Tag: 214.3046

A PDE6未-KRas Inhibitor Chemotype with up to Seven H-Bonds and Picomolar Affinity that Prevents Efficient Inhibitor Release by Arl2 was written by Martin-Gago, Pablo;Fansa, Eyad K.;Klein, Christian H.;Murarka, Sandip;Janning, Petra;Schuermann, Marc;Metz, Malte;Ismail, Shehab;Schultz-Fademrecht, Carsten;Baumann, Matthias;Bastiaens, Philippe I. H.;Wittinghofer, Alfred;Waldmann, Herbert. And the article was included in Angewandte Chemie, International Edition in 2017.Formula: C11H22N2O2 This article mentions the following:

Small-mol. inhibition of the interaction between the KRas oncoprotein and the chaperone PDE6未 impairs KRas spatial organization and signaling in cells. However, despite potent binding in vitro (K_D<10 nM), interference with Ras signaling and growth inhibition require 5-20 渭m compound concentrations We demonstrate that these findings can be explained by fast release of high-affinity inhibitors from PDE6未 by the release factor Arl2. This limitation is overcome by novel highly selective inhibitors that bind to PDE6未 with up to 7 hydrogen bonds, resulting in picomolar affinity. Their release by Arl2 is greatly decreased, and representative compounds selectively inhibit growth of KRas mutated and -dependent cells with the highest activity recorded yet. Our findings indicate that very potent inhibitors of the KRas-PDE6未 interaction may impair the growth of tumors driven by oncogenic KRas. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Formula: C11H22N2O2).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Formula: C11H22N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Design, synthesis and biological evaluation of pyridine derivatives as selective SHP2 inhibitors was written by Liu, Wen-Shan;Yang, Bing;Wang, Rui-Rui;Li, Wei-Ya;Ma, Yang-Chun;Zhou, Liang;Du, Shan;Ma, Ying;Wang, Run-Ling. And the article was included in Bioorganic Chemistry in 2020.Reference of 144222-22-0 This article mentions the following:

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which affects the transduction of multiple signaling pathways, including RAS-ERK, PI3K-AKT and JAK-STAT. SHP2 also plays an important role in the programmed cell death pathway (PD-1/PD-L1). Studies have shown that SHP2 is associated with a variety of cancers, including breast, liver and gastric cancers. Therefore, the development of SHP2 inhibitors has attracted extensive attention. In this study, based on the known inhibitor 1 (SHP099), novel SHP2 inhibitors were designed by means of scaffold hopping, and 35 pyridine derivatives as SHP2 inhibitors were found. The in vitro enzyme activity assay was performed on these compounds, and multiple selective SHP2 inhibitors with activity potency similar to that of SHP099 were obtained. Among them, compound (2-(4-(aminomethyl)piperidin-1-yl)-5-(2,3-dichlorophenyl)pyridin-3-yl)methanol (11a) was the most potent and highly selective SHP2 inhibitor with an in vitro enzyme activity IC₅₀ value of 1.36 渭M. Fluorescence titration assay verified that 11a bound directly to SHP2 protein. Subsequently, cell assay of representative compounds showed that these compounds could effectively inhibit the proliferation of Ba/F₃ cells. In addition, the pharmacokinetic characteristics of the designed compounds were analyzed by the in silico ADMET prediction. Mol. docking study provided more detailed information on the binding mode of compounds and SHP2 protein. In brief, this study reported for the first time that pyridine derivatives as novel SHP2 inhibitors had good inhibitory activity and selectivity, providing new clues for the development of small mol. SHP2 inhibitors. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Reference of 144222-22-0).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Reference of 144222-22-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors was written by Ushiyama, Fumihito;Amada, Hideaki;Mihara, Yasuhiro;Takeuchi, Tomoki;Tanaka-Yamamoto, Nozomi;Mima, Masashi;Kamitani, Masafumi;Wada, Reiko;Tamura, Yunoshin;Endo, Mayumi;Masuko, Aiko;Takata, Iichiro;Hitaka, Kosuke;Sugiyama, Hiroyuki;Ohtake, Norikazu. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Quality Control of 1-Boc-4-(Aminomethyl)piperidine This article mentions the following:

The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chem. class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC₉₀ values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 μg/mL, resp. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chem. class. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Quality Control of 1-Boc-4-(Aminomethyl)piperidine).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Quality Control of 1-Boc-4-(Aminomethyl)piperidine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening was written by Wellaway, Christopher R.;Amans, Dominique;Bamborough, Paul;Barnett, Heather;Bit, Rino A.;Brown, Jack A.;Carlson, Neil R.;Chung, Chun-wa;Cooper, Anthony W. J.;Craggs, Peter D.;Davis, Robert P.;Dean, Tony W.;Evans, John P.;Gordon, Laurie;Harada, Isobel L.;Hirst, David J.;Humphreys, Philip G.;Jones, Katherine L.;Lewis, Antonia J.;Lindon, Matthew J.;Lugo, Dave;Mahmood, Mahnoor;McCleary, Scott;Medeiros, Patricia;Mitchell, Darren J.;O’Sullivan, Michael;Le Gall, Armelle;Patel, Vipulkumar K.;Patten, Chris;Poole, Darren L.;Shah, Rishi R.;Smith, Jane E.;Stafford, Kayleigh A. J.;Thomas, Pamela J.;Vimal, Mythily;Wall, Ian D.;Watson, Robert J.;Wellaway, Natalie;Yao, Gang;Prinjha, Rab K.. And the article was included in Journal of Medicinal Chemistry in 2020.Related Products of 144222-22-0 This article mentions the following:

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small mol. inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochem., pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technol., with an N-Me pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Related Products of 144222-22-0).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Related Products of 144222-22-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Design and synthesis of Grp94 selective inhibitors based on Phe199 induced fit mechanism and their anti-inflammatory effects was written by Xu, Shicheng;Guo, Anping;Chen, Nan-nan;Dai, Wei;Yang, Huan-aoyu;Xie, Wenqin;Wang, Mengjie;You, Qi-Dong;Xu, Xiao-Li. And the article was included in European Journal of Medicinal Chemistry in 2021.Category: piperidines This article mentions the following:

Glucose-regulated protein 94 (Grp94), a member of the Heat shock protein 90 (Hsp90) family, is implicated in many human diseases, including cancer, neurodegeneration, inflammatory, and infectious diseases. Here, we describe our effort to design and develop a new series of Grp94 inhibitors based on Phe199 induced fit mechanism. Using an alkynyl-containing inhibitor as a starting point, we developed compound 4 (I), which showed potent inhibitory activity toward Grp94 in a fluorescence polarization-based assay. With improved physicochem. properties and suitable pharmacokinetic properties, compound 4 was advanced into in vivo bioactivity evaluation. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 4 showed anti-inflammatory property and reduced the levels of pro-inflammatory cytokines (TNF-α and IL-6). Together, these findings provide evidence that this approach may be promising for further Grp94 drug development efforts. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Category: piperidines).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A PDE6δ-KRas Inhibitor Chemotype with up to Seven H-Bonds and Picomolar Affinity that Prevents Efficient Inhibitor Release by Arl2 was written by Martin-Gago, Pablo;Fansa, Eyad K.;Klein, Christian H.;Murarka, Sandip;Janning, Petra;Schuermann, Marc;Metz, Malte;Ismail, Shehab;Schultz-Fademrecht, Carsten;Baumann, Matthias;Bastiaens, Philippe I. H.;Wittinghofer, Alfred;Waldmann, Herbert. And the article was included in Angewandte Chemie, International Edition in 2017.Formula: C11H22N2O2 This article mentions the following:

Small-mol. inhibition of the interaction between the KRas oncoprotein and the chaperone PDE6δ impairs KRas spatial organization and signaling in cells. However, despite potent binding in vitro (K_D<10 nM), interference with Ras signaling and growth inhibition require 5-20 μm compound concentrations We demonstrate that these findings can be explained by fast release of high-affinity inhibitors from PDE6δ by the release factor Arl2. This limitation is overcome by novel highly selective inhibitors that bind to PDE6δ with up to 7 hydrogen bonds, resulting in picomolar affinity. Their release by Arl2 is greatly decreased, and representative compounds selectively inhibit growth of KRas mutated and -dependent cells with the highest activity recorded yet. Our findings indicate that very potent inhibitors of the KRas-PDE6δ interaction may impair the growth of tumors driven by oncogenic KRas. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Formula: C11H22N2O2).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Formula: C11H22N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Design, synthesis and biological evaluation of pyridine derivatives as selective SHP2 inhibitors was written by Liu, Wen-Shan;Yang, Bing;Wang, Rui-Rui;Li, Wei-Ya;Ma, Yang-Chun;Zhou, Liang;Du, Shan;Ma, Ying;Wang, Run-Ling. And the article was included in Bioorganic Chemistry in 2020.Reference of 144222-22-0 This article mentions the following:

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which affects the transduction of multiple signaling pathways, including RAS-ERK, PI3K-AKT and JAK-STAT. SHP2 also plays an important role in the programmed cell death pathway (PD-1/PD-L1). Studies have shown that SHP2 is associated with a variety of cancers, including breast, liver and gastric cancers. Therefore, the development of SHP2 inhibitors has attracted extensive attention. In this study, based on the known inhibitor 1 (SHP099), novel SHP2 inhibitors were designed by means of scaffold hopping, and 35 pyridine derivatives as SHP2 inhibitors were found. The in vitro enzyme activity assay was performed on these compounds, and multiple selective SHP2 inhibitors with activity potency similar to that of SHP099 were obtained. Among them, compound (2-(4-(aminomethyl)piperidin-1-yl)-5-(2,3-dichlorophenyl)pyridin-3-yl)methanol (11a) was the most potent and highly selective SHP2 inhibitor with an in vitro enzyme activity IC₅₀ value of 1.36 μM. Fluorescence titration assay verified that 11a bound directly to SHP2 protein. Subsequently, cell assay of representative compounds showed that these compounds could effectively inhibit the proliferation of Ba/F₃ cells. In addition, the pharmacokinetic characteristics of the designed compounds were analyzed by the in silico ADMET prediction. Mol. docking study provided more detailed information on the binding mode of compounds and SHP2 protein. In brief, this study reported for the first time that pyridine derivatives as novel SHP2 inhibitors had good inhibitory activity and selectivity, providing new clues for the development of small mol. SHP2 inhibitors. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Reference of 144222-22-0).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Reference of 144222-22-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors was written by Ushiyama, Fumihito;Amada, Hideaki;Mihara, Yasuhiro;Takeuchi, Tomoki;Tanaka-Yamamoto, Nozomi;Mima, Masashi;Kamitani, Masafumi;Wada, Reiko;Tamura, Yunoshin;Endo, Mayumi;Masuko, Aiko;Takata, Iichiro;Hitaka, Kosuke;Sugiyama, Hiroyuki;Ohtake, Norikazu. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Quality Control of 1-Boc-4-(Aminomethyl)piperidine This article mentions the following:

The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chem. class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC₉₀ values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 μg/mL, resp. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chem. class. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Quality Control of 1-Boc-4-(Aminomethyl)piperidine).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Quality Control of 1-Boc-4-(Aminomethyl)piperidine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening was written by Wellaway, Christopher R.;Amans, Dominique;Bamborough, Paul;Barnett, Heather;Bit, Rino A.;Brown, Jack A.;Carlson, Neil R.;Chung, Chun-wa;Cooper, Anthony W. J.;Craggs, Peter D.;Davis, Robert P.;Dean, Tony W.;Evans, John P.;Gordon, Laurie;Harada, Isobel L.;Hirst, David J.;Humphreys, Philip G.;Jones, Katherine L.;Lewis, Antonia J.;Lindon, Matthew J.;Lugo, Dave;Mahmood, Mahnoor;McCleary, Scott;Medeiros, Patricia;Mitchell, Darren J.;O’Sullivan, Michael;Le Gall, Armelle;Patel, Vipulkumar K.;Patten, Chris;Poole, Darren L.;Shah, Rishi R.;Smith, Jane E.;Stafford, Kayleigh A. J.;Thomas, Pamela J.;Vimal, Mythily;Wall, Ian D.;Watson, Robert J.;Wellaway, Natalie;Yao, Gang;Prinjha, Rab K.. And the article was included in Journal of Medicinal Chemistry in 2020.Related Products of 144222-22-0 This article mentions the following:

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small mol. inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochem., pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technol., with an N-Me pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Related Products of 144222-22-0).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Related Products of 144222-22-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Design and synthesis of Grp94 selective inhibitors based on Phe199 induced fit mechanism and their anti-inflammatory effects was written by Xu, Shicheng;Guo, Anping;Chen, Nan-nan;Dai, Wei;Yang, Huan-aoyu;Xie, Wenqin;Wang, Mengjie;You, Qi-Dong;Xu, Xiao-Li. And the article was included in European Journal of Medicinal Chemistry in 2021.Category: piperidines This article mentions the following:

Glucose-regulated protein 94 (Grp94), a member of the Heat shock protein 90 (Hsp90) family, is implicated in many human diseases, including cancer, neurodegeneration, inflammatory, and infectious diseases. Here, we describe our effort to design and develop a new series of Grp94 inhibitors based on Phe199 induced fit mechanism. Using an alkynyl-containing inhibitor as a starting point, we developed compound 4 (I), which showed potent inhibitory activity toward Grp94 in a fluorescence polarization-based assay. With improved physicochem. properties and suitable pharmacokinetic properties, compound 4 was advanced into in vivo bioactivity evaluation. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 4 showed anti-inflammatory property and reduced the levels of pro-inflammatory cytokines (TNF-α and IL-6). Together, these findings provide evidence that this approach may be promising for further Grp94 drug development efforts. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Category: piperidines).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem