1914-20-1

Usage

Synthesis Reference(s)

Journal of the American Chemical Society, 79, p. 98, 1957 DOI: 10.1021/ja01558a026

InChI:InChI=1/C9H7NO3/c1-13-10-8(11)6-4-2-3-5-7(6)9(10)12/h2-5H,1H3

Upstream product

• 85-44-9 phthalic anhydride 
• 593-56-6 N-methoxylamine hydrochloride 

Downstream Products

• 67-62-9 O-Methylhydroxylamin 
• 88-99-3 benzene-1,2-dicarboxylic acid 
• 5323-50-2 N-propylphthalimide 
• 19532-95-7 N,N'-dipropylphthalamide 
• 2142-03-2 2-p-tolylisoindoline-1,3-dione 
• 7501-05-5 N-(2-phenylethyl)phthalimide 
• 38229-00-4 N,N’-bis(2-phenylethyl)phthalamide 
• 304-17-6 N-isopropylphthalimide 
• 38228-97-6 N¹,N²-diisopropylphthalamide 
• 1515-72-6 N-butylphthalimide 
• 19532-96-8 N,N'-dibutylamide of phthalic acid 
• 520-03-6 N-phenylphthalimide 
• 2464-33-7 N-(2-methylphenyl)phthalimide 
• 2142-01-0 N-benzylphthalimide 

Relevant academic research and scientific papers

Evaluation of the inhibitory activity of (aza)isoindolinone-type compounds: toward in vitro InhA action, Mycobacterium tuberculosis growth and mycolic acid biosynthesis

Inhibitors of the Mycobacterium tuberculosis enoyl-ACP reductase (InhA) are considered as potential promising therapeutics for the treatment of tuberculosis. Previously, we reported that azaisoindolinone-type compounds displayed, in vitro, inhibitory activity toward InhA. Herein, we describe chemical modifications of azaisoindolinone scaffold, the synthesis of 15 new compounds and their evaluations toward the in vitro InhA activity. Based on these results, a structure–InhA inhibitory activity relationship analysis and a molecular docking study, using the conformation of InhA found in the 2H7M crystal structure, were carried out to predict a possible mode of interaction of the best (aza)isoindolinone-type inhibitors with InhA in vitro. Then, the work was extended toward evaluations of these compounds against Mycobacterium tuberculosis (Mtb) growth, and finally, some of them were also investigated in respect of their ability to inhibit mycolic acid biosynthesis inside mycobacteria. Although, some azaisoindolinones were able to inhibit InhA activity and Mtb growth in vitro, they did not inhibit the mycolic acid biosynthesis inside Mtb.

Synthesis of 4-substituted chlorophthalazines, dihydrobenzoazepinediones, 2-pyrazolylbenzoic acid, and 2-pyrazolylbenzohydrazide via 3-substituted 3-hydroxyisoindolin-1-ones

Figure Persented: Herein we describe a general three-step synthesis of 4-substituted chlorophthalazines in good overall yields. In the key step, N,N-dimethylaminophthalimide (8a) directs the selective monoaddition of alkyl, aryl, and heteroaryl organometallic reagents to afford 3-substituted 3-hydroxyisoindolinones 9b, 9i-9am. Many of these hydroxyisoindolinones are converted to chlorophthalazines 1b-1v via reaction with hydrazine, followed by chlorination with POCl3. We have also discovered two novel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones 15a-15c via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and substituted hydrazines to afford 2-pyrazolyl benzoic acids 16a-16d and 2-pyrazolyl benzohydrazides 17a-17g rather than the expected alkynyl phthalazinones.