159390-33-7Relevant articles and documents
Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3, 4-dihydrospiro[chromene-2,4′-piperidine] analogs
Uto, Yoshikazu,Ueno, Yuko,Kiyotsuka, Yohei,Miyazawa, Yuriko,Kurata, Hitoshi,Ogata, Tsuneaki,Yamada, Makiko,Deguchi, Tsuneo,Konishi, Masahiro,Takagi, Toshiyuki,Wakimoto, Satoko,Ohsumi, Jun
, p. 4788 - 4796 (2010)
In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol- 2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID 50 = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC 50 (mouse) = 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg).
Access to Biphenyls by Palladium-Catalyzed Oxidative Coupling of Phenyl Carbamates and Phenols
Bach, Thorsten,Breitenlechner, Stefan,Jandl, Christian,P?thig, Alexander,Truchan, Nadina
, p. 3060 - 3076 (2019/08/07)
The oxidative cross-coupling of phenols (3 equiv) to various substituted phenyl N, N -diethylcarbamates was explored with a variety of substrates. Pd(OAc) 2 was employed as the catalyst (20 molpercent) and K 2 S 2 O 8
1,5-O → N Carbamoyl Snieckus-Fries-Type Rearrangement
Feberero, Claudia,Suárez-Pantiga, Samuel,Cabello, Zaida,Sanz, Roberto
supporting information, p. 2437 - 2440 (2018/04/27)
The reaction of o-lithiated O-aryl N,N-diethylcarbamates with (hetero)aromatic nitriles gives rise to functionalized salicylidene urea derivatives in high yields through a new 1,5-O → N carbamoyl migration. This Snieckus-Fries-type rearrangement nicely complements previously known O → C and O → O related shifts. In addition, when dimethylmalononitrile is used as the electrophilic partner, the carbamoyl shift is preferred over the expected transnitrilation reaction.
