32003-14-8

Usage

Uses

Used in Pharmaceutical Research and Development:
4-Benzyl-1(2H)-phthalazinone is used as a building block in the synthesis of heterocyclic compounds for its potential medicinal applications. Its unique structure and properties make it a valuable component in the development of new drugs.
Used in Medicinal Chemistry:
4-Benzyl-1(2H)-phthalazinone is used as a starting material in the design and synthesis of novel heterocyclic compounds with potential therapeutic properties. Its ability to exhibit various biological activities, such as anti-inflammatory, antimicrobial, or anticancer effects, makes it a promising candidate for further exploration in medicinal chemistry.
Used in Drug Discovery:
4-Benzyl-1(2H)-phthalazinone is used in drug discovery processes to identify and develop new pharmaceutical agents with potential therapeutic benefits. Its unique chemical properties and biological activities make it a valuable tool in the search for innovative treatments for various diseases and conditions.

Upstream product

• 4767-56-0 (Z)-3-benzylidenephthalide 
• 1875-48-5 N-aminophthalamide 
• 6921-34-2 benzylmagnesium chloride 
• 99763-56-1 2-amino-3-benzylideneisoindolin-1-one 
• 575-61-1 Isoaurone 
• 37740-37-7 4-benzyl-2-piperidinomethylphthalazin-1(2H)-one 
• 4770-23-4 3-benzyl-3-hydroxy-2-methyl-1,3-dihydroisoindol-1(3H)-one 
• 33157-76-5 2-ethyl-3-benzyl-3-hydroxy-isoindolin-1-one 
• 78928-28-6 3-benzyl-3-hydroxy-2-t-butylisoindolin-1-one 
• 550-44-7 N-methylphthalimide 
• 5022-29-7 N-ethylphthalimide 
• 2141-99-3 2-tert-butylisoindole-1,3-dione 
• 304-17-6 N-isopropylphthalimide 
• 100-39-0 benzyl bromide 

Downstream Products

• 118506-99-3 4-benzyl-1-oxo-2-<1(2H)phthalazonyl>methyl-p-aminophenylacetic acid 
• 118507-02-1 4-Benzyl-2-phenylaminomethyl-2H-phthalazin-1-one 
• 118507-03-2 4-[(4-Benzyl-1-oxo-1H-phthalazin-2-ylmethyl)-amino]-benzoic acid ethyl ester 
• 37740-38-8 4-benzyl-2-(2'-cyanoethyl)phthalazin-1(2H)-one 
• 132544-84-4 4-benzyl-1(2H)-oxophthalazin-2-acetic acid ethyl ester 
• 40848-53-1 1-benzyl-4-chlorophthalazine 
• 130090-87-8 2-(4-benzyl-1-oxophthalazin-2(1H)-yl)acetohydrazide 
• 130090-95-8 5-(4-benzyl-1-oxo-1H-phthalazin-2-ylmethyl)-4-amino-1,2,4-triazole-3-thione 
• 182916-37-6 (4-Benzyl-1-oxo-1H-phthalazin-2-yl)-acetic acid [1-methyl-3-oxo-but-(E)-ylidene]-hydrazide 

Relevant academic research and scientific papers

Design, Regiospecific Green Synthesis, Chemical Computational Analysis, and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

Phthalazines have received considerable attention for their wide antimicrobial activity. Regiospecific nucleophilic attack of 4-benzylphthalazin-1-ol by the 1-oxo rather than the aza group on different alkyl halides gave novel phthalazine heterocyclic derivatives. Moreover, a variety of nucleosides bonded to electron-withdrawing groups were synthesized using 4-benzylphthalazine-1-ol. The density functional theory has been used to investigate the electronic structure of the synthesized compounds. All of the synthesized derivatives showed remarkable activity when tested against Gram-positive and Gram-negative bacteria, Aspergillus niger, and Candida albicans. The reactivity of these nucleosides was expected to arise from their bonding with the lone pair of N-atom of the macromolecules of bacteria. These bonding were expected to inhibit the enzyme by forming highly stable complex with lower highest occupied molecular orbital energy. The structures of these synthesized derivatives were established by Fourier transform infrared, 1H-NMR, and 13C-NMR spectroscopic evidence.

A comparative synthesis of 6-benzyl-2,3-dihydroimidazo[2,1-a]phthalazine and 2H-7-benzyl-3,4-dihydropyrimido[2,1-a]phthalazine

Two new synthetic strategies have been developed for the synthesis of a new class of cyclophthalazine derivatives. 6-Benzyl-2,3-dihydroimidazo[2,1-a]phthalazine and 2H-7-benzyl-3,4-dihydropyrimido[2,1-a]phthalazine were obtained (i) by intramolecular cyclization of the 2-(aminoalkyl)-4-benzyl-2H-phthalazin-1-one or (ii) by intramolecular cyclization of the corresponding 2-(4-benzylphthalazin-1(2H)-ylideneamino)alcohols previously prepared. The second of the described routes afforded the desired derivatives in high yields.

Studies towards hypoxia-activated prodrugs of PARP inhibitors

Poly(ADP-ribose)polymerase (PARP) inhibitors (PARPi) have recently been approved for the treatment of breast and ovarian tumors with defects in homologous recombination repair (HRR). Although it has been demonstrated that PARPi also sensitize HRR competent tumors to cytotoxic chemotherapies or radiotherapy, normal cell toxicity has remained an obstacle to their use in this context. Hypoxia-activated prodrugs (HAPs) provide a means to limit exposure of normal cells to active drug, thus adding a layer of tumor selectivity. We have investigated potential HAPs of model PARPi in which we attach a bioreducible “trigger” to the amide nitrogen, thereby blocking key binding interactions. A representative example showed promise in abrogating PARPi enzymatic activity in a biochemical assay, with a ca. 160-fold higher potency of benzyl phthalazinone 4 than the corresponding model HAP 5, but these N-alkylated compounds did not release the PARPi upon one-electron reduction by radiolysis. Therefore, we extended our investigation to include NU1025, a PARPi that contains a phenol distal to the core binding motif. The resulting 2-nitroimidazolyl ether provided modest abrogation of PARPi activity with a ca. seven-fold decrease in potency, but released the PARPi efficiently upon reduction. This investigation of potential prodrug approaches for PARPi has identified a useful prodrug strategy for future exploration.

Copper(II)-Mediated ortho-Selective C(sp2)-H Tandem Alkynylation/Annulation and ortho-Hydroxylation of Anilides with 2-Aminophenyl-1H-pyrazole as a Directing Group

2-Aminophenyl-1H-pyrazole has been identified as a viable directing group to promote copper(II)-mediated ortho-selective sp2 C-H bond tandem alkynylation/annulation of anilides with terminal alkynes to offer arylmethylene isoindolinones. Meanwhile, copper(II)-mediated ortho-selective sp2 C-H hydroxylation of anilides has also been optimized as the major reaction pathway by using Cu(OAc)2 as the promoter and 1,1,3,3-tetramethylguanidine as an organic base. Recovery of the directing group was achieved by hydrazinolysis for arylmethylene isoindolinones and basic hydrolysis for the hydroxylation products.

Synthesis and vasorelaxant and antiplatelet activities of a new series of (4-Benzylphthalazin-1-ylamino)alcohol derivatives

A new series of phthalazine derivatives was synthesized by reaction of phthalic anhydride and different substituted phenylacetic acids to yield the benzyliden-3H-isobenzofuran-1-one intermediates 2a–d. Treatment of them with hydrazine afforded 4-benzyl-2H-phthalazin-1-one derivatives 3a–d, which were substituted with the corresponding aminoalkylalcohol to obtain the (4-benzylphthalazin-1-ylamino)alcohol derivatives 4a–h. In general, these phthalazine derivatives relaxed the contractions produced by phenylephrine both in intact or endothelium-denuded aortic rings. In addition, platelet aggregation induced by thrombin was also inhibited by compounds 4c and 4g.

Design and synthesis of new phthalazinone derivatives containing benzyl moiety with anticipated antitumor activity

The acetohydrazide derivative reacted with carbon electrophiles such as acid chlorides, acetylacetone, ethyl acetoacetate and aromatic aldehydes to give some interesting heterocyclic compounds. The hydrazide derivative reacted with acetophenone which in turn underwent Vielsmeier-Haack reaction. Also, the phthalazinethione has been synthesized and its behavior towards hydrazine hydrate, oxidizing agent and ethyl chloroacetate has been investigated. The newly synthesized compounds were characterized by spectroscopic data. The antimicrobial, the cytotoxic, and the antioxidant activities of some of the synthesized products were evaluated. Some of the tested compounds showed very strong cytotoxic activity with respect to the standard.

Design and synthesis of 4-benzyl-1-(2H)-phthalazinone derivatives as novel androgen receptor antagonists

The androgen receptor (AR) plays important roles in multiple physiological functions, including differentiation, growth, and maintenance of male reproductive organs, and also has effects on hair and skin. In this paper, we report the synthesis of nonsteroidal AR antagonists having a 4-benzyl-1-(2H)-phthalazinone skeleton. Among the synthesized compounds, 11c with two ortho-substituents on the phenyl group potently inhibited SC-3 cell proliferation (IC50: 0.18 μM) and showed high wt AR-binding affinity (IC50: 10.9 μM), comparable to that of hydroxyflutamide (3). Compound 11c also inhibited proliferation of LNCaP cells containing T877A-mutated AR. Docking study of 11c with the AR ligand-binding domain indicated that the benzyl group is important for the antagonism. These phthalazinone derivatives may be useful for investigating potential clinical applications of AR antagonists.

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C-H(sp2)/C-H(sp) coupling under mild conditions

A novel strategy for the construction of the phthalazin-1(2H)-one scaffold has been developed by means of a copper-mediated cascade C-H/C-H coupling and intramolecular annulations and a subsequent facile hydrazinolysis. This C-H activation transformation proceeds smoothly with wide generality, good functional tolerance and high stereo- And regioselectivity under mild conditions. Through the removal of the directing group, the resulting moiety could easily be transformed into the phthalazin-1(2H)-one scaffold, which is known to be a privileged moiety and a bioactive nucleus in pharmaceuticals.

Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds

RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively.

Synthesis and cytotoxic evaluation of some new phthalazinylpiperazine derivatives

A new series of 1,4-disubstituted phthalazinylpiperazine derivatives 7a-f, 12a-f and 20a-f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cancer cell lines in vitro. Among them, compounds 7a-f exhibited excellent selectivity for MDA-MB-231 with IC50 values ranging from 0.013 μM to 0.079 μM. The most promising compound, 7e (IC50 = 2.19 μM, 2.19 μM, 0.013 μM), was 9.3, 10, and 4.9 × 103 times more active than vatalanib (IC50 = 20.27 μM, 21.96 μM, 63.90 μM), respectively. A new series of 1,4-disubstituted phthalazinylpiperazine derivatives 7a-f, 12a-f and 20a-f were designed and synthesized, and their cytotoxic activities against A549, HT-29 and MDA-MB-231 cancer cell lines in vitro were compared to that of vatalanib.