78775-64-1Relevant articles and documents
Protected amino hydroxy adamantane carboxylic acid and process for its preparation
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, (2015/11/24)
Dipeptidyl peptidase IV (DP 4) inhibiting compounds are provided. The provided compounds can be used for treating diabetes and related diseases, especially Type II diabetes, and other diseases as set out herein, employing such DP 4 inhibitor or a combination of such DP 4 inhibitor and one or more of another antidiabetic agent such as metformin, glyburide, troglitazone, pioglitazone, rosiglitazone and/or insulin and/or one or more of a hypolipidemic agent and/or anti-obesity agent and/or other therapeutic agent.
Azepanone-based inhibitors of human cathepsin S: Optimization of selectivity via the P2 substituent
Kerns, Jeffrey K.,Nie, Hong,Bondinell, William,Widdowson, Katherine L.,Yamashita, Dennis S.,Rahman, Attiq,Podolin, Patricia L.,Carpenter, Donald C.,Jin, Qi,Riflade, Benoit,Dong, Xiaoyang,Nevins, Neysa,Keller, Paul M.,Mitchell, Laura,Tomaszek, Thaddeus
, p. 4409 - 4415 (2011/09/15)
A series of azepanone inhibitors of cathepsin S is described. Selectivity over both cathepsin K and cathepsin L was achieved by varying the P2 substituent. Ultimately, a balanced potency and selectivity profile was achieved in compound 39 possessing a 1-methylcyclohexyl alanine at P2 and nicotinamide as the P′ substituent. The cellular potency of selected analogs is also described.
Synthesis of Novel Potent Dipeptidyl Peptidase IV Inhibitors with Enhanced Chemical Stability: Interplay between the N-Terminal Amino Acid Alkyl Side Chain and the Cyclopropyl Group of α -Aminoacyl-L-cis-4,5-methanoprolinenitrile-Based Inhibitors
Magnin, David R.,Robl, Jeffrey A.,Sulsky, Richard B.,Augeri, David J.,Huang, Yanting,Simpkins, Ligaya M.,Taunk, Prakash C.,Betebenner, David A.,Robertson, James G.,Abboa-Offei, Benoni E.,Wang, Aiying,Cap, Michael,Xin, Li,Tao, Li,Sitkoff, Doree F.,Malley, Mary F.,Gougoutas, Jack Z.,Khanna, Ashish,Huang, Qi,Han, Song-Ping,Parker, Rex A.,Hamann, Lawrence G.
, p. 2587 - 2598 (2007/10/03)
A series of methanoprolinenitrile-containing dipeptide mimetics were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV (DPP-IV). The catalytic action of DPP-IV is the principle means of degradation of glucagon-like peptide-1, a key mediator of glucose-stimulated insulin secretion, and DPP-IV inhibition shows clinical benefit as a novel mechanism for treatment of type 2 diabetes. However, many of the reversible inhibitors to date suffer from chemical instability stemming from an amine to nitrile intramolecular cyclization. Installation of a cyclopropyl moiety at either the 3,4- or 4,5-position of traditional 2-cyanopyrrolidide proline mimetics led to compounds with potent inhibitory activity against the enzyme. Additionally, cis-4,5-methanoprolinenitriles with β-branching in the N-terminal amino acid provided enhanced chemical stability and high inhibitory potency. This class of inhibitors also exhibited the ability to suppress prandial glucose elevations after an oral glucose challenge in male Zucker rats.
Synthesis and Properties of Some tert-Alkylmalonic Acid Derivatives
Holmberg, Carl
, p. 748 - 760 (2007/10/02)
1,4-Addition of Grignard reagents to the alkylidenemalonic acid derivatives 1-8 affords the tert-alkyl malonic derivatives 9-18.The esters 9-17 give the acids 19-26 and from these the corresponding chlorides 27-34 are obtained.Bromination yields the bromo acids 35-36, the brominated acyl bromide 43, the bromonitrile 44, and the bromoacyl chlorides 37-42.The trimethylsilyl esters 50-52, the bis(2-bromoethyl) esters 53-54, the ethyl ester 14, and the tert-butyl ester 16 are brominated via the corresponding ester enolates giving the bromo esters 45-46 in pure form. - The dealkylation of malonic esters with chlorotrimethylsilane/sodium iodide has been carried out.
