51334-86-2Relevant academic research and scientific papers
Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents
Eldehna, Wagdy M.,Almahli, Hadia,Al-Ansary, Ghada H.,Ghabbour, Hazem A.,Aly, Mohamed H.,Ismael, Omnia E.,Al-Dhfyan, Abdullah,Abdel-Aziz, Hatem A.
, p. 600 - 613 (2017/11/10)
Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utiliz
Synthesis, Antiviral, and Antimicrobial Activity of N- and S-Alkylated Phthalazine Derivatives
Moustafa, Ahmed H.,El-Sayed, Hassan A.,Abd El-Hady, Rasha A.,Haikal, Abdelfattah Z.,El-Hashash, Maher
, p. 789 - 799 (2016/05/19)
A series of N-alkylphthalazinone were synthesized by the reaction of phthalazin-1(2H)-one derivatives 1a, 1b, 1c with alkylating agents namely, propargyl, allyl bromide, epichlorohydrin, 1,3-dichloro-2-propanol, 4-bromobutylacetate, and 1-(bromomethoxy)et
Synthesis of 4-Substituted Phthalazin-1(2H)-ones from 2-Acylbenzoic Acids: Controlling Hydrazine in a Pharmaceutical Intermediate through PAT-Guided Process Development
Mennen, Steven M.,Mak-Jurkauskas, Melody L.,Bio, Matthew M.,Hollis, L. Steven,Nadeau, Kelly A.,Clausen, Andrew M.,Hansen, Karl B.
, p. 884 - 891 (2015/07/27)
A simple one-pot, two-step process for the conversion of 2-acylbenzoic acids to phthalazin-1(2H)-ones was developed. A robust process was required that delivered the final isolated solid with consistently low levels of residual hydrazine, for further processing to the final drug substance. An in situ formed intermediate was critical to control reactivity and allowed for the controlled crystallization that prevented entrainment of hydrazine. Leveraging Process Analytical Technology (PAT), we investigated the reaction profile with in situ IR and Power Compensation Calorimetry (PCC) to aid development prior to a successful scale-up.
Discovery of N -(4-(3-(2-Aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1-amine (AMG 900), A Highly Selective, Orally Bioavailable Inhibitor of Aurora Kinases with Activity against Multidrug-Resistant Cancer Cell Lines
Geuns-Meyer, Stephanie,Cee, Victor J.,Deak, Holly L.,Du, Bingfan,Hodous, Brian L.,Nguyen, Hanh Nho,Olivieri, Philip R.,Schenkel, Laurie B.,Vaida, Karina R.,Andrews, Paul,Bak, Annette,Be, Xuhai,Beltran, Pedro J.,Bush, Tammy L.,Chaves, Mary K.,Chung, Grace,Dai, Yang,Eden, Patrick,Hanestad, Kelly,Huang, Liyue,Lin, Min-Hwa Jasmine,Tang, Jin,Ziegler, Beth,Radinsky, Robert,Kendall, Richard,Patel, Vinod F.,Payton, Marc
, p. 5189 - 5207 (2015/08/03)
Efforts to improve upon the physical properties and metabolic stability of Aurora kinase inhibitor 14a revealed that potency against multidrug-resistant cell lines was compromised by increased polarity. Despite its high in vitro metabolic intrinsic cleara
Synthesis of 1,2-dihydro-1-oxophthalazin-4-yl trifluoromethanesulfonate and its application in the synthesis of 4-(aryl/heteroaryl/alkynyl)phthalazin-1(2H)-one
Dhage, Ganesh Raosaheb,Deshmukh, Santosh Rangnath,Thopate, Shankar Ramchandra
, p. 33377 - 33384 (2015/04/27)
The regioselective synthesis of 1,2-dihydro-1-oxophthalazin-4-yl trifluoromethanesulfonate (3a) has been reported. The reaction of Tf2O (2a) with phthalhydrazide (1a) provides a rapid access to 3a with an excellent yield and a high level of reg
Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds
Ibrahim, Hany S.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Elaasser, Mahmoud M.,Abdel-Aziz, Marwa M.
, p. 480 - 486 (2014/09/03)
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 of 4-substituted chlorophthalazines, dihydrobenzoazepinediones, 2-pyrazolylbenzoic acid, and 2-pyrazolylbenzohydrazide via 3-substituted 3-hydroxyisoindolin-1-ones
Nguyen, Hanh Nho,Cee, Victor J.,Deak, Holly L.,Du, Bingfan,Faber, Kathleen Panter,Gunaydin, Hakan,Hodous, Brian L.,Hollis, Steven L.,Krolikowski, Paul H.,Olivieri, Philip R.,Patel, Vinod F.,Romero, Karina,Schenkel, Laurie B.,Geuns-Meyer, Stephanie D.
experimental part, p. 3887 - 3906 (2012/06/30)
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.
New antithrombotic 1-Phthalazinamines with Serotonin Antagonistic Properties
Johnsen, Matthias,Rehse, Klaus,Pertz, Heinz,Stasch, Johannes Peter,Bischoff, Erwin
, p. 591 - 597 (2007/10/03)
We report nineteen 4-aryl- and 4-arylalkyl-1-phthalazinamines (5-8) which we prepared and tested for antithrombotic properties. All compounds were assayed for their antiplatelet activity in the "Born test" with collagen as inducer of the aggregation. N-[4-(1H-1,2,4-triazol-1-yl)butyl]-4-phenyl-1-phthalazin-amine (7c) was the most potent compound, having an IC50 of 8 μM. When 5-HT (Serotonin) was used to start aggregation the N-(furan-2-yl-methyl)-4-phenyl-1-pthtalazinamine (8a) had an IC50 of 2 μM. In vivo potencies were highly significant. N-[5-(1H-1,2,4-triazol-1-yl)pentyl]-4-phenyl-1-phthalazinamine (7d) inhibited thrombus formation by 12% (P 2A receptor, which is most likely the mechanism of the inhibition of aggregation by this compound.
Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-imidazolyl)alkyl]- 1(2H)-phthalazinones
Yamaguchi,Kamei,Koga,Akima,Kuroki,Ohi
, p. 4052 - 4060 (2007/10/02)
A number of 4-substituted 2-[ω-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane A2 synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
