76263-24-6

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
3-[2-(Trifluoromethyl)phenoxy]azetidine is used as a chemical building block for the synthesis of new pharmaceutical agents due to its unique chemical and biological properties imparted by the trifluoromethyl and phenoxy groups. Its potential applications in medicinal chemistry would need to be further studied and elucidated to fully understand its therapeutic potential.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, 3-[2-(Trifluoromethyl)phenoxy]azetidine is employed as a key intermediate in the development of new drugs. Its specific properties, such as the presence of the trifluoromethyl and phenoxy groups, may contribute to the enhancement of drug efficacy, selectivity, and pharmacokinetics, making it a valuable component in the design and synthesis of innovative therapeutic agents.

Upstream product

• 960492-52-8 tert-butyl 3-(2-(trifluoromethyl)phenoxy)-azetidine-1-carboxylate 
• 444-30-4 2-(trifluoromethyl)phenol 

Relevant academic research and scientific papers

BISPECIFIC ANTAGONISTS OF RETINOL-BINDING PROTEIN 4 THAT STABILIZE TRANSTHYRETIN TETRAMERS, THEIR PREPARATION, AND USE IN THE TREATMENT OF COMMON AGE-RELATED COMORBIDITIES

The present invention provides a compound having the structure: Formula (I) wherein X is CR6 or N; R1, R2, R3, R4, and R6 are each independently -H, -F, -Cl, -Br, -I, -NO2, -CN, -CF3, -CF2H, -OCF3, -(alkyl), -(haloalkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(cycloalkyl), -(cycloalkylalkyl), -(heteroalkyl), heterocycle, heterocycloalkyl, -(alkylheteroalkyl), -(alkylaryl), -OH, -OAc, -0-(alkyl), -0-(alkenyl), -0-(alkynyl), -0-(aryl), -O- (heteroaryl), -SH, -S-(alkyl), -S-(alkenyl), -S-(alkynyl), -S- (aryl), -S-(heteroaryl), -NH2, -NH-(alkyl), -NH-(alkenyl), -NH- (alkynyl), -NH-(aryl), -NH-(heteroaryl), -C(O)R7, -S(O)R7, SO2R7, -NHSO2R7, -OC(O)R7, -SC(O)R7, -NHC(O)R8 or -NHC(S)R8, wherein R7 is, H, -(alkyl), -OH, -O(alkyl), -NH2, -NH(alkyl) or -N(alkyl)2, and wherein R6 is, -(alkyl), -O-(alkyl), -NH2, -NH(alkyl) or N(alkyl)2; Y is O, S, Ν, ΝΗ, or a bond; Z is O, S, N, NH, (CH2)O, or a bond; R5 is H, OH, halogen, alkyl, or R5 is (CH2)P and is bound to Y when Y is N to form a ring together with Z; o and p are independently 0, 1, 2, or 3; m and n are independently 0, 1, 2, 3, or 4; A, C, and D are each independently N or CR9; R9 is H, halogen, -OH, alkyl, cycloalkyl, cycloalkylalkyl, -O-(alkyl), -S-(alkyl), -NH2, -NH(alkyl), NH(alkyl)2, -CO2H, -CO(O-alkyl); B and E are N, CR9, or CFG wherein at least one of B or E is CFG; F is absent or present, and when present is Formula (II), Formula (III) G is H, substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, aryl, heteroaryl, alkyl, cycloalkyl, cycloalkylalkyl, CO2H, COOR10, OH, OR10, NH2, NHR10, NR10R11, SO2 (alkyl), SO2 (cycloalkyl), SO2(cycloalkylalkyl), CH2NHR10, CH2NR10R11, or CH2COOR10, wherein each R10 R11 are each independently H, alkyl, cycloalkyl, -C(O)-alkyl, -C(O)-cycloalkyl,-C(O)OH, -C(O)-O- alkyl, -C(O)-O-cycloalkyl, -C(O)NH2, -C(O)NH(alkyl), - C(O)NH(cycloalkyl), -C(O)N(alkyl)2, -CH2NH(alkyl), -CH2COOH, - SO2CH3, -OH, -O(alkyl), -NH2, -NH(alkyl), -N(alkyl)2, or a pharmaceutically acceptable salt thereof.

Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities

Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol (1) delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analogue (±)-44 possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding.

Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and stargardt disease

Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4-/-mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.

3-Phenoxy-1-azetidinecarboxamides

3-Phenoxy-1-azetidinecarboxamides having the formula STR1 wherein R1 is selected from the group consisting of hydrogen, fluoro, loweralkyl, loweralkoxy, trifluoromethyl, acetyl or aminocarbonyl having prolonged anticonvulsant activity are discl

Process for preparing 3-phenoxy-1-azetidines and carboxamide derivatives

An improved process is disclosed for preparing 3-phenoxyazetidines which utilizes a phase transfer catalyst to add the phenoxy group to azetidine blocked in the 1-position by a diphenylmethane group and utilizes a stabilizing tertiary amine base to prevent dimerization during hydrogenolysis to remove the blocking group. The crude product containing diphenylmethane may be used without purification to prepare 3-phenoxy-1-azetidinecarboxamides.

N-Formyl and N-hydroxymethyl-3-phenoxy-1-azetidinecarboxamides

N-Formyl and N-hydroxymethyl-3-phenoxy-1-azetidinecarboxamides having the formula: STR1 wherein R is selected from formyl and hydroxymethyl and R1 is selected from hydrogen, fluoro, loweralkyl, loweralkoxy, trifluoromethyl, acetyl, N-formylcarb