Month: November 2022

Ariawan, Daryl published the artcileThe nature of diamino linker and halogen bonding define selectivity of pyrrolopyrimidine-based LIMK1 Inhibitors, Name: (S)-N-(3-Bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide, the publication is Frontiers in Chemistry (Lausanne, Switzerland) (2021), 781213, database is CAplus and MEDLINE.

The LIM-domain kinase (LIMK) family consists of two isoforms, LIMK1 and LIMK2, which are highly homologous, making selective inhibitor development challenging. LIMK regulates dynamics of the actin cytoskeleton, thereby impacting many cellular functions including cell morphol. and motility. Here, we designed and synthesized analogs of a known pyrrolopyrimidine LIMK inhibitor with moderate selectivity for LIMK1 over LIMK2 to gain insights into which features contribute to both activity and selectivity. We incorporated a different stereochem. around a cyclohexyl central moiety to achieve better selectivity for different LIMK isoforms. Inhibitory activity was assessed by kinase assays, and biol. effects in cells were determined using an in vitro wound closure assay. Interestingly, a slight change in stereochem. alters LIMK isoform selectivity. Finally, a docking study was performed to predict how the new compounds interact with the target.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about 1116571-01-7. 1116571-01-7 belongs to piperazines, auxiliary class Other Aromatic Heterocyclic,Piperazine,Chiral,Nitrile,Bromide,Carbamidine,Amine,Benzene, name is (S)-N-(3-Bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide, and the molecular formula is C20H21BrN8, Name: (S)-N-(3-Bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide.

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

Goodarzi, Hassan published the artcileElectrochemical Synthesis of a New Derivative of 1,4-Dihydroxybenzene: Embedded Nucleophile in the Structure of Electrophile, SDS of cas: 67914-60-7, the publication is Journal of the Electrochemical Society (2018), 165(10), H667-H672, database is CAplus.

The electrochem. oxidation of 4-(Piperazin-1-yl)phenols (1a,b) was studied in the H₂O, MeCN and nitromethan by cyclic voltammetry and controlled-potential coulometry. P-quinone-imines generated of oxidation 4-(Piperazin-1-yl)phenols after the hydrolysis reaction participate in Michael-addition reactions with released piperazine of hydrolysis reaction of p-quinone imines. The present work led to the development of a facile and environmentally friendly electrochem. method for the synthesis of a new derivative of 1,4-dihydroxybenzene under green conditions. The effect of H₂O as a solute on the electrochem. response of 4-(Piperazin-1-yl)phenols (1a,b) was examined in the MeCN (AN) and nitromethane (NM) solvent.

Journal of the Electrochemical Society published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, SDS of cas: 67914-60-7.

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

Stefancich, Giorgio published the artcileAntibacterial and antifungal agents. XV. Synthesis and antifungal activity of structural analogs of bifonazole and ketoconazole, SDS of cas: 67914-60-7, the publication is Archiv der Pharmazie (Weinheim, Germany) (1992), 325(11), 687-94, database is CAplus and MEDLINE.

The synthesis and antifungal activities of the cis– and trans-1-acetyl-4-{4-[[2-(1,1′-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl}piperazines I are reported. Stereochem. assignments to diastereomeric pairs of cis/trans isomers were made on the basis of ¹H and ¹³C NMR data. Among test derivatives the best activity was shown by the benzoyl esters of the cis– and trans-[2-(1,1′-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methanols II (R = H, SO₂CH₃).

Archiv der Pharmazie (Weinheim, Germany) published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C7H7IN2O, SDS of cas: 67914-60-7.

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

Meddad-Belhabich, Nadia published the artcileDesign of new potent and selective secretory phospholipase A₂ inhibitors. 6-Synthesis, structure-activity relationships and molecular modelling of 1-substituted-4-[4,5-dihydro-1,2,4-(4H)-oxadiazol-5-one-3-yl(methyl)]-functionalized aryl piperazin/one/dione derivatives, Computed Properties of 67914-60-7, the publication is Bioorganic & Medicinal Chemistry (2010), 18(10), 3588-3600, database is CAplus and MEDLINE.

The group IIA human non-pancreatic secretory phospholipase A₂ (hnp-sPLA₂) is one of the enzymes implied in the inflammatory process. In the course of our work on inhibitors of this enzyme we investigated the influence of rigidity of the piperazine region on the biol. activity. Several modifications were explored. Various linkers, such as amide, urea, carbamate, or alkoxyphenyl were inserted between the piperazine and the lipophilic chain. Also, modification of the piperazine core to incorporate carbonyl groups was studied. In an in vitro fluorimetric assay using the human GIIA (HPLA₂) and porcine pancreatic GIB enzymes, compound 60a (I) had the optimal activity with an IC₅₀ = 30 nM on HPLA₂. By means of mol. modeling we attempted to get informations towards comprehension of differences in activity.

Bioorganic & Medicinal Chemistry published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, Computed Properties of 67914-60-7.

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

Modi, Gyan published the artcileStructural Modifications of Neuroprotective Anti-Parkinsonian (-)-N6-(2-(4-(Biphenyl-4-yl)piperazin-1-yl)-ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An Effort toward the Improvement of in Vivo Efficacy of the Parent Molecule, Related Products of piperazines, the publication is Journal of Medicinal Chemistry (2014), 57(4), 1557-1572, database is CAplus and MEDLINE.

In our overall goal to develop multifunctional dopamine D₂/D₃ agonist drugs for the treatment of Parkinson’s disease (PD), we previously synthesized potent D₃ preferring agonist D-264 (1a), which exhibited neuroprotective properties in two animal models of PD. To enhance the in vivo efficacy of 1a, a structure-activity relationship study was carried out. Competitive binding and [³⁵S]GTPγS functional assays identified compound (-)-9b as one of the lead mols. with preferential D₃ agonist activity (EC₅₀(GTPγS); D₃ = 0.10 nM; D₂/D₃ (EC₅₀): 159). Compounds (-)-9b and (-)-8b exhibited high in vivo activity in two PD animal models, reserpinized and 6-hydroxydopamine (OHDA)-induced unilateral lesioned rats. On the other hand, 1a failed to show any in vivo activity in these models unless the compound was dissolved in 5-10% beta-hydroxy Pr cyclodextrin solution Lead compounds exhibited appreciable radical scavenging activity. In vitro experiments with dopaminergic MN9D cells indicated neuroprotection by both 1a and (-)-9b from toxicity of MPP+.

Journal of Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, Related Products of piperazines.

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

Johnson, Mark published the artcileStructure-Activity Relationship Study of N⁶-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Development of Highly Selective D3 Dopamine Receptor Agonists along with a Highly Potent D2/D3 Agonist and Their Pharmacological Characterization [Erratum to document cited in CA157:094154], Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is Journal of Medicinal Chemistry (2013), 56(2), 589-590, database is CAplus and MEDLINE.

On page 5826, the abstract contained an incorrect structure; the corrected structure is given. On page 5828, Scheme 2 contained several incorrect structures; the corrected scheme is given. Corrected elemental anal. and mass spectrometry data are given for the Supporting Information and Table 1.

Journal of 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, Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

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

Johnson, Mark published the artcileStructure-Activity Relationship Study of N⁶-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Development of Highly Selective D3 Dopamine Receptor Agonists along with a Highly Potent D2/D3 Agonist and Their Pharmacological Characterization, SDS of cas: 945953-41-3, the publication is Journal of Medicinal Chemistry (2012), 55(12), 5826-5840, database is CAplus and MEDLINE.

In our effort to develop multifunctional drugs against Parkinson’s disease, a structure-activity-relationship study was carried out based on our hybrid mol. template targeting D2/D3 receptors. Competitive binding with [³H]spiroperidol was used to evaluate affinity (K_i) of test compounds Functional activity of selected compounds in stimulating [³⁵S]GTPγS binding was assessed in CHO cells expressing either human D2 or D3 receptors. Our results demonstrated development of highly selective compounds for D3 receptor (for (-)-40 (I) K_i, D3 = 1.84 nM, D2/D3 = 583.2; for (-)-45K_i, D3 = 1.09 nM, D2/D3 = 827.5). Functional data identified (-)-40 (EC₅₀, D2 = 114 nM, D3 = 0.26 nM, D2/D3 = 438) as one of the highest D3 selective agonists known to date. In addition, high affinity, nonselective D3 agonist (-)-19 (EC₅₀, D2 = 2.96 nM and D3 = 1.26 nM) was also developed. Lead compounds with antioxidant activity were evaluated using an in vivo PD animal model.

Journal of 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, SDS of cas: 945953-41-3.

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

Ghosh, Balaram published the artcileFurther delineation of hydrophobic binding sites in dopamine D₂/D₃ receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol, Product Details of C16H18N2, the publication is Bioorganic & Medicinal Chemistry (2010), 18(15), 5661-5674, database is CAplus and MEDLINE.

Here we report a structure-activity relationship (SAR) study of analogs of 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K _i), as measured with tritiated spiperone and HEK-293 cells expressing either D₂ or D₃ receptors. Functional activity of selected compounds was assessed with the GTPγS binding assay. Compound I was the most selective for the D₃ receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative I, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the mol. determinants of the binding pocket in D₂/D₃ receptors. Functional activity assays demonstrated high potency and selectivity of (+)-II (R¹ = H, R² = OH) and (-)-II (R¹ = OH, R² = H) (D₂/D₃ (ratio of EC₅₀): 105 and 202, resp.) for the D₃ receptor and both compounds were more selective compared to the reference drug ropinirole (D₂/D₃ (ratio of EC₅₀): 29.5).

Bioorganic & Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, Product Details of C16H18N2.

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

Kim, Seong Heon published the artcileIII. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold, Quality Control of 207284-20-6, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(23), 6982-6986, database is CAplus and MEDLINE.

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. One compound with single-digit CXCR3 affinity and good rat PK and hERG profiles has been identified as a lead for further study.

Bioorganic & Medicinal Chemistry Letters published new progress about 207284-20-6. 207284-20-6 belongs to piperazines, auxiliary class Piperazine,Chiral, name is (S)-2-Ethylpiperazine, and the molecular formula is C6H14N2, Quality Control of 207284-20-6.

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

Malgorzata, Kostecka published the artcileSynthesis and antifungal activity of new series of compounds against Ascosphaera apis, SDS of cas: 87179-40-6, the publication is Organic Chemistry: An Indian Journal (2010), 6(4), 284-292, database is CAplus.

The fungicidal compounds synthesized by us and applied in the studies are: 3,1-benzothiazine, variously substituted thioamides, N-heterocyclic carbothionyl derivatives and 2,5-disubstituted 1,3,4-thiadiazoles. Depending on their structure, their action can be oriented towards zoo- and geophilic fungi that destroy crops and raw material of vegetation origin as well as pathogenic for animals and man. The compounds are characterized by differentiated mechanism of mol. interactions in energetic cell processes and disubstituted 1,3,4-thiadiazole inhibiting squale epoxidase and squale accumulation seem to be an interesting group. Selective estimation of action of some compounds from individual groups against the strain Ascosphaera apis of the fungus isolated from insects infected with calciferous mycosis was made.

Organic Chemistry: An Indian Journal published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, SDS of cas: 87179-40-6.

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