Category: 45434-02-4

Gvozdev, V. D.; Shavrin, K. N.; Nefedov, O. M. published the artcile< A new synthesis of bicyclic N,O- and N,S-enaminals by the anionic cyclization of alk-4-ynals with amino alcohols and amino thiols>, Computed Properties of 45434-02-4, the main research area is arylmethylene pyrrolooxazine pyrrolooxazole pyrrolothiazole stereoselective preparation; bicyclic enaminal stereoselective preparation; base mediated cyclocondensation amino alc thiol alkynal.

4-Alkynals RCCCH2CR1R2CHO [R = Ph, 2-thienyl, 4-F3CC6H4; R1 = R2 = H, Me; R1R2 = (CH2)5] underwent base-mediated cyclocondensations with amino alcs. H2NCH2XCH2OH (X = bond, Me2C, 1,1-cyclopropanediyl) or 2-aminoethanethiol hydrochloride with KOH in DMSO to yield arylmethylene pyrrolooxazines, pyrrolooxazoles, and pyrrolothiazoles I [R = Ph, 2-thienyl, 4-F3CC6H4; R1 = R2 = H, Me; R1R2 = (CH2)5; X = bond, Me2C, 1,1-cyclopropanediyl; Y = O, S] (bicyclic enaminals) stereoselectively as the (E)-isomers in 30-82% yields.

Russian Chemical Bulletin published new progress about Alkynals Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (aryl). 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Computed Properties of 45434-02-4.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Kai, Hiroyuki; Morioka, Yasuhide; Tomida, Minoru; Takahashi, Tadashi; Hattori, Maki; Hanasaki, Kohji; Koike, Katsumi; Chiba, Hiroki; Shinohara, Shunji; Kanemasa, Toshiyuki; Iwamoto, Yuka; Takahashi, Kohji; Yamaguchi, Yoshitaka; Baba, Takahiko; Yoshikawa, Takayoshi; Takenaka, Hideyuki published the artcile< 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 2: Orally bioavailable compounds>, Recommanded Product: (1-(Aminomethyl)cyclopropyl)methanol, the main research area is cannabinoid receptor analgesia oral bioavailability thiazine derivative SAR.

Structure-activity relationships and efforts to optimize the pharmacokinetic profile of a class of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among the compounds examined, compound 14 showed potent affinity and high selectivity for CB2, and compound 23 showed potent affinities against CB1 and CB2. These compounds displayed oral bioavailability.

Bioorganic & Medicinal Chemistry Letters published new progress about Analgesics. 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Recommanded Product: (1-(Aminomethyl)cyclopropyl)methanol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

de Beer, Roseri J. A. C.; Boegels, Berry; Schaftenaar, Gijs; Zarzycka, Barbara; Quaedflieg, Peter J. L. M.; van Delft, Floris L.; Nabuurs, Sander B.; Rutjes, Floris P. J. T. published the artcile< Enzyme-Specific Activation versus Leaving Group Ability>, COA of Formula: C5H11NO, the main research area is trypsin catalysis dipeptide synthesis substrate preparation leaving group.

Enzyme-specific activation and the substrate mimetics strategy are effective ways to circumvent the limited substrate recognition often encountered in protease-catalyzed peptide synthesis. A key structural element in both approaches is the guanidinophenyl (OGp) ester, which enables important interactions for affinity and recognition by the enzyme; at least, this is usually the explanation given for its successful application. In this study we show that leaving group ability is of equal or even greater importance. To this end we used both exptl. and computational methods to examine: (1) synthesis of close analogs of OGp, and their evaluation in a dipeptide synthesis assay with trypsin, (2) mol. docking studies to provide insights into the binding mode, and (3) ab initio calculations to evaluate their electronic properties.

ChemBioChem published new progress about Dipeptides Role: BPN (Biosynthetic Preparation), BIOL (Biological Study), PREP (Preparation) (synthesis). 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, COA of Formula: C5H11NO.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Cowley, Phillip M.; Baker, James; Buchanan, Kirsteen I.; Carlyle, Ian; Clark, John K.; Clarkson, Thomas R.; Deehan, Maureen; Edwards, Darren; Kiyoi, Yasuko; Martin, Iain; Osbourn, Dawn; Walker, Glenn; Ward, Nick; Wishart, Grant published the artcile< Pharmacokinetic optimisation of novel indole-2-carboxamide cannabinoid CB1 antagonists>, Application In Synthesis of 45434-02-4, the main research area is cannabinoid CB antagonist indolecarboxamide preparation pharmacokinetics SAR.

The pharmacokinetic based optimization of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB1 receptor is disclosed. Compound 24 (I) was found to be a highly potent and selective cannabinoid CB1 antagonist with high predicted human oral bioavailability.

Bioorganic & Medicinal Chemistry Letters published new progress about Cannabinoid receptor 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Application In Synthesis of 45434-02-4.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Quevedo, Camilo E.; Bataille, Carole J. R.; Byrne, Simon; Durbin, Matthew; Elkins, Jon; Guillermo, Abigail; Jones, Alan M.; Knapp, Stefan; Nadali, Anna; Walker, Roderick G.; Wilkinson, Isabel V. L.; Wynne, Graham M.; Davies, Stephen G.; Russell, Angela J. published the artcile< Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family>, Computed Properties of 45434-02-4, the main research area is aminothiazolone drug discovery synthesis anticancer agent PIM kinase inhibitor.

We have previously reported the discovery of a series of rhodanine-based inhibitors of the PIM family of serine/threonine kinases. Here we described the optimization of those compounds to improve their physicochem. and ADME properties as well as reducing their off-targets activities against other kinases. Through mol. modeling and systematic structure activity relationship (SAR) studies, advanced mols. with high inhibitory potency, reduced off-target activity and minimal efflux were identified as new pan-PIM inhibitors. One example of an early lead, I, was found to inhibit PIMs with nanomolar potency (15 nM for PIM1), inhibit proliferation of two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, and to reduce intracellular phosphorylation of a PIM substrate in a concentration dependent manner.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Computed Properties of 45434-02-4.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Quevedo, Camilo E.; Bataille, Carole J. R.; Byrne, Simon; Durbin, Matthew; Elkins, Jon; Guillermo, Abigail; Jones, Alan M.; Knapp, Stefan; Nadali, Anna; Walker, Roderick G.; Wilkinson, Isabel V. L.; Wynne, Graham M.; Davies, Stephen G.; Russell, Angela J. published the artcile< Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family>, Computed Properties of 45434-02-4, the main research area is aminothiazolone drug discovery synthesis anticancer agent PIM kinase inhibitor.

We have previously reported the discovery of a series of rhodanine-based inhibitors of the PIM family of serine/threonine kinases. Here we described the optimization of those compounds to improve their physicochem. and ADME properties as well as reducing their off-targets activities against other kinases. Through mol. modeling and systematic structure activity relationship (SAR) studies, advanced mols. with high inhibitory potency, reduced off-target activity and minimal efflux were identified as new pan-PIM inhibitors. One example of an early lead, I, was found to inhibit PIMs with nanomolar potency (15 nM for PIM1), inhibit proliferation of two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, and to reduce intracellular phosphorylation of a PIM substrate in a concentration dependent manner.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Computed Properties of 45434-02-4.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Waldschmidt, Helen V.; Bouley, Renee; Kirchhoff, Paul D.; Lee, Pil; Tesmer, John J. G.; Larsen, Scott D. published the artcile< Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors>, Safety of (1-(Aminomethyl)cyclopropyl)methanol, the main research area is GPCR kinase inhibitor preparation structure; Crystallography; Docking; GPCRs; GRKs; Kinases.

G protein-coupled receptor (GPCR) kinases (GRKs) regulate the desensitization and internalization of GPCRs. Two of these, GRK2 and GRK5, are upregulated in heart failure and are promising targets for heart failure treatment. Although there have been several reports of potent and selective inhibitors of GRK2 there are few for GRK5. Herein, we describe a ligand docking approach utilizing the crystal structures of the GRK2-Gβγ·GSK180736A and GRK5·CCG215022 complexes to search for amide substituents predicted to confer GRK2 and/or GRK5 potency and selectivity. From this campaign, we successfully generated two new potent GRK5 inhibitors, although neither exhibited selectivity over GRK2.

Bioorganic & Medicinal Chemistry Letters published new progress about Crystal structure. 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Safety of (1-(Aminomethyl)cyclopropyl)methanol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Buchholz, Mirko; Heiser, Ulrich; Schilling, Stephan; Niestroj, Andre J.; Zunkel, Katrin; Demuth, Hans-Ulrich published the artcile< The first potent inhibitors for human glutaminyl cyclase: synthesis and structure-activity relationship>, SDS of cas: 45434-02-4, the main research area is thiourea imidazolylpropyl human glutaminyl cyclase inhibitor; Alzheimer disease treatment imidazolylpropylthiourea preparation; human glutaminyl cyclase inhibitor imidazolylpropylthiourea library preparation.

The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the mols., which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, SDS of cas: 45434-02-4.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Chan, Kelvin S. L.; Fu, Hai-Yan; Yu, Jin-Quan published the artcile< Palladium(II)-Catalyzed Highly Enantioselective C-H Arylation of Cyclopropylmethylamines>, Recommanded Product: (1-(Aminomethyl)cyclopropyl)methanol, the main research area is cyclopropylmethylamine CH activation arylation palladium catalyst enantioselectivity diastereoselectivity.

C-H arylation via a Pd(II)/Pd(IV) catalytic cycle has been one of the most extensively studied C-H activation reactions since the 1990s. Despite the rapid development of this reaction in the past two decades, an enantioselective version has not been reported to date. Herein, we report a Pd(II)-catalyzed highly enantioselective (up to 99.5% ee) arylation of cyclopropyl C-H bonds with aryl iodides using mono-N-protected amino acid (MPAA) ligands, providing a new route for the preparation of chiral cis-aryl-cyclopropylmethylamines, e.g., I [R1 = H, Me, CH2Ph, Ph, C6H3F2-2,6, CH2OSiMe2CMe3, CO2Me]. The enantiocontrol is also shown to override the diastereoselectivity of chiral substrates.

Journal of the American Chemical Society published new progress about Amino acids Role: CAT (Catalyst Use), USES (Uses) (mono-N-protected, chiral ligands for arylation catalysts). 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Recommanded Product: (1-(Aminomethyl)cyclopropyl)methanol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Waldschmidt, Helen V.; Bouley, Renee; Kirchhoff, Paul D.; Lee, Pil; Tesmer, John J. G.; Larsen, Scott D. published the artcile< Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors>, Safety of (1-(Aminomethyl)cyclopropyl)methanol, the main research area is GPCR kinase inhibitor preparation structure; Crystallography; Docking; GPCRs; GRKs; Kinases.

G protein-coupled receptor (GPCR) kinases (GRKs) regulate the desensitization and internalization of GPCRs. Two of these, GRK2 and GRK5, are upregulated in heart failure and are promising targets for heart failure treatment. Although there have been several reports of potent and selective inhibitors of GRK2 there are few for GRK5. Herein, we describe a ligand docking approach utilizing the crystal structures of the GRK2-Gβγ·GSK180736A and GRK5·CCG215022 complexes to search for amide substituents predicted to confer GRK2 and/or GRK5 potency and selectivity. From this campaign, we successfully generated two new potent GRK5 inhibitors, although neither exhibited selectivity over GRK2.

Bioorganic & Medicinal Chemistry Letters published new progress about Crystal structure. 45434-02-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C5H11NO, Safety of (1-(Aminomethyl)cyclopropyl)methanol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts