Month: January 2023

Fragment-based lead discovery of indazole-based compounds as AXL kinase inhibitors was written by Ng, Pearly Shuyi;Foo, Klement;Sim, Sandra;Wang, Gang;Huang, Chuhui;Tan, Li Hong;Poulsen, Anders;Liu, Boping;Tee, Doris Hui Ying;Ahmad, Nur Huda Binte;Wang, Sifang;Ke, Zhiyuan;Lee, May Ann;Kwek, Zekui P.;Joy, Joma;Anantharajan, Jothi;Baburajendran, Nithya;Pendharkar, Vishal;Manoharan, Vithya;Vuddagiri, Susmitha;Sangthongpitag, Kanda;Hill, Jeffrey;Keller, Thomas H.;Hung, Alvin W.. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Reference of 90721-35-0 This article mentions the following:

AXL is a member of the TAM (TYRO3, AXL, MER) subfamily of receptor tyrosine kinases. It is upregulated in a variety of cancers and its overexpression is associated with poor disease prognosis and acquired drug resistance. Utilizing a fragment-based lead discovery approach, a new indazole-based AXL inhibitor was obtained. The indazole fragment hit 11, identified through a high concentration biochem. screen, was expeditiously improved to fragment 24 by screening our inhouse expanded library of fragments (ELF) collection. Subsequent fragment optimization guided by docking studies provided potent inhibitor 54 with moderate exposure levels in mice. X-ray crystal structure of analog 50 complexed with the I650M mutated kinase domain of Mer revealed the key binding interactions for the scaffold. The good potency coupled with reasonable kinase selectivity, moderate in vivo exposure levels, and availability of structural information for the series makes it a suitable starting point for further optimization efforts. In the experiment, the researchers used many compounds, for example, 5-Bromoisoquinolin-8-amine (cas: 90721-35-0Reference of 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.Reference of 90721-35-0

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Dihydroisoquinolinones: the design and synthesis of a new series of potent inhibitors of poly(ADP-ribose) polymerase was written by Suto, M. J.;Turner, W. R.;Arundel-Suto, C. M.;Werbel, L. M.;Sebolt-Leopold. And the article was included in Anti-Cancer Drug Design in 1991.Safety of 7-Nitro-3,4-dihydroisoquinolin-1(2H)-one This article mentions the following:

A series of dihydroisoquinolinones I(R = 5-, 6-, 7-, 8-OH, 5-, 6-, 7-OMe, 5-, 7-NO₂, 5-, 7-NH₂, H) and isoquinolinones II (R¹ = H, OH, OMe, NO₂, NH₂), formally rigid analogs of 3-substituted benzamides, and a series of disubstituted benzamides III (R² = H, Me; R³ = Me, Et, Pr, vinyl) were synthesized and evaluated as inhibitors of poly(ADP-ribose) polymerase. The results indicated that the orientation of the amide with respect to the substituent on the aromatic ring was critical for optimum inhibitory activity. Selected compounds were also evaluated for their ability to modify the radiation response of mammalian cells to ionizing radiation. A number of the 5-substituted I were very potent inhibitors of the enzyme, were able to enhance the lethal effects of ionizing radiation in mammalian cells, as measured by changes in the survival curve parameters D_o and/or D_q. In the experiment, the researchers used many compounds, for example, 7-Nitro-3,4-dihydroisoquinolin-1(2H)-one (cas: 22245-96-1Safety of 7-Nitro-3,4-dihydroisoquinolin-1(2H)-one).

7-Nitro-3,4-dihydroisoquinolin-1(2H)-one (cas: 22245-96-1) belongs to isoquinoline derivatives. Quinoline and its derivatives are widely used as fungicides, biological agents, antibiotics, alkaloids, dyes, rubber chemicals and flavoring agents. Other industrial applications include their use as corrosion inhibitors, preservatives, and as solvents for resins and terpenes.Safety of 7-Nitro-3,4-dihydroisoquinolin-1(2H)-one

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Metal-, photocatalyst-, and light-free late-stage C-H alkylation of N-heteroarenes with organotrimethylsilanes using persulfate as a stoichiometric oxidant was written by Dong, Jianyang;Wang, Xiaochen;Wang, Zhen;Song, Hongjian;Liu, Yuxiu;Wang, Qingmin. And the article was included in Organic Chemistry Frontiers in 2019.HPLC of Formula: 36034-54-5 This article mentions the following:

Benzylsilanes and heteroatom substituted silanes underwent homolytic cleavage to form C(sp³)-centered radicals that can participate in C-H alkylation reactions with N-heteroarenes under oxidative conditions has been reported. These reactions take place under mild conditions with persulfate as a stoichiometric oxidant and do not require a metal, a photocatalyst, light, or high temperature, making the reactions suitable for late-stage C-H alkylation of complex mols. The utility of the method was demonstrated by the preparation or functionalization of several structurally complex drugs and natural products. In the experiment, the researchers used many compounds, for example, 4-Methoxyisoquinoline (cas: 36034-54-5HPLC of Formula: 36034-54-5).

4-Methoxyisoquinoline (cas: 36034-54-5) belongs to isoquinoline derivatives. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. Lewis acid activation and nucleophilic attack can produce multiple regioisomers in quinolines and pyridines; isoquinolines generally only undergo attack at the 1-position.HPLC of Formula: 36034-54-5

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Mass spectra of the aminoisoquinolines and 5-amino-15N-isoquinoline was written by Brown, Ellis V.;Mitchell, Stanley R.. And the article was included in Organic Mass Spectrometry in 1972.HPLC of Formula: 23707-37-1 This article mentions the following:

The mass spectra of the isomeric aminoisoquinolines and 5-amino-15N-isoquinoline are reported. In the aminoisoquinolines, the major fragmentation pathway was the loss of 2 mols. of HCN and a H atom to give the m/e 89 fragment ion. Two addnl. pathways culminating with this ion were observed The mass spectrum of 5-amino-15N-isoquinoline showed a preference of 4 to 1 for loss of HC15N (benzenoid amine group) over HC14N (heterocyclic N) from the mol. ion. In the experiment, the researchers used many compounds, for example, Isoquinolin-7-amine (cas: 23707-37-1HPLC of Formula: 23707-37-1).

Isoquinolin-7-amine (cas: 23707-37-1) belongs to isoquinoline derivatives. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. Most traditional methods of generating isoquinoline do so via oxidative aromatization of dihydro- or tetrahydro-isoquinolines, usually offering some environmental or economic advantage.HPLC of Formula: 23707-37-1

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

The imidazo[1,2-a]pyridine ring system as a scaffold for potent dual phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors was written by Stec, Markian M.;Andrews, Kristin L.;Bo, Yunxin;Caenepeel, Sean;Liao, Hongyu;McCarter, John;Mullady, Erin L.;San Miguel, Tisha;Subramanian, Raju;Tamayo, Nuria;Whittington, Douglas A.;Wang, Ling;Wu, Tian;Zalameda, Leeanne P.;Zhang, Nancy;Hughes, Paul E.;Norman, Mark H.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2015.Related Products of 23707-37-1 This article mentions the following:

Based on lead compound, which was discovered from a high-throughput screen, a series of PI3Kα/mTOR inhibitors were evaluated that contained an imidazo[1,2-a]pyridine as a core replacement for the benzimidazole contained in the lead. By exploring various ring systems that occupy the affinity pocket, two fragments containing a methoxypyridine were identified that gave <100 nM potency toward PI3Kα in enzyme and cellular assays with moderate stability in rat and human liver microsomes. With the two methoxypyridine groups selected to occupy the affinity pocket, analogs were prepared with various fragments intended to occupy the ribose pocket of PI3Kα and mTOR. From these analogs, tertiary alc. I was chosen for in vivo pharmacodynamic evaluation based on its potency in the PI3Kα cellular assay, microsomal stability, and in vivo pharmacokinetic properties. In a mouse liver pharmacodynamic assay, compound I showed 56% inhibition of HFG-induced AKT (Ser473) phosphorylation at a 30 mg/kg dose. In the experiment, the researchers used many compounds, for example, Isoquinolin-7-amine (cas: 23707-37-1Related Products of 23707-37-1).

Isoquinolin-7-amine (cas: 23707-37-1) belongs to isoquinoline derivatives. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. They are also used to make oil-soluble dyes, food colorants, pharmaceuticals, pH indicators and other organic compounds. Related Products of 23707-37-1

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Substituent effect on local aromaticity in mono and di-substituted heterocyclic analogs of naphthalene was written by Mohajeri, Afshan;Shahamirian, Mozhgan. And the article was included in Journal of Physical Organic Chemistry in 2010.Synthetic Route of C10H9NO This article mentions the following:

A quant. study on local aromaticity has been performed on a series of mono- and di-substituted biheterocycles (quinoline, isoquinoline, quinoxaline, quinazoline). Three electronically based indexes (PDI, ATI, and FLU) have been employed to investigate the substituent effect on the π-electron delocalization in both heterocycle and benzenoid rings. Three typical substituents (Cl, OCH₃, and CN) with different inductive and resonance power have been selected. Generally, substituent causes a reduction in aromaticity irresp. of whether it is electron attracting or electron donating. It is shown that the maximum aromaticity exhibits a similar trend of Cl > CN > OCH₃ for all the studied rings. Moreover, it is found that the substituent situation with respect to the heteroatom has a significant influence on the aromaticity. It results from our study that in di-substituted derivatives, irresp. of whether the two substituents form a meta or para isomer, they preferably choose the position which leads to the maximum aromaticity character. Copyright © 2009 John Wiley & Sons, Ltd. In the experiment, the researchers used many compounds, for example, 4-Methoxyisoquinoline (cas: 36034-54-5Synthetic Route of C10H9NO).

4-Methoxyisoquinoline (cas: 36034-54-5) belongs to isoquinoline derivatives. Quinoline and isoquinoline skeletons are among the most attractive frameworks with a wide range of biological and pharmacological activities. The discovery of chloroquine, the most well-known drug containing this stent, has helped bring about decades of malaria control and treatment.Synthetic Route of C10H9NO

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Protonation Switching to the Least-Basic Heteroatom of Carbamate through Cationic Hydrogen Bonding Promotes the Formation of Isocyanate Cations was written by Kurouchi, Hiroaki;Sumita, Akinari;Otani, Yuko;Ohwada, Tomohiko. And the article was included in Chemistry – A European Journal in 2014.Category: isoquinoline This article mentions the following:

Ortho-(methoxycarbonyl)phenyl phenethylcarbamates underwent rapid cyclocondensation mediated by triflic acid to yield dihydroisoquinolinones with improved chemoselectivities over other phenethylcarbamates; the improved rate of cyclization is attributed to the improved formation of labile protonated carbamates and isocyanates, formed by protonation of the carbamate ester oxygen atom (rather than the carbamate carbonyl oxygen atom) mediated through hydrogen bonding to the pendant methoxycarbonyl group. The mechanism of the cyclocondensations of ortho-(methoxycarbonyl)phenyl phenethylcarbamates was studied through determination of the kinetics of other substituted phenethylcarbamates and of the dependence of cyclocondensation rate on acidity, through calculations of the transition state free energies, entropies, and enthalpies, and through NMR spectroscopy of models of mono- and diprotonated salicylates. Triflic acid-mediated monoprotonation of the carbamoyl salicylates yielded reactive protonated carbamates and isocyanates; in contrast, superacid-mediated diprotonation at the Me ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo carbon-oxygen bond cleavage. In the experiment, the researchers used many compounds, for example, 7-Nitro-3,4-dihydroisoquinolin-1(2H)-one (cas: 22245-96-1Category: isoquinoline).

7-Nitro-3,4-dihydroisoquinolin-1(2H)-one (cas: 22245-96-1) belongs to isoquinoline derivatives. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. Lewis acid activation and nucleophilic attack can produce multiple regioisomers in quinolines and pyridines; isoquinolines generally only undergo attack at the 1-position.Category: isoquinoline

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Syntheses of hydrogenated quinolines and isoquinolines as analgesics. X. Oxidation of alkylpyridines was written by Sugimoto, Norio;Kugita, Hiroshi;Tanaka, Tadashi. And the article was included in Yakugaku Zasshi in 1956.Application of 135311-97-6 This article mentions the following:

Oxidation of 2- (I), 3- (II) and 4-EtC₅H₄N (III) and the 1-oxides with CrO₃ effected oxidation in the order of II > III > I to the corresponding AcC₅H₄N in 50-15% yield. Oxidation of 15 g. 5,6,7,8-tetrahydroisoquinoline in 80 ml. AcOH and 30 g. concentrated H₂SO₄ at 10-5° with 16 g. CrO₃ in 9 ml. water and 45 ml. AcOH by keeping overnight, removing the AcOH in vacuo, alkalifying with NaOH and extracting with Et₂O yielded 8-oxo- (IV), b₄ 123-4°, and 5-oxo-5,6,7,8-tetrahydroisoquinoline (V), b₄ 113-15°, in 2:1 ratio; IV.HCl, m. 227-9°, and V.HCl, m. 235-6°. In the experiment, the researchers used many compounds, for example, 6,7-Dihydroisoquinolin-8(5H)-one hydrochloride (cas: 135311-97-6Application of 135311-97-6).

6,7-Dihydroisoquinolin-8(5H)-one hydrochloride (cas: 135311-97-6) belongs to isoquinoline derivatives. Quinoline is a catabolite of tryptophan, the basic structure of some antihypertensive drugs, such as the peripheral vasodilators prazosin and doxazosin. It protonates to form salts upon treatment with strong acids, such as HCl. It forms adducts with Lewis acids, such as BF3.Application of 135311-97-6

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Mild and General Palladium-Catalyzed Synthesis of Methyl Aryl Ethers Enabled by the Use of a Palladacycle Precatalyst was written by Cheung, Chi Wai;Buchwald, Stephen L.. And the article was included in Organic Letters in 2013.Computed Properties of C10H9NO This article mentions the following:

A general method for the Pd-catalyzed coupling of methanol with (hetero)aryl halides is described. The reactions proceed under mild conditions with a wide range of aryl and heteroaryl halides to give Me aryl ethers in high yield. E.g., in presence of palladacycle precatalyst I (L = tBuBrettPhos) and the ligand tBuBrettPhos, arylation of MeOH by 4-Me₃CC₆H₄Cl gave 93% 4-Me₃CC₆H₄OMe. In the experiment, the researchers used many compounds, for example, 4-Methoxyisoquinoline (cas: 36034-54-5Computed Properties of C10H9NO).

4-Methoxyisoquinoline (cas: 36034-54-5) belongs to isoquinoline derivatives. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. The Pomeranz–Fritsch reaction provides a method for the preparation of isoquinoline. This reaction uses a benzaldehyde and aminoacetoaldehyde diethyl acetal, which in an acid medium react to form isoquinoline.Computed Properties of C10H9NO

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

DMSO as a Switchable Alkylating Agent in Heteroarene C-H Functionalization was written by Garza-Sanchez, R. Aleyda;Patra, Tuhin;Tlahuext-Aca, Adrian;Strieth-Kalthoff, Felix;Glorius, Frank. And the article was included in Chemistry – A European Journal in 2018.Synthetic Route of C9H8N2 This article mentions the following:

A novel strategy for the activation of DMSO to act as a versatile alkylating agent in heteroarene C-H functionalization. This direct, simple and mild switch between methylation/trideuteromethylation and methylthiomethylation of heteroarenes was achieved under reagent-controlled photoredox catalysis conditions. The proposed mechanism was supported by both exptl. and computational studies. 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. Isoquinoline is a structural isomer of quinoline, which have antiseptic, antipyretic and anti-cyclic properties, and can be used as antimalarial drugs and for the preparation of other antimalarial medicine. 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