Month: November 2021

An article Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors WOS:000526405300016 published article about SPHINGOLIPID METABOLISM; CELLULAR-RESPONSES; GAUCHER-DISEASE; SPHINGOSINE-1-PHOSPHATE; POTENT; GLUCOSYLSPHINGOSINE; GLUCOSYLCERAMIDE; ACCUMULATION; PURIFICATION; DEFICIENCY in [Lansbury, Peter; Liu, Min; Skerlj, Renato] Lysosomal Therapeut Inc, Cambridge, MA 02139 USA; [Di Martino, Simona; Tardia, Piero; Cilibrasi, Vincenzo; Caputo, Samantha; Mazzonna, Marco; Realini, Natalia; Margaroli, Natasha; Migliore, Marco; Pizzirani, Daniela; Scarpelli, Rita] Fdn Ist Italiano Tecnol, Drug Discovery & Dev D3 Validat, I-16163 Genoa, Italy; [Russo, Debora; Penna, Ilaria] Fdn Ist Italiano Tecnol, D3 Pharma Chem, I-16163 Genoa, Italy; [Ottonello, Giuliana; Bertozzi, Sine Mandrup; Armirotti, Andrea] Fdn Ist Italiano Tecnol, Analyt Chem Lab, I-16163 Genoa, Italy; [Duc Nguyen; Bongarzone, Ernesto R.] Univ Illinois, Coll Med, Dept Anat & Cell Biol, Myelin Regenerat Grp, Chicago, IL 60612 USA; [Sun, Ying] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Dept Pediat,Div Human Genet, Cincinnati, OH 45229 USA in 2020.0, Cited 58.0. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3. COA of Formula: C8H7NO

Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher’s and Krabbe’s diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.

About Indolin-2-one, If you have any questions, you can contact Di Martino, S; Tardia, P; Cilibrasi, V; Caputo, S; Mazzonna, M; Russo, D; Penna, I; Realini, N; Margaroli, N; Migliore, M; Pizzirani, D; Ottonello, G; Bertozzi, SM; Armirotti, A; Nguyen, D; Sun, Y; Bongarzone, ER; Lansbury, P; Liu, M; Skerlj, R; Scarpelli, R or concate me.. COA of Formula: C8H7NO

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

Recommanded Product: Indolin-2-one. In 2020 ACS CATAL published article about H BOND ACTIVATION; CATALYZED METHYLATION; BORYLATION; REACTIVITY; COMPLEXES; METHANOL; FUNCTIONALIZATION; GENERATION; PYRROLES; AGONIST in [Basak, Shyam; Melen, Rebecca L.; Morrill, Louis C.] Cardiff Univ, Sch Chem, Cardiff Catalysis Inst, Cardiff CF10 3AT, Wales; [Alvarez-Montoya, Ana; Winfrey, Laura; Pulis, Alexander P.] Univ Leicester, Sch Chem, Leicester LE1 7RH, Leics, England in 2020, Cited 60. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3.

The direct C3 alkylation of indoles and oxindoles is a challenging transformation, and only a few direct methods exist. Utilizing the underexplored ability of triaryl boranes to mediate the heterolytic cleavage of alpha-nitrogen C-H bonds in amines, we have developed a catalytic approach for the direct C3 alkylation of a wide range of indoles and oxindoles using amine-based alkylating agents. We also employed this borane-catalyzed strategy in an alkylation-ring opening cascade.

Recommanded Product: Indolin-2-one. About Indolin-2-one, If you have any questions, you can contact Basak, S; Alvarez-Montoya, A; Winfrey, L; Melen, RL; Morrill, LC; Pulis, AP or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

In 2020.0 ORG LETT published article about DIRECT ARYLATION; BITHIOPHENE COPOLYMERS; CONJUGATED POLYMER; HIGH-PERFORMANCE; MATERIALS DESIGN; CONVERSION in [Nitti, Andrea; Osw, Peshawa; Calcagno, Giuseppe; Pasini, Dario] Univ Pavia, Dept Chem, I-27100 Pavia, Italy; [Nitti, Andrea; Pasini, Dario] Univ Pavia, INSTM Res Unit, I-27100 Pavia, Italy; [Osw, Peshawa] Salahaddin Univ, Coll Sci, Dept Chem, Erbil 44001, Kurdistan, Iraq; [Botta, Chiara] CNR, Ist Studio Macromol ISMAC, I-20133 Milan, Italy; [Etkind, Samuel I.; Swager, Timothy M.] MIT, Dept Chem, Cambridge, MA 02139 USA; [Bianchi, Gabriele; Po, Riccardo] Ist Donegani SpA, Res Ctr Renewable Energies & Environm, I-28100 Novara, Italy in 2020.0, Cited 43.0. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3. Quality Control of Indolin-2-one

We demonstrate the broad applicability of the annulation protocol combining, in one pot, a direct arylation and cross aldol condensation for the straightforward synthesis at gram-scale of pi-extended thiophene-based scaffolds. The regiospecific direct arylation drives the subsequent cross-aldol condensation proceed under the same basic conditions, and the overall protocol has broad applicability in the synthesis of extended aromatics wherein the thiophene ring is annulated with furans, pyridines, indoles, benzothiophenes, and benzofurans. These scaffolds can be further elaborated into pi-extended, highly fluorescent oligomers with a central deficient benzothiadiazole unit with up to nine aromatic rings through coupling reactions.

Quality Control of Indolin-2-one. About Indolin-2-one, If you have any questions, you can contact Nitti, A; Osw, P; Calcagno, G; Botta, C; Etkind, SI; Bianchi, G; Po, R; Swager, TM; Pasini, D or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

Category: indolines-derivatives. I found the field of Chemistry; Engineering very interesting. Saw the article Selective C3-alkenylation of oxindole with aldehydes using heterogeneous CeO2 catalyst published in 2020.0, Reprint Addresses Siddiki, SMAH; Shimizu, K (corresponding author), Hokkaido Univ, Inst Catalysis, N-21,W-10, Sapporo, Hokkaido 0010021, Japan.; Shimizu, K (corresponding author), Kyoto Univ, Elements Strategy Initiat Catalysts & Batteries, Kyoto 6158520, Japan.. The CAS is 59-48-3. Through research, I have a further understanding and discovery of Indolin-2-one.

We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This. catalytic method is generally applicable to different aromatic and aliphatic aldehydes, giving 3-alkyledene-oxindoles in high yields (87%-99%) and high stereoselectivities (79%-93% to E-isomers). This is the first example of the catalytic synthesis of 3-alkenyl-oxindoles from oxindole and various aliphatic aldehydes. The Lewis acid-base interaction between Lewis acid sites on CeO2 and benzaldehyde was studied by in situ IR. The structure-activity relationship study using CeO2 catalysts with different sizes suggests that defect-free CeO2 surface is the active site for this reaction. (C) 2020, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Category: indolines-derivatives. About Indolin-2-one, If you have any questions, you can contact Rashed, MN; Touchy, AS; Chaudhari, C; Jeon, J; Siddiki, SMAH; Toyao, T; Shimizu, K or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

Quality Control of Indolin-2-one. Recently I am researching about SPHINGOLIPID METABOLISM; CELLULAR-RESPONSES; GAUCHER-DISEASE; SPHINGOSINE-1-PHOSPHATE; POTENT; GLUCOSYLSPHINGOSINE; GLUCOSYLCERAMIDE; ACCUMULATION; PURIFICATION; DEFICIENCY, Saw an article supported by the . Published in AMER CHEMICAL SOC in WASHINGTON ,Authors: Di Martino, S; Tardia, P; Cilibrasi, V; Caputo, S; Mazzonna, M; Russo, D; Penna, I; Realini, N; Margaroli, N; Migliore, M; Pizzirani, D; Ottonello, G; Bertozzi, SM; Armirotti, A; Nguyen, D; Sun, Y; Bongarzone, ER; Lansbury, P; Liu, M; Skerlj, R; Scarpelli, R. The CAS is 59-48-3. Through research, I have a further understanding and discovery of Indolin-2-one

Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher’s and Krabbe’s diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.

Quality Control of Indolin-2-one. About Indolin-2-one, If you have any questions, you can contact Di Martino, S; Tardia, P; Cilibrasi, V; Caputo, S; Mazzonna, M; Russo, D; Penna, I; Realini, N; Margaroli, N; Migliore, M; Pizzirani, D; Ottonello, G; Bertozzi, SM; Armirotti, A; Nguyen, D; Sun, Y; Bongarzone, ER; Lansbury, P; Liu, M; Skerlj, R; Scarpelli, R or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

Category: indolines-derivatives. In 2019 J MED CHEM published article about PLASMODIUM-FALCIPARUM M1; ACUTE NONLYMPHOCYTIC LEUKEMIA; MOLECULAR-DYNAMICS; CLINICAL-SIGNIFICANCE; EFFICIENT GENERATION; STRUCTURAL BASIS; AM1-BCC MODEL; CD13; BESTATIN; CANCER in [Lee, Jisook; Vinh, Natalie B.; Schembri, Luke S.; Gazdik, Michelle; Scammells, Peter J.] Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, Parkville Campus, Parkville, Vic 3052, Australia; [Charman, Susan A.] Monash Univ, Monash Inst Pharmaceut Sci, Ctr Drug Candidate Optimisat, Parkville Campus, Parkville, Vic 3052, Australia; [Drinkwater, Nyssa; Yang, Wei; Sivaraman, Komagal Kannan; McGowan, Sheena] Monash Univ, Infect & Immun Program, Biomed Discovery Inst, Clayton Campus, Clayton, Vic 3800, Australia; [Drinkwater, Nyssa; Yang, Wei; Sivaraman, Komagal Kannan; McGowan, Sheena] Monash Univ, Dept Microbiol, Clayton Campus, Clayton, Vic 3800, Australia; [Grin, Peter M.; Butler, Georgina S.; Overall, Christopher M.] Univ British Columbia, Life Sci Inst, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada; [Butler, Georgina S.; Overall, Christopher M.] Univ British Columbia, Life Sci Inst, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada; [Grin, Peter M.; Butler, Georgina S.; Overall, Christopher M.] Univ British Columbia, Life Sci Inst, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada in 2019, Cited 80. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3.

Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite Plasmodium falciparum M1 aminopeptidase (PfA-M1). Herein, we describe the rationale that underpins the repurposing of PfA-MI inhibitors as novel APN inhibitors. A series of novel hydroxamic acid analogues were developed using a structure-based design approach and evaluated their inhibition activities against APN. N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yOethyl)-4(methylsulfonamido)benzamide (6ad) proved to be an extremely potent inhibitor of APN activity in vitro, selective against other zinc-dependent enzymes such as matrix metalloproteases, and possessed limited cytotoxicity against Ad293 cells and favorable physicochemical and metabolic stability properties. The combined results indicate that compound 6ad may be a useful lead for the development of anticancer agents.

Category: indolines-derivatives. About Indolin-2-one, If you have any questions, you can contact Lee, J; Vinh, NB; Drinkwater, N; Yang, W; Sivaraman, KK; Schembri, LS; Gazdik, M; Grin, PM; Butler, GS; Overall, CM; Charman, SA; McGowan, S; Scammells, PJ or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

An article KinFragLib: Exploring the Kinase Inhibitor Space Using Subpocket-Focused Fragmentation and Recombination WOS:000608875100049 published article about MEDICINAL CHEMISTRY; PROTEIN-KINASES; DRUG DISCOVERY; DESIGN; POWERFUL; DATABASE; MUTANT; KLIFS in [Sydow, Dominique; Schmiel, Paula; Volkamer, Andrea] Charite, Inst Physiol, Silico Toxicol & Struct Bioinformat, D-10117 Berlin, Germany; [Mortier, Jeremie] Bayer AG, Digital Technol Computat Mol Design, D-13342 Berlin, Germany in 2020, Cited 49. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3. COA of Formula: C8H7NO

Protein kinases play a crucial role in many cell signaling processes, making them one of the most important families of drug targets. In this context, fragment-based drug design strategies have been successfully applied to develop novel kinase inhibitors. These strategies usually follow a knowledge-driven approach to optimize a focused set of fragments to a potent kinase inhibitor. Alternatively, KinFragLib explores and extends the chemical space of kinase inhibitors using data-driven fragmentation and recombination. The method builds on available structural kinome data from the KLIFS database for over 2500 kinase DFG-in structures cocrystallized with noncovalent kinase ligands. The computational fragmentation method splits the ligands into fragments with respect to their 3D proximity to six predefined functionally relevant subpocket centers. The resulting fragment library consists of six subpocket pools with over 7000 fragments, available at https://github.com/volkamerlab/KinFragLib. KinFragLib offers two main applications: on the one hand, in-depth analyses of the chemical space of known kinase inhibitors, subpocket characteristics, and connections, and on the other hand, subpocket-informed recombination of fragments to generate potential novel inhibitors. The latter showed that recombining only a subset of 624 representative fragments generated 6.7 million molecules. This combinatorial library contains, besides some known kinase inhibitors, more than 99% novel chemical matter compared to ChEMBL and 63% molecules compliant with Lipinski’s rule of five.

About Indolin-2-one, If you have any questions, you can contact Sydow, D; Schmiel, P; Mortier, J; Volkamer, A or concate me.. COA of Formula: C8H7NO

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

Recently I am researching about MEDICINAL CHEMISTRY; PROTEIN-KINASES; DRUG DISCOVERY; DESIGN; POWERFUL; DATABASE; MUTANT; KLIFS, Saw an article supported by the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [VO 2353/1-1]; Bundesministerium fur Bildung und Forschung [031A262C]. Safety of Indolin-2-one. Published in AMER CHEMICAL SOC in WASHINGTON ,Authors: Sydow, D; Schmiel, P; Mortier, J; Volkamer, A. The CAS is 59-48-3. Through research, I have a further understanding and discovery of Indolin-2-one

Protein kinases play a crucial role in many cell signaling processes, making them one of the most important families of drug targets. In this context, fragment-based drug design strategies have been successfully applied to develop novel kinase inhibitors. These strategies usually follow a knowledge-driven approach to optimize a focused set of fragments to a potent kinase inhibitor. Alternatively, KinFragLib explores and extends the chemical space of kinase inhibitors using data-driven fragmentation and recombination. The method builds on available structural kinome data from the KLIFS database for over 2500 kinase DFG-in structures cocrystallized with noncovalent kinase ligands. The computational fragmentation method splits the ligands into fragments with respect to their 3D proximity to six predefined functionally relevant subpocket centers. The resulting fragment library consists of six subpocket pools with over 7000 fragments, available at https://github.com/volkamerlab/KinFragLib. KinFragLib offers two main applications: on the one hand, in-depth analyses of the chemical space of known kinase inhibitors, subpocket characteristics, and connections, and on the other hand, subpocket-informed recombination of fragments to generate potential novel inhibitors. The latter showed that recombining only a subset of 624 representative fragments generated 6.7 million molecules. This combinatorial library contains, besides some known kinase inhibitors, more than 99% novel chemical matter compared to ChEMBL and 63% molecules compliant with Lipinski’s rule of five.

About Indolin-2-one, If you have any questions, you can contact Sydow, D; Schmiel, P; Mortier, J; Volkamer, A or concate me.. Safety of Indolin-2-one

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

SDS of cas: 59-48-3. In 2019 ADV SYNTH CATAL published article about SECONDARY AMIDES; N-ALKYLATION; CHEMOSELECTIVE REDUCTION; TERTIARY AMIDES; ACID; DERIVATIVES; CHEMISTRY; NITRILES; ESTERS; CARBON in [Pan, Yixiao; Luo, Zhenli; Xu, Xin; Zhao, Haoqiang; Han, Jiahong; Xu, Lijin] Renmin Univ China, Dept Chem, Beijing 100872, Peoples R China; [Fan, Qinghua] Chinese Acad Sci, Inst Chem, Beijing 100190, Peoples R China; [Xiao, Jianliang] Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Merseyside, England in 2019, Cited 59. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3.

A ruthenium(II)-catalyzed deoxygenative transfer hydrogenation of amides to amines using HCO2H/NEt3 as the reducing agent is reported for the first time. The catalyst system consisting of [Ru(2-methylallyl)(2)(COD)], 1,1,1-tris(diphenylphosphinomethyl) ethane (triphos) and Bis(trifluoromethane sulfonimide) (HNTf2) performed well for deoxygenative reduction of various secondary and tertiary amides into the corresponding amines in high yields with excellent selectivities, and exhibits high tolerance toward functional groups including those that are reduction-sensitive. The choice of hydrogen source and acid co-catalyst is critical for catalysis. Mechanistic studies suggest that the reductive amination of the in situ generated alcohol and amine via borrowing hydrogen is the dominant pathway.

SDS of cas: 59-48-3. About Indolin-2-one, If you have any questions, you can contact Pan, YX; Luo, ZL; Xu, X; Zhao, HQ; Han, JH; Xu, LJ; Fan, QH; Xiao, JL or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem

In 2020 ACS PHARMACOL TRANSL published article about GENE-RELATED PEPTIDE; CLASS-B GPCR; ACTIVITY-MODIFYING PROTEIN-2; CRYO-EM STRUCTURE; STRUCTURAL INSIGHTS; COUPLED RECEPTORS; BINDING SITES; CGRP RECEPTOR; ADRENOMEDULLIN; RECOGNITION in [Hendrikse, Erica R.; Bower, Rebekah L.; Jamaluddin, Muhammad A.; Prodan, Nicole; Richards, Keith D.; Walker, Christopher S.; Hay, Debbie L.] Univ Auckland, Sch Biol Sci, Auckland 1010, New Zealand; [Hendrikse, Erica R.; Bower, Rebekah L.; Jamaluddin, Muhammad A.; Walker, Christopher S.; Flanagan, Jack U.; Hay, Michael P.; Hay, Debbie L.] Univ Auckland, Maurice Wilkins Ctr Mol Biodiscovery, Auckland 1010, New Zealand; [Liew, Lydia P.; Bonnet, Muriel; Flanagan, Jack U.; Hay, Michael P.] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1023, New Zealand; [Pairaudeau, Garry] AstraZeneca, Hit Discovery, Discovery Sci, R&D, Cambridge CB2 0SL, England; [Smith, David M.] AstraZeneca, Emerging Innovat, R&D, Discovery Sci, Cambridge CB2 0SL, England; [Rujan, Roxana-Maria; Sudra, Risha; Reynolds, Christopher A.] Univ Essex, Sch Life Sci, Colchester CO4 3SQ, Essex, England; [Booe, Jason M.; Pioszak, Augen A.] Univ Oklahoma, Dept Biochem & Mol Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA in 2020, Cited 67. The Name is Indolin-2-one. Through research, I have a further understanding and discovery of 59-48-3. Computed Properties of C8H7NO

Class B G protein-coupled receptors are highly therapeutically relevant but challenges remain in identifying suitable small-molecule drugs. The calcitonin-like receptor (CLR) in particular is linked to conditions such as migraine, cardiovascular disease, and inflammatory bowel disease. The CLR cannot act as a cell-surface receptor alone but rather must couple to one of three receptor activity-modifying proteins (RAMPs), forming heterodimeric receptors for the peptides adrenomedullin and calcitonin gene-related peptide. These peptides have extended binding sites across their receptors. This is one reason why there are few small-molecule ligands that can modulate these receptors. Here we describe small molecules that are able to positively modulate the signaling of the CLR with all three RAMPs but are not active at the related calcitonin receptor. These compounds were selected from a beta-arrestin recruitment screen, coupled with rounds of medicinal chemistry to improve their activity. Translational potential is shown as the compounds can positively modulate cAMP signaling in a vascular cell line model. Binding experiments do not support an extracellular domain binding site; however, molecular modeling reveals potential allosteric binding sites in multiple receptor regions. These are the first small-molecule positive modulators described for the CLR:RAMP complexes.

Computed Properties of C8H7NO. About Indolin-2-one, If you have any questions, you can contact Hendrikse, ER; Liew, LP; Bower, RL; Bonnet, M; Jamaluddin, MA; Prodan, N; Richards, KD; Walker, CS; Pairaudeau, G; Smith, DM; Rujan, RM; Sudra, R; Reynolds, CA; Booe, JM; Pioszak, AA; Flanagan, JU; Hay, MP; Hay, DL or concate me.

Reference:
Indoline – Wikipedia,
,Indoline | C8H9N – PubChem