Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2

被引：131

作者：

Oslund, Rob C. ^{[1
]}

Cermak, Nathan ^{[1
]}

Gelb, Michael H. ^{[1
,2
]}

机构：

[1] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 15期

关键词：

D O I：

10.1021/jm800422v

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report a series of inhibitors of secreted phospholipases A(2) (sPLA(2)S) based on substituted indoles, 6,7-benzoindoles, and indolizines derived from LY315920, a well-known indole-based sPLA(2) inhibitor. Using the human group X sPLA2 crystal structure, we prepared a highly potent and selective indole-based inhibitor of this enzyme. Also, we report human and mouse group IIA and HE specific inhibitors and a substituted 6,7-benzoindole that inhibits nearly all human and mouse sPLAs in the low nanomolar range.

引用

页码：4708 / 4714

页数：7

共 25 条

[1] MULTIFUNCTIONAL ACTIVITY OF THE EXTRACELLULAR DOMAIN OF THE M-TYPE (180 KDA) MEMBRANE-RECEPTOR FOR SECRETORY PHOSPHOLIPASES A(2) [J].

ANCIAN, P ;

LAMBEAU, G ;

LAZDUNSKI, M .

BIOCHEMISTRY, 1995, 34 (40) :13146-13151

[2]

Bradley JD, 2005, J RHEUMATOL, V32, P417

[3] Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .2. Indole-3-acetamides with additional functionality [J].

Dillard, RD ;

Bach, NJ ;

Draheim, SE ;

Berry, DR ;

Carlson, DG ;

Chirgadze, NY ;

Clawson, DK ;

Hartley, LW ;

Johnson, LM ;

Jones, ND ;

McKinney, ER ;

Mihelich, ED ;

Olkowski, JL ;

Schevitz, RW ;

Smith, AC ;

Snyder, DW ;

Sommers, CD ;

Wery, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (26) :5137-5158

[4] Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .1. Indole-3-acetamides [J].

Dillard, RD ;

Bach, NJ ;

Draheim, SE ;

Berry, DR ;

Carlson, DG ;

Chirgadze, NY ;

Clawson, DK ;

Hartley, LW ;

Johnson, LM ;

Jones, ND ;

McKinney, ER ;

Mihelich, ED ;

Olkowski, JL ;

Schevitz, RW ;

Smith, AC ;

Snyder, DW ;

Sommers, CD ;

Wery, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (26) :5119-5136

[5] Indole inhibitors of human nonpancreatic secretory phospholipase A(2) .3. Indole-3-glyoxamides [J].

Draheim, SE ;

Bach, NJ ;

Dillard, RD ;

Berry, DR ;

Carlson, DG ;

Chirgadze, NY ;

Clawson, DK ;

Hartley, LW ;

Johnson, LM ;

Jones, ND ;

McKinney, ER ;

Mihelich, ED ;

Olkowski, JL ;

Schevitz, RW ;

Smith, AC ;

Snyder, DW ;

Sommers, CD ;

Wery, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (26) :5159-5175

[6] Potent inhibitors of secretory phospholipase A2: Synthesis and inhibitory activities of indolizine and indene derivatives [J].

Hagishita, S ;

Yamada, M ;

Shirahase, K ;

Okada, T ;

Murakami, Y ;

Ito, Y ;

Matsuura, T ;

Wada, M ;

Kato, T ;

Ueno, M ;

Chikazawa, Y ;

Yamada, K ;

Ono, T ;

Teshirogi, I ;

Ohtani, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (19) :3636-3658

[7] Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model [J].

Henderson, William R., Jr. ;

Chi, Emil Y. ;

Bollinger, James G. ;

Tien, Ying-tzang ;

Ye, Xin ;

Castelli, Luca ;

Rubtsov, Yuri P. ;

Singer, Alan G. ;

Chiang, Gertrude K. S. ;

Nevalainen, Timo ;

Rudensky, Alexander Y. ;

Gelb, Michael H. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (04) :865-877

[8]

Jain M K, 1992, Mediators Inflamm, V1, P85, DOI 10.1155/S0962935192000164

[9] COMPETITIVE-INHIBITION OF PHOSPHOLIPASE-A2 IN VESICLES [J].

JAIN, MK ;

YUAN, W ;

GELB, MH .

BIOCHEMISTRY, 1989, 28 (10) :4135-4139

[10]

Kitadokoro K, 1998, J BIOCHEM, V123, P619

← 1 2 3 →