40751-89-1Relevant articles and documents
Synthesis and evaluation of in vitro antiplatelet aggregation activities of 2-Methoxy-5-Aminobenzamides
Liu, Lili,Liu, Xiujie,Chen, Guangling,Qiu, Kai
, p. 1040 - 1050 (2019/10/28)
Objective: According to the principles of drug design, the structures of picotamide and betrixaban were combined to design novel series of 2-methoxy-5-aminobenzamides. A total of twenty new compounds 1a-1t have been synthesized and evaluated for their ant
Folding and Assembly of Short α, β, ?-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures
Zhang, Yukun,Zhong, Yulong,Connor, Alan L.,Miller, Daniel P.,Cao, Ruikai,Shen, Jie,Song, Bo,Baker, Erin S.,Tang, Quan,Pulavarti, Surya V.S.R.K.,Liu, Rui,Wang, Qiwei,Lu, Zhong-Lin,Szyperski, Thomas,Zeng, Huaqiang,Li, Xiaopeng,Smith, Richard D.,Zurek, Eva,Zhu, Jin,Gong, Bing
, p. 14239 - 14248 (2019/10/11)
Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, β-, and aromatic ?-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central αβ hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded β-turn containing an unusual hybrid α/β-amino acid sequence composed of glycine and β-alanine, two α- A nd β-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αβ vs βα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- A nd β-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded β-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.
TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS
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Page/Page column 66, (2014/01/08)
The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
