Synthesis and SAR of 2-phenyl-1-sulfonylaminocyclopropane carboxylates as ADAMTS-5 (Aggrecanase-2) inhibitors

被引：19

作者：

Shiozaki, Makoto ^{[1
]}

Imai, Hiroto ^{[1
]}

Maeda, Katsuya ^{[1
]}

Miura, Tomoya ^{[1
]}

Yasue, Katsutaka ^{[1
]}

Suma, Akira ^{[1
]}

Yokota, Masahiro ^{[1
]}

Ogoshi, Yosuke ^{[1
]}

Haas, Julia ^{[2
]}

Fryer, Andrew M. ^{[2
]}

Laird, Ellen R. ^{[2
]}

Littmann, Nicole M. ^{[2
]}

Andrews, Steven W. ^{[2
]}

Josey, John A. ^{[2
]}

Mimura, Takayuki ^{[1
]}

Shinozaki, Yuichi ^{[1
]}

Yoshiuchi, Hiromi ^{[1
]}

Inaba, Takashi ^{[1
]}

机构：

[1] Japan Tobacco Inc, Cent Pharmaceut Res Inst, Takatsuki Osaka 5691125, Japan

[2] Array BioPharma Inc, Boulder, CO 80301 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 21期

关键词：

SAR; ADAMTS-5 (Aggrecanase-2) inhibitors; 2-Phenyl-1sulfonylaminocyclopropanecarboxylates; LIGAND EFFICIENCY; CYCLOPROPANATION; ESTERS;

D O I：

10.1016/j.bmcl.2009.08.093

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1-sulfonylaminocyclopropanecarboxylates was synthesized as ADAMTS-5 (Aggrecanase-2) inhibitors. After an intensive investigation of the central cyclopropane core including its absolute stereochemistry and substituents, we found compound 22 with an Agg-2 IC(50) = 7.4 nM, the most potent ADAMTS-5 inhibitor reported so far. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6213 / 6217

页数：5

共 50 条

[41] Formation of 4-aroylhydrazono-2-methyl- 5-oxo-1-phenyl-3-phenylaminooxalyl-pyrrolidine-2-carboxylates
V. L. Gein
R. O. Dyrenkov
N. A. Kornienko
M. I. Vakhrin
G. A Veikhman
P. A. Slepukhin
Chemistry of Heterocyclic Compounds, 2012, 47 : 1590 - 1592
[42] Synthesis and antimicrobial activity of 2-acetyl-5-hydroxy-5-methyl-3-phenyl-1cyclohexanone and alkyl-4-hydroxy-4-methyl2-oxo-6-phenylcyclohexane-1-carboxylates
V. L. Gein
A. V. Vagapov
N. V. Nosova
E. V. Voronina
M. I. Vakhrin
A. P. Kriven’ko
Pharmaceutical Chemistry Journal, 2010, 44 : 245 - 247
[43] SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF 2-ACETYL-5-HYDROXY-5-METHYL-3-PHENYL-1-CYCLOHEXANONE AND ALKYL-4-HYDROXY-4-METHYL-2-OXO-6-PHENYLCYCLOHEXANE-1-CARBOXYLATES
Gein, V. L.
Vagapov, A. V.
Nosova, N. V.
Voronina, E. V.
Vakhrin, M. I.
Kriven'ko, A. P.
PHARMACEUTICAL CHEMISTRY JOURNAL, 2010, 44 (05) : 245 - 247
[44] Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: Synthesis and SAR studies
Lin, Xiaodong
Murray, Jeremy M.
Rico, Alice C.
Wang, Michael X.
Chu, Daniel T.
Zhou, Yasheen
Del Rosario, Merci
Kaufman, Susan
Ma, Sylvia
Fang, Eric
Crawford, Kenneth
Jefferson, A. B.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (16) : 4163 - 4168
[45] SYNTHESIS OF 1,2,4-TRIAZINES .14. REGIOSELECTIVE SYNTHESIS OF ETHYL 1,2,4-TRIAZINE-5-CARBOXYLATES
OHSUMI, T
NEUNHOEFFER, H
TETRAHEDRON, 1992, 48 (25) : 5227 - 5234
[46] Synthesis of 1-substituted-5-[(2-nitro-2-phenyl)-ethyl]imidazoles
Aulaskari, P
Pohjala, E
Vainiotalo, P
SYNTHETIC COMMUNICATIONS, 1997, 27 (15) : 2627 - 2635
[47] SYNTHESIS OF 2-PHENYL-4 [4'PHENYL-5'-MERCAPTO-1',2',4'-TRIAZOLYL]-1,2,3-TRIAZOLES
FERNANDES, PS
DCOSTA, R
NADKARNY, VV
JOURNAL OF THE INDIAN CHEMICAL SOCIETY, 1976, 53 (07) : 738 - 739
[48] Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes
Saito, T.
Nishida, K.
Furumatsu, T.
Yoshida, A.
Ozawa, M.
Ozaki, T.
OSTEOARTHRITIS AND CARTILAGE, 2013, 21 (01) : 165 - 174
[49] Synthesis and antimicrobial activity of 5,5'-dimethy1-2-oxido-[1,3,2]-dioxaphosphorinane-2-yl-amino carboxylates
Babu, B. Hari
Prasad, G. Syam
Reddy, C. Suresh
Raju, C. Naga
HETEROATOM CHEMISTRY, 2008, 19 (03) : 256 - 260
[50] Synthesis and crystal structure of 2-morpholinylthioformyl-2-phenyl-4-morpholinyl-5-phenyl-1, 3-dithiole
Zou, JP
Wang, XS
Zhang, J
Zeng, RS
Lu, ZE
CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2000, 19 (06) : 423 - 426

← 1 2 3 4 5 →