4775-27-3

Usage

Generation

Second-generation antihistamine

Uses

Treats allergy symptoms (sneezing, runny nose, itchy/watery eyes)

Mechanism of action

Blocks the action of histamine

Available forms

Tablets, syrup, chewable tablets

Side effects

Generally well-tolerated, but can cause drowsiness in some individuals (caution advised when driving or operating heavy machinery)

Upstream product

• 156453-05-3 3-(4'-chlorophenyl)phthalazinium-1-olate 
• 1234559-99-9 C₂₁H₁₅BrClNO₃ 
• 106-47-8 4-chloro-aniline 
• 933-88-0 ortho-toluoyl chloride 
• 65492-63-9 N-(4-chlorophenyl)-2-methylbenzamide 
• 119-67-5 o-carboxybenzaldehyde 
• 2417-73-4 methyl 2-bromomethylbenzoate 
• 65-85-0 benzoic acid 
• 127459-01-2 2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-1H-isoindol-1-one 
• 89-71-4 2-Methyl-benzoic acid methyl ester 
• 109949-64-6 2-(4-chlorophenyl)-2,3-dihydro-1H-isoindole 
• 480-91-1 oxisoindole 
• 637-87-6 1-Chloro-4-iodobenzene 
• 643-79-8 o-phthalic dicarboxaldehyde 

Downstream Products

• 31842-01-0 indoprofen 
• 67629-82-7 2-oxo-3-[4-(1-oxo-1,3-dihydro-isoindol-2-yl)-phenyl]-butyric acid 
• 36752-78-0 2-([1,1’-biphenyl]-4-yl)isoindolin-1-one 

Relevant academic research and scientific papers

Copper-promoted direct amidation of isoindolinone scaffolds by sodium persulfate

Isoindolinones are ubiquitous structural motifs in natural products and pharmaceuticals. Establishing an efficient method for structural modification of isoindolinones could significantly facilitate new drug development. Herein, we describe copper-promoted direct amidation of isoindolinone scaffolds mediated by sodium persulfate. The method exhibits mild reaction conditions and high site-selectivity, and enables the structural modification of the drug indobufen ester with various amides with yields of 49 to 98%. It is also gram-scalable. Additionally, the reaction mechanism appears to involve a radical and a carbocationic pathway.

Merging C-H Activation and Strain-Release in Ruthenium-Catalyzed Isoindolinone Synthesis

The merger of strain-release of 1,2-oxazetidines with carboxylic acid directed C-H activation in catalytic synthesis of isoindolinones is reported for the first time. This reaction opens a new and sustainable avenue to prepare a range of structurally dive

One-pot method to construct isoindolinones and its application to the synthesis of DWP205109 and intermediate of Lenalidomide

Herein a practical and efficient system for concise synthesis of isoindolinones is described by using substituted methyl 2-(halomethyl)benzoates and substituted amines. Structurally various methyl 2-(halomethyl)benzoates and amines were transformed into isoindolinones 80–99% yield and purity in catalyst-free and solvent-free conditions. The method has a wide substrate scope. The synthetic utility of the one-pot reaction was demonstrated by the concise syntheses of Lenalidomide intermediate and DWP205190.

Metal-Free Cascade Formation of Intermolecular C-N Bonds Accessing Substituted Isoindolinones under Cathodic Reduction

An electrochemical protocol for the construction of substituted isoindolinones via reduction/amidation of 2-carboxybenzaldehydes and amines has been realized. Under metal-free and external-reductant-free electrolytic conditions, the reaction achieves the cascade formation of intermolecular C-N bonds and provides a series of isoindolinones in moderate to good yields. The deuterium-labeling experiment proves that the hydrogen in the methylene of the product is mainly provided by H2O in the system.

One-pot synthesis of pyrrolidones from levulinic acid and amines/nitroarenes/nitriles over the Ir-PVP catalyst

The synthesis of pyrrolidones via reductive amination of levulinic acid with aniline was examined over polypyrrolidone-stabilized metal nanoparticle catalysts. Among them, Ir metal was the most effective and applicable for the reductive amination of levulinic acid with nitroarenes/nitriles. Importantly, this catalyst was used for the one-pot synthesis of the anti-inflammatory drug indoprofen from 2-formylbenzoic acid and 2-(4-nitrophenyl)propanoic acid.

A g-C3N4-based heterogeneous photocatalyst for visible light mediated aerobic benzylic C-H oxygenations

A metal-free heterogeneous photocatalytic system has been developed for highly efficient benzylic C-H oxygenations using oxygen as an oxidant. This visible light mediated oxidation reaction utilizes graphitic carbon nitride (g-C3N4) as a recyclable, nontoxic and low cost photocatalyst. Mild reaction conditions allow for the generation of synthetically and biologically valued isochromannones, phthalides, isoquinolinones, isoindolinones and xanthones from readily accessible alkyl aromatic precursors in good yields. The heterogeneous nature of the g-C3N4 catalytic system enables easy recovery and recycling as well as the use in multiple runs without loss of activity. The synthetic utility of this "green" methodology was further demonstrated by applying in bioactive and drug valued target syntheses.

α-Angelica Lactone in a New Role: Facile Access to N-Aryl Tetrahydroisoquinolinones and Isoindolinones via Organocatalytic α-CH2 Oxygenation

A method for the direct oxidation of various N-aryl tetrahydroisoquinolines and isoindolines to the corresponding lactams using α-angelica lactone as a catalyst was developed. The utility of the method was further demonstrated by synthesis of indoprofen and indobufen.

Synthesis and Broad Antiviral Activity of Novel 2-aryl-isoindolin-1-ones towards Diverse Enterovirus A71 Clinical Isolates

Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical isolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structure–activity relationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with potent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant antiviral activity (EC50 50) values in the range of 1.23–1.76 μM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of the reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was significantly decreased at both the protein and RNA level in a dose-dependent manner following treatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on the virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a promising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies.

Ruthenium(ii)-catalysed selective C(sp2)-H bond benzoxylation of biologically appealing: N -arylisoindolinones

Site- and regio-selective aromatic C-H bond benzoxylations were found to take place using biologically appealing N-arylisoindolinones under ruthenium(ii) catalysis in the presence of (hetero)aromatic carboxylic acid derivatives as coupling partners. Besides the presence of two potential C(sp2)-H sites available for functionalization in the substrates, exclusive ortho selectivity was achieved in the phenyl ring attached to the nitrogen atom. Notably, the reactions occurred in a selective manner as only mono-functionalized products were formed and they tolerated a large number of functional chemical groups. The ability of the cyclic tertiary amide within the isoindolinone skeleton to act as a weak directing group in order to accommodate six-membered ring ruthenacycle intermediates appears to be the key to reach such high levels of selectivity. In contrast, the more sterically demanding cyclic imides were unreactive under identical reaction conditions.

Site-Selective Ruthenium-Catalyzed C-H Bond Arylations with Boronic Acids: Exploiting Isoindolinones as a Weak Directing Group

Biologically relevant N-arylisoindolinones efficiently underwent arylation reactions under ruthenium catalysis via C-H bond functionalization. The reactions exclusively led to monoarylated products, and only ortho selectivity was observed in the aromatic ring connected to the nitrogen atom. Interestingly, no C-H bond functionalization was observed in the other benzene ring in the ortho position with respect to the carbonyl group. This ruthenium-catalyzed reaction displayed a high functional group tolerance, and it employed readily available and benchmark stable boronic acid and potassium aryltrifluoroborate derivatives as coupling partners. An appealing late-stage functionalization of indoprofen applying this methodology is showcased.