847555-98-0

Upstream product

• 119-61-9 benzophenone 
• 57260-70-5 4-benzyl-piperazine-1-carboxylic acid tert-butyl ester 
• 100-39-0 benzyl bromide 

Downstream Products

• 847553-76-8 3-oxo-1,1-diphenyltetrahydrooxazolo[3,4-a]pyrazine-7-carboxylic acid 9H-fluoren-9-ylmethyl ester 
• 847555-93-5 1,1-diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-one 

Relevant academic research and scientific papers

Structure-Activity Relationship Studies on Oxazolo[3,4- a]pyrazine Derivatives Leading to the Discovery of a Novel Neuropeptide S Receptor Antagonist with Potent in Vivo Activity

Neuropeptide S modulates important neurobiological functions including locomotion, anxiety, and drug abuse through interaction with its G protein-coupled receptor known as neuropeptide S receptor (NPSR). NPSR antagonists are potentially useful for the treatment of substance abuse disorders against which there is an urgent need for new effective therapeutic approaches. Potent NPSR antagonists in vitro have been discovered which, however, require further optimization of their in vivo pharmacological profile. This work describes a new series of NPSR antagonists of the oxazolo[3,4-a]pyrazine class. The guanidine derivative 16 exhibited nanomolar activity in vitro and 5-fold improved potency in vivo compared to SHA-68, a reference pharmacological tool in this field. Compound 16 can be considered a new tool for research studies on the translational potential of the NPSergic system. An in-depth molecular modeling investigation was also performed to gain new insights into the observed structure-activity relationships and provide an updated model of ligand/NPSR interactions.

General Procedures for the Lithiation/Trapping of N-Boc Piperazines

To provide α-substituted piperazines for early stage medicinal chemistry studies, a simple, general synthetic approach is required. Here, we report the development of two general and simple procedures for the racemic lithiation/trapping of N-Boc piperazin

Diamine-free lithiation-trapping of N-Boc heterocycles using s-BuLi in THF

A diamine-free protocol for the s-BuLi-mediated lithiation-trapping of N-Boc heterocycles has been developed. In the optimized procedure, lithiation is accomplished using s-BuLi in THF at -30 °C for only 5 or 10 min. Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered a range of functionalized pyrrolidines, imidazolidines, and piperazines in 43-83% yield.

Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor

Neuropeptide S (NPS) has been shown to modulate arousal, sleep wakefulness, anxiety-like behavior, and feeding after central administration of the peptide agonist to mice or rats. We report here the chemical synthesis and pharmacological characterization of SHA 66 (3-oxo-1,1-diphenyl-tetrahydro- oxazolo[3,4-a]pyrazine-7-carboxylic acid benzylamide) and SHA 68 (3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide), two closely related bicyclic piperazines with antagonistic properties at the NPS receptor (NPSR). The compounds block NPS-induced Ca2+ mobilization, and SHA 68 shows displaceable binding to NPSR in the nanomolar range. The antagonistic activity of SHA 68 seems to be specific because it does not affect signaling at 14 unrelated G protein-coupled receptors. Analysis of pharmacokinetic parameters of SHA 68 demonstrates that the compound reaches pharmacologically relevant levels in plasma and brain after i.p. administration. Furthermore, peripheral administration of SHA 68 in mice (50 mg/kg i.p.) is able to antagonize NPS-induced horizontal and vertical activity as well as stereotypic behavior. Therefore, SHA 68 could be a useful tool to characterize physiological functions and pharmacological parameters of the NPS system in vitro and in vivo. Copyright

BICYCLIC PIPERAZINE COMPOUND AND USE THEREOF

The present invention provides a compound represented by the formula: wherein R1 is an acyl group, R2 is a hydrocarbon group which may be substituted or the like, R3 is a hydrocarbon group which may be substituted or the like, R4 is a hydrocarbon group which may be substituted or the like, n is from 0 to 4, and X is an oxygen atom, a sulfur atom or the like, or a salt thereof. The invention also provides a compound which has a TGR23 antagonist activity and thus is useful for prevention and treatment of cancer.