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引用本文的文献

1
Discovery of a Selective S1P1 Receptor Agonist Efficacious at Low Oral Dose and Devoid of Effects on Heart Rate.发现一种低口服剂量有效且对心率无影响的选择性S1P1受体激动剂。
ACS Med Chem Lett. 2011 Mar 24;2(6):444-9. doi: 10.1021/ml2000214. eCollection 2011 Jun 9.
2
Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P1 and S1P5.AMG 369的发现，一种噻唑并[5,4-b]吡啶类S1P1和S1P5激动剂。
ACS Med Chem Lett. 2010 Dec 29;2(2):107-12. doi: 10.1021/ml100306h. eCollection 2011 Feb 10.

本文引用的文献

1
Benzofuran Derivatives as Potent, Orally Active S1P1 Receptor Agonists: A Preclinical Lead Molecule for MS.苯并呋喃衍生物作为强效、口服活性的S1P1受体激动剂：一种用于多发性硬化症的临床前先导分子。
ACS Med Chem Lett. 2010 Nov 9;2(2):97-101. doi: 10.1021/ml100227q. eCollection 2011 Feb 10.
2
Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.口服芬戈莫德或肌肉注射干扰素治疗复发型多发性硬化。
N Engl J Med. 2010 Feb 4;362(5):402-15. doi: 10.1056/NEJMoa0907839. Epub 2010 Jan 20.
3
A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis.一项口服芬戈莫德治疗复发性多发性硬化的安慰剂对照试验。
N Engl J Med. 2010 Feb 4;362(5):387-401. doi: 10.1056/NEJMoa0909494. Epub 2010 Jan 20.
4
FTY720 story. Its discovery and the following accelerated development of sphingosine 1-phosphate receptor agonists as immunomodulators based on reverse pharmacology.FTY720的故事。它的发现以及随后基于反向药理学将1-磷酸鞘氨醇受体激动剂作为免疫调节剂的加速研发。
Perspect Medicin Chem. 2007 Sep 6;1:11-23.
5
Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules.作为面向屏障的治疗分子的1-磷酸鞘氨醇受体化学调节剂
Nat Rev Drug Discov. 2009 Apr;8(4):297-307. doi: 10.1038/nrd2356. Epub 2009 Mar 20.
6
Sphingosine 1-phosphate receptor signaling.鞘氨醇-1-磷酸受体信号传导
Annu Rev Biochem. 2009;78:743-68. doi: 10.1146/annurev.biochem.78.072407.103733.
7
Principles of bioactive lipid signalling: lessons from sphingolipids.生物活性脂质信号传导原理：来自鞘脂类的经验教训。
Nat Rev Mol Cell Biol. 2008 Feb;9(2):139-50. doi: 10.1038/nrm2329.
8
Requirement of secondary lymphoid tissues for the induction of primary and secondary T cell responses against Listeria monocytogenes.次级淋巴组织对诱导针对单核细胞增生李斯特菌的初次和二次T细胞应答的需求。
Eur J Immunol. 2008 Jan;38(1):127-38. doi: 10.1002/eji.200737142.
9
Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology.健康与疾病中的1-磷酸鞘氨醇受体：基因敲除研究及反向药理学的机制见解
Pharmacol Ther. 2007 Jul;115(1):84-105. doi: 10.1016/j.pharmthera.2007.04.006. Epub 2007 May 22.
10
Metabolism and biological functions of two phosphorylated sphingolipids, sphingosine 1-phosphate and ceramide 1-phosphate.两种磷酸化鞘脂——1-磷酸鞘氨醇和1-磷酸神经酰胺的代谢及生物学功能
Prog Lipid Res. 2007 Mar;46(2):126-44. doi: 10.1016/j.plipres.2007.03.001. Epub 2007 Mar 14.

一种强效的、对1-磷酸鞘氨醇受体3（S1P3）有保留作用的1-磷酸鞘氨醇受体1（S1P1）苯并噻唑激动剂的发现。

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

作者信息

Lanman Brian A, Cee Victor J, Cheruku Srinivasa R, Frohn Mike, Golden Jennifer, Lin Jian, Lobera Mercedes, Marantz Yael, Muller Kristine M, Neira Susana C, Pickrell Alexander J, Rivenzon-Segal Dalia, Schutz Nili, Sharadendu Anurag, Yu Xiang, Zhang Zhaoda, Buys Janet, Fiorino Mike, Gore Anu, Horner Michelle, Itano Andrea, McElvain Michele, Middleton Scot, Schrag Michael, Vargas Hugo M, Xu Han, Xu Yang, Zhang Xuxia, Siu Jerry, Bürli Roland W

机构信息

Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States.

EPIX Pharmaceuticals Inc., 167 Worcester Street, Suite 201, Wellesley Hills, Massachusetts 02481, United States.

出版信息

ACS Med Chem Lett. 2010 Nov 9;2(2):102-6. doi: 10.1021/ml100228m. eCollection 2011 Feb 10.

DOI:10.1021/ml100228m
PMID:24900287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4018108/
Abstract

Optimization of a benzofuranyl S1P1 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 S1P1 agonist with minimal activity at S1P3. 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.

摘要

对苯并呋喃基S1P1激动剂先导化合物（3）进行优化，从而发现了1-(3-氟-4-(5-(2-氟苄基)苯并[d]噻唑-2-基)苄基)氮杂环丁烷-3-羧酸（14），这是一种强效S1P1激动剂，对S1P3的活性极小。以0.3 mg/kg的剂量口服给药时，14在给药后24小时显著降低了血液淋巴细胞计数，并减弱了对抗原攻击的迟发型超敏反应（DTH）。