A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties

被引：12

作者：

Choong, Ingrid C. ^{[1
]}

Serafimova, Iana ^{[1
]}

Fan, Junfa ^{[1
]}

Stockett, David ^{[1
]}

Chan, Erica ^{[1
]}

Cheeti, Sravanthi ^{[1
]}

Lu, Yafan ^{[1
]}

Fahr, Bruce ^{[1
]}

Pham, Phuongly ^{[1
]}

Arkin, Michelle R. ^{[1
]}

Walker, Duncan H. ^{[1
]}

Hoch, Ute ^{[1
]}

机构：

[1] Sunesis Pharmaceut, Med Chem, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 21期

关键词：

CDK; Cyclin; SNS-032; Kinase;

D O I：

10.1016/j.bmcl.2008.09.073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification of a selective CDK2, 7, 9 inhibitor 4 with improved permeability is described. Compound 4 exhibits comparable CDK selectivity profile to SNS-032, but shows improved permeability and higher bioavailability in mice. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5763 / 5765

页数：3

共 8 条

[1] REQUIREMENT FOR TFIIH KINASE-ACTIVITY IN TRANSCRIPTION BY RNA-POLYMERASE-II [J].

AKOULITCHEV, S ;

MAKELA, TP ;

WEINBERG, RA ;

REINBERG, D .

NATURE, 1995, 377 (6549) :557-560

[2] P-glycoprotein plays a role in the oral absorption of BMS-387032, a potent cyclin-dependent kinase 2 inhibitor, in rats [J].

Kamath, AV ;

Chong, S ;

Chang, M ;

Marathe, PH .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2005, 55 (02) :110-116

[3]

KIM KS, 2003, Patent No. 6521759

[4] PURIFICATION OF P-TEFB, A TRANSCRIPTION FACTOR REQUIRED FOR THE TRANSITION INTO PRODUCTIVE ELONGATION [J].

MARSHALL, NF ;

PRICE, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (21) :12335-12338

[5] Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase [J].

Marshall, NF ;

Peng, JM ;

Xie, Z ;

Price, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (43) :27176-27183

[6] N-(Cycloalkylamino)acyl-2-aminothiazole inhibitors of cyclin-dependent kinase -: 2.: N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent [J].

Misra, RN ;

Xiao, HY ;

Kim, KS ;

Lu, SF ;

Han, WC ;

Barbosa, SA ;

Hunt, JT ;

Rawlins, DB ;

Shan, WF ;

Ahmed, SZ ;

Qian, LG ;

Chen, BC ;

Zhao, RL ;

Bednarz, MS ;

Kellar, KA ;

Mulheron, JG ;

Batorsky, R ;

Roongta, U ;

Kamath, A ;

Marathe, P ;

Ranadive, SA ;

Sack, JS ;

Tokarski, JS ;

Pavletich, NP ;

Lee, FYF ;

Webster, KR ;

Kimball, SD .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (07) :1719-1728

[7] Complexities in the development of cyclin-dependent kinase inhibitor drugs [J].

Sausville, EA .

TRENDS IN MOLECULAR MEDICINE, 2002, 8 (04) :S32-S37

[8] Cyclin-dependent kinase pathways as targets for cancer treatment [J].

Shapiro, GI .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (11) :1770-1783

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