Category: 142253-56-3

Design and synthesis of cyanamides as potent and selective N-acylethanolamine acid amidase inhibitors was written by Malamas, Michael S.;Farah, Shrouq I.;Lamani, Manjunath;Pelekoudas, Dimitrios N.;Perry, Nicholas Thomas;Rajarshi, Girija;Miyabe, Christina Yume;Chandrashekhar, Honrao;West, Jay;Pavlopoulos, Spiro;Makriyannis, Alexandros. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Synthetic Route of C9H17NO3 This article mentions the following:

N-acylethanolamine acid amidase (NAAA) inhibition represents an exciting novel approach to treat inflammation and pain. NAAA is a cysteine amidase which preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA is an endogenous agonist of the nuclear peroxisome proliferator-activated receptor-伪 (PPAR-伪), which is a key regulator of inflammation and pain. Thus, blocking the degradation of PEA with NAAA inhibitors results in augmentation of the PEA/PPAR-伪 signaling pathway and regulation of inflammatory and pain processes. We have prepared a new series of NAAA inhibitors exploring the azetidine-nitrile (cyanamide) pharmacophore that led to the discovery of highly potent and selective compounds Key analogs demonstrated single-digit nanomolar potency for hNAAA and showed >100-fold selectivity against serine hydrolases FAAH, MGL and ABHD6, and cysteine protease cathepsin K. Addnl., we have identified potent and selective dual NAAA-FAAH inhibitors to investigate a potential synergism between two distinct anti-inflammatory mol. pathways, the PEA/PPAR-伪 anti-inflammatory signaling pathway,^1-4 and the cannabinoid receptors CB1 and CB2 pathways which are known for their antiinflammatory and antinociceptive properties.^5-8 Our ligand design strategy followed a traditional structure-activity relationship (SAR) approach and was supported by mol. modeling studies of reported X-ray structures of hNAAA. Several inhibitors were evaluated in stability assays and demonstrated very good plasma stability (t_1/2 > 2 h; human and rodents). The disclosed cyanamides represent promising new pharmacol. tools to investigate the potential role of NAAA inhibitors and dual NAAA-FAAH inhibitors as therapeutic agents for the treatment of inflammation and pain. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Synthetic Route of C9H17NO3).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R鈥昈鈭?. For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Under carefully controlled conditions, simple alcohols can undergo intermolecular dehydration to give ethers. This reaction is effective only with methanol, ethanol, and other simple primary alcohols.Synthetic Route of C9H17NO3

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

A base promoted multigram synthesis of aminoisoxazoles: valuable building blocks for drug discovery and peptidomimetics was written by Chalyk, Bohdan A.;Kandaurova, Inna Y.;Hrebeniuk, Kateryna V.;Manoilenko, Olga V.;Kulik, Irene B.;Iminov, Rustam T.;Kubyshkin, Vladimir;Tverdokhlebov, Anton V.;Ablialimov, Osman K.;Mykhailiuk, Pavel K.. And the article was included in RSC Advances in 2016.Name: 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

A practical multigram metal free synthesis of isoxazole-containing building blocks from com. available amino acids was elaborated. The key reaction was a regioselective [3+2]-cycloaddition of in-situ generated nitrile oxides with alkynes/enamines. The obtained building blocks were used in the preparation of bioactive compounds and peptidomimetics. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Name: 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R鈥昈鈭?. For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Name: 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Strategies toward optimization of the metabolism of a series of serotonin-4 partial agonists: investigation of azetidines as piperidine isosteres was written by Obach, Ronald Scott;LaChapelle, Erik A.;Brodney, Michael A.;Vanase-Frawley, Michelle;Kauffman, Gregory W.;Sawant-Basak, Aarti. And the article was included in Xenobiotica in 2016.Recommanded Product: 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

The first generation 5HT-4 partial agonist, 4-{4-[4-Tetrahydrofuran-3-yloxy-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol, PF-4995274 (TBPT), was metabolized to N-dealkylated (M1) and an unusual, cyclized oxazolidine (M2) metabolites. and demonstrated pharmacol. activity at 5HT receptor subtypes warranting further investigation into their dispositional properties in humans; was a minor component in vitro but was the pre-dominant metabolite identified in human plasma. To shift metabolism away from the piperidine ring of TBPT, a series of heterocyclic replacements were designed, synthesized, and profiled. Groups including azetidines, pyrrolidines, as well as functionalized piperidines were evaluated with the goal of identifying an alternative group that maintained the desired potency, functional activity, and reduced turnover in human hepatocytes. Activities of 4-substituted piperidines or pyrrolidine analogs at the pharmacol. target were not significantly altered, but the same metabolic pathways of N-dealkylation and oxazolidine formation were still observed Altering these to bridged ring systems lowered oxazolidine metabolite formation, but not N-dealkylation. The effort concluded with identification of azetidines as second-generation 5HT₄ partial agonists. These were neither metabolized via N-dealkylation nor converted to cyclized oxazolidine metabolites rather oxidized on the isoxazole ring. The use of azetidine as a replacement for aliphatic aza-heterocyclic rings in drug design to alter drug metabolism and pharmacol. is discussed. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Recommanded Product: 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom for the hydroxyl group. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Recommanded Product: 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities was written by Cioffi, Christopher L.;Muthuraman, Parthasarathy;Raja, Arun;Varadi, Andras;Racz, Boglarka;Petrukhin, Konstantin. And the article was included in Journal of Medicinal Chemistry in 2020.Application In Synthesis of 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analog I possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Application In Synthesis of 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Application In Synthesis of 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Design and synthesis of cyanamides as potent and selective N-acylethanolamine acid amidase inhibitors was written by Malamas, Michael S.;Farah, Shrouq I.;Lamani, Manjunath;Pelekoudas, Dimitrios N.;Perry, Nicholas Thomas;Rajarshi, Girija;Miyabe, Christina Yume;Chandrashekhar, Honrao;West, Jay;Pavlopoulos, Spiro;Makriyannis, Alexandros. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Synthetic Route of C9H17NO3 This article mentions the following:

N-acylethanolamine acid amidase (NAAA) inhibition represents an exciting novel approach to treat inflammation and pain. NAAA is a cysteine amidase which preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA is an endogenous agonist of the nuclear peroxisome proliferator-activated receptor-α (PPAR-α), which is a key regulator of inflammation and pain. Thus, blocking the degradation of PEA with NAAA inhibitors results in augmentation of the PEA/PPAR-α signaling pathway and regulation of inflammatory and pain processes. We have prepared a new series of NAAA inhibitors exploring the azetidine-nitrile (cyanamide) pharmacophore that led to the discovery of highly potent and selective compounds Key analogs demonstrated single-digit nanomolar potency for hNAAA and showed >100-fold selectivity against serine hydrolases FAAH, MGL and ABHD6, and cysteine protease cathepsin K. Addnl., we have identified potent and selective dual NAAA-FAAH inhibitors to investigate a potential synergism between two distinct anti-inflammatory mol. pathways, the PEA/PPAR-α anti-inflammatory signaling pathway,^1-4 and the cannabinoid receptors CB1 and CB2 pathways which are known for their antiinflammatory and antinociceptive properties.^5-8 Our ligand design strategy followed a traditional structure-activity relationship (SAR) approach and was supported by mol. modeling studies of reported X-ray structures of hNAAA. Several inhibitors were evaluated in stability assays and demonstrated very good plasma stability (t_1/2 > 2 h; human and rodents). The disclosed cyanamides represent promising new pharmacol. tools to investigate the potential role of NAAA inhibitors and dual NAAA-FAAH inhibitors as therapeutic agents for the treatment of inflammation and pain. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Synthetic Route of C9H17NO3).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Under carefully controlled conditions, simple alcohols can undergo intermolecular dehydration to give ethers. This reaction is effective only with methanol, ethanol, and other simple primary alcohols.Synthetic Route of C9H17NO3

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

A base promoted multigram synthesis of aminoisoxazoles: valuable building blocks for drug discovery and peptidomimetics was written by Chalyk, Bohdan A.;Kandaurova, Inna Y.;Hrebeniuk, Kateryna V.;Manoilenko, Olga V.;Kulik, Irene B.;Iminov, Rustam T.;Kubyshkin, Vladimir;Tverdokhlebov, Anton V.;Ablialimov, Osman K.;Mykhailiuk, Pavel K.. And the article was included in RSC Advances in 2016.Name: 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

A practical multigram metal free synthesis of isoxazole-containing building blocks from com. available amino acids was elaborated. The key reaction was a regioselective [3+2]-cycloaddition of in-situ generated nitrile oxides with alkynes/enamines. The obtained building blocks were used in the preparation of bioactive compounds and peptidomimetics. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Name: 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Name: 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Strategies toward optimization of the metabolism of a series of serotonin-4 partial agonists: investigation of azetidines as piperidine isosteres was written by Obach, Ronald Scott;LaChapelle, Erik A.;Brodney, Michael A.;Vanase-Frawley, Michelle;Kauffman, Gregory W.;Sawant-Basak, Aarti. And the article was included in Xenobiotica in 2016.Recommanded Product: 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

The first generation 5HT-4 partial agonist, 4-{4-[4-Tetrahydrofuran-3-yloxy-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol, PF-4995274 (TBPT), was metabolized to N-dealkylated (M1) and an unusual, cyclized oxazolidine (M2) metabolites. and demonstrated pharmacol. activity at 5HT receptor subtypes warranting further investigation into their dispositional properties in humans; was a minor component in vitro but was the pre-dominant metabolite identified in human plasma. To shift metabolism away from the piperidine ring of TBPT, a series of heterocyclic replacements were designed, synthesized, and profiled. Groups including azetidines, pyrrolidines, as well as functionalized piperidines were evaluated with the goal of identifying an alternative group that maintained the desired potency, functional activity, and reduced turnover in human hepatocytes. Activities of 4-substituted piperidines or pyrrolidine analogs at the pharmacol. target were not significantly altered, but the same metabolic pathways of N-dealkylation and oxazolidine formation were still observed Altering these to bridged ring systems lowered oxazolidine metabolite formation, but not N-dealkylation. The effort concluded with identification of azetidines as second-generation 5HT₄ partial agonists. These were neither metabolized via N-dealkylation nor converted to cyclized oxazolidine metabolites rather oxidized on the isoxazole ring. The use of azetidine as a replacement for aliphatic aza-heterocyclic rings in drug design to alter drug metabolism and pharmacol. is discussed. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Recommanded Product: 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom for the hydroxyl group. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Recommanded Product: 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities was written by Cioffi, Christopher L.;Muthuraman, Parthasarathy;Raja, Arun;Varadi, Andras;Racz, Boglarka;Petrukhin, Konstantin. And the article was included in Journal of Medicinal Chemistry in 2020.Application In Synthesis of 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analog I possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Application In Synthesis of 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Application In Synthesis of 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Development of a Late-Stage Diversification Strategy for the 4- and 5-Positions of 4,5,6-Trisubstituted Indazoles was written by Barber, Joyann S.;Burtea, Alexander;Collins, Michael R.;Tran-Dube, Michelle;Patman, Ryan L.;Scales, Stephanie;Smith, Graham;Spangler, Jillian E.;Wang, Fen;Wang, Wei;Yang, Shouliang;Zhu, JinJiang;Montgomery, T. Patrick. And the article was included in Organic Letters in 2020.SDS of cas: 142253-56-3 This article mentions the following:

Indazoles represent a privileged motif in drug discovery. However, the formation of highly substituted indazoles can require the execution of lengthy synthetic routes with minimal opportunities to introduce diversity. In this report, we disclose the development of a late-stage diversification strategy for the 4- and 5-positions of 4,5,6-trisubstituted indazoles. A regioselective C-H functionalization and subsequent nucleophilic aromatic substitution provide two sequential points of diversification. The synthetic sequence delivers rapid access to an array of 4,5,6-trisubstituted indazoles in only four steps from readily available starting materials. Materials processing safety is required when using DMSO in nucleophilic substitution reactions under basic conditions due to exothermic decomposition In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3SDS of cas: 142253-56-3).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Similar to water, an alcohol can be pictured as having an sp3 hybridized tetrahedral oxygen atom with nonbonding pairs of electrons occupying two of the four sp3 hybrid orbitals. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.SDS of cas: 142253-56-3

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

O₂-Assisted Four-Component Reaction of Vinyl Magnesium Bromide with Chiral N-tert-Butanesulfinyl Imines To Form syn-1,3-Amino Alcohols was written by Wang, Runping;Luo, Jingfan;Zheng, Chunmei;Zhang, Hongyun;Gao, Lu;Song, Zhenlei. And the article was included in Angewandte Chemie, International Edition in 2021.Name: 1-Boc-Azetidine-3-yl-methanol This article mentions the following:

An O₂-assisted, four-component reaction has been developed to synthesize a wide range of syn-1,3-amino alcs. in one step. The reaction proceeds by oxygenation of vinyl magnesium bromide (component-I) with O₂ (component-II) to give a magnesium enolate of acetaldehyde, which undergoes addition to a chiral N-tert-butanesulfinyl imine (component-III) followed by a sequential addition with excess vinyl magnesium bromide (component-IV). The approach allows diastereoselective synthesis of anti/syn- and syn/syn-3-amino-1,5-diols in good yields with high diastereoselectivity. The method was illustrated in an efficient, four-step synthesis of piperidine alkaloid (-)-2′-epi-ethylnorlobelol. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Name: 1-Boc-Azetidine-3-yl-methanol).

1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are about as acidic as water, and most other alcohols are somewhat less acidic. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Name: 1-Boc-Azetidine-3-yl-methanol

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts