Garenoxacin

Base Information

• Chemical Name: Garenoxacin
• CAS No.: 194804-75-6
• Deprecated CAS: 345632-74-8
• Molecular Formula: C23H20F2N2O4
• Molecular Weight: 426.42
• UNII: V72H9867WB
• DSSTox Substance ID: DTXSID30173135
• Nikkaji Number: J1.099.977D
• Wikipedia: Garenoxacin
• Wikidata: Q3758306
• NCI Thesaurus Code: C65800
• ChEMBL ID: CHEMBL215303
• Mol file: 194804-75-6.mol

Synonyms:BMS 284756;BMS-284756;BMS284756;garenoxacin

Chemical Property of Garenoxacin

Chemical Property:

• Vapor Pressure: 2.29E-14mmHg at 25°C
• Melting Point: 226-227°; mp 234-235°
• Boiling Point: 581.5 °C at 760 mmHg
• PKA: 6.44±0.50(Predicted)
• Flash Point: 305.5 °C
• PSA: 80.56000
• Density: 1.421g/cm³
• LogP: 4.79600
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMF (Slightly, Heated), DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• XLogP3: 2.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 5
• Exact Mass: 426.13911345
• Heavy Atom Count: 31
• Complexity: 771

Purity/Quality:

99.5% ^*data from raw suppliers

Garenoxacin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1C2=C(CN1)C=C(C=C2)C3=C(C4=C(C=C3)C(=O)C(=CN4C5CC5)C(=O)O)OC(F)F
• Isomeric SMILES: C[C@@H]1C2=C(CN1)C=C(C=C2)C3=C(C4=C(C=C3)C(=O)C(=CN4C5CC5)C(=O)O)OC(F)F
• Recent EU Clinical Trials: Thorough QT/QTc study for Garenoxacin
• Recent NIPH Clinical Trials: Clinical efficacy of garenoxacin for treatment of bacterial respiratory infection secondary to chronic respiratory disease
• Description: Garenoxacin is a new quinolone antimicrobial agent that exhibits a broad spectrum of activity against both Gram-negative and Gram-positive organisms, including the important community-acquired respiratory pathogens S.pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In addition, it has potent activity against several resistant strains such as multidrug-resistant S.pneumoniae, methicillin-resistant S.aureus (MRSA), and vancomycin-resistant enterococci (VRE). It was launched in Japan as an oral treatment for respiratory tract and otorhinolaryngological infections. As with other quinolone antibiotics marketed in recent years, the mechanism of action of garenoxacin involves dual inhibition of two essential bacterial enzymes, DNA gyrase and topoisomerase IV. The lack of 6-fluoro substituent does not adversely affect its potency of inhibiting DNA gyrase (Escherichia coli, IC50 0.17 mg/mL) or topoisomerase IV (S. aureus, IC50 2.19 mg/ mL).In human pharmacokinetic studies, oral garenoxacin results in dose-proportionate increases of plasma Cmax and AUC values at doses ranging from 50 to 1,200 mg. Its oral bioavailability is about 95%, and the mean terminal half-life is 15.4 h.The most common adverse events associated with garenoxacin were rash, dizziness, nausea, headache, and pruritus. Garenoxacin is chemically derived in a sequence of 14 steps, 12 of which entail the construction of a key quinolone intermediate, 7-bromo-1- cyclopropyl-8-(difluoromethoxy)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester. Subsequently, Suzuki cross-coupling reaction of this intermediate with (R)-[1-methyl-2-(trityl)isoindolin-5-yl]boronic acid, followed by deprotection of the trityl group and ester hydrolysis with hydrochloric acid gives garenoxacin. The chiral isoindoline reagent is obtained from racemic 5-bromo-2-methylisoindoline via coupling with N-CBZ-L-phenylalanine, separation of diastereomers by chromatography, cleavage of the chiral auxiliary, N-tritylation, halogen-metal exchange with butyllithium, and boronation with triisopropyl borate.
• Uses: Des-F(6)-quinolone antibacterial; topoisomerase II inhibitor. Antibacterial.

Technology Process of Garenoxacin

There total 6 articles about Garenoxacin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 86.0%

1-cyclopropyl-8-difluoromethoxy-7-(1-methyl-2,3-dihydro-1H-isoindol-5-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester → garenoxacin (194804-75-6,194804-72-3)

Guidance literature:

With hydrogenchloride; In ethanol; water; at 20 ℃; for 1h;

Reference yield:

1-cyclopropyl-8-(difluoromethoxy)-7-[(3R)-2,3-dihydro-3-methyl-1H-isoindol-1-one-6-yl]-4-oxoquinoline-3-carboxylic acid → garenoxacin (194804-75-6,194804-72-3)

Guidance literature:

With sodium tetrahydroborate; boron trifluoride diethyl etherate; In tetrahydrofuran; at 60 - 65 ℃;

Reference yield:

(+)-(R)-5-bromo-1-methyl-2-(triphenylmethyl)isoindoline (194805-14-6) → garenoxacin (194804-75-6,194804-72-3)

Guidance literature:

Multi-step reaction with 3 steps

1.1: n-BuLi; triisopropyl borate / tetrahydrofuran; hexane / 1 h / -65 °C

1.2: 87 percent / ethanol / 1 h / 45 °C

2.1: AcOH / 1,2-dimethoxy-ethane; H₂O / 0.5 h / 20 °C

2.2: 92 percent / [(C₆H₅)3P]2PdCl₂; Na₂CO₃ / 1.5 h / Heating

3.1: 86 percent / HCl / ethanol; H₂O / 1 h / 20 °C

With hydrogenchloride; n-butyllithium; Triisopropyl borate; acetic acid; In tetrahydrofuran; 1,2-dimethoxyethane; ethanol; hexane; water;

upstream raw materials:

(+)-(R)-5-bromo-1-methyl-2-(triphenylmethyl)isoindoline

2-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-1,3,6,2-dioxazaborocane

Refernces

• 1、 Hayashi, Kazuya,Takahata, Masahiro,Kawamura, Yasuhito,Todo, Yozo. "Synthesis, antibacterial activity, and toxicity of 7-(isoindolin-5-yl)-4-oxoquinoline-3-carboxylic acids: Discovery of the novel Des-F(6)-quinolone antibacterial agent garenoxacin (T-3811 or BMS-284756)". . p. 903 - 913. Retrieved 2007/10/03.