M.W=450-500 | Heterocyclic Building Blocks-piperazine

Shen, Mingyun’s team published research in Molecular BioSystems in 9 | CAS: 1116571-01-7

Molecular BioSystems 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 C6H17NO3Si, Category: piperazines.

Shen, Mingyun published the artcileTheoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: insight into structure-based inhibitor design, Category: piperazines, the publication is Molecular BioSystems (2013), 9(10), 2435-2446, database is CAplus and MEDLINE.

LIM kinases (LIMKs), downstream of Rho-associated protein kinases (ROCKs) and p21-activated protein kinases (PAKs), are shown to be promising targets for the treatment of cancers. In this study, the inhibition mechanism of 41 pyrrolopyrimidine derivatives as LIMK2 inhibitors was explored through a series of theor. approaches. First, a model of LIMK2 was generated through mol. homol. modeling, and the studied inhibitors were docked into the binding active site of LIMK2 by the docking protocol, taking into consideration the flexibility of the protein. The binding poses predicted by mol. docking for 17 selected inhibitors with different bioactivities complexed with LIMK2 underwent mol. dynamics (MD) simulations, and the binding free energies for the complexes were predicted by using the mol. mechanics/generalized born surface area (MM/GBSA) method. The predicted binding free energies correlated well with the exptl. bioactivities (r² = 0.63 or 0.62). Next, the free energy decomposition anal. was utilized to highlight the following key structural features related to biol. activity: (1) the important H-bond between Ile408 and pyrrolopyrimidine, (2) the H-bonds between the inhibitors and Asp469 and Gly471 which maintain the stability of the DFG-out conformation, and (3) the hydrophobic interactions between the inhibitors and several key residues (Leu337, Phe342, Ala345, Val358, Lys360, Leu389, Ile408, Leu458 and Leu472). Finally, a variety of LIMK2 inhibitors with a pyrrolopyrimidine scaffold were designed, some of which showed improved potency according to the predictions. Our studies suggest that the use of mol. docking with MD simulations and free energy calculations could be a powerful tool for understanding the binding mechanism of LIMK2 inhibitors and for the design of more potent LIMK2 inhibitors.

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

Harrison, Bryce A.’s team published research in Journal of Medicinal Chemistry in 52 | CAS: 1116571-01-7

Journal of Medicinal Chemistry 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, Formula: C20H21BrN8.

Harrison, Bryce A. published the artcileNovel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma, Formula: C20H21BrN8, the publication is Journal of Medicinal Chemistry (2009), 52(21), 6515-6518, database is CAplus and MEDLINE.

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma.

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

Sun, Jun-Rong’s team published research in Letters in Drug Design & Discovery in 8 | CAS: 1116571-01-7

Letters in Drug Design & Discovery 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 C12H14BNO2, Computed Properties of 1116571-01-7.

Sun, Jun-Rong published the artcile3D-QSAR and docking studies on pyrrolopyrimidine derivatives as LIM-kinase 2 inhibitors, Computed Properties of 1116571-01-7, the publication is Letters in Drug Design & Discovery (2011), 8(3), 229-240, database is CAplus.

The pyrrolopyrimidine derivatives have been regarded as a novel class of LIM-kinase 2 inhibitor. To explore the relationship between the structures of substituted pyrrolopyrimidine derivatives and their inhibitory activities against LIMK2, CoMFA and CoMSIA analyses, and mol. docking studies were performed on a dataset of forty-one compounds The two 3D-QSAR models resulted from thirty-one mols. in the training set gave r²_cv values of 0.635 and 0.660, r² values of 0.973 and 0.965, resp. The predictive ability of CoMFA and CoMSIA, determined using a test set of ten compounds, gave predictive correlation coefficients of 0.971 and 0.964, resp. 3D contour maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. The results can serve as a useful guideline to design novel LIMK2 inhibitors with better potencies.

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

Singh, Gagandip’s team published research in Medicinal Chemistry in 9 | CAS: 1116571-01-7

Medicinal Chemistry 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 C8H7NaO4S, Category: piperazines.

Singh, Gagandip published the artcileModeling of LIM-kinase 2 inhibitory activity of pyrrolopyrimidine analogues: useful in treatment of ocular hypertension and glaucoma, Category: piperazines, the publication is Medicinal Chemistry (2013), 9(3), 402-409, database is CAplus and MEDLINE.

The LIM-Kinase 2 (LIMK2) inhibitory activity of a series of pyrrolopyrimidine analogs has been analyzed through combinatorial protocol in multiple linear regressions (CP-MLR) and partial least square (PLS) using different descriptors obtained from DRAGON software. The empirical, topol. and charge descriptors have led to statistically significant QSAR models and showed good external predictivity as reflected in test set R² values (0.782 to 0.888). The obtained structure-activity correlations underlined the significance of bulkiness and mol. polarizability in improving the activity. The topol. descriptors suggested that open chain or branched substituents are favorable while cyclic /ring substituents are unfavorable for the activity. The descriptors identified in the study showed that pyrrolopyrimidine scaffold holds scope for modulating LIMK2 inhibitory activity. The study gives a direction for further exploration of chem. space of pyrrolopyrimidine analogs as LIMK2 inhibitors.

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

Leahy, James W.’s team published research in Journal of Medicinal Chemistry in 55 | CAS: 1033743-83-7

Journal of Medicinal Chemistry published new progress about 1033743-83-7. 1033743-83-7 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 4-((3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine-1-carboxylate, and the molecular formula is C21H33BN2O6S, HPLC of Formula: 1033743-83-7.

Leahy, James W. published the artcileDiscovery of a Novel Series of Potent and Orally Bioavailable Phosphoinositide 3-Kinase γ Inhibitors, HPLC of Formula: 1033743-83-7, the publication is Journal of Medicinal Chemistry (2012), 55(11), 5467-5482, database is CAplus and MEDLINE.

The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. A high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, I, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the x-ray structures of the sulfonylpiperazine scaffold and the second HTS hit, II, within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogs including advanced leads such as III with desirable potency, selectivity, and oral bioavailability.

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

Ariawan, Daryl’s team published research in Frontiers in Chemistry (Lausanne, Switzerland) in 9 | CAS: 1116571-01-7

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.

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.

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