112766-18-4Relevant articles and documents
Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors
Ksander, Gary M.,Ghai, Raj D.,deJesus, Reynalda,Diefenbacher, Clive G.,Yuan, Andrew,et al.
, p. 1689 - 1700 (1995)
The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described.In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo.Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys.Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment.A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements.Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a.Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.
Synthesis of Isotopically Labeled, Spin-Isolated Tyrosine and Phenylalanine for Protein NMR Applications
Cui, Yixin,Das, Jitendra,Kalodimos, Charalampos G.,Rankovic, Zoran,Rossi, Paolo,Slavish, P. Jake,Sowaileh, Munia,Young, Brandon M.
, p. 6288 - 6292 (2021)
Isotopically labeled amino acids are widely used to study the structure and dynamics of proteins by NMR. Herein we describe a facile, gram-scale synthesis of compounds 1b and 2b under standard laboratory conditions from the common intermediate 7. 2b is ob
Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors
Goldberg, Daniel R.,De Lombaert, Stéphane,Aiello, Robert,Bourassa, Patricia,Barucci, Nicole,Zhang, Qing,Paralkar, Vishwas,Stein, Adam J.,Valentine, Jim,Zavadoski, William
, p. 2855 - 2860 (2016)
An increasing number of diseases have been linked to a dysfunctional peripheral serotonin system. Given that tryptophan hydroxylase 1 (TPH1) is the rate limiting enzyme in the biosynthesis off serotonin, it represents an attractive target to regulate peripheral serotonin. Following up to our first disclosure, we report a new chemotype of TPH1 inhibitors where-by the more common central planar heterocycle has been replaced with an open-chain, acyl guanidine surrogate. Through our work, we found that compounds of this nature provide highly potent TPH1 inhibitors with favorable physicochemical properties that were effective in reducing murine intestinal 5-HT in vivo. Furthermore, we obtained a high resolution (1.90 ?) X-ray structure crystal structure of one of these inhibitors (compound 51) that elucidated the active conformation along with revealing a dimeric form of TPH1 for the first time.
Rhodium-Catalyzed Dealkenylative Arylation of Alkenes with Arylboronic Compounds
Das, Mowpriya,Glorius, Frank,Maisuls, Iván,Strassert, Cristian A.,Tan, Guangying
supporting information, p. 15650 - 15655 (2021/06/08)
The C?C bond formation reaction represents a fundamental and important transformation in synthetic chemistry, and exploring new types of C?C bond formation reactions is recognized as appealing, yet challenging. Herein, we disclose the first example of rhodium-catalyzed dealkenylative arylation of alkenes with arylboronic compounds, thereby providing an unconventional access to bi(hetero)aryls with excellent chemoselectivity. In this method, C(aryl)?C(alkenyl) and C(alkenyl)?C(alkenyl) bonds in various alkenes and 1,3-dienes can be cleaved via a hydrometalation and followed by β-carbon elimination pathway for Suzuki–Miyaura reactions. Furthermore, a series of novel organic fluorescent molecules with excellent photophysical properties has been efficiently constructed with this protocol.
P(III)/P(V)-Catalyzed Methylamination of Arylboronic Acids and Esters: Reductive C-N Coupling with Nitromethane as a Methylamine Surrogate
Li, Gen,Qin, Ziyang,Radosevich, Alexander T.
supporting information, p. 16205 - 16210 (2020/10/26)
The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.
