The diuretic activity of clorexolone and some related phthalimides and 1-oxoisoindolines

Cornish, E. J.; Lee, G. E.; Wragg, W. R.

doi:10.1111/j.2042-7158.1966.tb07828.x

Cited by 13 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clorexolone 17 is structurally related both to thiazides and chlorthalidone 16 . In vivo inhibition of CA has little contribution to the overall diuretic activity [ 43 ], while in vitro binding shows the average binding affinity within 42–500 nM for most CA isoforms.…”

Section: Discussionmentioning

confidence: 99%

Thiazide and other Cl-benzenesulfonamide-bearing clinical drug affinities for human carbonic anhydrases

et al. 2021

View full text Add to dashboard Cite

Twelve carbonic anhydrase (CA) isoforms catalyze carbon dioxide hydration to bicarbonate and acid protons and are responsible for many biological functions in human body. Despite their vital functions, they are also responsible for, or implicated in, numerous ailments and diseases such as glaucoma, high altitude sickness, and cancer. Because CA isoforms are highly homologous, clinical drugs designed to inhibit enzymatic activity of a particular isoform, can also bind to others with similar affinity causing toxic side effects. In this study, the affinities of twelve CA isoforms have been determined for nineteen clinically used drugs used to treat hypertension related diseases, i.e. thiazides, indapamide, and metolazone. Their affinities were determined using a fluorescent thermal shift assay. Stopped flow assay and isothermal titration calorimetry were also employed on a subset of compounds and proteins to confirm inhibition of CA enzymatic activity and verify the quantitative agreement between different assays. The findings of this study showed that pharmaceuticals could bind to human CA isoforms with variable affinities and inhibit their catalytic activity, even though the drug was intended to interact with a different (non-CA) protein target. Relatively minor structural changes of the compounds may cause significant changes in affinity and selectivity for a particular CA isoform.

show abstract

Section: Discussionmentioning

confidence: 99%

Thiazide and other Cl-benzenesulfonamide-bearing clinical drug affinities for human carbonic anhydrases

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The residue was refluxed with 2-propanol (l!/2 L), and the solid was collected and dried to give 416 g (77%) of 20. 4-Chloro-5-nitrophthalimide21 (21). A solution of 20 (15 g, 82 mmol) in 20% oleum (150 mL) and fuming nitric acid (18 mL) was heated at 80 °C for */2 h. The mixture was cooled to room temperature and poured slowly onto ice (1.5 kg).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones

Cherkez¹,

Herzig²,

Yellin³

1986

J. Med. Chem.

View full text Add to dashboard Cite

The synthesis of the isomeric series 6-chloro-7-sulfamoyl- and 7-chloro-6-sulfamoyl-1(2H)-phthalazinones (1 and 2) and 6-chloro-7-sulfamoyl- and 7-chloro-6-sulfamoyl-3,4-dihydo-1(2H)-phthalazinones (3 and 4), combining structural features characteristic to furosemide and hydralazine, is described, the mechanism of the formation of 1 and 2 is discussed, and their structure-activities relationships are studied. Preliminary screening in the rat shows that series 1 and 3 exhibit diuretic and saluretic activity similar to that of chlorothiazide with, however, Na+/K+ ratios more favorable than chlorothiazide and furosemide. The compounds of series 2 and 4 are practically inactive. All four series show initial antihypertensive activity lower than that of hydralazine. However, compounds 1a, 1c, and 4a show a higher activity at 8 and/or 24 h after administration and thus may offer a unique combination of a "loop" diuresis with direct long-acting peripheral vasodilating effects.

show abstract

“…Then the solid was washed with EtOAc. The filtrate was dried over Na2SO4 and evaporated under reduced pressure and the resulting residue was purified by flash column chromatography to give the corresponding product as a yellow solid (1.2 g, 52%); mp: >250 o C; Rf = 0.4 (Petroleum ether : ethyl acetate = 10 : 1); 1 H NMR (400 MHz, CDCl3, TMS) δ 10.22 (s, 1H), 7.55 (s, 1H), 7.29 (s, 1H), 4.25 (br, 2H). 13 C NMR (100 MHz, CDCl3) δ 191.…”

Section: Procedures For the Preparation Of Substratesmentioning

confidence: 99%

Catalytic Benzolactamization Through Isonitrile Insertion Enabled 1,4-Palladium Shift

Zhang¹,

Zhao²,

Li³

et al. 2021

Preprint

View full text Add to dashboard Cite

<b>Isoindolinone is a class of versatile <i>N</i>-heterocycles embedded in many bioactive molecules and natural products. The invention of new methods to synthesize these heterocyclic compounds with easily accessible chemicals is always attractive. Herein, a conceptually novel approach to access this bicyclic system via isonitrile insertion enabled 1,4-pallaidum shift is described. Compared with conventional isonitrile participated C-H bond activation, both carbon and nitrogen atoms in isonitrile moiety are engaged in new bond formation. Notably, two different isoindolinones can be obtained selectively by switching the bases employed. Mechanistic studies including DFT calculations have shed lights on the reaction mechanism and explained the selectivity led to different products. Moreover, the power of current benzolactamization is further demonstrated by providing concise routes to key intermediates of indoprofen, indobufen, aristolactams, lennoxamine and falipamil.</b>

show abstract

The diuretic activity of clorexolone and some related phthalimides and 1-oxoisoindolines

Cited by 13 publications

References 10 publications

Thiazide and other Cl-benzenesulfonamide-bearing clinical drug affinities for human carbonic anhydrases

Thiazide and other Cl-benzenesulfonamide-bearing clinical drug affinities for human carbonic anhydrases

Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones

Catalytic Benzolactamization Through Isonitrile Insertion Enabled 1,4-Palladium Shift

Contact Info

Product

Resources

About