Category: 552331-06-3

Teng, Min; Hilgers, Mark T.; Cunningham, Mark L.; Borchardt, Allen; Locke, Jeffrey B.; Abraham, Sunny; Haley, Gregory; Kwan, Bryan P.; Hall, Courtney; Hough, Grayson W.; Shaw, Karen J.; Finn, John published the artcile< Identification of Bacteria-Selective Threonyl-tRNA Synthetase Substrate Inhibitors by Structure-Based Design>, Synthetic Route of 552331-06-3, the main research area is bacteria threonyl tRNA synthetase substrate design crystal structure.

A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologs tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.

Journal of Medicinal Chemistry published new progress about Antimicrobial agents. 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Synthetic Route of 552331-06-3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Shi, Jianyi; Chen, Zhichao; Lu, Yantong; Xu, Shengting; Wen, Tingting; Luo, Yuehua; Zhu, Zhongzhi; Chen, Xiuwen published the artcile< Nucleophilic Dearomatization Strategy to Synthesize Disubstituted 3-Isoquinolinones under Transition Metal-Free Conditions>, Synthetic Route of 552331-06-3, the main research area is haloisoquinoline alkyl halide indole three component reaction green chem; benzyl indolyl dihydroisoquinolinone preparation.

Herein, a one-pot protocol for constructing the disubstituted isoquinolinone derivatives via the three-component reactions of 3-haloisoquinolines, alkyl halides, and indoles under transition-metal-free conditions was described. The reaction realized the trifunctionalization of isoquinoline via a dearomatization strategy, which displayed high chem. selectivity, excellent functional group tolerance, and a wide range of substrates, and was environmentally friendly. The three-component coupling involves the construction of new C-N, C=O, and C-C bonds in one step.

Journal of Organic Chemistry published new progress about Aralkyl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Synthetic Route of 552331-06-3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Mackman, Richard L.; Steadman, Victoria A.; Dean, David K.; Jansa, Petr; Poullennec, Karine G.; Appleby, Todd; Austin, Carol; Blakemore, Caroline A.; Cai, Ruby; Cannizzaro, Carina; Chin, Gregory; Chiva, Jean-Yves C.; Dunbar, Neil A.; Fliri, Hans; Highton, Adrian J.; Hui, Hon; Ji, Mingzhe; Jin, Haolun; Karki, Kapil; Keats, Andrew J.; Lazarides, Linos; Lee, Yu-Jen; Liclican, Albert; Mish, Michael; Murray, Bernard; Pettit, Simon B.; Pyun, Peter; Sangi, Michael; Santos, Rex; Sanvoisin, Jonathan; Schmitz, Uli; Schrier, Adam; Siegel, Dustin; Sperandio, David; Stepan, George; Tian, Yang; Watt, Gregory M.; Yang, Hai; Schultz, Brian E. published the artcile< Discovery of a potent and orally bioavailable cyclophilin inhibitor derived from the sanglifehrin macrocycle>, Synthetic Route of 552331-06-3, the main research area is cyclic peptidomimetic total synthesis orally bioavailable cyclophilin inhibitor; drug discovery antihepatitis C virus agent structure activity; isoquinoline peptide Stille coupling hydrolysis reduction vinylation RCM macrolactamization; mol docking crystal structure.

Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead (I) derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor (II). The macrocycle ring size was reduced by one atom, and an internal hydrogen bond drove improved permeability and drug-like properties. II demonstrates potent Cyp inhibition (Kd = 5 nM), potent anti-HCV 2a activity (EC50 = 98 nM), and high oral bioavailability in rat (100%) and dog (55%). The synthetic accessibility and properties of II support its potential as an anti-HCV agent and for interrogating the role of Cyp inhibition in a variety of diseases.

Journal of Medicinal Chemistry published new progress about Anti-hepatitis C virus agents. 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Synthetic Route of 552331-06-3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Liang, Jun; Van Abbema, Anne; Balazs, Mercedesz; Barrett, Kathy; Berezhkovsky, Leo; Blair, Wade S.; Chang, Christine; Delarosa, Donnie; De Voss, Jason; Driscoll, Jim; Eigenbrot, Charles; Goodacre, Simon; Ghilardi, Nico; MacLeod, Calum; Johnson, Adam; Bir Kohli, Pawan; Lai, Yingjie; Lin, Zhonghua; Mantik, Priscilla; Menghrajani, Kapil; Nguyen, Hieu; Peng, Ivan; Sambrone, Amy; Shia, Steven; Smith, Jan; Sohn, Sue; Tsui, Vickie; Ultsch, Mark; Williams, Karen; Wu, Lawren C.; Yang, Wenqian; Zhang, Birong; Magnuson, Steven published the artcile< Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model>, Synthetic Route of 552331-06-3, the main research area is imidazopyridine derivative preparation TYK2 inhibitor psoriasis; IL-23; Imidazopyridine; Kinase; Psoriasis; TYK2.

Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model. In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients.

Bioorganic & Medicinal Chemistry Letters published new progress about Antipsoriatic agents. 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Synthetic Route of 552331-06-3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zhu, Gui-Dong; Gong, Jianchun; Claiborne, Akiyo; Woods, Keith W.; Gandhi, Viraj B.; Thomas, Sheela; Luo, Yan; Liu, Xuesong; Shi, Yan; Guan, Ran; Magnone, Shayna R.; Klinghofer, Vered; Johnson, Eric F.; Bouska, Jennifer; Shoemaker, Alexander; Oleksijew, Anatol; Stoll, Vincent S.; De Jong, Ron; Oltersdorf, Tilman; Li, Qun; Rosenberg, Saul H.; Giranda, Vincent L. published the artcile< Isoquinoline-pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity>, Synthetic Route of 552331-06-3, the main research area is isoquinoline pyridine derivative preparation Akt kinase inhibitor.

The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major shortcomings of the lead compound (I), including poor pharmacokinetic profiles in several species (e.g., mouse iv t1/2 = 0.3 h, po F = 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t1/2 = 5.0 h, po F = 51%) but resulted in >500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog (II) significantly slowed the tumor growth, however was accompanied by toxicity.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Synthetic Route of 552331-06-3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Liang, Jun; Van Abbema, Anne; Balazs, Mercedesz; Barrett, Kathy; Berezhkovsky, Leo; Blair, Wade S.; Chang, Christine; Delarosa, Donnie; De Voss, Jason; Driscoll, Jim; Eigenbrot, Charles; Goodacre, Simon; Ghilardi, Nico; MacLeod, Calum; Johnson, Adam; Bir Kohli, Pawan; Lai, Yingjie; Lin, Zhonghua; Mantik, Priscilla; Menghrajani, Kapil; Nguyen, Hieu; Peng, Ivan; Sambrone, Amy; Shia, Steven; Smith, Jan; Sohn, Sue; Tsui, Vickie; Ultsch, Mark; Williams, Karen; Wu, Lawren C.; Yang, Wenqian; Zhang, Birong; Magnuson, Steven published the artcile< Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model>, Computed Properties of 552331-06-3, the main research area is imidazopyridine derivative preparation TYK2 inhibitor psoriasis; IL-23; Imidazopyridine; Kinase; Psoriasis; TYK2.

Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model. In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients.

Bioorganic & Medicinal Chemistry Letters published new progress about Antipsoriatic agents. 552331-06-3 belongs to class isoquinoline, and the molecular formula is C9H5BrClN, Computed Properties of 552331-06-3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

552331-06-3,552331-06-3, 6-Bromo-3-chloroisoquinoline is a isoquinoline compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

3-Chloro-6-(pyrimidin-5-yl)isoquinoline Method E A suspension of 6-bromo-3-chloroisoquinoline (62 mg, 0.27 mmol), pyrimidin-5- ylboronic acid (45 mg, 0.36 mmol), Pd(PPh3)4 (29.5 mg, 0.026 mmol) and CsF (1 17 mg, 0.77 mmol) in DME/MeOH (3/1 mL) was stirred at 150 X1 under microwave irradiation for 30 minutes. The reaction mixture was filtered and concentrated in vacuo. The residue was purified using Biotage silica gel column chromatography eluting with between 20- 60% EtOAc in cyclohexane to afford the title compound (26 mg, 42%). 1 H NMR (500 MHz, CDCI3): delta 9.32 (s, 1 H), 9.17 (s, 1 H), 9.09 (s, 2H), 8.16 (dt, J = 8.5, 0.9 Hz, 1 H), 7.98 (dd, J = 1 .8, 0.9 Hz, 1 H), 7.88 – 7.78 (m, 2H). LCMS (ESI) Rt = 2.14 minutes MS m/z 242 [M+H]+

As the paragraph descriping shows that 552331-06-3 is playing an increasingly important role.

Reference£º
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; HOELDER, Swen; BLAGG, Julian; CHEUNG, Jack; ATRASH, Butrus; SHELDRAKE, Peter; WO2014/37751; (2014); A1;,
Isoquinoline – Wikipedia
Isoquinoline | C9H7N – PubChem

552331-06-3,552331-06-3, 6-Bromo-3-chloroisoquinoline is a isoquinoline compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Synthesis of Compound 2e: A solution of 6-bromo-3-chloro-isoquinoline (Frontier Scientific, Logan, Utah USA) (8.0 g, 33 mmol) and tributyl-(1-ethoxy-vinyl)-stannane (14.88 g, 14 mL, 41.2 mmol) in toluene (100 mL) was degassed with nitrogen for 30 min. Bis(triphenylphosphine)palladium(ll) dichloride (1.16 g, 1 .65 mmol, 5 mol%) was added and the reaction mixture was heated at 60 C for 20 h. The reaction mixture was cooled to room temperature, the mixture was filtered and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of /’so-hexanes/ethyl acetate 20:1 to 10:1 to afford the title compound (7.1 g, 92%) as a pale yellow solid.

As the paragraph descriping shows that 552331-06-3 is playing an increasingly important role.

Reference£º
Patent; GILEAD SCIENCES, INC.; SELCIA LIMITED; STEADMAN, Victoria Alexandra; POULLENNEC, Karine G.; LAZARIDES, Linos; ACIRO, Caroline; DEAN, David Kenneth; KEATS, Andrew John; SIEGEL, Dustin Scott; SCHRIER, Adam James; MACKMAN, Richard; JANSA, Petr; WO2013/185093; (2013); A1;,
Isoquinoline – Wikipedia
Isoquinoline | C9H7N – PubChem

552331-06-3,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.552331-06-3,6-Bromo-3-chloroisoquinoline,as a common compound, the synthetic route is as follows.

A solution of 6-bromo-3-chloro-isoquinoline (8.0 g, 33 mmol) and tributyl-(1 -ethoxyvinyl)- tin (14.88 g, 14 ml_, 41 .2 mmol) in toluene (100 ml.) was degassed with nitrogen for 30 min. Bis(triphenylphosphine)palladium(ll) dichloride (1.16 g, 1 .65 mmol, 5 mol%) was added and the reaction mixture was heated at 60C for 20 h. The reaction mixture was cooled to RT, the mixture was filtered and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of /’so-hexanes/ethyl acetate 20:1 to 10:1 to afford the title compound (7.1 g, 92%) as a yellow solid

The synthetic route of 552331-06-3 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; GILEAD SCIENCES, INC.; SELCIA LIMITED; ACIRO, Caroline; STEADMAN, Victoria Alexandra; PETTIT, Simon Neil; POULLENNEC, Karine G.; LAZARIDES, Linos; DEAN, David Kenneth; DUNBAR, Neil Andrew; HIGHTON, Adrian John; KEATS, Andrew John; SIEGEL, Dustin Scott; KARKI, Kapil Kumar; SCHRIER, Adam James; JANSA, Petr; MACKMAN, Richard; WO2013/185103; (2013); A1;,
Isoquinoline – Wikipedia
Isoquinoline | C9H7N – PubChem

552331-06-3,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.552331-06-3,6-Bromo-3-chloroisoquinoline,as a common compound, the synthetic route is as follows.

Step 2 To a mixture of 6-bromo-3-chloro-isoquinoline (XII) (0.5 g, 2.06 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(trideuteriomethyl)pyrazole (LXX) (1.305 g, 6.19 mmol) and SPhos Pd G4 (81.9 mg, 0.100 mmol) in 1,4-dioxane (10 mL) and was added a 2 M aqueous solution of K2CO3 (3.88 mL, 7.77 mmol). N2 gas was bubbled into the mixture for 10 min and then the mixture was heated to 110 C. for 0.5 h in a microwave. The organic layer was carefully separated, absorbed on silica gel and purified by column chromatography (0?100% hexanes/EtOAc) to obtain 3-chloro-6-[1-(trideuteriomethyl)pyrazol-4-yl]isoquinoline (LXXI) (400 mg, 1.62 mmol, 78.6% yield) as an off-white solid. ESIMS found for C13H7[2H3]ClN3 m/z 246.9 (M+1).

The synthetic route of 552331-06-3 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Samumed, LLC; KC, Sunil Kumar; Mittapalli, Gopi Kumar; Hofilena, Brian Joseph; Marakovits, Joseph Timothy; Chiruta, Chandramouli; Mak, Chi Ching; Cao, Jianguo; (324 pag.)US2017/313681; (2017); A1;,
Isoquinoline – Wikipedia
Isoquinoline | C9H7N – PubChem