- Synthesis and Reactivity of 18F-Labeled α,α-Difluoro-α-(aryloxy)acetic Acids
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In this work, we describe the 18F-labeling of α,α-difluoro-α-(aryloxy)acetic acid derivatives and demonstrate that these building blocks are amenable to post-18F-fluorination functionalization. Protodecarboxylation offers a new entry to 18F-difluoromethoxyarene, and the value of this approach is further demonstrated with coupling processes leading to representative 18F-labeled TRPV1 inhibitors and TRPV1 antagonists.
- Khotavivattana, Tanatorn,Calderwood, Samuel,Verhoog, Stefan,Pfeifer, Lukas,Preshlock, Sean,Vasdev, Neil,Collier, Thomas L.,Gouverneur, Véronique
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supporting information
p. 568 - 571
(2017/02/10)
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- Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
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The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. 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.
- Kim, Myeong Seop,Ki, Yooran,Ahn, Song Yeon,Yoon, Suyoung,Kim, Sung-Eun,Park, Hyeung-Geun,Sun, Wei,Son, Karam,Cui, Minghua,Choi, Sun,Pearce, Larry V.,Esch, Timothy E.,Deandrea-Lazarus, Ian A.,Blumberg, Peter M.,Lee, Jeewoo
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p. 382 - 385
(2014/01/17)
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- Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
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The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. 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.
- Kim, Myeong Seop,Ki, Yooran,Ahn, Song Yeon,Yoon, Suyoung,Kim, Sung-Eun,Park, Hyeung-Geun,Lee, Jeewoo,Sun, Wei,Son, Karam,Cui, Minghua,Choi, Sun,Pearce, Larry V.,Esch, Timothy E.,DeAndrea-Lazarus, Ian A.,Blumberg, Peter M.
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p. 382 - 385
(2015/03/18)
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- Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
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The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. 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.
- Kim, Myeong Seop,Ki, Yooran,Ahn, Song Yeon,Yoon, Suyoung,Kim, Sung-Eun,Park, Hyeung-Geun,Sun, Wei,Son, Karam,Cui, Minghua,Choi, Sun,Pearce, Larry V.,Esch, Timothy E.,Deandrea-Lazarus, Ian A.,Blumberg, Peter M.,Lee, Jeewoo
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p. 382 - 385
(2015/08/19)
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- TRPV1 ANTAGONISTS
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Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, prodrugs, or combinations thereof, wherein X1, L, Rx, Ry, Rz, R1, R2, A, m, n, p, q, and r are defined in
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Paragraph 0200
(2014/02/15)
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- Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists
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Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent 45Ca2+ uptake inhibitions in rat DRG neuron with IC50s of 25, 32 and 28 nM, respectively.
- Li, Fu-Nan,Kim, Nam-Jung,Chang, Dong-Jo,Jang, Jaebong,Jang, Hannah,Jung, Jong-Wha,Min, Kyung-Hoon,Jeong, Yeon-Su,Kim, Sun-Young,Park, Young-Ho,Kim, Hee-Doo,Park, Hyeung-Geun,Suh, Young-Ger
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experimental part
p. 8149 - 8160
(2010/03/25)
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- PROCESS OF SULFONATING 4-AMINOBENZONITRILES
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A process of producing a compound of formula (3), wherein R1 is a C1-5 alkyl group, R2 is a halogen atom, a C1-5 alkyl group, a C2-5 alkenyl group, a C2-5 alkynyl group, a C1-5 a
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Page/Page column 24-25
(2008/06/13)
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- NOVEL COMPOUNDS, ISOMER THEREOF OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF AS VANILLOID RECEPTOR ANTAGONIST; AND A PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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This present invention relates to novel compounds, isomer thereof or pharmaceutically acceptable salts thereof as vanilloid receptor (Vanilloid Receptor 1; VR1; TRPV1 )antagonist; and a pharmaceutical composition containing the same. The present invention
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Page/Page column 46
(2010/11/23)
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- PENTAFLUOROSULPHANYL-SUBSTITUTED COMPOUND AND ITS USE FOR PRODUCING MEDICAMENTS
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The present invention relates to pentafluorosulphanyl-substituted compounds, processes for preparing them, medicaments comprising these compounds, and the use of these compounds for producing medicaments.
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Page/Page column 40; 41
(2008/06/13)
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- Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects
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A novel non-vanilloid VR1 antagonist consisting of a new vanilloid equivalent exhibits excellent analgesic effects as well as highly potent antagonistic activities in both capsaicin single channel and calcium uptake assays. In addition, the structural requirement for the vanilloid equivalent of the potent VR1 antagonist has also been elucidated.
- Suh, Young-Ger,Lee, Yong-Sil,Min, Kyung-Hoon,Park, Ok-Hui,Seung, Ho-Sun,Kim, Hee-Doo,Park, Hyoung-Geun,Choi, Ji-Yeon,Lee, Jeewoo,Kang, Sang-Wook,Oh, Uh-Taek,Koo, Jae-Yeon,Joo, Yung-Hyup,Kim, Sun-Young,Kim, Jin Kwan,Park, Young-Ho
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p. 4389 - 4393
(2007/10/03)
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- High affinity antagonists of the vanilloid receptor
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The vanilloid receptor VR1 has attracted great interest as a sensory transducer for capsaicin, protons, and heat, and as a therapeutic target. Here we characterize two novel VR1 antagonists, KJM429 [N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea] and JYL1421 [N-(4-tertbutylbenzyl)-N′-[3-fluoro-4-(methylsulfonylamino)benzyl] -thiourea], with enhanced activity compared with capsazepine on rat VR1 expressed in Chinese hamster ovary (CHO) cells. JYL1421, the more potent of the two novel antagonists, inhibited [3H]resiniferatoxin binding to rVR1 with an affinity of 53.5 ± 6.5 nM and antagonized capsaicin-induced calcium uptake with an EC50 of 9.2 ± 1.6 nM, reflecting 25- and 60-fold greater potencies than capsazepine. Both JYL1421 and KJM429 antagonized RTX as well as capsaicin and their mechanism was competitive. The responses to JYL1421 and KJM429 differed for calcium uptake by rVR1 induced by heat or pH. JYL1421 antagonized the response to both pH 6.0 and 5.5, whereas KJM429 antagonized at pH 6.0 but was an agonist at lower pH (5.5). For heat, JYL1421 fully antagonized and KJM429 partially antagonized. Capsazepine showed only weak antagonism for both pH and heat. Responses of rVR1 to different activators could thus be differentially affected by different ligands. In cultured dorsal root ganglion neurons, JYL1421 and KJM429 likewise behaved as antagonists for capsaicin, confirming that the antagonism is not limited to heterologous expression systems. Finally, JYL1421 and KJM429 had little or no effect on ATP-induced calcium uptake in CHO cells lacking rVR1, unlike capsazepine. 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.
- Wang, Yun,Szabo, Tamas,Welter, Jacqueline D.,Toth, Attila,Tran, Richard,Lee, Jiyoun,Kang, Sang Uk,Suh, Young-Ger,Blumberg, Peter M.,Lee, Jeewoo
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p. 947 - 956
(2007/10/03)
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