Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents

被引：92

作者：

Biftu, T

Feng, D

Fisher, M

Liang, GB

Qian, XX

Scribner, A

Dennis, R

Lee, S

Liberator, PA

Brown, C

Gurnett, A

Leavitt, PS

Thompson, D

Mathew, J

Misura, A

Samaras, S

Tamas, T

Sina, JF

McNulty, KA

McKnight, CG

Schmatz, DM

Wyvratt, M

机构：

[1] Merck & Co Inc, Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Human & Anim Infect Dis Res, Rahway, NJ 07065 USA

[3] Scynexis Inc, Res Triangle Pk, NC 27709 USA

[4] Merck Res Labs, Dept Genet & Cellular Toxicol, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 09期

关键词：

protein kinase G; antiprotozoan; anticoccidial; imidazopyridine;

D O I：

10.1016/j.bmcl.2006.01.092

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies. (C) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2479 / 2483

页数：5

共 6 条

[1] [Anonymous], PROG MUTAT RES
[2] Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents
Biftu, T
Feng, D
Ponpipom, M
Girotra, N
Liang, GB
Qian, XX
Bugianesi, R
Simeone, J
Chang, L
Gurnett, A
Liberator, P
Dulski, P
Leavitt, PS
Crumley, T
Misura, A
Murphy, T
Rattray, S
Samaras, S
Tamas, T
Mathew, J
Brown, C
Thompson, D
Schmatz, D
Fisher, M
Wyvratt, M
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (13) : 3296 - 3301
[3] Donald R.G.K., 2002, MOL BIOCHEM PARASIT, V180, P136
[4] Purification and molecular characterization of cGMP-dependent protein kinase from apicomplexan parasites - A novel chemotherapeutic target
Gurnett, AM
Liberator, PA
Dulski, PM
Salowe, SP
Donald, RGK
Anderson, JW
Wiltsie, J
Diaz, CA
Harris, G
Chang, B
Darkin-Rattray, SJ
Nare, B
Crumley, T
Blum, PS
Misura, AS
Tamas, T
Sardana, MK
Yuan, J
Biftu, T
Schmatz, DM
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (18) : 15913 - 15922
[5] REVISED METHODS FOR THE SALMONELLA MUTAGENICITY TEST
MARON, DM
AMES, BN
[J]. MUTATION RESEARCH, 1983, 113 (3-4): : 173 - 215
[6] A compartmentalised model for the estimation of the cost of coccidiosis to the world's chicken production industry
Williams, RB
[J]. INTERNATIONAL JOURNAL FOR PARASITOLOGY, 1999, 29 (08) : 1209 - 1229

← 1 →