Conversion of oxadiazolo[3,4-b]pyrazines to imidazo[4,5-b]pyrazines via a tandem reduction-cyclization sequence generates new mitochondrial uncouplers

被引：5

作者：

Dai, Yumin ^{[1
,2
]}

Santiago-Rivera, Jose A. ^{[1
,2
]}

Hargett, Stefan ^{[3
,4
]}

Salamoun, Joseph M. ^{[1
,2
]}

Hoehn, Kyle L. ^{[3
,4
,5
]}

Santos, Webster L. ^{[1
,2
]}

机构：

[1] Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA

[2] Virginia Tech, Ctr Drug Discovery, Blacksburg, VA 24061 USA

[3] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA

[4] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA

[5] Univ New South Wales, Sch Biotechnol & Biomol Sci, Kensington, NSW 2033, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2022年 / 73卷

关键词：

PALLADIUM-CATALYZED AMIDATION; BIOLOGICAL EVALUATION; POTENT; DERIVATIVES; DISCOVERY; IMIDAZOPYRIDINES; IDENTIFICATION; IMIDAZOLES; INHIBITORS; MECHANISM;

D O I：

10.1016/j.bmcl.2022.128912

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report new mitochondrial uncouplers derived from the conversion of [1,2,5]oxadiazolo[3,4-b]pyrazines to 1H-imidazo[4,5-b]pyrazines. The in situ Fe-mediated reduction of the oxadiazole fragment followed by cyclization gave access to imidazopyrazines in moderate to good yields. A selection of orthoesters also allowed functionalization on the 2-position of the imidazole ring. This method afforded a variety of imidazopyrazine derivatives with varying substitution on the 2, 5 , 6 positions. Our studies suggest that both a 2-trifluoromethyl group and N-methylation are crucial for mitochondrial uncoupling capacity.

引用

页数：6

共 10 条

[1] Structure-activity relationships of furazano[3,4-b]pyrazines as mitochondrial uncouplers [J].

Kenwood, Brandon M. ;

Calderone, Joseph A. ;

Taddeo, Evan P. ;

Hoehn, Kyle L. ;

Santos, Webster L. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (21) :4858-4861

[2] Conversion of tetraphenylethylene-substituted oxadiazolo[3,4- b ]pyrazines into the corresponding imidazo[4,5- b ]- and pyrazino[2,3- b ]pyrazines, as chemosensors for the selective detection of nitroaromatics in aqueous media [J].

Kvashnin, Yuriy A. ;

Zhilina, Ekaterina F. ;

Dubovik, Alyona I. ;

Gazizov, Denis A. ;

V. Mekhaev, Alexandr ;

Krynina, Elizaveta M. ;

Rusinov, Gennady L. ;

Verbitskiy, Egor V. ;

Charushin, Valery N. .

DYES AND PIGMENTS, 2024, 228

[3] Synthesis of Imidazo[4,5-b]pyridines and Imidazo[4,5-b]pyrazines by Palladium Catalyzed Amidation of 2-Chloro-3-amino-heterocycles [J].

Rosenberg, Adam J. ;

Zhao, Jinbo ;

Clark, Daniel A. .

ORGANIC LETTERS, 2012, 14 (07) :1764-1767

[4] Synthesis of [1,3,2]dithiazolo[4,5-b][1,2,5]oxadiazolo[3,4-e]pyrazines [J].

Konstantinova, Lidia S. ;

Popov, Vadim V. ;

Obruchnikova, Natalia V. ;

Lyssenko, Konstantin A. ;

Ananyev, Ivan V. ;

Rakitin, Oleg A. .

ARKIVOC, 2011, :69-81

[5] Direct arylalkenylation of furazano[3,4-b]pyrazines via a new C-H functionalization protocol [J].

Kazin, Nikita A. ;

Kvashnin, Yuriy A. ;

Irgashev, Roman A. ;

Dehaen, Wim ;

Rusinov, Gennady L. ;

Charushin, Valery N. .

TETRAHEDRON LETTERS, 2015, 56 (14) :1865-1869

[6] Metal-free protocol for the synthesis of novel 6-(het)aryl-5-aryl-5H-imidazo[4,5-b][1,2,5]oxadiazolo[3,4-e]pyrazines [J].

Kvashnin, Yuriy A. ;

Rusinov, Gennady L. ;

Charushin, Valery N. .

MENDELEEV COMMUNICATIONS, 2018, 28 (05) :461-463

[7] One-Pot Synthesis of Benzo[4,5]imidazo[2,1-a]isoquinolines and Isoquinolino[3,4-b]quinoxalines via Tandem Cyclization Strategies [J].

Bagdasarian, Alex L. ;

Nguyen, Huy H. ;

Palazzo, Teresa A. ;

Fettinger, James C. ;

Haddadin, Makhluf J. ;

Kurth, Mark J. .

JOURNAL OF ORGANIC CHEMISTRY, 2016, 81 (09) :3924-3928

[8] A facile, metal-free, oxidative coupling of new 6-(hetero) aryl-[1,2,5]-oxadiazolo[3,4-b] pyrazines with pyrroles, indoles and carbazoles [J].

Kvashnin, Yuriy A. ;

Kazin, Nikita A. ;

Verbitskiy, Egor V. ;

Svalova, Tatyana S. ;

Ivanova, Alla V. ;

Kozitsina, Alisa N. ;

Slepukhin, Pavel A. ;

Rusinov, Gennady L. ;

Chupakhin, Oleg N. ;

Charushin, Valery N. .

ARKIVOC, 2016, :279-300

[9] Rapid Construction of an Imidazo[4,5-b]pyridine Skeleton from 2-Chloro-3-nitropyridine via Tandem Reaction in H2O-IPA Medium [J].

Padmaja, R. D. ;

Devi, Vishnu C. ;

Mukku, Narasimharao ;

Chanda, Kaushik ;

Maiti, Barnali .

ACS OMEGA, 2018, 3 (04) :4583-4590

[10] New Palladium-Catalyzed Domino Reaction with Intramolecular Ring Closure of an N-(2-Chloro-3-heteroaryl) arylamide: First Synthesis of OxazoloACHTUNGTRENUNG[ 4,5-b] pyrazines [J].

Demmer, Charles S. ;

Hansen, Jacob C. ;

Kehler, Jan ;

Bunch, Lennart .

ADVANCED SYNTHESIS & CATALYSIS, 2014, 356 (05) :1047-1055

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