Synthesis and structure-activity relationship of new 1,5-dialkyl-1,5-benzodiazepines as cholecystokinin-2 receptor antagonists

被引：11

作者：

Roberts, Karen ^{[1
]}

Ursini, Antonella ^{[1
]}

Barnaby, Robert ^{[1
]}

Cassara, Paolo G. ^{[1
]}

Corsi, Mauro ^{[1
]}

Curotto, Giovanni ^{[1
]}

Donati, Daniele ^{[1
]}

Feriani, Aldo ^{[1
]}

Finizia, Gabriella ^{[1
]}

Marchioro, Carla ^{[1
]}

Niccolai, Daniela ^{[1
]}

Oliosi, Beatrice ^{[1
]}

Polinelli, Stefano ^{[1
]}

Ratti, Emiliangelo ^{[1
]}

Reggiani, Angelo ^{[1
]}

Tedesco, Giovanna ^{[1
]}

Tranquillini, Maria E. ^{[1
]}

Trist, David G. ^{[1
]}

van Amsterdam, Franciscus T. M. ^{[1
]}

机构：

[1] GlaxoSmithKline, Med Res Ctr, I-37100 Verona, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 14期

关键词：

1,5-Benzodiazepine; Cholecystokinin; CCK2; antagonists; Anxiety; CCK-B ANTAGONISTS; GASTRIN; POTENT; ANALOGS; BRAIN; 1,5-BENZODIAZEPINES; DERIVATIVES; RESOLUTION; LIGANDS; SUBSTITUTION;

D O I：

10.1016/j.bmc.2011.05.057

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：

This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 was replaced with more hydrophilic substituents, like alkyl groups bearing basic functions. In some cases, the resolution of the racemic key intermediates 3-amino-benzodiazepines was also accomplished. Among the compounds synthesized and characterised so far in this class, the 5-morpholinoethyl derivative 54, was selected as potential follow up of GV150013 and submitted for further evaluation. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4257 / 4273

页数：17

共 50 条

[31] CHED 472-Synthesis of 2,3-dihydro-1H-1,5-benzodiazepines
Conklin, Adrienne
Yamaguchi, Kenneth
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2008, 235
[32] Catalytic synthesis of 2,3-dihydro-1H-1,5-benzodiazepines by ferric perchlorate
Heravi, Majid M.
Zadsirjan, Vahideh
Behbahani, Farahnaz K.
Oskooie, Hossien A.
JOURNAL OF MOLECULAR CATALYSIS A-CHEMICAL, 2006, 259 (1-2) : 201 - 204
[33] Novel pyrazolo[1,5-a]pyridines as orally active EP1 receptor antagonists: Synthesis, structure-activity relationship studies, and biological evaluation
Umei, Kentaro
Nishigaya, Yosuke
Kondo, Atsushi
Tatani, Kazuya
Tanaka, Nobuyuki
Kohno, Yasushi
Seto, Shigeki
BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (09) : 2635 - 2642
[34] Preparation and Application of a New Supported Nicotine-Based Organocatalyst for Synthesis of Various 1,5-Benzodiazepines
Mehri Moeini korbekandi
Mahboobeh Nasr-Esfahani
Iraj Mohammadpoor-Baltork
Majid Moghadam
Shahram Tangestaninejad
Valiollah Mirkhani
Catalysis Letters, 2019, 149 : 1057 - 1066
[35] Preparation and Application of a New Supported Nicotine-Based Organocatalyst for Synthesis of Various 1,5-Benzodiazepines
Korbekandi, Mehri Moeini
Nasr-Esfahani, Mahboobeh
Mohammadpoor-Baltork, Iraj
Moghadam, Majid
Tangestaninejad, Shahram
Mirkhani, Valiollah
CATALYSIS LETTERS, 2019, 149 (04) : 1057 - 1066
[36] 2-Methoxyethanol as an alternative reaction solvent for the synthesis of 1,5-benzodiazepines under microwave irradiation
Zangade, Sainath
Mokle, Shyam
Chavan, Shivaji
Vibhute, Yeshwant
ORBITAL-THE ELECTRONIC JOURNAL OF CHEMISTRY, 2011, 3 (03): : 144 - 149
[37] Reaction of 4-aryl-2,3-dihydro-2-phenyl-1H-1,5-benzodiazepines with 2-chloroacetyl chloride.: Synthesis of N-acyl- and azeto[1,2-a]-1,5-benzodiazepines
Insuasty, Braulio
Quiroga, Jairo
Abonia, Rodrigo
Insuasty, Henry
Escobar, Henry
Diaz, Emilso
Nogueras, Manuel
HETEROCYCLIC COMMUNICATIONS, 2006, 12 (05) : 347 - 354
[38] Synthesis of 1-H-1,5-Benzodiazepines Derivatives Using SiO2/ZnCl2
Jacob, Raquel G.
Radatz, Catia S.
Rodrigues, Mariele B.
Alves, Diego
Perin, Gelson
Lenardao, Eder J.
Savegnago, Lucielli
HETEROATOM CHEMISTRY, 2011, 22 (02) : 180 - 185
[39] RESEARCH ON 1,5-BENZODIAZEPINES .4. SYNTHESIS OF 2,4-BIS-(DIALKYLAMINO)-1-PHENYL-1H-1,5-BENZODIAZEPINE
ROMA, G
DIBRACCIO, M
MAZZEI, M
ERMILI, A
FARMACO-EDIZIONE SCIENTIFICA, 1980, 35 (12): : 997 - 1004
[40] Synthesis and antimicrobial and antinociceptive activity of 4-substituted 2-trichloromethyl-3H-1,5-benzodiazepines
O. A. Myshkina
S. Yu. Balandina
R. R. Makhmudov
M. V. Dmitriev
N. Yu. Lisovenko
Russian Chemical Bulletin, 2021, 70 : 1408 - 1414

← 1 2 3 4 5 →