Discovery of ((4R,5S)-5-amino-4-(2,4,5-trifluorophenyl)cyclohex-1-enyl)-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

被引：44

作者：

Pei, Zhonghua ^{[1
]}

Li, Xiaofeng ^{[1
]}

von Geldern, Thomas W. ^{[1
]}

Madar, David J. ^{[1
]}

Longenecker, Kenton ^{[1
]}

Yong, Hong ^{[1
]}

Lubben, Thomas H. ^{[1
]}

Stewart, Kent D. ^{[1
]}

Zinker, Bradley A. ^{[1
]}

Backes, Bradley J. ^{[1
]}

Judd, Andrew S. ^{[1
]}

Mulhern, Mathew ^{[1
]}

Ballaron, Stephen J. ^{[1
]}

Stashko, Michael A. ^{[1
]}

Mika, Amanda K. ^{[1
]}

Beno, David W. A. ^{[1
]}

Reinhart, Glenn A. ^{[1
]}

Fryer, Ryan M. ^{[1
]}

Preusser, Lee C. ^{[1
]}

Kempf-Grote, Anita J. ^{[1
]}

Sham, Hing L. ^{[1
]}

Trevillyan, James M. ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Metab Dis Res, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 22期

关键词：

D O I：

10.1021/jm060955d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibition has become a useful therapy for type 2 diabetes. Optimization of the high-throughput screening lead 6 led to the discovery of 25 (ABT-341), a highly potent, selective, and orally bioavailable DPP4 inhibitor. When dosed orally, 25 dose-dependently reduced glucose excursion in ZDF rats. Amide 25 is safe in a battery of in vitro and in vivo tests and may represent a new therapeutic agent for the treatment of type 2 diabetes.

引用

页码：6439 / 6442

页数：4

共 31 条

[1] (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine:: A potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Kim, D
Wang, LP
Beconi, M
Eiermann, GJ
Fisher, MH
He, HB
Hickey, GJ
Kowalchick, JE
Leiting, B
Lyons, K
Marsilio, F
McCann, ME
Patel, RA
Petrov, A
Scapin, G
Patel, SB
Roy, RS
Wu, JK
Wyvratt, MJ
Zhang, BB
Zhu, L
Thornberry, NA
Weber, AE
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) : 141 - 151
[2] Novel methyl substituted 1-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanones are P2X7 antagonists
Rudolph, Dale A.
Alcazar, Jesus
Ameriks, Michael K.
Belen Anton, Ana
Ao, Hong
Bonaventure, Pascal
Carruthers, Nicholas I.
Chrovian, Christa C.
De Angelis, Meri
Lord, Brian
Rech, Jason C.
Wang, Qi
Bhattacharya, Anindya
Ignacio Andres, Jose
Letavic, Michael A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (16) : 3157 - 3163
[3] Microwave-Assisted Synthesis and Antituberculosis Screening of Some 4-((3-(Trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-l)methyl)benzenamine Hybrids
Patil, Yogesh
Shingare, Ramesh
Choudhari, Amit
Sarkar, Dhiman
Madje, Balaji
JOURNAL OF HETEROCYCLIC CHEMISTRY, 2019, 56 (02) : 434 - 442
[4] MEDI 4-Discovery of cyclohexene-constrained phenethylamine, ABT-341: A highly potent, selective, safe and orally available dipeptidyl peptidase IV inhibitor for the treatment of Type 2 diabetes
Pei, Zhonghua
Li, Xiaofeng
von Geldern, Thomas W.
Madar, David J.
Longenecker, Kenton
Hong, Yong
Zinker, Bradley A.
Lubben, Thomas H.
Stewart, Kent D.
Backes, Bradley J.
Stashko, Michael A.
Ballaron, Stephen J.
Beno, David W. A.
Mika, Amanda K.
Reinhart, Glenn A.
Fryer, Ryan M.
Preusser, Lee C.
Kempf-Grote, Anita J.
Sham, Hing L.
Trevillyan, James M.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232
[5] (3R)-4-1(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Biftu, Tesfaye
Feng, Dennis
Qian, Xiaoxia
Liang, Gui-Bai
Kieczykowski, Gerard
Eiermann, George
Huaibing, He
Lelting, Barbara
Lyons, Kathy
Petrov, Aleksandr
Sinha-Roy, Ranabir
Zhang, Bei
Scapin, Giovanna
Patel, Sangita
Gao, Ying-Duo
Singh, Suresh
Wu, Joseph
Zhang, Xiaoping
Thornberry, Nancy A.
Weber, Ann E.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (01) : 49 - 52
[6] Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): A highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Yoshida, Tomohiro
Akahoshi, Fumihiko
Sakashita, Hiroshi
Kitajima, Hiroshi
Nakamura, Mitsuharu
Sonda, Shuji
Takeuchi, Masahiro
Tanaka, Yoshihito
Ueda, Naoko
Sekiguchi, Sumie
Ishige, Takayuki
Shima, Kyoko
Nabeno, Mika
Abe, Yuji
Anabuki, Jun
Soejima, Aki
Yoshida, Kumiko
Takashina, Yoko
Ishii, Shinichi
Kiuchi, Satoko
Fukuda, Sayaka
Tsutsumiuchi, Reiko
Kosaka, Keigo
Murozono, Takahiro
Nakamaru, Yoshinobu
Utsumi, Hiroyuki
Masutomi, Naoya
Kishida, Hiroyuki
Miyaguchi, Ikuko
Hayashi, Yoshiharu
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (19) : 5705 - 5719
[7] (2S, 3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl4-oxo-2-(4-[1,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide:: A selective α-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Edmondson, Scott D.
Mastracchio, Anthony
Mathvink, Robert J.
He, Jiafang
Harper, Bart
Park, You-Jung
Beconi, Maria
Di Salvo, Jerry
Eiermann, George J.
He, Huaibing
Leiting, Barbara
Leone, Joseph F.
Levorse, Dorothy A.
Lyons, Kathryn
Patel, Reshma A.
Patel, Sangita B.
Petrov, Aleksandr
Scapin, Giovanna
Shang, Jackie
Roy, Ranabir Sinha
Smith, Aaron
Wu, Joseph K.
Xu, Shiyao
Zhu, Bing
Thornberry, Nancy A.
Weber, Ann E.
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (12) : 3614 - 3627
[8] Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279):: A very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes
Madar, David J.
Kopecka, Hana
Pireh, Daisy
Yong, Hong
Pei, Zhonghua
Li, Xiaofeng
Wiedeman, Paul E.
Djuric, Stevan W.
Von Geldern, Thomas W.
Fickes, Michael G.
Bhagavatula, Lakshmi
McDermott, Todd
Wittenberger, Steven
Richards, Steven J.
Longenecker, Kenton L.
Stewart, Kent D.
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (21) : 6416 - 6420
[9] Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity
Elliott, Richard L.
Cameron, Kimberly O.
Chin, Janice E.
Bartlett, Jeremy A.
Beretta, Elena E.
Chen, Yue
Jardine, Paul Da Silva
Dubins, Jeffrey S.
Gillaspy, Melissa L.
Hargrove, Diane M.
Kalgutkar, Amit S.
LaFlamme, Janet A.
Lame, Mary E.
Martin, Kelly A.
Maurer, Tristan S.
Nardone, Nancy A.
Oliver, Robert M.
Scott, Dennis O.
Sun, Dexue
Swick, Andrew G.
Trebino, Catherine E.
Zhang, Yingxin
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (22) : 6797 - 6801
[10] Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity
Boezio, Alessandro A.
Copeland, Katrina W.
Rex, Karen
Albrecht, Brian K.
Bauer, David
Bellon, Steven F.
Boezio, Christiane
Broome, Martin A.
Choquette, Deborah
Coxon, Angela
Dussault, Isabelle
Hirai, Satoko
Lewis, Richard
Lin, Min-Hwa Jasmine
Lohman, Julia
Liu, Jingzhou
Peterson, Emily A.
Potashman, Michele
Shimanovich, Roman
Teffera, Yohannes
Whittington, Douglas A.
Vaida, Karma
Harmange, Jean-Christophe
JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (06) : 2328 - 2342

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