161455-97-6Relevant articles and documents
Synthesis of Oxindole Derivatives via Intramolecular C–H Insertion of Diazoamides Using Ru(II)-Pheox Catalyst
Phan Thi Thanh, Nga,Dang Thi Thu, Huong,Tone, Masaya,Inoue, Hayato,Iwasa, Seiji
, (2020/10/02)
This work presented the efficient intramolecular aromatic C–H insertion of diazoacetamide. The 1a–1o diazo compounds (except for 1k) were converted into their corresponding oxindoles via an intramolecular C–H insertion reaction in the presence of a Ru catalyst. The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products in excellent yield (99%). The efficiency of the Ru catalyst reached 580 (TON) and 156 min?1 (TOF).
Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5- dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity
Elliott, Richard L.,Cameron, Kimberly O.,Chin, Janice E.,Bartlett, Jeremy A.,Beretta, Elena E.,Chen, Yue,Jardine, Paul Da Silva,Dubins, Jeffrey S.,Gillaspy, Melissa L.,Hargrove, Diane M.,Kalgutkar, Amit S.,Laflamme, Janet A.,Lame, Mary E.,Martin, Kelly A.,Maurer, Tristan S.,Nardone, Nancy A.,Oliver, Robert M.,Scott, Dennis O.,Sun, Dexue,Swick, Andrew G.,Trebino, Catherine E.,Zhang, Yingxin
supporting information; experimental part, p. 6797 - 6801 (2011/01/04)
We describe the design, synthesis, and structure-activity relationships of triazolobenzodiazepinone CCK1 receptor agonists. Analogs in this series demonstrate potent agonist activity as measured by in vitro and in vivo assays for CCK1 agonism. Our efforts
Tetraazabenzo[e]azulene derivatives and analogs thereof
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Page/Page column 39, (2010/02/14)
This invention relates to CCK-A agonists of Formula (I) wherein R1-R4, A, B, X, D, E and G are as defined in the specificiation, as well as, among other things, pharmaceutical compositions containing the compounds and methods of use of the compounds and compositions. The compounds are useful in treating obesity.
Kinetics and Mechanism of the Nucleophilic Displacement Reactions of Chloroacetanilide Herbicides: Investigation of α-Substituent Effects
Lippa, Katrice A.,Demel, Sandra,Lau, Irvin H.,Roberts, A. Lynn
, p. 3010 - 3021 (2007/10/03)
The ease with which α-chloroacetanilide herbicides undergo displacement reactions with strong nucleophiles, and their recalcitrance toward weak ones, is intimately related to their herbicidal properties and environmental chemistry. In this study, we investigate the kinetics and mechanisms of nucleophilic substitution reactions of propachlor and alachlor in aqueous solution. The role played by the α-amide group was examined by including several structurally related analogs of propachlor possessing modified α substituents. The overall second-order nature of the reaction, the negative ΔS? values, the weak influence of ionic strength on reactivity, and structure-reactivity trends together support an intermolecular SN2 mechanism rather than an intramolecular reaction for α-chlomacetanilides as well as the a-chlorothioacetanilide analog of propachlor. In contrast, the α-methylene analog exhibits kinetics and a salt effect consistent with anchimeric assistance by the aniline nitrogen. Electronic interactions with the α-anilide substituent, rather than neighboring group participation, can be inferred to govern the reactivity of α-chloroacetanilides toward nucleophiles.
METHOD OF INDUCING CHOLECYSTOKININ AGONIST ACTIVITY USING 1,4-BENZODIAZEPINE COMPOUNDS
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, (2008/06/13)
A method of inducing a Cholescystokinin-A receptor agonist response in a mammal by administering a compound of formula (I), STR1 where R 1 is C 1-C 6 alkyl, C 3-6 cycloalkyl, phenyl, or substituted phenyl; R 2 is C 3-6 alkyl, C 3-6 cycloalkyl, C 3-6 alkenyl, benzyl, phenylC 1-3 alkyl or substituted phenyl; or NR 1 R 2 together form 1,2,3,4-tetrahydroquinoline or benzazepine mono-, di-, or trisubstituted independently with C 1-6 alkyl, C 1-6 alkoxy or halogen substituents; n is an integer selected from the grouping consisting of 0, 1,2 or 3; p is the integer 0 or 1; q is the integer 0 or 1; r is the integer 0 or 1, provided that when q is 0 then r is 0; R 3, R 4, R 5 and R 8 are selected from a variety of substituents; X is nitrogen, nitroso or R 8 ; m is an integer selected from the group consisting of 0, 1, 2 or 3; Y and Z are hydrogen or halogen, novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).
Optimization of 3-(1H-Indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists
Henke, Brad R.,Aquino, Christopher J.,Birkemo, Larry S.,Croom, Dallas K.,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Queen, Kennedy L.,Sherrill, Ronald G.,Sugg, Elizabeth E.,Suh, Edward M.,Szewczyk, Jerzy W.,Unwalla, Rayomand J.,Yingling, Jeff,Willson, Timothy M.
, p. 2706 - 2725 (2007/10/03)
We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5- benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the CS and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at CS. Structure-activity relationships at the N1- anilidoacetamide 'trigger' moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the Nl-anilidoacetamide moiety. Evaluation of several analogs in an in vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.
Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity. 1. Optimization of the agonist "trigger"
Aquino, Christopher J.,Armour, Duncan R.,Berman, Judd M.,Birkemo, Larry S.,Carr, Robin A. E.,Croom, Dallas K.,Dezube, Milana,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Head, Julie E.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Miller, Laurence J.,Queen, Kennedy L.,Rimele, Thomas J.,Smith, David N.,Sugg, Elizabeth E.
, p. 562 - 569 (2007/10/03)
Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonis