57559-52-1Relevant articles and documents
Efficient cosubstrate enzyme pairs for sequence-specific methyltransferase-directed photolabile caging of DNA
Heimes, Michael,Kolmar, Leonie,Brieke, Clara
, p. 12718 - 12721 (2018)
Supplemented with synthetic surrogates of their natural cosubstrate S-adenosyl-l-methione (AdoMet), methyltransferases represent a powerful toolbox for the functionalization of biomolecules. By employing novel cosubstrate derivatives in combination with p
Intramolecular Pd-catalyzed reductive amination of enolizable sp3-C-H bonds
Ford, Russell L.,Alt, Isabel,Jana, Navendu,Driver, Tom G.
, p. 8827 - 8831 (2019/10/28)
A palladium-catalyzed reductive cyclization of nitroarenes has been designed to construct sp3-C-NHAr bonds from sp3-C-H bonds by using an enolizable nucleophile to intercept a nitrosoarene intermediate. Exposure of ortho-substituted nitroarenes to 5 mol ?% of Pd(OAc)2 and 10 mol ?% of phenanthroline under 2 atm of CO constructs partially saturated 5-, 6-, or 7-membered N-heterocycles using α-pyridyl carboxylates, malonates, 1,3-dimethylbarbituric acid, 1,3-diones, or difurans as the nucleophile.
Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human β3-Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects
Wada, Yasuhiro,Shirahashi, Hiromitsu,Iwanami, Taisuke,Ogawa, Masami,Nakano, Seiji,Morimoto, Akifumi,Kasahara, Ken-Ichi,Tanaka, Eiichi,Takada, Yoshio,Ohashi, Shigeki,Mori, Mutsuhiro,Shuto, Satoshi
supporting information, p. 6048 - 6057 (2015/08/24)
Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human β3-adrenergic receptor (AR) agonists. Although the initial hit compound 5 exhibited significant β3-AR agonistic activity (EC50 = 21 nM), it also exhibited agonistic activity at the α1A-AR (EC50 = 219 nM, selectivity: α1A/β3 = 10-fold). The major metabolite of 5, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for β3-AR agonistic activity versus α1A-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound 11 with potent β3-AR agonistic activity (EC50 = 13 nM) and high selectivity (α1A/β3 = >769-fold). Compound 11 was also inactive toward β1 and β2-ARs and showed dose dependent β3-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats.