Synthesis, Stereochemical Separation, and Biological Evaluation of Selective Inhibitors of Human MAO-B: 1-(4-Arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines

被引：39

作者：

Chimenti, Franco ^{[1
]}

Secci, Daniela ^{[1
]}

Bolasco, Adriana ^{[1
]}

Chimenti, Paola ^{[1
]}

Granese, Arianna ^{[1
]}

Carradori, Simone ^{[1
]}

Yanez, Matilde ^{[2
,3
]}

Orallo, Francisco ^{[2
,3
]}

Sanna, M. Luisa ^{[4
]}

Gallinella, Bruno ^{[4
]}

Cirilli, Roberto ^{[4
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, I-00185 Rome, Italy

[2] Univ Santiago de Compostela, Fac Farm, Dept Farmacol, E-15782 Santiago De Compostela, La Coruna, Spain

[3] Univ Santiago de Compostela, Fac Farm, Inst Farm Ind, E-15782 Santiago De Compostela, La Coruna, Spain

[4] Ist Super Sanita, Dipartimento Farmaco, I-00161 Rome, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 17期

关键词：

MONOAMINE-OXIDASE-B; PARKINSONS-DISEASE; 2-THIAZOLYLHYDRAZONE DERIVATIVES; RASAGILINE; GENE;

D O I：

10.1021/jm100120s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazine derivatives have been investigated for their ability to inhibit selectively the activity of the human B isoform of monoamine oxidase. These compounds were obtained as racemates and (R)-enantiomers by a stereoconservative synthetic pattern in high yield and enantiomeric excess. The (S)-enantiomers of the most active derivatives have been separated by enantioselective HPLC. All compounds showed selective activity against hMAO-B with IC(50) ranging between 21.90 and 0.018 mu M.

引用

页码：6516 / 6520

页数：5

共 30 条

[1] Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class [J].

Binda, C ;

Hubálek, F ;

Li, M ;

Herzig, Y ;

Sterling, J ;

Edmondson, DE ;

Mattevi, A .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (07) :1767-1774

[2]

Blandini F, 2005, CNS DRUG REV, V11, P183

[3] Recent development of monoamine oxidase inhibitors [J].

Bolasco, A ;

Fioravanti, R ;

Carradori, S .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (12) :1763-1782

[4] Monoamine oxidase inactivation: From pathophysiology to therapeutics [J].

Bortolato, Marco ;

Chen, Kevin ;

Shih, Jean C. .

ADVANCED DRUG DELIVERY REVIEWS, 2008, 60 (13-14) :1527-1533

[5]

Carreiras MC, 2004, CURR PHARM DESIGN, V10, P3167

[6] Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones [J].

Chimenti, Franco ;

Maccioni, Elias ;

Secci, Daniela ;

Bolasco, Adriana ;

Chimenti, Paola ;

Granese, Arianna ;

Carradori, Simone ;

Alcaro, Stefano ;

Ortuso, Francesco ;

Yanez, Matilde ;

Orallo, Francisco ;

Cirilli, Roberto ;

Ferretti, Rosella ;

La Torre, Francesco .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (16) :4874-4880

[7] Synthesis and in vitro activity of 2-thiazolylhydrazone derivatives compared with the activity of clotrimazole against clinical isolates of Candida spp. [J].

Chimenti, Franco ;

Bizzarri, Bruna ;

Maccioni, Elias ;

Secci, Daniela ;

Bolasco, Adriana ;

Fioravanti, Rossella ;

Chimenti, Paola ;

Granese, Arianna ;

Carradori, Simone ;

Rivanera, Daniela ;

Lilli, Daniela ;

Zicari, Alessandra ;

Distinto, Simona .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (16) :4635-4640

[8] Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives [J].

Chimenti, Franco ;

Maccioni, Elias ;

Secci, Daniela ;

Bolasco, Adriana ;

Chimenti, Paola ;

Granese, Arianna ;

Befani, Olivia ;

Turini, Paola ;

Alcaro, Stefano ;

Ortuso, Francesco ;

Cardia, Maria C. ;

Distinto, Simona .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) :707-712

[9] Synthesis and selective inhibition of human monoamine oxidases of a large scaffold of (4,5-substituted-thiazol-2-yl)hydrazones [J].

Chimenti, Franco ;

Secci, Daniela ;

Bolasco, Adriana ;

Chimenti, Paola ;

Granese, Arianna ;

Carradori, Simone ;

D'Ascenzio, Melissa ;

Yanez, Matilde ;

Orallo, Francisco .

MEDCHEMCOMM, 2010, 1 (01) :61-72

[10] Synthesis and Biological Evaluation of Novel Conjugated Coumarin-Thiazole Systems [J].

Chimenti, Franco ;

Carradori, Simone ;

Secci, Daniela ;

Bolasco, Adriana ;

Chimenti, Paola ;

Granese, Arianna ;

Bizzarri, Bruna .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2009, 46 (03) :575-578

← 1 2 3 →