- Tedizolid phosphate impurity as well as preparation method and application thereof
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The invention provides a tedizolid phosphate impurity as well as a preparation method and application thereof, and belongs to the field of chemical pharmacy. The structural formula of the impurity isshown as a formula I in the specification. The impurity is generated in the process of synthesizing a 2-(2-methyl-2H-tetrazole-5-yl)-5-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborocyclopentane-2-yl) pyridine intermediate, and the quality of a product is seriously influenced by the impurity. The impurity is synthesized and separated, the purity is higher than 96%, and the quality requirements of impurity reference substances related to national pharmacopoeia and Chinese pharmacopoeia are met. The impurity preparation process is simple and stable and good in repeatability; and the prepared impurity2-(2-methyl-tetrazole)-5-azido pyridine can be used as a reference substance to be applied to quality control of tedizolid phosphate API, crude drugs and preparations, can also provide a reliable monitoring means for process research and promote the process optimization and determination procedures and has a good application prospect.
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Paragraph 0016; 0096; 0101-0105; 0120; 0125-0129
(2020/12/10)
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- Purification method of 5-bromo-2-(2-methyl-2H-tetrazol-5-yl) pyridine
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The invention discloses a purification method of 5-bromine-2-(2-methyl-2H-tetrazol-5-yl) pyridine. The purification method comprises the following steps: (1) dissolving 5-bromo-2-(2-methyl-2H-tetrazol-5-yl) pyridine in a solvent, dropwise adding an acidic ethanol solution, stirring and heating, keeping, then cooling to separate out crystals, filtering, washing the crystals with ethanol, and dryingto obtain 5-bromo-2-(2-methyl-2H-tetrazol-5-yl) pyridine acid salt; and 2) adding the 5-bromine-2-(2-methyl-2H-tetrazol-5-yl) pyridine salt into water for dissolving, adding a solvent, dropwise adding liquid caustic soda, stirring, heating, keeping, cooling to separate out crystals, filtering, washing the crystals with ethanol, and drying to obtain the 5-bromine-2-(2-methyl-2H-tetrazol-5-yl) pyridine. The purification method disclosed by the invention has the characteristics of mild purification conditions, safety, simplicity and convenience in operation, high purity, high yield and the like,reduces the production cost, and overcomes the problems of low product purity and need of repeated recrystallization due to the use of a large amount of isopropyl acetate in the existing process.
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Paragraph 0021-0022
(2020/07/06)
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- TRIAZOLOTRIAZINE DERIVATIVES AS A2A RECEPTOR ANTAGONISTS
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The present invention provides triazolotriazine derivatives of formula (1) as A2A receptor antagonists. Compounds of formula (1) and pharmaceutical compositions including the compounds can be used for the treatment of disorders related to A2A receptor hyp
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Page/Page column 45-46
(2020/01/24)
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- PREPARATION METHOD OF INTERMEDIATE FOR OXAZOLIDINONE DERIVATIVE
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Disclosed is a method of preparing an intermediate for an oxazolidinone derivative, which enables 5-bromo-2-(2-methyl-2H-tetrazol-5-yl)pyridine to be produced at high yield and high purity, thus exhibiting high preparation efficiency under optimal processing conditions and making it suitable for industrial mass production.
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Paragraph 51; 52; 53; 54; 55; 56; 57
(2017/07/06)
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- Preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole
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The invention relates to a preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole. The method is simple in reaction steps and high in yield, and can realize mass production.
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Paragraph 0016; 0017; 0018; 0019; 0020; 0021
(2017/07/21)
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- Preparation method of 2-methyl-5-(5-bromopyridine-2-yl)tetrazole
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The invention relates to a new method for preparing 2-methyl-5-(5-bromopyridine-2-yl)tetrazole. In the method, formaldehyde is adopted as a raw material, the reaction technology is simple, the safety and yield is high, and mass production is feasible.
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Paragraph 0018-0019
(2017/07/11)
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- Synthesis method of tedizolid intermediate
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The invention provides a synthesis method of a tedizolid intermediate. The synthesis method comprises the following steps: Step A: generating a compound (II) or acidic salt of the compound (II) through addition reaction of a cyano group in a compound (I) and alcohol; Step B: generating a compound (III) by replacing an alkoxy on the compound (II) or the acidic salt of the compound (II) with a hydrazine group or a methylhydrazine group; Step C: generating a tedizolid intermediate (IV) through reaction of the compound (III) and sodium nitrite under an acidic condition. The overall reaction formula is shown in the original specification. According to the synthesis method disclosed by the invention, the problems of easy explosion and poison of reaction reagent, difficulty in separation of a methyl-isomer by-product and so on are solved.
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- A oxazolidinone compounds of preparation method (by machine translation)
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The invention provides a oxazolidinone compounds of the preparation method. Specifically provides the type 1 compound preparation method. The formula 1 compound preparation method comprises, formula 2 N - methyl - D - grape amine compound in the presence of a catalytic reduction, direct formula 1 compound. The present invention provides a preparation has simplified the reaction step, shorten the reaction route, can make the final yield of the product is higher, and, better purity. (by machine translation)
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Paragraph 0050
(2017/05/12)
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- Copper Catalyzed Assembly of N-Aryloxazolidinones: Synthesis of Linezolid, Tedizolid, and Rivaroxaban
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The total synthesis of oxazolidinone-based pharmaceuticals, linezolid, tedizolid and rivaroxaban is reported. They are synthesized using a recently reported copper-catalyzed one-pot cyclization and arylation as the key step to construct the N-aryloxazolidinone core. Active pharmaceutical ingredients (API) were synthesized from a common synthetic pool of a simple protected amino alcohol in 22 %, 61 % and 40 % total synthesis yields, respectively.
- Mahy, William,Leitch, Jamie A.,Frost, Christopher G.
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p. 1305 - 1313
(2016/03/19)
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- Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent
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A series of novel substituted pyridyl phenyl oxazolidinone analogues were synthesized and their structure-activity relationship (SAR) was investigated based on in vitro and in vivo antibacterial activities. The minimum inhibitory concentrations (MICs) of the synthesized compounds against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) ranged from 0.12 to 2.0 μg/mL, and against Haemophilus influenzae (Hi) from 2.0 to 8.0 μg/mL. Compared to linezolid, only four compounds (11, 12, 21 and 29) showed higher in vitro antibacterial activities and better in vivo protective effects in mice. To improve the aqueous solubility, various prodrugs of compound 11 (DA-7157), which exerted a potency that was enhanced by 2-8-fold compared to that of linezolid, were synthesized. Among the prodrugs, the phosphate compound 42 exhibited excellent aqueous solubility (>50 mg/mL in DW) and good pharmacokinetic profiles, along with better in vivo efficacy than linezolid. This compound 42 is currently undergoing clinical trials with the brand name Torezolid.
- Im, Weon Bin,Choi, Sun Ho,Park, Ju-Young,Choi, Sung Hak,Finn, John,Yoon, Sung-Hwa
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experimental part
p. 1027 - 1039
(2011/04/17)
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- METHODS FOR PREPARING OXAZOLIDINONES AND COMPOSITIONS CONTAINING THEM
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Methods of preparing a class of oxazolidinones useful to impede bacterial growth are disclosed.
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Page/Page column 15-16
(2010/04/28)
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- ANTIMICROBIAL HETEROCYCLIC COMPOUNDS FOR TREATMENT OF BACTERIAL INFECTIONS
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The present invention provides heterocyclic compounds of the following formula (I) : or pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof useful as antibacterial agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
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Page/Page column 52
(2008/12/08)
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- OXAZOLIDINONE DERIVATIVES AS ANTIMICROBIALS
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The present invention relates to certain substituted phenyl oxazolidinones and to processes for the synthesis of the same. This invention also relates to pharmaceutical compositions containing the compounds of the present invention as antimicrobials. The compounds are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria, for example, multiple-resistant staphylococci, streptococci and enterococci as well as anaerobic organisms, for example, Bacterioides spp. and Clostridia spp. species, and acid fast organisms, for example, Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.
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Page/Page column 67-68
(2010/10/20)
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- NOVEL OXAZOLIDINONE DERIVATIVES
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The present invention relates to novel derivatives of oxazolidinone, a method thereof and pharmaceutical compositions comprising the derivatives for use in an antibiotic. The oxazolidinone derivatives of the present invention show inhibitory activity against a broad spectrum of bacteria and lower toxicity. The prodrugs, prepared by reacting the compound having hydroxyl group with amino acid or phosphate, have an excellent efficiency on solubility thereof against water. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Accordingly, the compositions comprising the oxazolidinone are used in an antibiotic.
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Page/Page column 26; 27
(2008/06/13)
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- 3- `4- {6-SUBSTITUTED ALKANOYL) PYRIDIN-3-YL} -3-PHENYL! -5- (1H-1, 2, 3-TRIAZOL-1-YLMETHYL) -1, 3-OXAZOLIDIN-2-ONES AS ANTIBACTERIAL AGENTS
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Compounds of formula (I) as well as pharmaceutically-acceptable salts and pro-drugs thereof are disclosed wherein R1, R2, R3, and R4 are defined herein. Also disclosed are processes for making compounds of formula (I) as well as methods of using compounds of formula (I) for treating bacterial infections.
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Page/Page column 50
(2010/02/15)
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- 3- {4- (PYRIDIN-3-YL) PHENYL} -5- (1H-1, 2, 3-TRIAZOL-1-YLMETHYL) -1, 3-OXAZOLIDIN-2-ONES AS ANTIBACTERIAL AGENTS
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Compounds of formula (I), as well as pharmaceutically-acceptable salts and pro-drugs thereof, are disclosed wherein R1, R2, R3, and R4 are defined herein. Also disclosed are processes for making compounds of formula (I) as well as methods of using compounds of formula (I) for treating bacterial infections.
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Page/Page column 67-68
(2010/02/15)
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- Synthesis and antibacterial activity of oxazolidinones containing pyridine substituted with heteroaromatic ring
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Oxazolidinone derivatives containing pyridine substituted with heteroaromatic ring were synthesized and exhibited potent in vitro and in vivo antibacterial activities against many antibiotic-resistant microbial strains. A series of oxazolidinone derivatives, which morpholino group of linezolid was replaced with heteroaromatic ring substituted pyridine moiety, were newly synthesized, and their substituted effects on in vitro and in vivo antibacterial activities were evaluated against four problematic gram-positive strains including drug resistant strains and two gram-negative strains. Most compounds exhibited the enhanced in vitro activities with 4-16-fold and three compounds exerted more than 2-fold increased in vivo efficacies than linezolid.
- Jo, Yeong Woo,Im, Weon Bin,Rhee, Jae Keol,Shim, Mi Ja,Kim, Won Bae,Choi, Eung Chil
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p. 5909 - 5915
(2007/10/03)
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- Antibacterial compounds with improved pharmacokinetic profiles
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Antibacterial compounds with improved pharmacokinetic profiles having formula (I) and salts, prodrugs, and salts of prodrugs thereof, processes for making the compounds and intermediates used in the processes, compositions containing the compounds, and methods for prophylaxis and treatment of bacterial infections using the compounds are disclosed.
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Page/Page column 9
(2010/02/05)
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- CHEMICAL COMPOUNDS
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A compound of the formula (I), or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof: Wherein C is selected from (D) and (E), R2a, R6a, and R3a ar e independently selected from for example H, CF3, Me and Et; R2b and R6b are independently selected from for example H,F, CF3, Me and Et; R1b is for example optionally substituted diazolyl, triazolyl or tetrazolyl; R4 is for example an optionally substituted 5- or 6-membered heterocyclic ring system. Methods for making compounds of the formula (I), compositions containing them and their use as antibacterial agents are also described.
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- OXAZOLIDINONE DERIVATIVES AS ANTIBACTERIAL AGENTS
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A compound of the formula (I), or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof: formula (I) wherein C is selected from D and E, formula (D), formula (E) R2a, R6a, and R3a are independently selected from for example H, CF3, Me and Et; R2b and R6b are independently selected from for example H, F, CF3, Me and Et; R1b is for example acetamido; R4 is for example an optionally substituted 5- or 6- membered heterocyclic ring system. Methods for making compounds of the formula (I), compositions containing them and their use as antibacterial agents are also described.
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- OXAZOLIDINONE DERIVATIVES AS ANTIBACTERIAL
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A compound of the formula (I), or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof : formula (I), wherein C is selected from D and E, formula (D), formula (E), R2a, R6a, and R3a are independently selected from for example H, CF3, Me and Et; R2b and R6b are independently selected from for example H, F, CF3, Me and Et; R1b is -X-Z wherein X is O or S and Z is a C-linked 5- or 6-membered heteroaryl ring; R4 is for example an optionally substituted 5- or 6-membered heterocyclic ring system. Methods for making compounds of the formula (I), compositions containing them and their use as antibacterial agents are also described.
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- ANTIBACTERIAL OXAZOLIDINONES
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A compound of the formula (I), or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof: formula (I)wherein C is selected from D and E, formula (II) R2a, R6a, and R3a are independently selected from for example H, CF3, Me and Et;R2b and R6b are independently selected from for example H, F, CF3, Me and Et; R1b is -NRz-Z wherein Rz is for example hydrogen and Z is a 5- or 6-membered heteroaryl ring;R4 is for example an optionally substituted 5- or 6-membered heterocyclic ring system. Methods for making compounds of the formula (I), compositions containing them and their use as antibacterial agents are also described.
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- Novel oxazolidinone derivatives and a process for the preparation thereof
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The present invention relates to novel oxazolidinone derivatives, their pharmaceutically acceptable salts and a process for the preparation thereof. More particularly, the present invention relates to oxazolidinone derivatives having pyridine or pyrimidine moeity substituted by heterocycle and heteroaromaticcycle at 4-position of phenyl ring. The compounds of the present invention have wide antibacterial spectrum, superior antibacterial activity and low toxicity, such that the compound of this invention can be used as an antibacterial agent.
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