194804-75-6 Usage
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.
Definition
ChEBI: A quinolinemonocarboxylic acid that is 1,4-dihydroquinoline-3-carboxylic acid that is substituted by a cyclopropyl group at position 1, an oxo group at position 4, a (1R)-1-methyl-2,3-dihydro-1H-isoindol-5-yl group at po
ition 7, and a difluoromethoxy group at position 8.
Brand name
Geninax
Check Digit Verification of cas no
The CAS Registry Mumber 194804-75-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,9,4,8,0 and 4 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 194804-75:
(8*1)+(7*9)+(6*4)+(5*8)+(4*0)+(3*4)+(2*7)+(1*5)=166
166 % 10 = 6
So 194804-75-6 is a valid CAS Registry Number.
InChI:InChI=1/C23H20F2N2O4.CH4O3S/c1-11-15-5-2-12(8-13(15)9-26-11)16-6-7-17-19(21(16)31-23(24)25)27(14-3-4-14)10-18(20(17)28)22(29)30;1-5(2,3)4/h2,5-8,10-11,14,23,26H,3-4,9H2,1H3,(H,29,30);1H3,(H,2,3,4)/t11-;/m1./s1
194804-75-6Relevant articles and documents
Preparation method for garenoxacin and intermediate thereof
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Paragraph 0043; 0044; 0045; 0046; 0047; 0048, (2017/07/20)
The invention provides a preparation method for garenoxacin and an intermediate thereof. The preparation method comprises the following steps: with a compound 5 as a raw material, reacting the compound 5 with bis(pinacolato)diboron or triisopropyl borate so as to obtain a compound 4; separately adding 7-bromo-1-cyclopropyl-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-ethyl carboxylate, a palladium catalyst and inorganic aqueous alkali and carrying out a reaction so as to obtain a compound 3; and subjecting the compound 3 to hydrolysis and a reduction reaction so as to obtain a compound 2 and garenoxacin (a compound 1). The compound 3 has excellent stability; raw materials for preparation of garenoxacin are cheap and easily available; reaction operation is simple; yield is high; litter waste gas, waste water and industrial residue are produced; and thus, the preparation method has good industrial prospects.