Category: isoquinoline

Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen was written by Atkinson, Benjamin N.;Steadman, David;Zhao, Yuguang;Sipthorp, James;Vecchia, Luca;Ruza, Reinis R.;Jeganathan, Fiona;Lines, Georgie;Frew, Sarah;Monaghan, Amy;Kjaer, Svend;Bictash, Magda;Jones, E. Yvonne;Fish, Paul V.. And the article was included in MedChemComm in 2019.Synthetic Route of C9H8N2 This article mentions the following:

NOTUM is a carboxylesterase that has been shown to act by mediating the O-depalmitoleoylation of Wnt proteins resulting in suppression of Wnt signaling. Here, we describe the development of NOTUM inhibitors that restore Wnt signaling for use in in vitro disease models where NOTUM over activity is an underlying cause. A crystallog. fragment screen with NOTUM identified 2-phenoxyacetamide 3 as binding in the palmitoleate pocket with modest inhibition activity (IC₅₀ 33 μM). Optimization of hit 3 by SAR studies guided by SBDD identified indazole 38 (IC₅₀ 0.032 μM) and isoquinoline 45 (IC₅₀ 0.085 μM) as potent inhibitors of NOTUM. The binding of 45 to NOTUM was rationalized through an X-ray co-crystal structure determination which showed a flipped binding orientation compared to 3. However, it was not possible to combine NOTUM inhibition activity with metabolic stability as the majority of the compounds tested were rapidly metabolized in an NADPH-independent manner. In the experiment, the researchers used many compounds, for example, Isoquinolin-7-amine (cas: 23707-37-1Synthetic Route of C9H8N2).

Isoquinolin-7-amine (cas: 23707-37-1) belongs to isoquinoline derivatives. Quinoline is a mancude organic heterobicyclic parent, an azaarene, an ortho-fused heteroarene and a member of isoquinolines. They are also used to make oil-soluble dyes, food colorants, pharmaceuticals, pH indicators and other organic compounds. Synthetic Route of C9H8N2

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

New N-aryl-N’-(3-(substituted)phenyl)-N’-methylguanidines as leads to potential PET radioligands for imaging the open NMDA receptor was written by Naumiec, Gregory R.;Cai, Lisheng;Pike, Victor W.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2015.Electric Literature of C9H7BrN2 This article mentions the following:

An expansive set of N-aryl-N’-(3-(substituted)phenyl)-N’-(methyl)guanidine was prepared in a search for new leads to prospective PET ligands for imaging of the open channel of the N-methyl-D-aspartate (NMDA) receptor in vivo. The N-aryl rings and their substituents were varied, whereas the N-methyl-group was maintained as a site for potential labeling with the positron-emitter, carbon-11 (t_1/2 = 20.4 min). At micromolar concentration, over half of the prepared compounds strongly inhibited the binding of [³H]TCP to its binding site in the open NMDA receptor in vitro. Four ligands displayed affinities that are similar or superior to those of the promising SPECT radioligand ([¹²³I]CNS1261). The 3′-dimethylamine-derivative (K_i 36.7 nM), 3′-trifluoromethyl-derivative (K_i 18.3 nM) and 3′-methylthio-derivative (K_i 39.8 nM) of N-(1-naphthyl)-N’-(phenyl)-N’-(methyl)guanidine were identified as especially attractive leads for PET radioligand development. The synthesis of the target compounds was achieved using amines as reactants, such as 3-bromo-4-fluoro-N-(methyl)benzenamine, 1-naphthalenamine, 2-naphthalenamine, 1-isoquinolinamine, 5-isoquinolinamine, 8-quinolinamine and related substances [N-(methyl)arenamine] derivatives The title compounds thus formed included N-methyl-N-[3-(methylthio)phenyl]-N‘-(1-naphthalenyl)guanidine, N-methyl-N‘-(1-naphthalenyl)-N-[3-(trifluoromethyl)phenyl]guanidine, N-(4-fluoro-3-methylphenyl)-N-methyl-N‘-(-naphthalenyl)guanidine. In the experiment, the researchers used many compounds, for example, 5-Bromoisoquinolin-8-amine (cas: 90721-35-0Electric Literature of C9H7BrN2).

5-Bromoisoquinolin-8-amine (cas: 90721-35-0) belongs to isoquinoline derivatives. Quinoline is a mancude organic heterobicyclic parent, an azaarene, an ortho-fused heteroarene and a member of isoquinolines. Lewis acid activation and nucleophilic attack can produce multiple regioisomers in quinolines and pyridines; isoquinolines generally only undergo attack at the 1-position.Electric Literature of C9H7BrN2

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Polyazanaphthalenes. VII. Some derivatives of quinazoline and 1,3,5-triazanaphthalene was written by Oakes, V.;Rydon, H. N.;Undheim, K.. And the article was included in Journal of the Chemical Society in 1962.Related Products of 7574-67-6 This article mentions the following:

2,4-Diamino-6-methylquinazoline was synthesized and converted, by side-chain bromination of its dibenzoyl derivative, condensation with ethyl p-aminobenzoatc, and removal of the benzoyl and ester groups, into the pteroic acid analog (I). A similar procedure has led to the successful synthesis of pteroic acid analogs derived from 2,4-diamino- and 2-amino-4-hydroxy-1,3,5-triazanaphthalene. The expected preferential reactivity of the 4-chlorine atom in 2,4-dichloro-6-methylquinazoline is exhibited in its reactions with ammonia, hydrazine, and benzylamine, but not in that with aniline. In the experiment, the researchers used many compounds, for example, 3-Chloroisoquinolin-1-amine (cas: 7574-67-6Related Products of 7574-67-6).

3-Chloroisoquinolin-1-amine (cas: 7574-67-6) belongs to isoquinoline derivatives. Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. Isoquinoline-type alkaloids show biological activities similar to those of morphinane-, protoberberine-, and benzophenanthridine-type alkaloids.Related Products of 7574-67-6

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Design and synthesis of unique thiazoloisoquinolinium thiolates and derivatives was written by Ahmed, Wasim;Huang, Zi-Hao;Cui, Zi-Ning;Tang, Ri-Yuan. And the article was included in Chinese Chemical Letters in 2021.COA of Formula: C10H9NO This article mentions the following:

The synthesis of unique mesoionic thiazoloisoquinolinium thiolates stabilized by aromatization and 1,3-dipolarization. Herein, compounds were synthesized via the three component [2+2+1] cycloaddition reaction of isoquinolines with Et propionate and elemental sulfur in the absence of any metal catalyst and additives. Importantly, thiazoloisoquinolinium thiolates were transformed to thioether-containing thiazoloisoquinolinium halides. A selective [4+2] cycloaddition were also used to form S-bridged fused tetracyclic compounds with a thiothiamide ring unit and two quaternary carbon centers. Compound I showed good bioactivity against the chlorophyll of duckweed (Lemna minor) with inhibition rate of 51.5μg/mL. In the experiment, the researchers used many compounds, for example, 4-Methoxyisoquinoline (cas: 36034-54-5COA of Formula: C10H9NO).

4-Methoxyisoquinoline (cas: 36034-54-5) belongs to isoquinoline derivatives. Being an analog of pyridine, isoquinoline is a weak base, with a pKa of 5.14. It protonates to form salts upon treatment with strong acids, such as HCl. It forms adducts with Lewis acids, such as BF3.COA of Formula: C10H9NO

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Effect of acid on the electronic spectra of amines derived from heterocyclic aromatic amines was written by Basu, Sadhan. And the article was included in Journal de Chimie Physique et de Physico-Chimie Biologique in 1959.Product Details of 23707-37-1 This article mentions the following:

The shift in wave length of the electronic bands of several quinoline and isoquinoline amines in acid solution from the wave lengths in neutral solution are calculated by using mol. orbital methods. 2-, 3-, 4-, 5-, 6-, 7-, and 8-aminoquinolines have calculated (observed) shifts of -7 (-3), 22 (14), 0 (0), 73 (18), 31 (18), 38(10), and 50 (21) mμ. 1-, 3-, 4-, 5-, 6-, 7-, and 8-aminoisoquinolines similarly have shifts of -2 (6), 37 (28), 12 (17), 8 (19), 11 (11), 36 (18), 18 (14) mμ. Quinoline and isoquinoline themselves have shifts of 8 (6) and 13 (13) mμ. In the experiment, the researchers used many compounds, for example, Isoquinolin-7-amine (cas: 23707-37-1Product Details of 23707-37-1).

Isoquinolin-7-amine (cas: 23707-37-1) belongs to isoquinoline derivatives. Quinoline is a mancude organic heterobicyclic parent, an azaarene, an ortho-fused heteroarene and a member of isoquinolines. Other industrial applications include their use as corrosion inhibitors, preservatives, and as solvents for resins and terpenes.Product Details of 23707-37-1

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On the Pariser and Parr semiempirical method for computing molecular wave functions. The basic strength of N-heteroatomic compounds and their monoamines was written by Paradejordi, Federico. And the article was included in Cahiers de Physique in 1963.Recommanded Product: 23707-37-1 This article mentions the following:

The significance of the Pariser and Parr (PP) approximation is discussed; it is 1st intended to reproduce the results of the nonempirical S.C.F. method, while reducing considerably the calculations by suitable hypotheses; it is then intended to obtain a better agreement with exptl. data, and the at. bielectronic Coulomb integrals are estimated from the spectroscopic data of the free atoms; the PP approximations are justified for highly sym. hydrocarbons, and for conjugated hydrocarbons. Such approximations can be used, with a self-consistent mol. field, even for heteroat. mols., and without iteration in the calculations The semiempirical method is then applied for interpreting the basic strength of N-heteroat. mols. (pyridine, isoquinoleine, quinoleine, acridine) and their monoamines. Two terms of their energy of protonation, ΔE, (for B + H⁺ â‡?BH⁺) are computed; ΔE_π, for the delocalized bonds, is estimated by the PP semiempirical method; ΔE_solv., for solvatation, is computed by the modified Born formula. ΔE_π and ΔE_solv. are the major parts of ΔE, and ΔE_solv. is about 27% of ΔE_π; since ΔE_solv. depends mainly on the mol. size, only within a given family of mols. can the variations of pK_a = A ⁺ ΔE/2.3RT be predicted by considering the variations of ΔE_π alone. Still better agreement between theory and experiments should be obtained if the terms ΔEσ, for localized bonds, and ΔE_ster., for steric energy, could be computed. 116 references. In the experiment, the researchers used many compounds, for example, Isoquinolin-7-amine (cas: 23707-37-1Recommanded Product: 23707-37-1).

Isoquinolin-7-amine (cas: 23707-37-1) belongs to isoquinoline derivatives. Quinoline and its derivatives are widely used as fungicides, biological agents, antibiotics, alkaloids, dyes, rubber chemicals and flavoring agents. Isoquinoline-type alkaloids show biological activities similar to those of morphinane-, protoberberine-, and benzophenanthridine-type alkaloids.Recommanded Product: 23707-37-1

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

A Borrowing Hydrogen Strategy for Dehydrative Coupling of Aminoisoquinolines with Benzyl Alcohols in Water was written by Hikawa, Hidemasa;Tan, Rie;Tazawa, Aoi;Kikkawa, Shoko;Azumaya, Isao. And the article was included in European Journal of Organic Chemistry in 2020.COA of Formula: C9H8N2 This article mentions the following:

We report a borrowing hydrogen strategy for a palladium-catalyzed dehydrative coupling of aminoisoquinolines with benzylic alcs. in water. This cascade reaction using the π-benzylpalladium system can be achieved in an atom-economic process without the need for base or other additives, furnishing the N-benzylated aminoisoquinolines in moderate to excellent yields along with water as the sole co-product. The crossover experiment using [D₇]benzyl alc. and 4-methoxybenzyl alc. afforded H/D scrambled products. KIE experiments showed that benzylic C-H bond cleavage of benzyl alc. was involved in the turnover limiting step (KIE = 4.4). The coupling reaction was found to be first order in benzyl alc. with a kinetic solvent isotope effect (KSIE) of 1.6. These exptl. results are consistent with a borrowing hydrogen mechanism in water. Notably, the water-soluble Pd⁰/TPPMS system can be applied to the more challenging catalytic benzylic amination with aminoisoquinoline nucleophiles despite the possible deactivation of Pd^II species. In the experiment, the researchers used many compounds, for example, Isoquinolin-7-amine (cas: 23707-37-1COA of Formula: C9H8N2).

Isoquinolin-7-amine (cas: 23707-37-1) belongs to isoquinoline derivatives. Quinoline and its derivatives are widely used as fungicides, biological agents, antibiotics, alkaloids, dyes, rubber chemicals and flavoring agents. Isoquinoline-type alkaloids show biological activities similar to those of morphinane-, protoberberine-, and benzophenanthridine-type alkaloids.COA of Formula: C9H8N2

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

The swamping catalyst effect. VI. The halogenation of isoquinoline and quinoline was written by Gordon, Marshall;Pearson, D. E.. And the article was included in Journal of Organic Chemistry in 1964.Recommanded Product: 90721-35-0 This article mentions the following:

Halogenation of the aluminum chloride complexes of isoquinoline or quinoline gave in good yield halogen derivatives substituted in the benzenoid ring. Bromination of the aluminum chloride-isoquinoline complex gave the following sequence in substitution: 5-bromo-, 5,8-dibromo-, 5,7,8-tribromo-. To obtain good yields of 5,7,8-tribromoisoquinoline, it was necessary to brominate 5,8-dibromoisoquinoline, not isoquinoline itself. Bromination of the aluminum chloride complex of quinoline gave similar results except that 5,6,8-tribromoquinoline was obtained by bromination of 5,8-dibromoquinoline. Chlorination of the aluminum chloride complexes of both quinoline and isoquinoline gave results very similar to bromination. 5,6,7,8-Tetrabromo- and 5,6,7,8-tetrachloroquinoline were isolated also. Identification of many of these compounds was carried out by synthesis from known compounds In the experiment, the researchers used many compounds, for example, 5-Bromoisoquinolin-8-amine (cas: 90721-35-0Recommanded Product: 90721-35-0).

5-Bromoisoquinolin-8-amine (cas: 90721-35-0) belongs to isoquinoline derivatives. Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. Isoquinoline-type alkaloids show biological activities similar to those of morphinane-, protoberberine-, and benzophenanthridine-type alkaloids.Recommanded Product: 90721-35-0

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Iron-catalyzed tandem oxidative coupling and acetal hydrolysis reaction to prepare formylated benzothiazoles and isoquinolines was written by Wu, Yue;Guo, Peng;Chen, Long;Duan, Weijie;Yang, Zengzhuan;Wang, Tao;Chen, Ting;Xiong, Fei. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2021.Recommanded Product: 36034-54-5 This article mentions the following:

The direct formylation of benzothiazoles and isoquinolines was reported. The reaction features a novel iron-catalyzed Minisci-type oxidative coupling process using com. available 1,3-dioxolane as a formylated reagent followed by acetal hydrolysis without a separation process. The reaction was performed under exceedingly mild reaction conditions and exhibited broad functional group tolerance. In the experiment, the researchers used many compounds, for example, 4-Methoxyisoquinoline (cas: 36034-54-5Recommanded Product: 36034-54-5).

4-Methoxyisoquinoline (cas: 36034-54-5) belongs to isoquinoline derivatives. Being an analog of pyridine, isoquinoline is a weak base, with a pKa of 5.14. Lewis acid activation and nucleophilic attack can produce multiple regioisomers in quinolines and pyridines; isoquinolines generally only undergo attack at the 1-position.Recommanded Product: 36034-54-5

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Heterocyclic compounds. I. Synthesis of aminoisoquinoline derivatives was written by Okano, Teisuke;Goya, Shujiro;Tsuda, Yoshinao. And the article was included in Yakugaku Zasshi in 1966.Synthetic Route of C9H7ClN2 This article mentions the following:

A new method for the synthesis of 3-aminoisoquinoline derivatives was proposed where Me o-cyanomethylbenzoate (I) was treated with aqueous amine under mild conditions to give an isoquinoline ring with NH₂ group in 3-position. Thus, 20 g. o-carboxyphenylacetonitrile is added to an ethereal solution of 5.6 g. CH₂N₂, the whole kept overnight, AcOH added, evaporated, and the residue distilled in vacuo to give 19 g. I, b₂ 135-7°, m. 48.5-49° (MeOH). Methylation of o-cyanomethylbenzoic acid also gave I. I (4 g.) and 50 ml. 28% NH₄OH are heated in a sealed tube at 50-60° for 40 hrs. to give 1.8 g. 3-aminoisocarbostyril (II), m. 265° (decomposition) (MeOH); diacetate m. 177°; benzoate m. 271-2°. Similar treatment of I with MeNH₂ gives 2-methyl-3-aminoisocarbostyril, m. 188° (EtOH). II (1 g.) is refluxed 3 hrs. with 11 ml. POCl₃, an excess of POCl₃ removed in vacuo, the residue poured into iced H₂O, and the mixture made alk. with 10% NaOH and distilled with steam to give 0.9 g. 1-chloro-2-aminoisoquinoline (III), yellow plates, m. 147-8°. Catalytic reduction of 0.2 g. III in EtOH (containing KOH) using 10% Pd-C gives 0.1 g. 3-aminoisoquinoline, yellow needles, m. 177-8° (C₆H₆). Heating of 3 g. 1,3-dichloroisoquinoline in a sealed tube at 175° 6 hrs. with 50 ml. 28% NH₄OH and a small amount of CuSO₄ gives 2.8 g. 1-amino-3-chloroisoquinoline, m. 154-5° (EtOH) which is further subjected to catalytic reduction to give 1-aminoisoquinoline, m. 122-3° (C₆H₆); picrate m. 280°. In the experiment, the researchers used many compounds, for example, 3-Chloroisoquinolin-1-amine (cas: 7574-67-6Synthetic Route of C9H7ClN2).

3-Chloroisoquinolin-1-amine (cas: 7574-67-6) belongs to isoquinoline derivatives. Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. Isoquinoline-type alkaloids show biological activities similar to those of morphinane-, protoberberine-, and benzophenanthridine-type alkaloids.Synthetic Route of C9H7ClN2

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem