5625-67-2Relevant academic research and scientific papers
Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
Falkenstein, Markus,Reiner-Link, David,Zivkovic, Aleksandra,Gering, Ian,Willbold, Dieter,Stark, Holger
, (2021/10/29)
Alzheime?s disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.
Preparation method of sitagliptin intermediate
-
Paragraph 0024; 0028-0029; 0053-0054, (2021/02/13)
The invention relates to a preparation method of a sitagliptin intermediate, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems of low product yield andpoor environmental protection property in the prior art, the invention provides a preparation method of a sitagliptin intermediate, and the method comprises the following steps: reacting 2-piperazinone with hydrazine hydrate in an alcohol solvent to generate piperazine hydrazone; in an acetonitrile or ether solvent, reacting the piperazine hydrazone with ethyl trifluoroacetate to obtain a corresponding intermediate N -[(2Z-) piperazine -2-subunit] trifluoroacethydrazide; and performing cyclization and salification reaction on the N -[(2Z-) piperazine -2-subunit] trifluoroacethydrazide in an alcohol solvent under the action of hydrochloric acid to obtain the corresponding sitagliptin intermediate 3-trifluoromethyl 5, 6, 7, 8-tetrahydro-1, 2, 4-triazole [4, 3-a] pyrazine hydrochloride. The reaction has the effects of high selectivity and high product yield.
NH insertion reactions catalyzed by reusable water-soluble ruthenium(II)-hm-phenyloxazoline complex
Abu-Elfotoh, Abdel-Moneim
supporting information, p. 4750 - 4754 (2017/11/29)
A water-soluble Ru(II)-hm-pheox complex was efficiently catalyzed NH insertion of EDA with a broad class of amine derivatives in water/ether biphasic medium to deliver the biologically active precursors α-aminoester products with excellent yields (up to >99%). The products were separated by decantation and the catalyst was washed and reused several times (at least 8 times) without any specific loss of its catalytic activity. The plausible mechanism of the reaction was explained. Additionally, In case of ethylene diamine, the NH insertion product could be transformed to biological active piperazinone compound in high yield. The asymmetric version of this catalytic reaction is under investigation.
Containing acyl piperazones substituent pyrazole piperidine ketone compound, and its composition and use thereof (by machine translation)
-
Paragraph 0159-0160, (2017/02/28)
The invention relates to pyrazolopiperidone compounds, pharmaceutically-acceptable salts of the compounds and use of the compounds in preparation of medicines for treating Xa factor related diseases. Particularly, the invention relates to novel acyl piperazinone substituent-containing pyrazolopiperidone compounds, pharmaceutical compositions containing the compounds and use of the compounds in the preparation of the medicines for treating the Xa factor related diseases.
Enantioselective synthesis of α-secondary and α-tertiary piperazin-2- Ones and piperazines by catalytic asymmetric allylic alkylation
Korch, Katerina M.,Eidamshaus, Christian,Behenna, Douglas C.,Stoltz, Brian M.,Nam, Sangkil,Horne, David
supporting information, p. 179 - 183 (2015/02/05)
The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2- ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.
Synthesis and spectral characterization of related substances of vardenafil, an erectile dysfunction drug
Reddy, Vajrala Venkata,Naga Brahmeswara Rao, Mandava Venkata,Reddy, Ghanta Mahesh,Mukkanti, Khagga,Reddy, Ganta Madhusudhan
experimental part, p. 3513 - 3523 (2012/10/18)
Vardenafil hydrochloride trihydrate (Levitra) is used to treat erectile dysfunction (ED) and is an inhibitor of phosphodiesterase type 5 (PDE-5) enzyme. It maintains higher levels of cyclic guanosine monophosphate (cGMP), relaxes smooth muscles, promotes penile blood flow, and enhances erectile function. During the bulk drug synthesis of vardenafil hydrochloride trihydrate, six related substances (impurities), vardenafil dimer, vardenafil N-oxide, vardenafil glycene, vardenafil oxopiperazine, vardenafil oxoacetic acid, and phenyl vardenafil were identified, and these are reported herein for the first time. The present work describes the synthesis and characterization of these impurities.
O-H insertion and tandem N-H insertion/cyclization reactions using an iron porphyrin as catalyst with diazo compounds as carbene sources
Mbuvi, Harun M.,Klobukowski, Erik R.,Roberts, Gina M.,Woo, L. Keith
experimental part, p. 284 - 292 (2010/12/19)
Iron(III) tetraphenylporphyrin chloride, Fe(TPP)Cl, efficiently catalyzed the insertion of carbenes derived from methyl 2-phenyldiazoacetates into O-H bonds of aliphatic and aromatic alcohols, with yields generally above 80%. Although the analogous N-H insertions are rapid at room temperature, the O-H insertion reactions are slower and required heating in refluxing methylene chloride for about 8 hours using 1.0 mol.% catalyst. Fe(TPP)Cl was also found to be effective for tandem N-H insertion/cyclization reactions when 1,2-diamines and 1,2-alcoholamines were treated with diazo reagents to give piperazinones and morpholinones and related analogs such as quinoxalinones and benzoxazin-2-ones. This approach provides a new one-pot route for synthesizing these classes of heterocyclic compounds.
2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
-
, (2008/06/13)
The present invention has its object to provide a 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented with the Formula (1) , or the pharmaceutically acceptable salt, which is effective as a therapeutic and prophylactic agent for diabetes, diabetic nephropathy, or glomerulosclerosis.
2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
-
Page/Page column 80, (2010/11/30)
A 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented by the generalformula (1): [Chemical formula 1] (1) or a pharmaceutically acceptable saltthereof. They are useful as a therapeutic/preventive agent for diabetes, diabeticnephropathy, or glomerulosclerosis.
Calcium channel blockers comprising two benzhydril moieties
-
, (2008/06/13)
Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.
