Day: October 26, 2022

On March 15, 2004, Grubbs, Russell A.; Lewis, Mechelle M.; Owens-Vance, Connie; Gay, Elaine A.; Jassen, Amy K.; Mailman, Richard B.; Nichols, David E. published an article.HPLC of Formula: 58142-46-4 The title of the article was 8,9-Dihydroxy-1,2,3,11b-tetrahydrochromeno[4,3,2,-de]isoquinoline (dinoxyline), a high affinity and potent agonist at all dopamine receptor isoforms. And the article contained the following:

The synthesis and preliminary pharmacol. evaluation of 8,9-dihydroxy-1,2,3,11b-tetrahydrochromeno[4,3,2,-de]isoquinoline (5, now named dinoxyline) is described. This mol. was designed as a potential bioisostere that would conserve the essential elements of our β-phenyldopamine D1 pharmacophore (i.e., position and orientation of the nitrogen, hydroxyls, and Ph rings). Previously, we have rigidified these elements using alkyl bridges, as exemplified in the dopamine D1 full agonist mols. dihydrexidine (1) and dinapsoline (2). This approach has been modified and we now show that it is possible to tether these elements using an ether linkage. Preliminary pharmacol. has revealed that 5 is a potent full D1 agonist (K0.5 <10 nM; EC50=30 nM), but also has high affinity for brain D2-like and cloned D2 and D3 receptors. Interestingly, whereas 1 and 2 and their analogs have only moderate affinity for the human D4 receptor, 5 also has high affinity for this isoform. Moreover, although N-alkylation of 1 and 2 increases D2 affinity, the N-allyl (15) and N-Pr (17) derivatives of 5 had decreased D2 affinity. Therefore, 5 may be engaging different amino acid residues than do 1 and 2 when they bind to the D2 receptor. This is the first example of a ligand with high affinity at all dopamine receptors, yet with functional characteristics similar to dopamine. These rigid ligands also will be useful tools to determine specific residues of the receptor transmembrane domains that are critical for agonist ligand selectivity for the D4 receptor. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).HPLC of Formula: 58142-46-4

The Article related to dinoxyline analog preparation dopamine receptor agonist, Pharmacology: Structure-Activity and other aspects.HPLC of Formula: 58142-46-4

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On November 22, 2017, Fish, Inbar; Stossel, Anne; Eitel, Katrin; Valant, Celine; Albold, Sabine; Huebner, Harald; Moller, Dorothee; Clark, Mary J.; Sunahara, Roger K.; Christopoulos, Arthur; Shoichet, Brian K.; Gmeiner, Peter published an article.Safety of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one The title of the article was Structure-Based Design and Discovery of New M2 Receptor Agonists. And the article contained the following:

Muscarinic receptor agonists are characterized by apparently strict restraints on their tertiary or quaternary amine and their distance to an ester or related center. On the basis of the active state crystal structure of the muscarinic M2 receptor in complex with iperoxo, the authors explored potential agonists that lacked the highly conserved functionalities of previously known ligands. Using structure-guided pharmacophore design followed by docking, the authors found two agonists (compounds 3 (2-(3-methoxyphenyl)-N,N,N-trimethylethan-1-aminium formate) and 17 (2-(benzofuran-6-yl)-N,N,N-trimethylethan-1-aminium formate)), out of 19 docked and synthesized compounds, that fit the receptor well and were predicted to form a hydrogen-bond conserved among known agonists. Structural optimization led to compound 28 (2-(2,3-dihydrobenzofuran-6-yl)-N,N,N-trimethylethan-1-aminium formate), which was 4-fold more potent than its parent 3. Fortified by the discovery of this new scaffold, the authors sought a broader range of chemotypes by docking 2.2 million fragments, which revealed another three micromolar agonists unrelated either to 28 or known muscarinics. Even pockets as tightly defined and as deeply studied as that of the muscarinic reveal opportunities for the structure-based design and the discovery of new chemotypes. The experimental process involved the reaction of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one(cas: 74904-29-3).Safety of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

The Article related to muscarinic m2 receptor agonist structure based design preparation docking, Pharmacology: Structure-Activity and other aspects.Safety of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On February 5, 2015, Koizumi, Noriko; Okumura, Naoki; Kinoshita, Shigeru published a patent.Recommanded Product: 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one The title of the patent was Drug for prevention or treatment of diseases associated with abnormalities in extracellular matrix (ECM) of corneal endothelium. And the patent contained the following:

The drug, especially for diseases associated with Fuchs’ corneal endothelial dystrophy. contains a TGF-β signal inhibitor. Also claimed are the TGF-β signal inhibitor for the drug, and the treatment/prevention method by administration of the TGF-β inhibitor. Such diseases include photophobia, blurred vision, vision disorders, eye pain, tearing, hyperemia, pain, bullous keratopathy, eye discomfort, contrast reduction, glare, edema of the corneal stroma, bullous keratopathy and corneal opacity. The TGF β-signal inhibitor may be 4-[4-(1,3-benzodioxole-5-yl)-5-(2-pyridinyl)-1H-imidazole-2-yl]benzamide. The experimental process involved the reaction of 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one(cas: 1009104-85-1).Recommanded Product: 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one

The Article related to tgf signal inhibitor corneal endothelial ecm disease fuchs dystrophy, Pharmaceuticals: Formulation and Compounding and other aspects.Recommanded Product: 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Alvarez, M.; Joule, J. A. published an article in 2005, the title of the article was Product class 6: isoquinolinones.Quality Control of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one And the article contains the following content:

A review primarily covering methods of preparation of 1(2H)-isoquinolinones and 3(2H)-isoquinolinones. Synthetic methods include cyclization, ring transformation, and substituent modification. The experimental process involved the reaction of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one(cas: 74904-29-3).Quality Control of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

The Article related to review isoquinolinone preparation cyclization ring transformation, Heterocyclic Compounds (One Hetero Atom): Reviews and other aspects.Quality Control of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On April 1, 2004, Blanco-Pillado, Maria-Jesus; Chappell, Mark Donald; Garcia De la Torre, Marta; Diaz Buezo, Nuria; Fritz, James Erwin; Holloway, William Glen; Matt, James Edward, Jr.; Mitch, Charles Howard; Pedregal-Tercero, Concepcion; Quimby, Steven James; Siegel, Miles Goodman; Smith, Dana Rae; Stucky, Russell Dean; Takeuchi, Kumiko; Thomas, Elizabeth Marie; Wolfe, Chad Nolan published a patent.Reference of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one The title of the patent was Preparation of [[(aminoalkyl)aryl]oxy]nicotinamides and analogs as opioid receptor antagonist for treatment of obesity and related conditions. And the patent contained the following:

Title diaryl ethers I [wherein X1-X10 = independently C, CH, or N; provided that each of rings A or B has no more than 2 N atoms; E = O or NH; R1 and R2 = independently H or (un)substituted (cyclo)alkyl, alkenyl, alkynyl, (alkyl)aryl, (aryl)heterocyclyl, (cyclo)alkylheterocyclyl, (cyclo)alkanoylalkyl, aroylalkyl, aryloxyalkyl, benzhydryl, bicyclyl(alkyl), benzoyl(alkyl), alkoxyalkyl, alkoxycarbonyl, (aryl)alkylsulfonyl, heterocyclylalkylsulfonyl, cycloalkylalkyl, carboxyalkyl, carbamoylalkyl, etc.; R3 and R3′ = independently H, alkyl, alkenyl, alkynyl, (alkyl)aryl, or alkylcycloalkyl; R4 and R5 = independently H, (halo)alkyl, alkenyl, alkynyl, alkoxy(halo)alkyl, thioalkyl, halo, aryl(alkyl), alkanoyl, alkoxycarbonyl, aminoalkyl, cycloalkylalkyl, etc.; R6 and R7 = independently H, (cyclo)alkyl, alkenyl, alkynyl, alkanoyl, OH, alkoxy, (aryl)alkylsulfonyl, heterocyclylalkylsulfonyl, aryl(alkyl), carbamoyl(alkyl), etc.; m = 1-3; n = 0-3; p = 0-3; or pharmaceutically acceptable salts, solvates, enantiomers, racemates, diastereomers, or mixtures thereof] were prepared as μ-, κ-, and δ-opioid receptor antagonists. For example, reductive amination of 6-(2-fluoro-4-formylphenoxy)nicotinamide and 3-methylbutylamine provided II (99%). The latter inhibited ex vivo binding of [3H]-diprenorphine in rat striatum/nucleus accumbens by >65% at a concentration of 7 mg/kg. In an acute feeding rat obesity assay, II suppressed opioid receptors at a dose of 0.3 μg/kg. In addition, diet-induced obese rats achieved an energy balance (caloric intake minus utilization) of -81 kcal/kg/day upon administration of 0.3 mg/kg p.o. of II in an indirect calorimetry assay. Thus, I and their pharmaceutical compositions are useful for the treatment, prevention, or amelioration of obesity and related diseases. The experimental process involved the reaction of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one(cas: 74904-29-3).Reference of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

The Article related to aryloxy nicotinamide preparation opioid receptor antagonist antiobesity, aryl heteroaryl ether preparation opioid receptor antagonist antiobesity, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Reference of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On December 31, 1993, Shanker, P. Sathya; Rao, G. S. R. Subba published an article.Recommanded Product: 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one The title of the article was Synthesis of isoquinolines from indanones: total synthesis of illudinine. And the article contained the following:

Schmidt reaction of 5-methoxy or 7-methoxyindan-1-ones or their derivatives results exclusively in isocarbostyrils which are converted into 6-methoxy or 8-methoxyisoquinolines in good yields. This strategy has been extended to the total synthesis of illudinine Me ester (I) starting from hexahydroindacenecarboxylate II. The experimental process involved the reaction of 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one(cas: 74904-29-3).Recommanded Product: 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

The Article related to schmidt reaction methoxyindanone, amination ring expansion methoxyindanone, isoquinolinone tetrahydro, illudinine, Alkaloids: Alkaloids Containing One Nitrogen Atom In A Ring and other aspects.Recommanded Product: 8-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On August 2, 2012, Heller, Stefan; Ronaghi, Mohammad; Oshima, Kazuo published a patent.Application In Synthesis of 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one The title of the patent was Methods for generating inner ear cells in vitro from pluripotent stem cells. And the patent contained the following:

Methods, compositions and kits are provided for generating inner ear cells in vitro. These methods find use a number of applications, such as in preparing inner ear cells for in vitro screening for agents that are toxic to inner ear cells, for in vitro screening for agents that prevent against, mitigate, or reverse the toxic effects of such agents, and for in vitro screening for agents that promote otoregeneration. The experimental process involved the reaction of 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one(cas: 1009104-85-1).Application In Synthesis of 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one

The Article related to inner ear cell pluripotent stem in vitro, Fermentation and Bioindustrial Chemistry: Animal Cell Culture and other aspects.Application In Synthesis of 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On October 7, 2021, Cheruvallath, Zacharia; Green, Jason; Johnson, Ben; Jones, Bejamin; Schleicher, Kristin; Sun, Huikai; Tang, Mingnam published a patent.Application In Synthesis of 5-Methylisoquinoline-1-carbonitrile The title of the patent was N-Heteroarylalkyl-2-(heterocyclyl and heterocyclylmethyl) acetamide derivatives as SSTR4 agonists and their preparation. And the patent contained the following:

Disclosed are compounds of formula I, and pharmaceutically acceptable salts thereof. This disclosure also relates to materials and methods for preparing compounds of formula I, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with SSTR4. Compounds of formula I wherein when X3 is NH and derivatives and O, X4 is a single bond, and X5 is N and CR5, and R1R2 are taken together to form (un)substituted benzene ring; when X3 is CR3c, X4 is N and CR4, and X5 is N and CR5, and R1R2 are taken together to form (un)substituted furan, (un)substituted pyrazole or (un)substituted benzene ring; L is O when A is CHR6; L is a bond when n is absent and CHR6; R3c and N are independently H, halo, OH, CN, (un)substituted C3-6 cycloalkyl, etc.; R6 is H; R5R6 can be taken together to form ethane-1,2-diyl bridge; R7 and R8 are independently H and (un)substituted C1-4 alkyl; R9 is H and (un)substituted C1-4 alkyl; R10 is azetidin-1-ylmethyl, pyrrolidin-1-ylmethyl and heterocyclyl; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by amidation of 2-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)acetic acid with 2-(1,7-dimethyl-1H-indazol-3-yl)propan-2-amine followed by hydrolysis; the resulting 7-(2-(1,7-dimethyl-1H-indazol-3-yl)propan-2-yl)-2-(pyrrolidin-2- yl)acetamide underwent reductive methylation with formaldehyde to give compound II. The invention compounds were evaluated for their SSTR4 inhibitory activity. From the assay, it was determined that compound II exhibited pEC50 value of 8.2 and pIC50 value of 7.2. The experimental process involved the reaction of 5-Methylisoquinoline-1-carbonitrile(cas: 1367744-24-8).Application In Synthesis of 5-Methylisoquinoline-1-carbonitrile

The Article related to heteroarylalkyl heterocyclylacetamide preparation sstr4 agonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Application In Synthesis of 5-Methylisoquinoline-1-carbonitrile

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On April 9, 2004, D’Orchymont, Hugues; Van Hijfte, Luc; Zimmermann, Andre published a patent.Reference of 4-Bromo-5-nitroisoquinoline The title of the patent was Preparation of indazolecarboxamides as CDK1, CDK2, and CDK4 inhibitors for treating CDK-related diseases, in particular cancer. And the patent contained the following:

Title compounds I [R1 = H, halo, NH2, NHR2, NHCOR2, NO2, CN, CH2NH2, CH2NHR2, (un)substituted Ph, heteroaryl; Ar = (un)substituted Ph, heteroaryl; R2 = Ph, heteroaryl, (un)substituted alkyl (substituent = Ph or heteroaryl); n = 0, 1, 2, or 3; PG = protecting group selected from trimethylsilylethoxymethyl, mesitylenesulfonyl; their free bases, addition salts with acids, solvates and hydrates; with the exclusion of certain compounds] were prepared as cyclin-dependent kinase (CDK)-1, CDK2, and CDK4 inhibitors for treating cdk-related diseases, in particular cancer. For instance, reacting indazole-3-carboxylic acid with N-phenyl-1,4-phenylenediamine in the presence of DCC gave 58% II. I displayed IC50 values < 20 μM for the inhibition of CDK2, CDK1, and CDK4 in a test for measuring the enzymic activity of CDK2/Cyclin A, CDK1/Cyclin B, and CDK4/Cyclin D1, resp. I are useful for treating cancers, autoimmune diseases, inflammations, cardiovascular diseases, viral and fungal infections, hematol. diseases, and degenerative diseases of muscular system. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Reference of 4-Bromo-5-nitroisoquinoline

The Article related to indazolecarboxamide preparation cdk1 cdk2 cdk4 inhibitor antitumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Reference of 4-Bromo-5-nitroisoquinoline

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On February 28, 2021, Aseem, Sayed Obaidullah; Jalan-Sakrikar, Nidhi; Chi, Cheng; Navarro-Corcuera, Amaia; De Assuncao, Thiago M.; Hamdan, Feda H.; Chowdhury, Shiraj; Banales, Jesus M.; Johnsen, Steven A.; Shah, Vijay H.; Huebert, Robert C. published an article.Computed Properties of 1009104-85-1 The title of the article was Epigenomic Evaluation of Cholangiocyte Transforming Growth Factor-β Signaling Identifies a Selective Role for Histone 3 Lysine 9 Acetylation in Biliary Fibrosis. And the article contained the following:

Transforming growth factor β (TGFβ) upregulates cholangiocyte-derived signals that activate myofibroblasts and promote fibrosis. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) was used to investigate changes in chromatin accessibility. TGFβ stimulation caused widespread changes in histone 3 lysine 27 acetylation (H3K27ac), and was associated with global TGFβ-mediated transcription. In contrast, H3K9ac was gained in a smaller group of chromatin sites and was associated with fibrosis pathways. These pathways included overexpression of hepatic stellate cell (HSC) activators such as fibronectin 1 (FN1) and SERPINE1. The promoters of these genes showed H3K9ac enrichment following TGFβ. Of the acetyltransferases responsible for H3K9ac, cholangiocytes predominantly express Lysine Acetyltransferases 2A (KAT2A). Small interfering RNA knockdown of KAT2A or H3K9ac inhibition prevented the TGFβ-mediated increase in FN1 and SERPINE1. SMAD3 ChIP-seq and ATAC-seq suggested that TGFβ-mediated H3K9ac occurs through SMAD signaling, which was confirmed using colocalization and genetic knockdown studies. Pharmacol. inhibition or cholangiocyte-selective deletion of Kat2a was protective in mouse models of biliary fibrosis. Cholangiocyte expression of HSC-activating signals occurs through SMAD-dependent, KAT2A-mediated, H3K9ac, and can be targeted to prevent biliary fibrosis. The experimental process involved the reaction of 1-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one(cas: 1009104-85-1).Computed Properties of 1009104-85-1

The Article related to biliary fibrosis cholangiocyte transforming growth factor histone h3 acetylation, epigenetics, fn, pai1, Mammalian Pathological Biochemistry: Digestive Tract Diseases and other aspects.Computed Properties of 1009104-85-1

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem