Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel class of EP1 receptor antagonists

被引：16

作者：

Atobe, Masakazu ^{[1
]}

Naganuma, Kenji ^{[1
]}

Kawanishi, Masashi ^{[1
]}

Morimoto, Akifumi ^{[1
]}

Kasahara, Ken-ichi ^{[1
]}

Ohashi, Shigeki ^{[1
]}

Suzuki, Hiroko ^{[1
]}

Hayashi, Takahiko ^{[1
]}

Miyoshi, Shiro ^{[1
]}

机构：

[1] Asahi Kasei Pharma Corp, Pharmaceut Res Ctr, Izunokuni, Shizuoka 4102321, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 22期

关键词：

EP1 receptor antagonist; Pyrazole; Thiazole; Overactive bladder; HTS; URINARY-BLADDER; PROSTANOID RECEPTORS;

D O I：

10.1016/j.bmcl.2013.09.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe a medicinal chemistry approach to generate a series of 2-(1H-pyrazol-1-yl)thiazole compounds that act as selective EP1 receptor antagonists. The obtained results suggest that compound 12 provides the best EP1 receptor antagonist activity and demonstrates good oral pharmacokinetics. (c) 2013 Elsevier Ltd. All rights reserved.

引用

页码：6064 / 6067

页数：4

共 12 条

[1]

ANDERSON KE, 1993, PHARMACOL REV, V45, P253

[2] Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles [J].

Antilla, JC ;

Baskin, JM ;

Barder, TE ;

Buchwald, SL .

JOURNAL OF ORGANIC CHEMISTRY, 2004, 69 (17) :5578-5587

[3] Prostaglandin facilitates afferent nerve activity via EP1 receptors during urinary bladder inflammation in rats [J].

Ikeda, Makoto ;

Kawatani, Masahito ;

Maruyama, Takayuki ;

Ishihama, Hiroko .

BIOMEDICAL RESEARCH-TOKYO, 2006, 27 (02) :49-54

[4] Role of prostaglandins in the urinary bladder: an update [J].

Khan, MA ;

Thompson, CS ;

Mumtaz, FH ;

Jeremy, JY ;

Morgan, RJ ;

Mikhailidis, DP .

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 1998, 59 (06) :415-422

[5] PROSTANOIDS AS LOCAL MODULATORS OF REFLEX MICTURITION [J].

MAGGI, CA .

PHARMACOLOGICAL RESEARCH, 1992, 25 (01) :13-20

[6] ONO-8130, a selective prostanoid EP1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis [J].

Miki, Takahiro ;

Matsunami, Maho ;

Nakamura, Saori ;

Okada, Hiroki ;

Matsuya, Hidekazu ;

Kawabata, Atsufumi .

PAIN, 2011, 152 (06) :1373-1381

[7] Prostanoid receptors: Structures, properties, and functions [J].

Narumiya, S ;

Sugimoto, Y ;

Ushikubi, F .

PHYSIOLOGICAL REVIEWS, 1999, 79 (04) :1193-1226

[8] PROSTAGLANDIN-E RECEPTORS [J].

NEGISHI, M ;

SUGIMOTO, Y ;

ICHIKAWA, A .

JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING, 1995, 12 (2-3) :379-391

[9] ONO-8539, A NOVEL EP1 RECEPTOR ANTAGONIST, SUPPRESSES BLADDER HYPERACTIVITY VIA EXCESSIVE PRODUCTION OF PROSTAGLANDIN E2 (PGE2) INDUCED BY INTRAVESICAL INSTILLATION OF ATP IN URODYNAMIC EVALUATION OF CYNOMOLGUS MONKEYS [J].

Okada, H. ;

Konemura, T. ;

Maruyama, T. .

EUROPEAN UROLOGY SUPPLEMENTS, 2010, 9 (02) :72-72

[10] Pharmacological characterization of thromboxane and prostanoid receptors in human isolated urinary bladder [J].

Palea, S ;

Toson, G ;

Pietra, C ;

Trist, DG ;

Artibani, W ;

Romano, O ;

Corsi, M .

BRITISH JOURNAL OF PHARMACOLOGY, 1998, 124 (05) :865-872

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