Discovery of indane propanamides as potent and selective TRPV1 antagonists

被引：12
|
作者：
Ahn, Songyeon [1 ]
Kim, Yong Soo [1 ]
Kim, Myeong Seup [1 ]
Ann, Jihyae [1 ]
Ha, Heejin [2 ]
Yoo, Young Dong [2 ]
Kim, Young Ho [2 ]
Blumberg, Peter M. [3 ]
Frank-Foltyn, Robert [4 ]
Bahrenberg, Gregor [4 ]
Stockhausen, Hannelore [4 ]
Christoph, Thomas [4 ]
Lee, Jeewoo [1 ]
机构：
[1] Seoul Natl Univ, Coll Pharm, Lab Med Chem, Seoul 08826, South Korea
[2] Medifron DBT, Ansan 15426, Gyeonggi Do, South Korea
[3] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[4] Grunenthal GmbH, Grunenthal Innovat, D-52078 Aachen, Germany
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 03期
基金：
新加坡国家研究基金会;
关键词：
Vanilloid receptor 1; TRPV1; antagonist; Analgesic; C-REGION ANALOGS; VANILLOID-1; ANTAGONISTS; CAPSAICIN RECEPTOR; 2-(3-FLUORO-4-METHYLSULFONYLAMINOPHENYL)PROPANAMIDES; PYRIDINE; PAIN; 2-(3-FLUORO-4-METHYLSULFONAMIDOPHENYL)PROPANAMIDES; PHARMACOLOGY;
D O I：
10.1016/j.bmcl.2019.126838
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of indane-type acetamide and propanamide analogues were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that indane A-region analogues exhibited better antagonism than did the corresponding 2,3-dihydrobenzofuran and 1,3-benzodioxole surrogates. Among them, antagonist 36 exhibited potent and selective antagonism toward capsaicin for hTRPV1 and mTRPV1. Further, in vivo studies indicated that antagonist 36 showed excellent analgesic activity in both phases of the formalin mouse pain model and inhibited the pain behavior completely at a dose of 1 mg/kg in the 2nd phase.
引用
收藏
页数：5
相关论文
共 50 条
  • [1] 2-(Halogenated Phenyl) acetamides and propanamides as potent TRPV1 antagonists
    Kang, Jin Mi
    Kwon, Sun Ok
    Ann, Jihyae
    Lee, Sunho
    Kim, Changhoon
    Do, Nayeon
    Jeong, Jin Ju
    Blumberg, Peter M.
    Ha, Heejin
    Vu, Thi Ngoc Lan
    Yoon, Sanghee
    Choi, Sun
    Frank-Foltyn, Robert
    Lesch, Bernhard
    Bahrenberg, Gregor
    Stockhausen, Hannelore
    Christoph, Thomas
    Lee, Jeewoo
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2021, 48
  • [2] Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists
    Kim, Changhoon
    Ann, Jihyae
    Lee, Sunho
    Sun, Wei
    Blumberg, Peter M.
    Frank-Foltyn, Robert
    Bahrenberg, Gregor
    Stockhausen, Hannelore
    Christoph, Thomas
    Lee, Jeewoo
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (14) : 2539 - 2542
  • [3] MEDI 317-Discovery of potent, selective and orally active TRPV1 antagonists for the relief of pain
    Nakao, Kazunari
    Nagayama, Satoshi
    Shishido, Yuji
    Hirano, Misato
    Sudo, Masaki
    Takada, Junji
    Kanai, Yoshihito
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232
  • [4] Novel, potent TRPV1 receptor antagonists
    Brown, Brian S.
    Keddy, Ryan G.
    Zheng, Guo Zhu
    Schmidt, Robert G.
    Koenig, John Robert
    Honore, Prisca
    Jarvis, Michael F.
    Surowy, Carol S.
    Faltynek, Connie R.
    Lee, Chih-Hung
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 230 : U2545 - U2546
  • [5] Discovery of small molecule antagonists of TRPV1
    Rami, HK
    Thompson, M
    Wyman, P
    Jerman, JC
    Egerton, J
    Brough, S
    Stevens, AJ
    Randall, AD
    Smart, D
    Gunthorpe, MJ
    Davis, JB
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (14) : 3631 - 3634
  • [6] Discovery of piperidine carboxamide TRPV1 antagonists
    Cheung, Wing S.
    Calvo, Raul R.
    Tounge, Brett A.
    Zhang, Sui-Po
    Stone, Dennis R.
    Brandt, Michael R.
    Hutchinson, Tasha
    Flores, Christopher M.
    Player, Mark R.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (16) : 4569 - 4572
  • [7] Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists
    Schmidt, Robert G.
    Bayburt, Erol K.
    Latshaw, Steven P.
    Koenig, John R.
    Daanen, Jerome F.
    McDonald, Heath A.
    Bianchi, Bruce R.
    Zhong, Chengmin
    Joshi, Shailen
    Honore, Prisca
    Marsh, Kennan C.
    Lee, Chih-Hung
    Faltynek, Connie R.
    Gomtsyan, Arthur
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (05) : 1338 - 1341
  • [8] Identification of potent, soluble, and orally active TRPV1 antagonists
    Ratcliffe, Paul
    Maclean, John
    Abernethy, Lynn
    Clarkson, Tom
    Dempster, Maureen
    Easson, Anna-Marie
    Edwards, Darren
    Everett, Katy
    Feilden, Helen
    Littlewood, Peter
    McArthur, Duncan
    McGregor, Deborah
    McLuskey, Hazel
    Nimz, Olaf
    Nisbet, Lesley-Anne
    Palin, Ronnie
    Tracey, Heather
    Walker, Glenn
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (08) : 2559 - 2563
  • [9] Potent and orally efficacious benzothiazole amides as TRPV1 antagonists
    Besidski, Yevgeni
    Brown, William
    Bylund, Johan
    Dabrowski, Michael
    Dautrey, Sophie
    Harter, Magali
    Horoszok, Lucy
    Hu, Yin
    Johnson, Dean
    Johnstone, Shawn
    Jones, Paul
    Leclerc, Sandrine
    Kolmodin, Karin
    Kers, Inger
    Labarre, Maryse
    Labrecque, Denis
    Laird, Jennifer
    Lundstrom, Therese
    Martino, John
    Maudet, Mickael
    Munro, Alexander
    Nylof, Martin
    Penwell, Andrea
    Rotticci, Didier
    Slaitas, Andis
    Sundgren-Andersson, Anna
    Svensson, Mats
    Terp, Gitte
    Villanueva, Huascar
    Walpole, Christopher
    Zemribo, Ronald
    Griffin, Andrew M.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (19) : 6205 - 6211
  • [10] Spiro-piperidine azetidinones as potent TRPV1 antagonists
    Xiao, Dong
    Palani, Anandan
    Aslanian, Robert
    McKittrick, Brian A.
    McPhail, Andrew T.
    Correll, Craig C.
    Phelps, P. Tara
    Anthes, John C.
    Rindgen, Diane
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (03) : 783 - 787
12345