A novel approach to cyclin-dependent kinase 5/p25 inhibitors: A potential treatment for Alzheimer's disease

被引：41

作者：

Shiradkar, Mahendra Ramesh

Padhalingappa, Mallikarjuna Bandrehally

Bhetalabhotala, Sastry

Akula, Kalyan Chakravarthy

Tupe, Dattu Anna

Pinninti, Raghotham Reddy

Thummanagoti, Suman

机构：

[1] Dr Reddys Labs, Hyderabad 500016, Andhra Pradesh, India

[2] St Johns Coll Pharm, Bangalore 560040, Karnataka, India

[3] Andhra Univ, Dept Pharmaceut Sci, Waltair 530003, Andhra Pradesh, India

[4] Govt Coll Pharm, Dept Biopharmaceuts, Karad, Maharashtra 415124, India

[5] Univ Kentucky, Coll Pharm, Lexington, KY 40536 USA

[6] Kakatiya Univ, Dept Chem, Warangal 506002, Andhra Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 19期

关键词：

thienyl; triazole; cdk5/p25; Alzheimer's disease;

D O I：

10.1016/j.bmc.2007.06.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Based on the earlier results of our in-house database and compound library, a series of novel clubbed thienyl triazoles was designed which may emerge as potential cdk5/p25 inhibitors, for the treatment of Alzheimer's disease. A benign synthesis was planned so as to take an advantage of MAOS (Microwave Assisted Organic Synthesis) method. Evaluation of the SAR of this series has allowed the identification of compounds 4, 5, 7 and 8 from series I while 13, 14, 16 and 17 from series 11 as significant cdk5/p25 inhibitors and thus have potential as possible treatments for Alzheimer's disease. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：6397 / 6406

页数：10

共 26 条

[1] ALKYLATION OF POTASSIUM ACETATE IN DRY MEDIA THERMAL-ACTIVATION IN COMMERCIAL MICROWAVE-OVENS
BRAM, G
LOUPY, A
MAJDOUB, M
GUTIERREZ, E
RUIZHITZKY, E
[J]. TETRAHEDRON, 1990, 46 (15) : 5167 - 5176
[2] COOPER CB, 2002, Patent No. 1256578
[3] A decade of CDK5
Dhavan, R
Tsai, LH
[J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (10) : 749 - 759
[4] Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer's disease
Helal, CJ
Sanner, MA
Cooper, CB
Gant, T
Adam, M
Lucas, JC
Kang, ZJ
Kupchinsky, S
Ahlijanian, MK
Tate, B
Menniti, FS
Kelly, K
Peterson, M
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (22) : 5521 - 5525
[5] Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents
Holla, B. Shivarama
Rao, B. Sooryanarayana
Sarojini, B. K.
Akberali, P. M.
Kumari, N. Suchetha
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2006, 41 (05) : 657 - 663
[6] EVIDENCE FOR CDK5 AS A MAJOR ACTIVITY PHOSPHORYLATING TAU-PROTEIN IN PORCINE BRAIN EXTRACT
HOSOI, T
UCHIYAMA, M
OKUMURA, E
SAITO, T
ISHIGURO, K
UCHIDA, T
OKUYAMA, A
KISHIMOTO, T
HISANAGA, S
[J]. JOURNAL OF BIOCHEMISTRY, 1995, 117 (04) : 741 - 749
[7] JAMES AB, 1999, NATURE, V402, P669
[8] Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: Synthesis, X-ray crystallographic analysis, and biological activities
Kim, KS
Kimball, SD
Misra, RN
Rawlins, DB
Hunt, JT
Xiao, HY
Lu, SF
Qian, LG
Han, WC
Shan, WF
Mitt, T
Cai, ZW
Poss, MA
Zhu, H
Sack, JS
Tokarski, JS
Chang, CY
Pavletich, N
Kamath, A
Humphreys, WG
Marathe, P
Bursuker, I
Kellar, KA
Roongta, U
Batorsky, R
Mulheron, JG
Bol, D
Fairchild, CR
Lee, FY
Webster, KR
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (18) : 3905 - 3927
[9] Cdk5 as a drug target for the treatment of Alzheimer's disease
Lau, LF
Seymour, PA
Sanner, MA
Schachter, JB
[J]. JOURNAL OF MOLECULAR NEUROSCIENCE, 2002, 19 (03) : 267 - 273
[10] Lau Lit-Fui, 2002, Current Topics in Medicinal Chemistry, V2, P395, DOI 10.2174/1568026024607526

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