Category: 945953-41-3

Lee, Minhee published the artcileStructure-Activity Relationship of Sulfonyl Piperazine LpxH Inhibitors Analyzed by an LpxE-Coupled Malachite Green Assay, Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is ACS Infectious Diseases (2019), 5(4), 641-651, database is CAplus and MEDLINE.

The UDP-2,3-diacylglucosamine pyrophosphatase LpxH in the Raetz pathway of lipid A biosynthesis is an essential enzyme in the vast majority of Gram-neg. pathogens and an excellent novel antibiotic target. The ³²P-radioautog. thin-layer chromatog. assay has been widely used for anal. of LpxH activity, but it is inconvenient for evaluation of a large number of LpxH inhibitors over an extended time period. Here, we report a coupled, nonradioactive LpxH assay that utilizes the recently discovered Aquifex aeolicus lipid A 1-phosphatase LpxE for quant. removal of the 1-phosphate from lipid X, the product of the LpxH catalysis; the released inorganic phosphate is subsequently quantified by the colorimetric malachite green assay, allowing the monitoring of the LpxH catalysis. Using such a coupled enzymic assay, we report the biochem. characterization of a series of sulfonyl piperazine LpxH inhibitors. Our anal. establishes a preliminary structure-activity relationship for this class of compounds and reveals a pharmacophore of two aromatic rings, two hydrophobic groups, and one hydrogen-bond acceptor. We expect that our findings will facilitate the development of more effective LpxH inhibitors as potential antibacterial agents.

ACS Infectious Diseases published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Tahirovic, Yesim A. published the artcileDiscovery of N-Alkyl Piperazine Side Chain Based CXCR4 Antagonists with Improved Drug-like Properties, Synthetic Route of 945953-41-3, the publication is ACS Medicinal Chemistry Letters (2018), 9(5), 446-451, database is CAplus and MEDLINE.

A novel series of CXCR4 antagonists with piperidinyl and piperazinyl alkylamine side chains designed as Bu amine replacements are described. Several of these compounds showed similar activity to the parent compound TIQ-15 (5) in a SDF-1 induced calcium flux assay. Preliminary structure-activity relationship investigations led us to identify a series containing N-Pr piperazine side chain analogs exemplified by 16 with improved off-target effects as measured in a muscarinic acetylcholine receptor (mAChR) calcium flux assay and in a limited drug safety panel screen. Further efforts to explore SAR and optimize drug properties led to the identification of the N’-ethyl-N-propyl-piperazine tetrahydroisoquinoline derivative 44 and the N-propyl-piperazine benzimidazole compound 37, which gave the best overall profiles with no mAChR or CYP450 inhibition, good permeability in PAMPA assays, and metabolic stability in human liver microsomes.

ACS Medicinal Chemistry Letters published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C12H14IN, Synthetic Route of 945953-41-3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Makowski, Kamil published the artcileSudemycin K: A Synthetic Antitumor Splicing Inhibitor Variant with Improved Activity and Versatile Chemistry, SDS of cas: 945953-41-3, the publication is ACS Chemical Biology (2017), 12(1), 163-173, database is CAplus and MEDLINE.

Important links exist between the process of pre-mRNA splicing and cancer, as illustrated by the frequent mutation of splicing factors in tumors and the emergence of various families of anti-tumor drugs that target components of the splicing machinery, notably SF3B1, a protein subunit of spliceosomal U2 small nuclear Ribonucleoprotein Particle (snRNP). Sudemycins are synthetic compounds that harbor a pharmacophore common to various classes of splicing inhibitors. Here we describe the synthesis and functional characterization of novel Sudemycin analogs that functionally probe key functional groups within this pharmacophore. Our results confirm the importance of a conjugated diene group and in addition reveal significant spatial flexibility in this region of the mol. Sudemycin K, a derivative that replaces the pharmacophore oxycarbonyl by an amide group, displays improved potency as an inhibitor of cancer cell proliferation, as a regulator of alternative splicing in cultured cells and as an inhibitor of in vitro spliceosome assembly. Sudemycin K displays higher stability, likely related to the replacement of the oxycarbonyl group, which can be substrate of esterases, by an amide group. The activity and special reactivity of Sudemycin K can pave the way to the synthesis and evaluation of a variety of novel Sudemycin derivatives

ACS Chemical Biology published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, SDS of cas: 945953-41-3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Brown, Dennis A. published the artcileInvestigation of various N-heterocyclic substituted piperazine versions of 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol: Effect on affinity and selectivity for dopamine D3 receptor, Application of tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is Bioorganic & Medicinal Chemistry (2009), 17(11), 3923-3933, database is CAplus and MEDLINE.

The design and synthesis of several heterocyclic analogs belonging to the 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol series of mols., are reported. Compounds were subjected to [³H]spiperone binding assays, carried out with HEK-293 cells expressing either D2 or D3 dopamine receptors, in order to evaluate their inhibition constant (K_i) at these receptors. Results indicate that N-substitution on the piperazine ring can accommodate various substituted indole rings. The results also show that in order to maintain high affinity and selectivity for the D3 receptor the heterocyclic ring does not need to be connected directly to the piperazine ring as the majority of compounds included here are linked either via an amide or a methylene linker to the heterocyclic moiety. The enantiomers of the most potent racemic compound I exhibited differential activity with (-)-I (K _i; D2 = 47.5 nM, D3 = 0.57 nM) displaying higher affinity at both D2 and D3 receptors compared to its enantiomer (+)-I (K _i; D2 = 113 nM, D3 = 3.73 nM). Addnl., compound (-)-I was more potent and selective for the D3 receptor compared to either 7-OH-DPAT or 5-OH-DPAT. Among the bioisosteric derivatives, the indazole derivative and benzo[b]thiophene derivative exhibited the highest affinity for D2 and D3 receptors. In the functional GTP¦ÃS binding study, one of the lead mols., (-)-II, exhibited potent agonist activity at both D2 and D3 receptors with preferential affinity at D3.

Bioorganic & Medicinal Chemistry published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Application of tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Brown, Dennis A. published the artcileInvestigation of various N-heterocyclic substituted piperazine versions of 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol: Effect on affinity and selectivity for dopamine D3 receptor, Application of tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is Bioorganic & Medicinal Chemistry (2009), 17(11), 3923-3933, database is CAplus and MEDLINE.

The design and synthesis of several heterocyclic analogs belonging to the 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol series of mols., are reported. Compounds were subjected to [³H]spiperone binding assays, carried out with HEK-293 cells expressing either D2 or D3 dopamine receptors, in order to evaluate their inhibition constant (K_i) at these receptors. Results indicate that N-substitution on the piperazine ring can accommodate various substituted indole rings. The results also show that in order to maintain high affinity and selectivity for the D3 receptor the heterocyclic ring does not need to be connected directly to the piperazine ring as the majority of compounds included here are linked either via an amide or a methylene linker to the heterocyclic moiety. The enantiomers of the most potent racemic compound I exhibited differential activity with (-)-I (K _i; D2 = 47.5 nM, D3 = 0.57 nM) displaying higher affinity at both D2 and D3 receptors compared to its enantiomer (+)-I (K _i; D2 = 113 nM, D3 = 3.73 nM). Addnl., compound (-)-I was more potent and selective for the D3 receptor compared to either 7-OH-DPAT or 5-OH-DPAT. Among the bioisosteric derivatives, the indazole derivative and benzo[b]thiophene derivative exhibited the highest affinity for D2 and D3 receptors. In the functional GTP¦ÃS binding study, one of the lead mols., (-)-II, exhibited potent agonist activity at both D2 and D3 receptors with preferential affinity at D3.

Bioorganic & Medicinal Chemistry published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Application of tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics