Category: 371-99-3

Ramurthy, Savithri published the artcileDiscovery and optimization of novel pyridines as highly potent and selective glycogen synthase kinase 3 inhibitors, Computed Properties of 371-99-3, the publication is Bioorganic & Medicinal Chemistry Letters (2020), 30(4), 126930, database is CAplus and MEDLINE.

Glycogen synthase kinase-3 plays an essential role in multiple biochem. pathways in the cell, particularly in regards to energy regulation. As such, Glycogen synthase kinase-3 is an attractive target for pharmacol. intervention in a variety of disease states, particularly non-insulin dependent diabetes mellitus. However, due to homol. with other crucial kinases, such as the cyclin-dependent protein kinase CDC2, developing compounds that are both potent and selective is challenging. A novel series of derivatives of 5-nitro-N2-(2-(pyridine-2-ylamino)ethyl)pyridine-2,6-diamine were synthesized and potently inhibit glycogen synthase kinase-3 (GSK3). Potency in the low nanomolar range was obtained along with remarkable selectivity. The compounds activate glycogen synthase in insulin receptor-expressing CHO-IR cells and in primary rat hepatocytes, and have acceptable pharmacokinetics and pharmacodynamics to allow for oral dosing. The x-ray co-crystal structure of human GSK3-β in complex with compound 1-(6-((2-((6-amino-5-nitropyridin-2-yl)amino)ethyl)amino)-2-(2,4-dichlorophenyl)pyridin-3-yl)-4-methylpiperazin-2-one is reported and provides insights into the structural determinants of the series responsible for its potency and selectivity.

Bioorganic & Medicinal Chemistry Letters published new progress about 371-99-3. 371-99-3 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2-((2,2,2-Trifluoroethyl)amino)ethanol, and the molecular formula is C4H8F3NO, Computed Properties of 371-99-3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Dow, Robert L. published the artcileDiscovery of 2-(2-Chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyrazolo[3,4-f][1,4]oxazepin-8(5H)-one (PF-514273), a Novel, Bicyclic Lactam-Based Cannabinoid-1 Receptor Antagonist for the Treatment of Obesity, SDS of cas: 371-99-3, the publication is Journal of Medicinal Chemistry (2009), 52(9), 2652-2655, database is CAplus and MEDLINE.

The design, synthesis, and structure-activity relationships of novel bicyclic lactams I (R¹ = 2-ClC₆H₄; R² = 4-ClC₆H₄; R³ = H, Et, i-Pr, i-Bu, cyclopentyl, CH₂CF₂Me, etc.) and II (R⁴ = H, i-Pr, CH₂CF₃, CH₂CF₂Me, CH₂CF₂Et) as cannabinoid type 1 (CB₁) receptor antagonists is described. Members of these series are potent, selective antagonists in in vitro/in vivo efficacy models of CB₁ antagonism and exhibit robust oral activity in rodent models of food intake. These efforts led to the identification of II (R⁴ = CH₂CF₂Me), which has been advanced to human clin. trials for weight management.

Journal of Medicinal Chemistry published new progress about 371-99-3. 371-99-3 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2-((2,2,2-Trifluoroethyl)amino)ethanol, and the molecular formula is C4H8F3NO, SDS of cas: 371-99-3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Lazarus, Robert A. published the artcileMechanism of hydrolysis of phosphorylethanolamine diesters. Intramolecular nucleophilic amine participation, Computed Properties of 371-99-3, the publication is Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) (1980), 373-9, database is CAplus.

Intramol. displacement reactions at P in 7 RNHCH₂CH₂OP(O)(O^–)OAr (R = Et, Ar = substituted Ph) and 4 analogs (R = MeOCH₂CH₂, CF₃CH₂) were examined by pH-rate profiles and ³¹P NMR of the products of hydrolysis in H₂O at 35° and ionic strength 1.0 (KCl). The amine has a nucleophilic role. A rate enhancement of 10^6-7 is observed Structure-reactivity correlations derived using different pK_a values for amines and leaving groups give Broensted β_nucleophile and β_1g values of â‰?.7 and and â‰?1.25, resp. An uncoupled concerted mechanism is involved. The role of amine and oxyanion groups in the nucleophilic reactions of di- and triesters is discussed. Changing the catalyst from carboxy to an amino group increases the reactivity of a diester 1000-fold compared with a triester.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) published new progress about 371-99-3. 371-99-3 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2-((2,2,2-Trifluoroethyl)amino)ethanol, and the molecular formula is C4H8F3NO, Computed Properties of 371-99-3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Lazarus, Robert A. published the artcileMechanism of hydrolysis of phosphorylethanolamine triesters. Multiple catalytic effects of an intramolecular amino group, Safety of 2-((2,2,2-Trifluoroethyl)amino)ethanol, the publication is Journal of the American Chemical Society (1979), 101(15), 4300-12, database is CAplus.

Intramol. displacement reactions at P are examined in N-alkyl-O-(arylphenylphosphoryl)ethanolamines in 45% dioxane-water (volume) at 35°. The examination of the pH-rate profiles, the detection of external buffer catalysis, and the observation of D solvent effects reveal the concurrent operation of 3 types of P-O bond cleavage mechanisms: electrostatic catalysis by the protonated ammonium moiety of external nucleophilic attack by buffer bases at D, general base-catalyzed intramol. nucleophilic attack by the amino function to form the cyclic phosphoramidate, and intramol. amine-assisted water displacement of the substituted phenol. A Broensted plot for the general base-catalyzed cyclization reaction supports either a concerted mechanism for the cyclization process bypassing the formation of a pentacovalent intermediate with a discrete lifetime or a mechanism involving H bonding stabilization of the rate-determining decomposition of the intermediate providing that this is faster than the diffusion away of the catalyst. In either case the lifetime of the pentacovalent intermediate is <10^-12s.

Journal of the American Chemical Society published new progress about 371-99-3. 371-99-3 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2-((2,2,2-Trifluoroethyl)amino)ethanol, and the molecular formula is C4H8F3NO, Safety of 2-((2,2,2-Trifluoroethyl)amino)ethanol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts