132871-10-4

Upstream product

• 86666-85-5 N^α-Boc-Ala-N^α-benzylglycine ethyl ester 
• 100-46-9 benzylamine 
• 118375-95-4 methyl (S)-2-(2-chloroacetamido)propanoate 
• 100-52-7 benzaldehyde 
• 761357-45-3 [((S)-2-Amino-propionyl)-benzyl-amino]-acetic acid ethyl ester 

Downstream Products

• 194925-84-3 (S)-2-Benzyl-4-methyl-1,2-dihydro-2,4a,9-triaza-anthracene-3,10-dione 
• 132871-12-6 (S)-3-Methyl-1-(phenylmethyl)piperazine 
• 169447-69-2 tert-Butyl (S)-2-methyl-4-(phenylmethyl)-1-piperazinecarboxylate 
• 194925-99-0 (1R,4S)-2-Benzyl-4-methyl-1-(4-methyl-benzyl)-1,2-dihydro-2,4a,9-triaza-anthracene-3,10-dione 
• 194926-01-7 (1S,4S)-2-Benzyl-4-methyl-1-(4-methyl-benzyl)-1,2-dihydro-2,4a,9-triaza-anthracene-3,10-dione 
• 357666-69-4 (1S,4S)-2-benzyl-4-methyl-1-ethoxy-2,4-dihydro-1H-pyrazino[2,1-b]quinozoline-3,6-dione 
• 169447-70-5 (S)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester 

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.

Highly efficient enantioselective synthesis of 1,3-disubstituted 2,5-diketopiperazine derivatives via microwave irradiation

Chiral 2,5-diketopiperazine (2,5-DKP) derivatives have a broad range of biological activities in the medicinal field. The synthetic protocols of 1,3-disubstituted 2,5-DKPs via base-catalyzed cyclization of chloroacetamide have been reported. However, there are several drawbacks, such as an overly long reaction time, low to moderate yield, and racemization of the products. The sequence modified herein of 1,3-disubstituted 2,5-DKPs involves microwave-assisted cyclization. It increases yields and reduces reaction time. Furthermore, employing N-PMB protection prevents racemization, which frequently occurs in the base-catalyzed cyclization reaction. Consequently, the rapid synthetic method of enantiomerically pure 1,3-disubstituted 2,5-DKPs via microwave reaction was established successfully.

Efficient one-pot synthesis of enantiomerically pure: N -protected-α-substituted piperazines from readily available α-amino acids

A new pathway towards enantiomerically pure 3-substituted piperazines, bearing a benzyl protecting group, has been developed in good overall yields (83-92%), starting from commercially available N-protected amino acids. The methodology represents an efficient and simple one-pot procedure, employing a synthetic sequence consisting of an Ugi-4 component reaction, a Boc-deprotection, an intramolecular cyclisation reaction and a final reduction (UDCR). From the benzyl protected precursors, the 2-substituted piperazines bearing a Boc-protecting group could consequently also be obtained via a simple protection and deprotection step of the corresponding piperazines. The practical utility of this methodology was demonstrated for chiral drug synthesis.

Enantiomerically pure piperazines via NaBH4/I2reduction of cyclic amides

Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (3S,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure L-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine.

Synthesis and structure of 1,4-dipiperazino benzenes: Chiral terphenyl-type peptide helix mimetics

(Chemical Equation Presented) The terphenyl structure has been proven to be an ideal scaffold mimicking side-chain functionalities of peptidic α-helices. The synthesis of 1,4-dipiperazino benzenes, using stepwise transition metal-catalyzed N-arylation of chiral piperazines to a central benzene core is reported. The structure determination by X-ray crystallography reveals a geometrical arrangement of the hydrophobic side chains resembling the orientation of key i, i + 3, and i + 7 positions in a peptidic α-helix or in terphenyl helix mimetics.

Microwave-assisted synthesis of 2,5-piperazinediones under solvent-free conditions

A general, efficient and environmentally friendly procedure for the synthesis of 2,5-piperazinediones is described, involving the microwave irradiation of N-Boc dipeptide esters. Georg Thieme Verlag Stuttgart.

A novel and facile method to synthesize (R)- and (S)-2-methylpiperazine

A concise and efficient synthesis of (R)- and (S)-2-methylpiperazine in only five steps from (D)- and (L)-alanine is described. The key step is reaction of benzylamine with a bifunctional molecule to build a six-membered ring.

Exploring the structure-activity relationships of [1-(4-(4- tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), a high-affinity and selective δ-opioid receptor nonpeptide agonist ligand

SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4- benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the δ-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation. To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH2-O-CH2-Ph; b = Me; c = CH2Ph; d = CH2OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the δ- receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.