint Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Kwanak Ku, South Korea
    Bioorg Med Chem Lett 11:961-4. 2001
    ..The results indicate that ester analogue 23 was found to be a potent inhibitor of Escherichia coli methionyl-tRNA synthetase, and its interaction with the active site was proposed by a molecular modeling study...
  15. ncbi request reprint Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy-2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid receptor agonists and analgesics
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, 151 742, Seoul, South Korea
    Bioorg Med Chem 10:1171-9. 2002
    ..The aminoethyl analogue of the amide template 13 was a potent analgesic with an EC50=0.96 microg/kg in the AA-induced writhing test and with better in vivo stability than the parent phenol...
  16. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to protein kinase C (PK-C). Implications
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlin Dong, Kwanak Ku, Seoul 151 742, South Korea
    J Med Chem 44:4309-12. 2001
    ..Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue known to date...
  17. ncbi request reprint Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Kwanak Ku, South Korea
    Bioorg Med Chem Lett 11:965-8. 2001
    ..A molecular modeling study demonstrated that in 18, isovanillate and hydroxamate served as proper surrogates for adenine and ribose in isoleucyl adenylate, respectively...
  18. ncbi request reprint 5-acyloxy-5-hydroxymethyltetrahydro-2-furancarboxylate as a novel template for protein kinase C (PKC) binding
    J Lee
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Farmaco 56:203-10. 2001
    ..The correlation between their binding affinities for PKC-alpha and a conformational fit to phorbol ester indicates they mimic a pharmacophore model comprising the C20-OH, C3-C=O and C9-OH rather than that including the C13-C=O moiety...
  19. ncbi request reprint N-4-Substituted-benzyl-N'-tert-butylbenzyl thioureas as vanilloid receptor ligands: investigation on the role of methanesulfonamido group in antagonistic activity
    Hyeung geun Park
    Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 14:787-91. 2004
    ....
  20. ncbi request reprint Conformationally constrained analogues of diacylglycerol (DAG). Effect on protein kinase C (PK-C) binding by the isosteric replacement of sn-1 and sn-2 esters in DAG-lactones
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    Bioorg Med Chem 11:2529-39. 2003
    ..The discrete K(i) analysis from the sn-1 and sn-2 isosteres further confirms that the DAG-lactones bind preferentially to the C1-domain in the sn-2 binding mode, as previously suggested...
  21. ncbi request reprint Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
    Sung Eun Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:3389-93. 2005
    ..coli MRS revealed that the lack of the two hydroxyl groups on ribose was compensated by the formation of an extra hydrogen bond between the ring oxygen and His24, resulting in a small activity reduction...
  22. ncbi request reprint TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides
    Tae Hwan Ha
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 21:6657-64. 2013
    ..Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode. ..
  23. pmc Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies
    Jin Hee Lee
    College of Pharmacy, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
    J Comput Aided Mol Des 25:317-27. 2011
    ..Through the homology modeling, docking and mutational studies, we obtained important insights into the ligand-receptor interactions at the molecular level which should prove of value in the design of novel TRPV1 ligands...
  24. ncbi request reprint Stereospecific high-affinity TRPV1 antagonists: chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues
    Hyungchul Ryu
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 51:57-67. 2008
    ..A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1...
  25. ncbi request reprint Synthesis of N,N',N"-trisubstituted thiourea derivatives and their antagonist effect on the vanilloid receptor
    Hyeung geun Park
    Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 13:601-4. 2003
    ..32 microM), showed 2-fold higher antagonistic activity than that of capsazepine (3, IC(50)=0.65 microM) against the vanilloid receptor in a (45)Ca(2+)-influx assay...
  26. ncbi request reprint Alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists
    Jae Uk Chung
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 15:6043-53. 2007
    ..In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K(i)=41 and 39.2 nM and K(i(ant))=4.5 and 37 nM)...
  27. doi request reprint 2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: structure activity relationships of the 2-oxy pyridine C-region
    Shivaji A Thorat
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Eur J Med Chem 64:589-602. 2013
    ....
  28. pmc The SAR analysis of TRPV1 agonists with the α-methylated B-region
    Yongsung Cho
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 22:5227-31. 2012
    ..The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding...
  29. ncbi request reprint Novel potent antagonists of transient receptor potential channel, vanilloid subfamily member 1: structure-activity relationship of 1,3-diarylalkyl thioureas possessing new vanilloid equivalents
    Young ger Suh
    College of Pharmacy, and Sensory Research Center, CRI, Seoul National University, San 56 1, Shinlim Dong, Kwanak gu, Seoul 151 742, Korea
    J Med Chem 48:5823-36. 2005
    ....
  30. pmc N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region
    Yong Soo Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 20:215-24. 2012
    ..A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency...
  31. ncbi request reprint Macrocyclic diacylglycerol-bis-lactones as conformationally constrained analogues of diacylglycerol-lactones. Interactions with protein kinase C
    Ji Hye Kang
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Korea
    J Med Chem 47:4000-7. 2004
    ....
  32. doi request reprint Structure-activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template
    Phuong Thao Tran
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 21:3821-30. 2013
    ..Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-Aβ and Aβ plaques in cells and transgenic animals...
  33. pmc Conformationally constrained analogues of N'-(4-tert-butylbenzyl)-N-(4-methylsulfonylaminobenzyl)thiourea as TRPV1 antagonists
    Ju Ok Lim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Eur J Med Chem 44:322-31. 2009
    ..The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues may be an important factor for their unfavorable interaction with the receptor...
  34. ncbi request reprint N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
    Jeewoo Lee
    Laboratory of Medicinal Chemistry, RIPS, College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 13:1087-92. 2003
    ....
  35. pmc Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin
    Dong Wook Kang
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 18:8092-105. 2010
    ..77 and 2.19nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6'-iodononivamide...
  36. pmc Non-vanillyl resiniferatoxin analogues as potent and metabolically stable transient receptor potential vanilloid 1 agonists
    Hyun Kyung Choi
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 17:690-8. 2009
    ..Molecular modeling analyses with selected analogues provide evidence that the conformational differences could affect their binding affinities, especially for the ester versus amide at the B-region...
  37. ncbi request reprint Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
    Myeong Seop Kim
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 24:382-5. 2014
    ..The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R. ..
  38. pmc 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region
    Myeong Seop Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    J Med Chem 55:8392-408. 2012
    ....
  39. pmc Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism
    Rahul S Bhondwe
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
    Bioorg Med Chem Lett 22:3656-60. 2012
    ..The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor...
  40. ncbi request reprint α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists
    Ho Shin Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 24:2685-8. 2014
    ..The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant. ..
  41. ncbi request reprint Pharmacophore-based virtual screening: the discovery of novel methionyl-tRNA synthetase inhibitors
    Su Yeon Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 16:4898-907. 2006
    ..In this study, potent lead compounds with a novel skeleton, including compound 27 with IC50 = 237 nM, were successfully identified as Escherichia coli MetRS inhibitors...
  42. doi request reprint 2-[2-Substituted-3-(3,4-dichlorobenzylamino)propylamino]-1H-quinolin-4-ones as Staphylococcus aureus methionyl-tRNA synthetase inhibitors
    - Farhanullah
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Eur J Med Chem 44:239-50. 2009
    ..aureus and Enterococci for their antibacterial activities. Among the compounds, 26b, 31c and 31e displayed significant inhibitory properties against various strains of Enterococci compared to compound 2...
  43. pmc Polar 3-alkylidene-5-pivaloyloxymethyl-5'-hydroxymethyl-gamma-lactones as protein kinase C ligands and antitumor agents
    Ji Hye Kang
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 20:1008-12. 2010
    ....
  44. pmc Receptor activity and conformational analysis of 5'-halogenated resiniferatoxin analogs as TRPV1 ligands
    Kwang Su Lim
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 21:299-302. 2011
    ....
  45. ncbi request reprint Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects
    Young ger Suh
    College of Pharmacy, Seoul National University, San 56 1, Shinlim Dong, Kwanak gu, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 13:4389-93. 2003
    ..In addition, the structural requirement for the vanilloid equivalent of the potent VR1 antagonist has also been elucidated...
  46. doi request reprint The carbonate analogues of 5'-halogenated resiniferatoxin as TRPV1 ligands
    Kwang Su Lim
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Eur J Med Chem 68:233-43. 2013
    ..The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism...
  47. doi request reprint Ligand-based design, synthesis, and biological evaluation of 2-aminopyrimidines, a novel series of receptor for advanced glycation end products (RAGE) inhibitors
    Young Taek Han
    College of Pharmacy, Seoul National University, 599 Gwanak Ro, Gwanak Gu, Seoul 151 742, Korea
    J Med Chem 55:9120-35. 2012
    ..We also predicted the binding mode of the 4,6-bis(4-chlorophenyl)pyrimidine analogs to the RAGE V-domain through flexible docking study...
  48. ncbi request reprint Synthesis of 2-substituted-pyrrolidinethiourea derivatives and their antagonist effect on vanilloid receptor
    Hyeung geun Park
    Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    Bioorg Med Chem Lett 13:197-200. 2003
    ..Among them, the two carbon extended derivatives, 4a (IC(50)=55 microM) and 4b (IC(50)=3 microM), both showed different levels of antagonist activity against the vanilloid receptor in a (45)Ca(2+)-influx assay...
  49. ncbi request reprint 3D-QSAR analysis of conformationally constrained diacylglycerol (DAG) analogues as potent protein kinase C (PK-C) ligands
    Su Yeon Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 12:2639-44. 2004
    ..The resultant QSAR model will be useful for designing highly potent and selective PK-C ligands...
  50. ncbi request reprint 3-D-QSAR study and molecular docking of methionyl-tRNA synthetase inhibitors
    Su Yeon Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, South Korea
    Bioorg Med Chem 11:5325-31. 2003
    ....
  51. ncbi request reprint Design and synthesis of quinolinones as methionyl-tRNA synthetase inhibitors
    - Farhanullah
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 14:7154-9. 2006
    ..aureus, two Enterococcus faecalis, and one Enterococcus faecium. Among all the synthesized quinolinones, compound 20 displayed significant inhibitory activities in the strains of E. faecalis and E. faecium...
  52. ncbi request reprint Chain-branched 1,3-dibenzylthioureas as vanilloid receptor 1 antagonists
    Chong Hyun Ryu
    College of Pharmacy, Sookmyung Women s University, Seoul 140 742, Republic of Korea
    Bioorg Med Chem Lett 14:1751-5. 2004
    ..R)-Methyl or ethyl-branched 1,3-dibenzylthiourea derivatives showed the most potent antagonist activity up to the IC(50) value of 0.05 microM which is 10-fold more potent than capsazepine...
  53. ncbi request reprint Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced antagonism to capsaicin
    Dong Wook Kang
    Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 17:214-9. 2007
    ..Compounds 23c and 31b were found to be potent full antagonists with K(i) (as functional antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively...
  54. ncbi request reprint Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE)
    Young Taek Han
    College of Pharmacy, Woosuk University, Wanju 565 701, Republic of Korea
    Eur J Med Chem 79:128-42. 2014
    ..Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described. ..
  55. ncbi request reprint Aminopropyl carbazole analogues as potent enhancers of neurogenesis
    Hye Jin Yoon
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 21:7165-74. 2013
    ..We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis. ..
  56. doi request reprint Intracellular amyloid-β accumulation in calcium-binding protein-deficient neurons leads to amyloid-β plaque formation in animal model of Alzheimer's disease
    Minho Moon
    Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
    J Alzheimers Dis 29:615-28. 2012
    ..Our results provide new insights into several long-standing gaps in AD research, namely how Aβ plaques are formed, what happens to iAβ and how Aβ causes selective neuronal loss in AD patients...
  57. doi request reprint Physiologically based pharmacokinetic modeling of SNU-0039, an anti-Alzheimer's agent, in rats
    Kyeong Ryoon Lee
    Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul 151 742, South Korea
    J Pharmacokinet Pharmacodyn 38:637-51. 2011
    ..Assuming a flow-limited distribution, the simulated concentration profiles for SNU-0039 in the physiologically based pharmacokinetic model were in reasonable agreement with the observed concentrations in plasma and nine tissues in rats...
  58. doi request reprint Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model
    Sung Hoon Baik
    Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea
    Neurobiol Aging 35:1286-92. 2014
    ..These findings suggest a new molecular process underlying the pathophysiology of Alzheimer's disease. ..
  59. ncbi request reprint Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1
    Attila Toth
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bldg 37, Room 4048, 37 Convent Dr, MSC 4255, Bethesda, MD 20892 4255, United States
    Life Sci 76:2921-32. 2005
    ..We conclude that structurally diverse vanilloid agonists induce marked diversity in the patterns of Ca2+ response. This diversity of response may provide opportunities for pharmacological exploitation...
  60. ncbi request reprint Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCalpha
    Maria Laura Garcia-Bermejo
    Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
    J Biol Chem 277:645-55. 2002
    ..An attractive hypothesis is that selective activation of PKC isozymes by pharmacological agents in cells can be achieved by differential intracellular targeting of each PKC...
  61. ncbi request reprint High affinity antagonists of the vanilloid receptor
    Yun Wang
    National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Pharmacol 62:947-56. 2002
    ..We conclude that JYL1421 is a competitive antagonist of rVR1, blocking response to all three of the agonists (capsaicin, heat, and protons) with enhanced potency relative to capsazepine...
  62. ncbi request reprint Synthesis and evaluation of fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives for dopamine D4 receptor imaging
    Seung Jun Oh
    Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon Dong, Kangnam Ku, Seoul 135 710, South Korea
    Bioorg Med Chem 12:5505-13. 2004
    ..Based on their in vitro binding properties and calculated logP values, ligand 6 appears to have the most promise for dopamine D(4) receptor imaging...
  63. ncbi request reprint High-affinity partial agonists of the vanilloid receptor
    Yun Wang
    National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892 4255, USA
    Mol Pharmacol 64:325-33. 2003
    ..Our results emphasize, moreover, the strong dependence of such partial agonists on other modulators of rVR1 and predict that their biological behavior will depend strongly on biological context...
  64. pmc Calcium-dependent and independent mechanisms of capsaicin receptor (TRPV1)-mediated cytokine production and cell death in human bronchial epithelial cells
    Christopher A Reilly
    Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA
    J Biochem Mol Toxicol 19:266-75. 2005
    ....
  65. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 19. Synthesis and protein kinase C binding affinity of diacylglycerol lactones bearing an N-hydroxylamide side chain
    Yongseok Choi
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    J Med Chem 46:2790-3. 2003
    ..Here, we report the synthesis and complete characterization of 1a and 1b together with the associated biological activity in terms of PK-C binding affinity...
  66. pmc Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors
    Larry V Pearce
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Naunyn Schmiedebergs Arch Pharmacol 377:149-57. 2008
    ..A further implication is that it may be desirable to tailor screening approaches for drug discovery to reflect the desired regulatory state of the targeted TRPV1...
  67. pmc Conformationally constrained analogues of diacylglycerol. 29. Cells sort diacylglycerol-lactone chemical zip codes to produce diverse and selective biological activities
    Dehui Duan
    Laboratory of Medicinal Chemistry, National Cancer Institute at Frederick, National Institutes of Health, 376 Boyles Street, Frederick, Maryland 21702, USA
    J Med Chem 51:5198-220. 2008
    ..Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCalpha to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses...
  68. ncbi request reprint Conformationally constrained analogues of diacylglycerol. 24. Asymmetric synthesis of a chiral (R)-DAG-lactone template as a versatile precursor for highly functionalized DAG-lactones
    Ji Hye Kang
    Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
    Org Lett 6:2413-6. 2004
    ..The synthesis of the most potent DAG-lactones known to date, (Z)-10 and (E)-10, served to confirm PK-C's exclusive preference for the (R)-stereochemistry in this class of compounds...
  69. ncbi request reprint Kinetics of penetration influence the apparent potency of vanilloids on TRPV1
    Jozsef Lazar
    Molecular Mechanism of Tumor Promotion, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bldg 37, Room 4048, 37 Convent Drive, MSC 4255, Bethesda, MD 20892 4255, USA
    Mol Pharmacol 69:1166-73. 2006
    ..5 nM if added simultaneously. We conclude that some vanilloids may have slow kinetics of uptake; this slow uptake may affect assessment of structure activity relations and may represent a significant factor for vanilloid drug design...
  70. ncbi request reprint Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice
    In Ho Park
    Brain Disease Research Center, Ajou University School of Medicine, Suwon, South Korea
    Neurobiol Aging 24:637-43. 2003
    ..Our results suggest that low plasma cholesterol levels might be a risk factor for AD in females...