Tag: M.W=150-200

Nguyen, William published the artcileOptimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents, Computed Properties of 178928-58-0, the publication is European Journal of Medicinal Chemistry (2020), 112254, database is CAplus and MEDLINE.

Here, two strategies to further improve the activation of viral gene expression and physicochem. properties of this class was implemented. Firstly, rigidification of the central oxy-carbon linker with a variety of saturated heterocycles and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety was explored. The optimization process afforded lead compounds, imidazopyridine derivatives such as I from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The imidazopyridine derivatives from each class demonstrated potent activation of HIV gene expression in the FlpIn. FM HEK293 cellular assay (both with LTR EC₅₀s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC₅₀ 220 and 320 nM resp.), but consequently activated gene expression non-specifically in the FlpIn. FM HEK293 cellular assay (CMV EC₅₀ 70 and 270 nM resp.) manifesting in cellular cytotoxicity. The lead compounds had potential for further development as novel latency reversing agents.

European Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Computed Properties of 178928-58-0.

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

Waltemate, Jana published the artcile10-(4-Phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and related compounds: Synthesis, antiproliferative activity and inhibition of tubulin polymerization, Related Products of piperazines, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 127687, database is CAplus and MEDLINE.

As part of our continuing search for potent inhibitors of tubulin polymerization, two novel series of 42 10-(4-phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and N-benzoylated acridones were synthesized on the basis of a retrosynthetic approach. All newly synthesized compounds were tested for antiproliferative activity and interaction with tubulin. Several analogs potently inhibited tumor cell growth. Among the compounds tested, 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)acridin-9(10H)-one (17c, I) exhibited excellent growth inhibitory effects on 93 tumor cell lines, with an average GI₅₀ value of 5.4 nM. We were able to show that the strong cytotoxic effects are caused by disruption of tubulin polymerization, as supported by the EBI (N,N’-Ethylenebis(iodoacetamide)) assay and the fact that the most potent inhibitors of cancer cell growth turned out to be the most efficacious tubulin polymerization inhibitors. Potencies were nearly comparable or superior to those of the antimitotic reference compounds Closely related to this, the most active analogs inhibited cell cycling at the G2/M phase at concentrations down to 30 nM and induced apoptosis in K562 leukemia cells. We believe that our work not only proves the excellent suitability of the acridone scaffold for the design of potent tubulin polymerization inhibitors but also enables synthetic access to further potentially interesting N-acylated acridones.

Bioorganic & Medicinal Chemistry Letters published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C8H8O3, Related Products of piperazines.

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

Yu, Lei published the artcileA structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFR^L858R/T790M mutant with improved pharmacokinetic properties, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is European Journal of Medicinal Chemistry (2017), 1107-1117, database is CAplus and MEDLINE.

Structural optimization of pyrido[2,3-d]pyrimidin-7-ones was conducted to yield a series of new selective EGFR^T790M inhibitors with improved pharmacokinetic properties. One of the most promising compound 9s (N-(3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)-5-(trifluoromethyl)phenyl)acrylamide) potently suppressed EGFR^L858R/T790M kinase and inhibited the proliferation of H1975 cells with IC₅₀ values of 2.0 nM and 40 nM, resp. The compound dose-dependently induced reduction of the phosphorylation of EGFR and downstream activation of ERK in NCI-H1975 cells. It also exhibited moderate plasma exposure after oral administration and an oral bioavailability value of 16%. Compound 9s may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer (NSCLC) patients.

European Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C15H14O, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

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

Wollweber, H. published the artcile3-Amino-2H-1,2,4-benzothiadiazine-1,1-dioxides with antihypertensive and possibly diabetogenic activity, Synthetic Route of 71260-16-7, the publication is Arzneimittel-Forschung (1981), 31(2), 279-88, database is CAplus and MEDLINE.

Aminobenzothiadiazine dioxides I (R = Cl, OPh, SPh, CF₃; R¹ = amino) (74 compounds) were prepared by substitution in I (R¹ = Cl, SMe, SO₂Me). Some I have antihypertensive activity and are devoid of diuretic or antidiuretic activity, but some them inhibited insulin secretion.

Arzneimittel-Forschung published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C12H9N3O4, Synthetic Route of 71260-16-7.

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

Wilson, Colin R. published the artcileNovel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure-Activity Relationship and Target Identification Studies, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Journal of Medicinal Chemistry (2017), 60(24), 10118-10134, database is CAplus and MEDLINE.

A BioFocus DPI SoftFocus library of ∼35,000 compounds was screened against Mycobacterium tuberculosis (Mtb) to identify novel hits with antitubercular activity. The hits were evaluated in biol. triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc₁ complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clin. Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed This suggested a novel mechanism of action, which was confirmed by chemoproteomic anal. leading to the identification of BCG_3193 and BCG_3827 as putative targets of the series with unknown function. Initial structure-activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochem. properties.

Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H4BrF10N, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

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

Keith, John M. published the artcileDual serotonin transporter/histamine H₃ ligands: Optimization of the H₃ pharmacophore, Application In Synthesis of 71260-16-7, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(3), 702-706, database is CAplus and MEDLINE.

A series of tetrahydroisoquinolines, e.g., I, acting as dual histamine H₃/serotonin transporter ligands is described. A highly regio-selective synthesis of the tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH₃ was developed. In vitro and in vivo data are discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C8H16N2O, Application In Synthesis of 71260-16-7.

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

Cheung, Peter K. published the artcileA Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing, Application In Synthesis of 55403-35-5, the publication is Journal of Medicinal Chemistry (2016), 59(5), 1869-1879, database is CAplus and MEDLINE.

A 256-compound library was evaluated in an anti-HIV screen to identify structural “mimics” of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1_IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC₅₀‘s of 0.6 and 0.9 μM, resp. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC₅₀‘s ranging from 0.9 to 1.5 μM. The CC₅₀ value obtained in a cytotoxicity assay for compound 9 was >100 μM, corresponding to a therapeutic index (CC₅₀/EC₅₀) of approx. 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent mol. 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.

Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Application In Synthesis of 55403-35-5.

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

Butini, Stefania published the artcileDiscovery of a New Class of Potential Multifunctional Atypical Antipsychotic Agents Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors: Design, Synthesis, and Effects on Behavior, Safety of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2009), 52(1), 151-169, database is CAplus and MEDLINE.

Dopamine D₃ antagonism combined with serotonin 5-HT_1A and 5-HT_2A receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacol. features of 5i are a high affinity for dopamine D₃, serotonin 5-HT_1A and 5-HT_2A receptors, together with a low affinity for dopamine D₂ receptors (to minimize extrapyramidal side effects), serotonin 5-HT_2C receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacol. and biochem. data, including specific c-fos expression in mesocorticolimbic areas, confirmed an atypical antipsychotic profile of 5i in vivo, characterized by the absence of catalepsy at antipsychotic dose.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

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

Blass, Benjamin E. published the artcileDesign, synthesis, and evaluation of novel, selective γ-butyrolactones sigma-2 ligands, Recommanded Product: 1-(3-Cyanophenyl)piperazine, the publication is Medicinal Chemistry Research (2021), 30(9), 1713-1727, database is CAplus.

Nearly 40 years after the first disclosure of sigma receptors, the sigma-2 (σ2) receptor was recently identified as the Transmembrane Protein 97 (TMEM97, also known as MAC30 (Meningioma-associated protein)). This macromol. has been associated with a number of disease states such as schizophrenia, Alzheimer’s disease, neuropathic pain, traumatic brain injury, and cancer. We have recently identified a series of novel, functionalized γ-butyrolactones that are potent σ2 receptor ligands that are drug-like and identified a potential candidate (I) for future in vivo study.

Medicinal Chemistry Research published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Recommanded Product: 1-(3-Cyanophenyl)piperazine.

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

Zhang, Chenghong published the artcileStrategies to Mitigate the Bioactivation of Aryl Amines, Category: piperazines, the publication is Chemical Research in Toxicology (2020), 33(7), 1950-1959, database is CAplus and MEDLINE.

The bioactivation of xenobiotics to yield reactive metabolites can lead to tolerability and toxicity concerns within a drug discovery program. Development of strategies for mitigating the metabolic liability of commonly encountered toxicophores, such as anilines, relies on an understanding of the relative tendency of these functionalities to undergo bioactivation. In this report, we present the first systematic study of the structure-activity relationships of the bioactivation of aryl amine fragments (mol. weight < 250 Da) using a glutathione (GSH) trapping assay in the presence of human liver microsomes and the reduced form of NADP. This study demonstrates that conversion of anilines to nitrogen-containing heteroarylamines results in a lower abundance of GSH conjugates in the order Ph > pyrimidine ≈ pyridine > pyridazine. Introduction of electron-withdrawing functionality on the aromatic ring had a less pronounced effect on the extent of GSH conjugation. Examination of more drug-like compounds sourced from inhouse drug discovery programs revealed similar trends in bioactivation between matched pairs containing (hetero)aryl amines. This study provides medicinal chemists with insights and qual. guidance for the minimization of risks related to aryl amine metabolism

Chemical Research in Toxicology published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C20H32B2O4, Category: piperazines.

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