898157-46-5Relevant articles and documents
Application of Flow and Biocatalytic Transaminase Technology for the Synthesis of a 1-Oxa-8-azaspiro[4.5]decan-3-amine
Kohrt, Jeffrey T.,Dorff, Peter H.,Burns, Michael,Lee, Chewah,O'Neil, Steven V.,Maguire, Robert J.,Kumar, Rajesh,Wagenaar, Melissa,Price, Loren,Lall, Manjinder S.
, p. 616 - 623 (2021/05/06)
Spirocyclic ring systems are useful intermediates in the design and synthesis of medicinally active agents and commonly found as cores in natural products. Recently, syntheses of a key intermediate Boc-protected-1-oxa-8-azaspiro[4.5]decan-3-amine 1 were examined. While multigram quantities of the racemic material could be made from the reduction of an energic azide intermediate, larger scale reactions and a chiral synthesis required further investigations. Herein, we describe the use of a continuous three-step flow process to scale the formation and reduction of an azide intermediate, and the use of a transaminase to prepare the desired enantiomer in high yield and enantiomeric excess.
1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS
-
Paragraph 0226; 0299; 0301, (2018/08/09)
The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 2. Discovery of 7-azaspiro[3.5]nonane urea PF-04862853, an orally efficacious inhibitor of fatty acid amide hydrolase (FAAH) for pain
Meyers, Marvin J.,Long, Scott A.,Pelc, Matthew J.,Wang, Jane L.,Bowen, Scott J.,Schweitzer, Barbara A.,Wilcox, Mark V.,McDonald, Joseph,Smith, Sarah E.,Foltin, Susan,Rumsey, Jeanne,Yang, Young-Sun,Walker, Mark C.,Kamtekar, Satwik,Beidler, David,Thorarensen, Atli
, p. 6545 - 6553 (2011/12/04)
Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase responsible for the degradation of fatty acid amide signaling molecules such as endocannabinoid anandamide (AEA), which has been shown to possess cannabinoid-like analgesic properties. Herein we report the optimization of spirocyclic 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane urea covalent inhibitors of FAAH. Using an iterative design and optimization strategy, lead compounds were identified with a remarkable reduction in molecular weight and favorable CNS drug like properties. 3,4-Dimethylisoxazole and 1-methyltetrazole were identified as superior urea moieties for this inhibitor class. A dual purpose in vivo efficacy and pharmacokinetic screen was designed to be the key decision enabling experiment affording the ability to move quickly from compound synthesis to selection of preclinical candidates. On the basis of the remarkable potency, selectivity, pharmacokinetic properties and in vivo efficacy, PF-04862853 (15p) was advanced as a clinical candidate.
