76263-18-8

Usage

Uses

Used in Pharmaceutical Industry:
3-Phenoxyazetidine is used as a key intermediate in the preparation of dihydropyrimidine carboxamide derivatives, which serve as TREX1 modulators. These modulators are useful in the treatment of TREX1-mediated diseases, offering potential therapeutic benefits for patients suffering from such conditions. By acting as a crucial component in the synthesis of these modulators, 3-phenoxyazetidine plays a significant role in advancing the development of novel treatments for a range of diseases associated with TREX1 dysregulation.

Upstream product

• 82622-43-3 3-phenoxy-1-(diphenylmethyl)azetidine 
• 301335-39-7 3-phenoxyazetidine hydrochloride salt 

Downstream Products

• 1309205-42-2 (E)-6-(3-oxo-3-(3-phenoxyazetidin-1-yl)prop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one 

Relevant academic research and scientific papers

PYRIDINE AMIDE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS

The invention relates pyridine amide derivative of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are independently hydrogen, linear o branched (C1-C3)alkyl or joined together they form a cyclopropyl ring; R is independently selected from the group consisting of halogens and trifluoromethyl and p is 1, 2 or 3; A is C or N; E is a group of formula (B) or (C), wherein B is C(O)OH, C(O)O(C1-C3)alkyl, and C is selected from the group consisting of formula (I) m is 1,2 or 3, n is 0 or 1, W is —O—, —O(C1-C3 alkyl)-; —(C1-C3 alkyl)O—; —C(O)—; —C(═N—O(C1-C3 alkyl))-; —NH— or —NH(C1-C3alkyl)-; Ar is phenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, methyl, —NH(C1-C3alkyl)-; —N(C1-C3alkyl)(C1-C3alkyl)-, a from 5 to 7 membered heterocyclic ring containing one nitrogen atom which is covalently bonded to Ar and optionally containing one or two heteroatoms selected from N, O and S; and a 5- or 6-membered heteroaromatic ring containing 1 to 3 heteroatoms selected from S, O e N, such heteroaromatic ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl. The compounds of the invention could be used for manufacturing a medicament for the treatment of pathologies which require the use of an antagonist of the EP4 receptor, such as the treatment of acute and chronic pain, inflammatory pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, endometriosis and migraine.

Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors

Phosphodiesterase 9A inhibitors have shown activity in preclinical models of cognition with potential application as novel therapies for treating Alzheimers disease. Our clinical candidate, PF-04447943 (2), demonstrated acceptable CNS permeability in rats with modest asymmetry between central and peripheral compartments (free brain/free plasma = 0.32; CSF/free plasma = 0.19) yet had physicochemical properties outside the range associated with traditional CNS drugs. To address the potential risk of restricted CNS penetration with 2 in human clinical trials, we sought to identify a preclinical candidate with no asymmetry in rat brain penetration and that could advance into development. Merging the medicinal chemistry strategies of structure-based design with parallel chemistry, a novel series of PDE9A inhibitors was identified that showed improved selectivity over PDE1C. Optimization afforded preclinical candidate 19 that demonstrated free brain/free plasma ≥1 in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF.

PYRIDINE AMIDE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS

The invention relates pyridine amide derivative of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are independently hydrogen, linear o branched (C1-C3)alkyl or joined together they form a cyclopropyl ring; R is independently selected from the group consisting of halogens and trifluoromethyl and p is 1, 2 or 3; A is C or N; E is a group of formula (B) or (C), wherein B is C(O)OH, C(O)O(C1-C3)alkyl, and C is selected from the group consisting of formula (I) m is 1,2 or 3, n is 0 or 1, W is -O-, -O(C1-C3 alkyl)-; -(C1-C3 alkyl)O-; -C(O)-; -C(=N-O(C1-C3 alkyl))-; -NH- or -NH(C1-C3alkyl)-; Ar is phenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, methyl, -NH(C1-C3alkyl)-; -N(C1-C3alkyl)(C1-C3alkyl)-, a from 5 to 7 membered heterocyclic ring containing one nitrogen atom which is convalently bonded to Ar and optionally containing one or two heteroatoms selected from N, O and S; and a 5- or 6-membered heteroaromatic ring containing 1 to 3 heteroatoms selected from S, O e N, such heteroaromatic ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl. The compounds of the invention could be used for manufacturing a medicament for the treatment of pathologies which require the use of an antagonist of the EP4 receptor, such as the treatment of acute and chronic pain, inflammatory pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid artrhritis, cancer, endometriosis and migraine.

Substituted triazole derivatives as oxytocin antagonists

The present invention relates to substituted triazoles of formula (I), uses thereof, processes for the preparation thereof and compositions containing said compounds. These inhibitors have utility in a variety of therapeutic areas including sexual dysfunction.

Aryloxy and aryloxyalklazetidines as antiarrhythmic and anticonvulsant agents

Methods of treating cardiac arrhythmias and convulsions in warm-blooded animas and pharmaceutical compositions therefor are disclosed. The compounds useful in the methods of treatment and compositions are represented by the formula STR1 where n is 0 to 3 and R is H, C1 -C4 alkyl or arylalkyl and Ar is phenyl or substituted phenyl.

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.

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

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