Tag: 300-400

Macrocyclic Peptides as a Novel Class of NNMT Inhibitors: A SAR Study Aimed at Inhibitory Activity in the Cell was written by Hayashi, Kyohei;Uehara, Shota;Yamamoto, Shiho;Cary, Douglas R.;Nishikawa, Junichi;Ueda, Taichi;Ozasa, Hiroki;Mihara, Kousuke;Yoshimura, Norito;Kawai, Taeko;Ono, Takashi;Yamamoto, Saki;Fumoto, Masataka;Mikamiyama, Hidenori. And the article was included in ACS Medicinal Chemistry Letters in 2021.Recommanded Product: 86069-86-5 The following contents are mentioned in the article:

Nicotinamide N-methyltransferase (NNMT), which catalyzes the methylation of nicotinamide, is a cytosolic enzyme that has attracted much attention as a therapeutic target for a variety of diseases. However, despite the considerable interest in this target, reports of NNMT inhibitors have still been limited to date. In this work, utilizing in vitro translated macrocyclic peptide libraries, we identified peptide 1 as a novel class of NNMT inhibitors. Further exploration based on the X-ray cocrystal structures of the peptides with NNMT provided a dramatic improvement in inhibitory activity (peptide 23: IC₅₀ = 0.15 nM). Furthermore, by balance of the peptides’ lipophilicity and biol. activity, inhibitory activity against NNMT in cell-based assay was successfully achieved (peptide 26: cell-based IC₅₀ = 770 nM). These findings illuminate the potential of cyclic peptides as a relatively new drug discovery modality even for intracellular targets. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Recommanded Product: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Recommanded Product: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Macrocyclic Peptides as a Novel Class of NNMT Inhibitors: A SAR Study Aimed at Inhibitory Activity in the Cell was written by Hayashi, Kyohei;Uehara, Shota;Yamamoto, Shiho;Cary, Douglas R.;Nishikawa, Junichi;Ueda, Taichi;Ozasa, Hiroki;Mihara, Kousuke;Yoshimura, Norito;Kawai, Taeko;Ono, Takashi;Yamamoto, Saki;Fumoto, Masataka;Mikamiyama, Hidenori. And the article was included in ACS Medicinal Chemistry Letters in 2021.Formula: C21H21NO4 The following contents are mentioned in the article:

Nicotinamide N-methyltransferase (NNMT), which catalyzes the methylation of nicotinamide, is a cytosolic enzyme that has attracted much attention as a therapeutic target for a variety of diseases. However, despite the considerable interest in this target, reports of NNMT inhibitors have still been limited to date. In this work, utilizing in vitro translated macrocyclic peptide libraries, we identified peptide 1 as a novel class of NNMT inhibitors. Further exploration based on the X-ray cocrystal structures of the peptides with NNMT provided a dramatic improvement in inhibitory activity (peptide 23: IC₅₀ = 0.15 nM). Furthermore, by balance of the peptides’ lipophilicity and biol. activity, inhibitory activity against NNMT in cell-based assay was successfully achieved (peptide 26: cell-based IC₅₀ = 770 nM). These findings illuminate the potential of cyclic peptides as a relatively new drug discovery modality even for intracellular targets. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Formula: C21H21NO4).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. 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.Formula: C21H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway was written by Wu, Qiong;Song, Jingfang;Meng, Danxin;Chang, Quanzhong. And the article was included in Journal of Molecular Neuroscience in 2019.Recommanded Product: 1222780-33-7 The following contents are mentioned in the article:

High level of corticosterone (CORT) is toxic to neurons and plays an important role in depression-like behavior and chronic stress. Our previous study showed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor (sEHI), induces an antidepressant effect in animal models. However, the underlying mechanism is not clear. In this study, we investigated the protective effect of TPPU on PC12 cells against CORT-induced cytotoxicity and its underlying mechanism. We found that TPPU and the sEH substrate epoxyeicosatrienoic acids (EETs) protected PC12 cells from the CORT-induced injury by increasing cell viability and inhibiting apoptosis. Furthermore, TPPU and EETs also blocked the CORT-mediated downregulation of BDNF. Blocking the BDNF-TrkB pathway by the TrkB inhibitor K252a abolished the protective effect of TPPU. Taken together, our results suggest that sEHI could protect PC12 cells against the CORT-induced cytotoxicity via the BDNF-TrkB signaling pathway. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Recommanded Product: 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Recommanded Product: 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Analogues of AVP modified in the N-terminal part of the molecule with Pip isomers: TFA-catalyzed peptide bond hydrolysis was written by Sobolewski, Dariusz;Prahl, Adam;Kwiatkowska, Anna;Slaninova, Jirina;Lammek, Bernard. And the article was included in Journal of Peptide Science in 2009.Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Using SPPS techniques, six new analogs of AVP (arginine vasopressin) and some of its agonists were synthesized. The peptides were designed by substitution of Phe at position 3 of AVP, [Mpa¹] AVP (dAVP) and [Mpa¹,Val⁴,D-Arg⁸]VP (dVDAVP) with L– or D-Pip (Mpa = 3-mercaptopropionic acid; Pip = pipecolic acid, a non-coded α-imino acid, also known as homoproline). Surprisingly enough, both the analogs of AVP and [Mpa¹]AVP with identical substituents at position 2 turned out to be highly sensitive to TFA used for the deprotection and resin cleavage step, and it was the reason why the authors were not able to obtain these four peptides. The mechanisms of their fragmentation were proposed in this study. Unfortunately, all the new analogs were inactive in bioassays for the pressor, antidiuretic and uterotonic in vitro activities in the rat. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Recommanded Product: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Analogues of AVP modified in the N-terminal part of the molecule with Pip isomers: TFA-catalyzed peptide bond hydrolysis was written by Sobolewski, Dariusz;Prahl, Adam;Kwiatkowska, Anna;Slaninova, Jirina;Lammek, Bernard. And the article was included in Journal of Peptide Science in 2009.Category: piperidines The following contents are mentioned in the article:

Using SPPS techniques, six new analogs of AVP (arginine vasopressin) and some of its agonists were synthesized. The peptides were designed by substitution of Phe at position 3 of AVP, [Mpa¹] AVP (dAVP) and [Mpa¹,Val⁴,D-Arg⁸]VP (dVDAVP) with L– or D-Pip (Mpa = 3-mercaptopropionic acid; Pip = pipecolic acid, a non-coded α-imino acid, also known as homoproline). Surprisingly enough, both the analogs of AVP and [Mpa¹]AVP with identical substituents at position 2 turned out to be highly sensitive to TFA used for the deprotection and resin cleavage step, and it was the reason why the authors were not able to obtain these four peptides. The mechanisms of their fragmentation were proposed in this study. Unfortunately, all the new analogs were inactive in bioassays for the pressor, antidiuretic and uterotonic in vitro activities in the rat. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Category: piperidines).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Designing a small fluorescent inhibitor to investigate soluble epoxide hydrolase engagement in living cells was written by Brunst, Steffen;Schoenfeld, Julia;Breunig, Peter;Burgers, Luisa D.;DeMeglio, Murphy;Ehrler, Johanna H. M.;Lillich, Felix F.;Weizel, Lilia;Hefendehl, Jasmin K.;Fuerst, Robert;Proschak, Ewgenij;Hiesinger, Kerstin. And the article was included in ACS Medicinal Chemistry Letters in 2022.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Soluble epoxide hydrolase (sEH) is a promising target for a number of inflammation-related diseases. In addition, inhibition of sEH has been shown to reduce neuroinflammation, which plays a critical role in the development of central nervous system (CNS) diseases such as Alzheimer’s disease. In this study, we present the rational design of a small fluorescent sEH inhibitor. Starting from the clin. candidate GSK2256294A, we replaced the triazine moiety with the 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) fluorophore. The resulting fluorescent sEH inhibitor displayed excellent potency in an in vitro enzyme activity assay (IC₅₀ < 2 nM). The developed inhibitor is applicable in a NanoBRET-based assay system suitable for studying sEH target engagement in living cells. Furthermore, the inhibitor can be used to visualize sEH in sEH-transfected HEK293 cells and in primary mouse astrocytes by fluorescence microscopy. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Formula: C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) 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.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Introduction of Pro and its analogues in the conserved P₁‘ position of trypsin inhibitor SFTI-1 retains its inhibitory activity was written by Legowska, Anna;Debowski, Dawid;Lukajtis, Rafal;Sztabkowska, Emilia;Mizeria, Aneta;Brzozowski, Krzysztof;Wysocka, Magdalena;Lesner, Adam;Rolka, Krzysztof. And the article was included in Protein & Peptide Letters in 2011.SDS of cas: 86069-86-5 The following contents are mentioned in the article:

A number of monocyclic SFTI-1 analogs modified in the conserved inhibitor P₁‘ position by Pro, its L-hydroxyproline (Hyp) derivative as well as mimetics with different ring size were synthesized by the solid-phase method. Replacement of Ser6 by Pro, Hyp, and a four-member ring, L-azetidine-2-carboxylic acid (Aze), retained trypsin or chymotrypsin inhibitory activity. The determined association equilibrium constants of these analogs with a cognate enzyme were about two orders of magnitude lower than those obtained for ones with conserved Ser6. In all analogs, with the exception of one, [Phe⁵,Aze⁶]SFTI-1, the P₁-P₁‘ reactive site remained intact. The results provide first evidence that the conserved Ser in the P₁‘ position of Bowman-Birk inhibitors can be successfully replaced by an amino acid with a secondary amine group. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5SDS of cas: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.SDS of cas: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Introduction of Pro and its analogues in the conserved P₁‘ position of trypsin inhibitor SFTI-1 retains its inhibitory activity was written by Legowska, Anna;Debowski, Dawid;Lukajtis, Rafal;Sztabkowska, Emilia;Mizeria, Aneta;Brzozowski, Krzysztof;Wysocka, Magdalena;Lesner, Adam;Rolka, Krzysztof. And the article was included in Protein & Peptide Letters in 2011.Recommanded Product: 86069-86-5 The following contents are mentioned in the article:

A number of monocyclic SFTI-1 analogs modified in the conserved inhibitor P₁‘ position by Pro, its L-hydroxyproline (Hyp) derivative as well as mimetics with different ring size were synthesized by the solid-phase method. Replacement of Ser6 by Pro, Hyp, and a four-member ring, L-azetidine-2-carboxylic acid (Aze), retained trypsin or chymotrypsin inhibitory activity. The determined association equilibrium constants of these analogs with a cognate enzyme were about two orders of magnitude lower than those obtained for ones with conserved Ser6. In all analogs, with the exception of one, [Phe⁵,Aze⁶]SFTI-1, the P₁-P₁‘ reactive site remained intact. The results provide first evidence that the conserved Ser in the P₁‘ position of Bowman-Birk inhibitors can be successfully replaced by an amino acid with a secondary amine group. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Recommanded Product: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) 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.Recommanded Product: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Potent bactericidal antimycobacterials targeting the chaperone ClpC1 based on the depsipeptide natural products Ecumicin and Ohmyungsamycin A was written by Hawkins, Paige M. E.;Hoi, David M.;Cheung, Chen-Yi;Wang, Trixie;Quan, Diana;Sasi, Vishnu Mini;Liu, Dennis Y.;Linington, Roger G.;Jackson, Colin J.;Oehlers, Stefan H.;Cook, Gregory M.;Britton, Warwick J.;Clausen, Tim;Payne, Richard J.. And the article was included in Journal of Medicinal Chemistry in 2022.Application of 86069-86-5 The following contents are mentioned in the article:

Ohmyungsamycin A and ecumicin are structurally related cyclic depsipeptide natural products that possess activity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Herein, we describe the design and synthesis of a library of analogs of these two natural products using an efficient solid-phase synthesis and late-stage macrolactamization strategy. Lead analogs possessed potent activity against Mtb in vitro (min. inhibitory concentration 125-500 nM) and were shown to inhibit protein degradation by the mycobacterial ClpC1-ClpP1P2 protease with an associated enhancement of ClpC1 ATPase activity. The most promising analog from the series exhibited rapid bactericidal killing activity against Mtb, capable of sterilizing cultures after 7 days, and retained bactericidal activity against hypoxic non-replicating Mtb. This natural product analog was also active in an in vivo zebrafish model of infection. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Application of 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. 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.Application of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Potent bactericidal antimycobacterials targeting the chaperone ClpC1 based on the depsipeptide natural products Ecumicin and Ohmyungsamycin A was written by Hawkins, Paige M. E.;Hoi, David M.;Cheung, Chen-Yi;Wang, Trixie;Quan, Diana;Sasi, Vishnu Mini;Liu, Dennis Y.;Linington, Roger G.;Jackson, Colin J.;Oehlers, Stefan H.;Cook, Gregory M.;Britton, Warwick J.;Clausen, Tim;Payne, Richard J.. And the article was included in Journal of Medicinal Chemistry in 2022.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

Ohmyungsamycin A and ecumicin are structurally related cyclic depsipeptide natural products that possess activity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Herein, we describe the design and synthesis of a library of analogs of these two natural products using an efficient solid-phase synthesis and late-stage macrolactamization strategy. Lead analogs possessed potent activity against Mtb in vitro (min. inhibitory concentration 125-500 nM) and were shown to inhibit protein degradation by the mycobacterial ClpC1-ClpP1P2 protease with an associated enhancement of ClpC1 ATPase activity. The most promising analog from the series exhibited rapid bactericidal killing activity against Mtb, capable of sterilizing cultures after 7 days, and retained bactericidal activity against hypoxic non-replicating Mtb. This natural product analog was also active in an in vivo zebrafish model of infection. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Application In Synthesis of (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem