6346/9/4 Archives - Page 2 of 2 - Alcohols-buliding-blocks

Perry, Matthew W. D.’s team published research in Journal of Medicinal Chemistry in 60 | CAS: 6346-09-4

Journal of Medicinal Chemistry published new progress about 6346-09-4. 6346-09-4 belongs to alcohols-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Ether, name is 4,4-Diethoxybutan-1-amine, and the molecular formula is C8H19NO2, Category: alcohols-buliding-blocks.

Perry, Matthew W. D. published the artcileDesign and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration, Category: alcohols-buliding-blocks, the publication is Journal of Medicinal Chemistry (2017), 60(12), 5057-5071, database is CAplus and MEDLINE.

PI3Kδ is a lipid kinase that is believed to be important in the migration and activation of cells of the immune system. Inhibition is hypothesized to provide a powerful yet selective immunomodulatory effect that may be beneficial for the treatment of conditions such as asthma or rheumatoid arthritis. In this work, identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation is described. The initially identified compound I had good potency and isoform selectivity but was not suitable for inhalation. Addition of basic substituents to a region of the mol. pointing to solvent was tolerated (enzyme inhibition pIC₅₀ > 9), and by careful manipulation of the pK_a and lipophilicity, the authors were able to discover compounds II (R = Me or i-Bu) with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Nicholson, William I.’s team published research in Angewandte Chemie, International Edition in 60 | CAS: 6346-09-4

Angewandte Chemie, International Edition published new progress about 6346-09-4. 6346-09-4 belongs to alcohols-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Ether, name is 4,4-Diethoxybutan-1-amine, and the molecular formula is C8H19NO2, Quality Control of 6346-09-4.

Nicholson, William I. published the artcileDirect Amidation of Esters by Ball Milling, Quality Control of 6346-09-4, the publication is Angewandte Chemie, International Edition (2021), 60(40), 21868-21874, database is CAplus and MEDLINE.

The direct mechanochem. amidation of esters RC(O)OR¹ (R = Cy, Ph, pyridin-2-yl, etc.; R¹ = Me, Et) by ball milling is described. The operationally simple procedure requires an ester, amines R²NHR³ (R² = H, Me, Et; R³ = i-Pr, Ph, 2,4,6-trimethylphenyl, etc.; R²R³ = -(CH₂)₂O(CH₂)₂-, -(CH₂)₅-, -(CH₂)₆-, etc.) and 1,2,3,4-tetrahydroquinoline, and substoichiometric KOtBu, and was used to prepare a large and diverse library of 78 amide structures RC(O)N(R²)R³ and (3,4-dihydroquinolin-1(2H)-yl)(phenyl)methanone with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochem. protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochems. as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Rai, Roopa’s team published research in Bioorganic & Medicinal Chemistry Letters in 26 | CAS: 6346-09-4

Bioorganic & Medicinal Chemistry Letters published new progress about 6346-09-4. 6346-09-4 belongs to alcohols-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Ether, name is 4,4-Diethoxybutan-1-amine, and the molecular formula is C8H19NO2, Application of 4,4-Diethoxybutan-1-amine.

Rai, Roopa published the artcileTemozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide, Application of 4,4-Diethoxybutan-1-amine, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(20), 5103-5109, database is CAplus and MEDLINE.

Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O⁶-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain:plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Preston, Alex’s team published research in ACS Medicinal Chemistry Letters in 11 | CAS: 6346-09-4

ACS Medicinal Chemistry Letters published new progress about 6346-09-4. 6346-09-4 belongs to alcohols-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Ether, name is 4,4-Diethoxybutan-1-amine, and the molecular formula is C8H19NO2, Synthetic Route of 6346-09-4.

Preston, Alex published the artcileGSK973 Is an Inhibitor of the Second Bromodomains (BD2s) of the Bromodomain and Extra-Terminal (BET) Family, Synthetic Route of 6346-09-4, the publication is ACS Medicinal Chemistry Letters (2020), 11(8), 1581-1587, database is CAplus and MEDLINE.

Pan-BET inhibitors have shown profound efficacy in a number of in vivo preclin. models and have entered the clinic in oncol. trials where adverse events have been reported. These inhibitors interact equipotently with the eight bromodomains of the BET family of proteins. To better understand the contribution of each domain to their efficacy and to improve from their safety profile, selective inhibitors are required. This Letter discloses the profile of GSK973, a highly selective inhibitor of the second bromodomains of the BET proteins that has undergone extensive preclin. in vitro and in vivo characterization.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Lucas, Simon C. C.’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 6346-09-4

Lucas, Simon C. C. published the artcileOptimization of a Series of 2,3-Dihydrobenzofurans as Highly Potent, Second Bromodomain (BD2)-Selective, Bromo and Extra-Terminal Domain (BET) Inhibitors, Category: alcohols-buliding-blocks, the publication is Journal of Medicinal Chemistry (2021), 64(15), 10711-10741, database is CAplus and MEDLINE.

Herein, a series of 2,3-dihydrobenzofurans have been developed as highly potent bromo and extra-terminal domain (BET) inhibitors with 1000-fold selectivity for the second bromodomain over the first bromodomain. Investment in the development of two orthogonal synthetic routes delivered inhibitors that were potent and selective but had raised in vitro clearance and suboptimal solubility Insertion of a quaternary center into the 2,3-dihydrobenzofuran core blocked a key site of metabolism and improved the solubility This led to the development of inhibitor I (GSK852): a potent, 1000-fold-selective, highly soluble compound with good in vivo rat and dog pharmacokinetics.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Harrison, Lee A.’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 6346-09-4

Harrison, Lee A. published the artcileIdentification of a Series of N-Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins, HPLC of Formula: 6346-09-4, the publication is Journal of Medicinal Chemistry (2021), 64(15), 10742-10771, database is CAplus and MEDLINE.

Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicol. aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving >1000-fold selectivity for BD2 over BD1, while retaining favorable phys. chem. properties, compound 36 was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with >1 mg/mL solubility in FaSSIF media. 36 Represents a valuable new in vivo ready mol. for the exploration of the BD2 phenotype.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Shi, Qiu’s team published research in Nature Communications in 2022 | CAS: 6346-09-4

4,4-Diethoxybutan-1-amine(cas: 6346-09-4) belongs to anime. Milder oxidation, using reagents such as NaOCl, can remove four hydrogen atoms from primary amines of the type RCH2NH2 to form nitriles (RâCâ¡N), and oxidation with reagents such as MnO2 can remove two hydrogen atoms from secondary amines (R2CHâNHRâ? to form imines (R2C=NRâ?. Tertiary amines can be oxidized to enamines (R2C=CHNR2) by a variety of reagents.Quality Control of 4,4-Diethoxybutan-1-amine

Shi, Qiu; Liao, Zhehui; Liu, Zhili; Wen, Jiajia; Li, Chenguang; He, Jiamin; Deng, Jiazhen; Cen, Shan; Cao, Tongxiang; Zhou, Jinming; Zhu, Shifa published their research in Nature Communications on December 31 ,2022. The article was titled ãDivergent synthesis of benzazepines and bridged polycycloalkanones via dearomative rearrangementã?Quality Control of 4,4-Diethoxybutan-1-amine The article contains the following contents:

Here, a catalyst-free dearomative rearrangement of o-nitrophenyl alkynes I (R = Ts, Ms; R1 = H, Me, Cl, methoxycarbonyl, etc.; R2 = H, Et, Ph; R3 = H, Cl, F, OMe, methoxycarbonyl; R1R3 = -O-CH2-O-; R4 = H, F; X = C, N; n = 2,3) and II (R = Ts, Ms, Boc; R5 = H, Me; R1 R5 = -CH=CH-CH=CH-) is successfully established by leveraging the remote oxygen transposition and a weak N-O bond acceleration. This reaction features high atom-, step- and redox-economy, which provides a divergent entry to a series of biol. important benzazepines III and bridged polycycloalkanones IV. The reaction is proposed to proceed through a tandem oxygen transfer cyclization/(3 + 2) cycloaddition/(homo-)hetero-Claisen rearrangement reaction. The resulting polycyclic system is richly decorated with transformable functionalities, such as carbonyl, imine and diene, which enables diversity-oriented synthesis of alkaloid-like polycyclic frameworks e.g., V. The experimental part of the paper was very detailed, including the reaction process of 4,4-Diethoxybutan-1-amine(cas: 6346-09-4Quality Control of 4,4-Diethoxybutan-1-amine)

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Smolobochkin, Andrey’s team published research in Molecules in 2019 | CAS: 6346-09-4

4,4-Diethoxybutan-1-amine(cas: 6346-09-4) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).SDS of cas: 6346-09-4

ãSynthesis of novel 2-(het)arylpyrrolidine derivatives and evaluation of their anticancer and anti-biofilm activityã?was published in Molecules in 2019. These research results belong to Smolobochkin, Andrey; Gazizov, Almir; Sazykina, Marina; Akylbekov, Nurgali; Chugunova, Elena; Sazykin, Ivan; Gildebrant, Anastasiya; Voronina, Julia; Burilov, Alexander; Karchava, Shorena; Klimova, Maria; Voloshina, Alexandra; Sapunova, Anastasia; Klimanova, Elena; Sashenkova, Tatyana; Allayarova, Ugulzhan; Balakina, Anastasiya; Mishchenko, Denis. SDS of cas: 6346-09-4 The article mentions the following:

A library of novel 2-(het)arylpyrrolidine-1-carboxamides I [R = H, n-hexyl, 4-MeOC6H4, etc.; Ar = 4-hydroxy-6-methyl-pyran-2-one-3-yl, 4-hydroxycoumarin-3-yl, 1,3-benzodioxol-5-ol-6-yl, 6-chloro-4-((4-yl-3-hydroxyphenyl)amino)-5-nitrobenzo[c][1,2,5]oxadiazole 1-oxide] was obtained via a modular approach based on the intramol. cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds toward M-Hela tumor cell lines was twice that of reference drug tamoxifen, whereas cytotoxicity toward normal Chang liver cell did not exceed tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Addnl., some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds were promising candidates for further development both as anti-cancer and anti-bacterial agents. In the experiment, the researchers used 4,4-Diethoxybutan-1-amine(cas: 6346-09-4SDS of cas: 6346-09-4)

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Sharma, Vishal R.’s team published research in RSC Advances in 2020 | CAS: 6346-09-4

4,4-Diethoxybutan-1-amine(cas: 6346-09-4) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Name: 4,4-Diethoxybutan-1-amine

In 2020,RSC Advances included an article by Sharma, Vishal R.; Mehmood, Arshad; Janesko, Benjamin G.; Simanek, Eric E.. Name: 4,4-Diethoxybutan-1-amine. The article was titled ãEfficient syntheses of macrocycles ranging from 22-28 atoms through spontaneous dimerization to yield bis-hydrazonesã? The information in the text is summarized as follows:

Acid treatment of a triazine displaying both a tethered acetal and BOC-protected hydrazine group leads to spontaneous condensation to yield macrocyclic dimers I (n = 1, 2; m = 1, 2, 3) in excellent yields and purity. By varying the length of the tether-the condensation product of an amino acid and amino acetal-rings comprising 22-28 atoms can be accessed. Glycine and β-alanine were used for the amino acid. The amino acetal comprised 2, 3 or 4 carbon atoms in the backbone. High-performance liquid chromatog. (HPLC) was employed to assess purity as well as to fingerprint the six homodimeric products. By combining the protected monomers and subjecting them to acid, mixtures of homodimers and heterodimers are obtained. When all six protected monomers are combined, at least 14 of the 21 theor. dimeric products are observed by HPLC. Single crystal X-ray diffraction and solution NMR studies reveal the diversity of shapes available to these mols. In the experimental materials used by the author, we found 4,4-Diethoxybutan-1-amine(cas: 6346-09-4Name: 4,4-Diethoxybutan-1-amine)

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts