Discovery of a Potent, S1P3-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P1)

被引：16

作者：

Lanman, Brian A. ^{[1
]}

Cee, Victor J. ^{[1
]}

Cheruku, Srinivasa R. ^{[2
]}

Frohn, Mike ^{[1
]}

Golden, Jennifer ^{[1
]}

Lin, Jian ^{[2
]}

Lobera, Mercedes ^{[2
]}

Marantz, Yael ^{[2
]}

Muller, Kristine M. ^{[1
]}

Neira, Susana C. ^{[1
]}

Pickrell, Alexander J. ^{[1
]}

Rivenzon-Segal, Dalia ^{[2
]}

Schutz, Nili ^{[2
]}

Sharadendu, Anurag ^{[2
]}

Yu, Xiang ^{[2
]}

Zhang, Zhaoda ^{[2
]}

Buys, Janet ^{[1
]}

Fiorino, Mike ^{[1
]}

Gore, Anu ^{[1
]}

Horner, Michelle ^{[1
]}

Itano, Andrea ^{[1
]}

McElvain, Michele ^{[1
]}

Middleton, Scot ^{[1
]}

Schrag, Michael ^{[1
]}

Vargas, Hugo M. ^{[1
]}

Xu, Han ^{[1
]}

Xu, Yang ^{[1
]}

Zhang, Xuxia ^{[1
]}

Siu, Jerry ^{[1
]}

Buerli, Roland W. ^{[1
]}

机构：

[1] Amgen Inc, Thousand Oaks, CA 91320 USA

[2] EPIX Pharmaceut Inc, Wellesley Hills, MA 02481 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2011年 / 2卷 / 02期

关键词：

Sphingosine-1-phosphate receptor; S1P(1); agonist; inflammation; lymphocyte; SPHINGOSINE 1-PHOSPHATE RECEPTOR; RELAPSING MULTIPLE-SCLEROSIS; LYMPHOID ORGANS; ORAL FINGOLIMOD; HEART-RATE; FTY720; RATS; IMMUNOSUPPRESSANT; SPHINGOLIPIDS; EXPRESSION;

D O I：

10.1021/ml100228m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Optimization of a benzofuranyl SIP, agonist lead compound (3) led to the discovery of 1-(3-fluoro-4-(5-(2-fluorobenzyl)benzo[d]thiazol-2-yl)benzyl)-azetidine-3-carboxylic acid (14), a potent SIP, agonist with minimal activity at S1P(3). Dosed orally at 0.3 mg/kg, 14 significantly reduced blood lymphocyte counts 24 h postdose and attenuated a delayed type hypersensitivity (DTH) response to antigen challenge.

引用

页码：102 / 106

页数：5

共 50 条

[21] Sphingosine-1-phosphate receptor S1P1 is a key regulator of endothelial cell function.
Krump-Konvalinkova, V
Yasuda, S
Rubic, T
Erl, W
Vosseler, C
Kirkpatrick, CJ
Tigyi, G
Siess, W
JOURNAL OF VASCULAR RESEARCH, 2005, 42 : 49 - 49
[22] Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity
Scott, F. L.
Clemons, B.
Brooks, J.
Brahmachary, E.
Powell, R.
Dedman, H.
Desale, H. G.
Timony, G. A.
Martinborough, E.
Rosen, H.
Roberts, E.
Boehm, M. F.
Peach, R. J.
BRITISH JOURNAL OF PHARMACOLOGY, 2016, 173 (11) : 1778 - 1792
[23] Differential regulation of P-selectin-dependent rolling by Sphingosine-1-Phosphate (S1P) receptors S1P1 and S1P3
Nussbaum, C.
Bannenberg, S.
Keul, P.
Sperandio, M.
Levkau, B.
JOURNAL OF VASCULAR RESEARCH, 2011, 48 : 327 - 327
[24] Pyrazole derived from (+)-3-carene; a novel potent, selective scaffold for sphingosine-1-phosphate (S1P1) receptor agonists
Zecri, Frederic J.
Albert, Rainer
Landrum, Gregory
Hinterding, Klaus
Cooke, Nigel G.
Guerini, Danilo
Streiff, Markus
Bruns, Christian
Nuesslein-Hildesheim, Barbara
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (01) : 35 - 37
[25] The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis
Kono, M
Mi, YD
Liu, YJ
Sasaki, T
Allende, ML
Wu, YP
Yamashita, T
Proia, RL
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (28) : 29367 - 29373
[26] SPHINGOSINE-1-PHOSPHATE RECEPTORS S1P1 AND S1P3 REGULATE THE TRANSENDOTHELIAL TRANSPORT OF HDL AND LDL ANTAGONISTICALLY
Velagapudi, Srividya
Yalcinkaya, Mustafa
Rohrer, Lucia
von Eckardstein, Arnold
ATHEROSCLEROSIS SUPPLEMENTS, 2018, 32 : 125 - 125
[27] Sphingosine 1-Phosphate Receptor 1 (S1P1) Upregulation and Amelioration of Experimental Autoimmune Encephalomyelitis by an S1P1 Antagonist
Cahalan, Stuart M.
Gonzalez-Cabrera, Pedro J.
Nhan Nguyen
Guerrero, Miguel
Cisar, Elizabeth A. George
Leaf, Nora B.
Brown, Steven J.
Roberts, Edward
Rosen, Hugh
MOLECULAR PHARMACOLOGY, 2013, 83 (02) : 316 - 321
[28] Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)
Guo, Junqing
Watterson, Scott H.
Kempson, James
Spergel, Steve H.
Langevine, Charles L.
Moquin, Robert V.
Shen, Ding Ren
Yarde, Melissa
Cvijic, Mary Ellen
Banas, Dana
Liu, Richard
Suchard, Suzanne J.
Gillooly, Kathleen
Taylor, Tracy
RexRabe, Sandra
Shuster, Dave J.
McIntyre, Kim W.
Cornelius, Georgia
Darienzo, Celia
Marino, Anthony
Balimane, Praveen
Saltercid, Luisa
McKinnon, Murray
Barrish, Joel C.
Carter, Percy H.
Pitts, William J.
Xie, Jenny
Dyckman, Alaric J.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2011, 242
[29] Discovery of a 1-Methyl-3,4-dihydronaphthalene-Based Sphingosine-1-Phosphate (S1P) Receptor Agonist Ceralifimod (ONO-4641). A S1P1 and S1P5 Selective Agonist for the Treatment of Autoimmune Diseases
Kurata, Haruto
Kusumi, Kensuke
Otsuki, Kazuhiro
Suzuki, Ryo
Kurono, Masakuni
Komiya, Takaki
Hagiya, Hiroshi
Mizuno, Hirotaka
Shioya, Hiroki
Ono, Takeji
Takada, Yuka
Maeda, Tatsuo
Matsunaga, Norikazu
Kondo, Tetsu
Tominaga, Sachiko
Nunoya, Ken-Ici
Kiyoshi, Hidekazu
Komeno, Masaharu
Nakade, Shinji
Habashita, Hiromu
JOURNAL OF MEDICINAL CHEMISTRY, 2017, 60 (23) : 9508 - 9530
[30] Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 ( S1P1)
Guo, Junqing
Watterson, Scott H.
Spergel, Steven H.
Kempson, James
Langevine, Charles M.
Shen, Ding Ren
Yarde, Melissa
Cvijic, Mary Ellen
Banas, Dana
Liu, Richard
Suchard, Suzanne J.
Gillooly, Kathleen
Taylor, Tracy
Rex-Rabe, Sandra
Shuster, David J.
McIntyre, Kim W.
Cornelius, Georgia
D'Arienzo, Celia
Marino, Anthony
Balimane, Praveen
Salter-Cid, Luisa
McKinnon, Murray
Barrish, Joel C.
Carter, Percy H.
Pitts, William J.
Xie, Jenny
Dyckman, Alaric J.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (10) : 2470 - 2474

← 1 2 3 4 5 →