M.W=150-200| Page 34 of 107 | Heterocyclic Building Blocks-Isoquinoline

Dastjerdi, Neda Mollakarimi’s team published research in Green Chemistry Letters and Reviews in 2020 | CAS: 86-51-1

Green Chemistry Letters and Reviews published new progress about Condensation reaction. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, SDS of cas: 86-51-1.

Dastjerdi, Neda Mollakarimi published the artcileUltrasound-promoted green approach for the synthesis of multisubstituted pyridines using stable and reusable SBA-15@ADMPT/H5PW10V2O40 nanocatalyst at room temperature, SDS of cas: 86-51-1, the main research area is silica ADMPT nanocatalyst pyridine synthesis room temperature.

A facile one-pot protocol for the synthesis of 2-amino-3-cyanopyridins using SBA-15@Triazine/H5PW10V2O40 as an efficient catalyst under ultrasonic conditions has been developed. The nanohybrid catalyst was prepared by the chem. anchoring of Keggin heteropolyacid H5PW10V2O40 onto the surface of SBA-15 mesoporous silica modified with 2-APTS -4,6-bis(3,5-dimethyl-1H-pyrazol- 1-yl)-1,3,5-triazine (ADMPT) linker. Then the nanohybrid was used as a green, efficient, eco-friendly, and highly recyclable catalyst for the one-pot and multi-component synthesis of 2-amino-3-cyanopyridin derivatives from the reaction of aldehydes, malononitrile, cyclic ketones and ammonium acetate under ultrasound waves with good to excellent yields (79-95%) and in a short span of time. This nanocatalyst was characterized by using FT-IR, XRD, SEM, TEM, BET, and EDX techniques.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Li, Peijun’s team published research in Organic Letters in 2021-12-17 | CAS: 104-01-8

Organic Letters published new progress about Alkylation catalysts. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Category: isoquinoline.

Li, Peijun published the artcileThe Direct Decarboxylative N-Alkylation of Azoles, Sulfonamides, Ureas, and Carbamates with Carboxylic Acids via Photoredox Catalysis, Category: isoquinoline, the main research area is alkyl heterocycle preparation; carboxylic acid azole decarboxylative alkylation photo catalyst.

A method for direct decarboxylative C-N coupling of carboxylic acids RC(O)OH (R = naphthalen-1-yl, 2-phenylpropan-2-yl, 1,2,3,4-tetrahydronaphthalen-1-yl, etc.) with a range of nitrogen nucleophiles, e.g., 5-(4-bromophenyl)-2H-1,2,3,4-tetrazol-2-yl has been described. This platform employs visible-light-mediated photoredox catalysis and an iodine(III) reagent to generate carbocation intermediates directly from aliphatic carboxylic acids via a radical-polar crossover mechanism. A variety of C-N bond-containing products, e.g., I are constructed from a diverse array of nitrogen heterocycles, including pyrazoles, imidazoles, indazoles, and purine bases. Furthermore, sulfonamides, ureas, and carbamates can also be utilized as a nucleophile to generate a selection of N-alkylated products. Notably, a two-step approach to construct free amines directly from the carboxylic acids is accomplished using Cbz-protected amine as a nucleophile.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Yan, Jiahang’s team published research in Organic & Biomolecular Chemistry in 2022 | CAS: 104-01-8

Organic & Biomolecular Chemistry published new progress about Cascade rearrangement. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Computed Properties of 104-01-8.

Yan, Jiahang published the artcileEnantioselective direct vinylogous Michael addition for constructing enantioenriched γ,γ-dialkyl substituted butyrolactams and octahydroindoles, Computed Properties of 104-01-8, the main research area is dialkyl substituted butyrolactam octahydroindole preparation Michael addition.

A nickel(II)-catalyzed asym. direct vinylogous Michael addition of γ-alkyl monosubstituted α,β-unsaturated butyrolactams to α,β-unsaturated carbonyl compounds has been disclosed, affording γ,γ-dialkyl substituted butyrolactams in good yields and satisfactory enantioselectivities. A tandem catalytic asym. vinylogous Michael addition/intramol. Michael addition has also been developed based on this reaction, which enabled the construction of enantioenriched octahydroindoles with three consecutive stereogenic carbon centers.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Yang, Ya-Jun’s team published research in Journal of Asian Natural Products Research in 2021 | CAS: 104-01-8

Journal of Asian Natural Products Research published new progress about Cation-pi interaction. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Related Products of isoquinoline.

Yang, Ya-Jun published the artcileDesign, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors, Related Products of isoquinoline, the main research area is dipeptide proteasome inhibitor synthesis biol evaluation; 20S proteasome inhibitors; dipeptides; non-covalent.

Based on the interaction modes of the natural 20S proteasome inhibitors , we have previously discovered a dipeptide . To explore the SAR around compound , we designed and synthesized a series of dipeptides () with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC50 values at the submicromolar level, which were comparable or even superior to the parent compound Meanwhile, they displayed no significant inhibition against trypsin-like and caspase-like activities of 20S proteasome. The results suggested the feasibility to design dipeptides as novel and potent 20S proteasome inhibitors.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Dastjerdi, Neda Mollakarimi’s team published research in Green Chemistry Letters and Reviews in 2020 | CAS: 86-51-1

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Montgomery, Deanna’s team published research in Molecules in 24 | CAS: 371766-08-4

Molecules published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Product Details of C9H8BNO2.

Montgomery, Deanna published the artcileStructure-activity relationships of 7-substituted dimethyltyrosine-tetrahydroisoquinoline opioid peptidomimetics, Product Details of C9H8BNO2, the publication is Molecules (2019), 24(23), 4302, database is CAplus and MEDLINE.

The opioid receptors modulate a variety of biol. functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure-activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogs maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Cox, Robert M.’s team published research in Nature Microbiology in 5 | CAS: 371766-08-4

Nature Microbiology published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Recommanded Product: Isoquinolin-5-ylboronic acid.

Cox, Robert M. published the artcileOrally efficacious broad-spectrum allosteric inhibitor of paramyxovirus polymerase, Recommanded Product: Isoquinolin-5-ylboronic acid, the publication is Nature Microbiology (2020), 5(10), 1232-1246, database is CAplus and MEDLINE.

In a high-throughput screen for inhibitors of HPIV3 (a major cause of acute respiratory infection), we identified GHP-88309-a non-nucleoside inhibitor of viral polymerase activity that possesses unusual broad-spectrum activity against diverse paramyxoviruses including respiroviruses (i.e., HPIV1 and HPIV3) and morbilliviruses (i.e., MeV). Resistance profiles of distinct target viruses overlapped spatially, revealing a conserved binding site in the central cavity of the viral polymerase (L) protein that was validated by photoaffinity labeling-based target mapping. Mechanistic characterization through viral RNA profiling and in vitro MeV polymerase assays identified a block in the initiation phase of the viral polymerase. GHP-88309 showed nanomolar potency against HPIV3 isolates in well-differentiated human airway organoid cultures, was well tolerated (selectivity index > 7,111) and orally bioavailable, and provided complete protection against lethal infection in a Sendai virus mouse surrogate model of human HPIV3 disease when administered therapeutically 48 h after infection. Recoverees had acquired robust immunoprotection against reinfection, and viral resistance coincided with severe attenuation. This study provides proof of the feasibility of a well-behaved broad-spectrum allosteric antiviral and describes a chemotype with high therapeutic potential that addresses major obstacles of anti-paramyxovirus drug development.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Yu, Mingfeng’s team published research in European Journal of Medicinal Chemistry in 214 | CAS: 371766-08-4

European Journal of Medicinal Chemistry published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C5H5BrN2, HPLC of Formula: 371766-08-4.

Yu, Mingfeng published the artcilePotent and orally bioavailable CDK8 inhibitors: Design, synthesis, structure-activity relationship analysis and biological evaluation, HPLC of Formula: 371766-08-4, the publication is European Journal of Medicinal Chemistry (2021), 113248, database is CAplus and MEDLINE.

CDK8 regulates transcription either by phosphorylation of transcription factors or, as part of a four-subunit kinase module, through a reversible association of the kinase module with the Mediator complex, a highly conserved transcriptional coactivator. Deregulation of CDK8 has been found in various types of human cancer, while the role of CDK8 in suppressing anti-cancer response of natural killer cells is being understood. Currently, CDK8-targeting cancer drugs are highly sought-after. Herein authors detail the discovery of a series of novel pyridine-derived CDK8 inhibitors. Medicinal chem. optimization gave rise to I (AU1-100), a potent CDK8 inhibitor with oral bioavailability. The compound inhibited the proliferation of MV4-11 acute myeloid leukemia cells with the kinase activity of cellular CDK8 dampened. No systemic toxicol. was observed in the mice treated with I. These results warrant further pre-clin. studies of I as an anti-cancer agent.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Paulsen, Janet L.’s team published research in Bioorganic & Medicinal Chemistry Letters in 23 | CAS: 371766-08-4

Bioorganic & Medicinal Chemistry Letters published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, HPLC of Formula: 371766-08-4.

Paulsen, Janet L. published the artcileStructural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species, HPLC of Formula: 371766-08-4, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(5), 1279-1284, database is CAplus and MEDLINE.

A novel strategy for targeting the pathogenic organisms Candida albicans and Candida glabrata focuses on the development of potent and selective antifolates effective against dihydrofolate reductase. Crystal structure anal. suggested that an essential loop at the active site (Thr 58-Phe 66) differs from the analogous residues in the human enzyme, potentially providing a mechanism for achieving selectivity. In order to probe the role of this loop, we employed chem. synthesis, crystal structure determination and mol. dynamics simulations. The results of these analyses show that the loop residues undergo ligand-induced conformational changes that are similar among the fungal and human species.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Carpenter, Joseph’s team published research in Journal of Medicinal Chemistry in 60 | CAS: 371766-08-4

Journal of Medicinal Chemistry published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Synthetic Route of 371766-08-4.

Carpenter, Joseph published the artcileUtilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT_2C Receptor Agonists, Synthetic Route of 371766-08-4, the publication is Journal of Medicinal Chemistry (2017), 60(14), 6166-6190, database is CAplus and MEDLINE.

Agonism of the 5-HT_2C receptor represents one of the most well-studied and clin. proven mechanisms for pharmacol. weight reduction Selectivity over the closely related 5-HT_2A and 5-HT_2B receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT_2C receptor to identify atypical agonist structures. We addnl. report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT_2C. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT_2C with high selectivity over the related 5-HT_2A and 5-HT_2B receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT_2C antagonist.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem