519003-01-1

Upstream product

• 501939-82-8 (5R)-methanesulfonic acid 3-(3-fluoro-4-iodophenyl)-2-oxo-oxazolidin-5-ylmethyl ester 
• 149524-42-5 (5R)-3-(3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one 
• 372-19-0 meta-fluoroaniline 

Downstream Products

• 149524-45-8 (S)-N-[3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidine-5-ylmethyl]acetamide 
• 501939-95-3 (5R)-3-(3-fluoro-4-iodophenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one 
• 677727-01-4 C₁₇H₁₅FN₄O₃ 
• 677727-21-8 C₁₇H₁₂FN₅O₂ 
• 916888-23-8 (5R)-3-(3-fluoro-4-iodo-phenyl)-5-(4-trimethylsilanyl-[1,2,3]triazol-1-ylmethyl)-oxazolidin-2-one 
• 700370-33-8 (5R)-3-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one 
• 1202701-57-2 C₁₉H₁₆FN₇O₂ 
• 1202701-61-8 (R)-3-(3-fluoro-4-([1,2,4]triazolo[1,5-a]pyridin-7-yl)phenyl)-5-([1,2,3]triazol-1-yl)methyloxazolidin-2-one 
• 698981-89-4 (5R)-3-{2-fluoro-4`-[5-(hydroxymethyl)-4,5-dihydroisoxazol-3-yl]-3`-methoxy-1,1`-biphenyl-4-yl}-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one 
• 698981-84-9 (5R)-3-{4'-[5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,5-dihydroisoxazol-3-yl]-2-fluoro-3`-methoxy-1,1`-biphenyl-4-yl}-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one 
• 698981-94-1 (5R)-3-{4`-[5-({[tert-butyl(dimethyl)silyl]oxv}methyl)-4,5-dihydroisoxazol-3-yl]-2,3`-difluoro-1,1`-binhenyl-4-yl}-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one 
• 1188917-94-3 (S,R)-3-[2-fluoro-4'-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yloxymethyl)-biphenyl-4-yl]-5-[1,2,3]triazol-1-ylmethyl-oxazolidin-2-one 

Relevant academic research and scientific papers

Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity

Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (7.4 1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts.

Process for the synthesis of triazoles

The present invention relates to processes for the preparation of triazoles. These compounds are useful as anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents.

Novel substituted (pyridin-3-yl)phenyloxazolidinones: Antibacterial agents with reduced activity against monoamine oxidase A and increased solubility

Oxazolidinones represent a new and promising class of antibacterial agents. Current research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Oxazolidinones bearing a (pyridin-3-yl)phenyl moiety (e.g., 3) generally show improved antibacterial activity compared to linezolid but suffer from potent monoamine oxidase A (MAO-A) inhibition and low solubility. We now disclose the finding that new analogues of 3 with acyclic substituents on the pyridyl moiety exhibit excellent activity against Gram-positive pathogens, including linezolid-resistant Streptococcus pneumoniae. Generally, more bulky substituents yielded significantly reduced MAO-A inhibition relative to the unsubstituted compound 3. The MAO-A SAR can be rationalized on the basis of docking studies using a MAO-A/MAO-B homology model. Solubility was enhanced with incorporation of polar groups. One optimized analogue, compound 13, showed low clearance in the rat and efficacy against S. pneumoniae in a mouse pneumonia model.

BIARYL HETEROCYCLIC COMPOUNDS AND METHODS OF MAKING AND USING THE SAME

The present invention relates generally to the field of anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. More particularly, the invention relates to a family of tricyclic compounds that are useful as such agents.

3-[4-(6-{4,5-DIHYDROISOXAZOL-3-YL}PYRIDIN-3-YL)-3-PHENYL]-5-(1H-1,2,3-TRIAZOL-1-YLMETHYL)-1,3-OXAZOLIDIN-2-ONES AS ANTIBACTERIAL AGENTS

Compounds of the formula (I): or a pharmaceutically- acceptable salt or pro-drug thereof: wherein R1 is selected for example from hydrogen, halogen, optionally substituted methyl; R2 and R3 are independently selected from

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

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.

3- (4- (2-DIHYDROISOXAZOL-3-YLPYRIDIN-5-YL) PHENYL) -5-TRIAZOL-1-YLMETHYLOXAZOLIDIN-2-ONE DERIVAIVES AS MAO INHIBITORS FOR THE TREATMENT OF BACTERIAL INFECTIONS

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 formu

3- {4- (PYRIDIN-3-YL) PHENYL} -5- (1H-1, 2, 3-TRIAZOL-1-YLMETHYL) -1, 3-OXAZOLIDIN-2-ONES AS ANTIBACTERIAL AGENTS

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.

OXAZOLIDINONE ANTIBIOTICS AND DERIVATIVES THEREOF

This invention relates to new oxazolidinones having a cyclopropyl moiety, which are effective against aerobic and anerobic pathogens such as multi-resistant staphylococci, streptococci and enterococci, Bacteroides spp., Clostridia spp. Species, as well as acid-fast organisms such as Mycobacterium tuberculosis and other mycobacterial species. The compounds are represented by structural formula: (I); its enantiomer, diastereomer, or pharmaceutically acceptable salt or ester thereof.

ANTIBACTERIAL COMPOUNDS

A compound of the formula (I), or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof wherein in (I) C is for example formula (D), (E), (H) wherein A and B are independently selected from formulae (i) and (ii) and R2b and R6b, R2b and R6a, R3a and R5a, are for example selected from H, F, OMe and Me; R2b’ and R6b’, R2a’ and R6a’, R3a’, R5a’ are for example selected from H, OMe and Me; R1a and R1b are for example selected from hydroxy, -OSi(tri-(1-6C)alkyl), NR5C(=W) R4, formla (a), formula (b) wherein HET-1 is for example isoxazolyl and HET-2 is for example triazolyl or tetrazolyl. Methods for making compounds of the formula (I), compositions containing them and their use as antibacterial agents are also described.