Regioselectivity of the amination of some nitroisoquinolines by liquid ammonia/potassium permanganate

Woźniak, M.; Barański, A.; Nowak, Krystyna; Poradowska, H.

doi:10.1002/jlac.1990199001124

Cited by 21 publications

(3 citation statements)

References 11 publications

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“…5-Amino-1-methoxyisoquinoline ( 33 ) was prepared from 1-hydroxyisoquinoline ( 29 ) by conversion to the 1-chloro compound ( 30 ) with POCl 3 , followed by nitration in c.H 2 SO 4 /f.HNO 3 /KNO 3 to give 1-chloro-5-nitroisoquinoline ( 31 ). , Reaction of this with Na in dry MeOH gave 1-methoxy-5-nitroisoquinoline ( 32 ), which was hydrogenated over Pd/C to give the required 33 in 87% overall yield (Scheme 1A). The synthesis of 8-aminoisoquinoline ( 37 ) proved a particular problem.…”

Section: Chemistrymentioning

confidence: 99%

Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents

et al. 2002

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Heterocyclic phenazinecarboxamides were prepared by condensation of aminoheterocycles and 2-halo-3-nitrobenzoic acids, followed by reductive ring closure and amidation. They showed similar inhibition of paired cell lines that underexpressed topo II or overexpressed P-glycoprotein, indicating a non topo II mechanism of cytotoxicity and indifference to P-glycoprotein mediated multidrug resistance. Compounds with a fused five-membered heterocyclic ring were generally less potent than the pyrido[4,3-a]phenazines. A 4-methoxypyrido[4,3-a]phenazine (IC(50)s 2.5-26 nM) gave modest (ca. 5 day) growth delays in H69/P xenografts with oral dosing.

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Section: Chemistrymentioning

confidence: 99%

Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents

et al. 2002

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“…Na2CO3 [75]; x, SiO2, hexane, EtOAc [67,73,74]; xi, NH3, EtOH, autoclave [67] or NH3, EtOH, ambient temperature [74] or NH3, MeOCH2CH2OH, reflux [73]; xii, HNO3, H2SO4, 0C-20C [76][77][78] or KNO3, H2SO4 [79,80]; xiv, AcOH, 100C [78] or aq. HCl, reflux [81]; xiii, HgSO4, H2SO4, acetone, reflux [82]. Eloy and Deryckere [68] devised a new approach to 5substituted isoquinolin-1-ones 23 through formation of ortho-substituted cinnamoyl azides 21, which were then thermolysed in diphenyl ether at 230C, triggering a Curtius rearrangement to the isocyanates 22 and electrophilic cyclisation.…”

Section: Synthesis Of 5-aiqmentioning

confidence: 99%

“…Acetolysis of the 1-chloro of 33 and hydrolysis of the ester upon work-up forms 5-nitroisoquinolin-1-one 20, from which the target 1 can be obtained readily [77]. The hydrolysis of 33 to 20 can also be achieved in lower yield with aqueous hydrochloric acid [81]. This new sequence 32 → 33 → 20 → 1 proceeds in 54% overall yield [78].…”

Section: Synthesis Of 5-aiqmentioning

confidence: 99%

5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

Threadgill

2015

CMC

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5-Aminoisoquinolin-1-one (5-AIQ) is a water-soluble inhibitor of the poly(ADPribose) polymerases (PARPs), lacking isoform-selectivity. Although of only moderate potency in vitro against PARP-1, it is highly active in many assays in cells and in models in vivo, indicating excellent uptake. Optimisation of the several synthetic sequences to 5-AIQ has led to development of a short and efficient route from 1-chloroisoquinoline. It has been used widely as a biochemical and pharmacological tool to study the effects of inhibition of the PARPs. It ameliorates the damage to cells and tissues following reperfusion of ischaemic tissue, showing significant protective activity in a rodent model of haemorrhagic shock at the remarkably low dose of 30 µg Kg(-1). Protection is also seen in models of myocardial infarction, ischaemic kidney and liver disorders, stroke and organ transplantation. Inhibition of PARP-1 by 5-AIQ causes down-regulation of the activity of NF-κB, which then down-regulates the expression of several gene products. Thus 5-AIQ has anti-inflammatory activity in vivo, through modulating the expression of cytokines and adhesion molecules. This indirect inhibition of expression is relevant in the activity of 5-AIQ in models of arthritis, Parkinson's disease, multiple sclerosis, spinal cord injury, periodontitis and inflammatory conditions of the lung. Inhibition of expression of matrix metalloproteinases and other factors gives rise to anti-angiogenic activity and to remarkable anti-metastatic activity in a mouse model. Thus, although it has been overtaken by other PARP-inhibiting drugs in the oncological clinic, 5-AIQ remains a valuable tool to study the roles of PARPs in health and in diverse diseases.

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2011

Name Reactions in Heterocyclic Chemistry II

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Regioselectivity of the amination of some nitroisoquinolines by liquid ammonia/potassium permanganate

Cited by 21 publications

References 11 publications

Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents

Structure−Activity Relationships for Pyrido-, Imidazo-, Pyrazolo-, Pyrazino-, and Pyrrolophenazinecarboxamides as Topoisomerase-Targeted Anticancer Agents

5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

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