Molecular modeling and QSAR studies on KATP channel openers of the benzopyran type

Uhrig, Ulrike; Höltje, Hans‐Dieter; Mannhold, Raimund; Weber, Hendrik; Lemoine, Horst

doi:10.1016/s1093-3263(02)00107-9

Cited by 5 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Test compounds were added in a volume comprising 10 % of total buffer volume and gently mixed resulting in a time-dependent reduction of fluorescence indicating hyperpolarization of the membrane potential. Maximum hyperpolarization was induced with 30 mm NNC414 [33] in CHO (SUR1/Kir6.2) cells and with 3 mm KC399 [34] in HEK 293 (SUR2B/Kir6.1) cells.…”

Section: Pharmacological Methodsmentioning

confidence: 98%

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of K_ATP Channels

et al. 2009

Self Cite

View full text Add to dashboard Cite

4H-1,2,4-Benzothiadiazine-1,1-dioxides with various substituents in positions 3, 5, and 7 were synthesized and tested as K(ATP) channel agonists in artificial cell systems (CHO cells transfected with SUR1/Kir6.2, and HEK 293 transfected with SUR2B/Kir6.1) as model systems for insulin-secreting pancreatic beta-cells and for smooth muscle cells, respectively. The effects of agonists were tested in intact cells using DiBAC4(3) [bis-(1,3-dibarbituric acid)trimethine oxanol] as a membrane potential dye, and the results compared with their binding affinity for the SUR2B-type K(ATP) channels using the radioligand [(3)H]P1075. Compounds with cycloalkyl and (cycloalkyl)methyl side chains in position 3 had higher affinities towards the SUR2B/Kir6.1 receptor compared with the parent compound diazoxide (1 a). Compounds with bulky, nonpolar residues in position 3 exhibited remarkable selectivity for SUR2B-type K(ATP) channels. The compound substituted with a bulky (1-adamantyl)methyl residue exhibited micromolar affinity and activity on SUR2B-type K(ATP) channels without being able to activate the SUR1-type K(ATP) channels.

show abstract

Section: Pharmacological Methodsmentioning

confidence: 98%

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of K_ATP Channels

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…The poly (pyrazolyl) borates (HB), presented in green square in 6, were chosen for the chemical stabilization of metal complexes [29]. The alkyl chain bonded in phosphine atom (represented in red square in 6) increased lipophilicity, while the CN substituents increased inhibition [30]. 4 ]PF 6 (9) was 18.22 ± 2.11 (A549) and [Cu(PTA) 4] PF 6 (10) was 17.40 ± 1.76 (A549).…”

Section: Phosphine (Derived) Ligandsmentioning

confidence: 99%

Phosphine- and Isatin-Copper Complexes: Anticancer Activity, Mechanisms of Action and Structure-Activity Relationship Examples from the Last Ten Years

Nascimento-Júnior¹

2019

MACIJ

View full text Add to dashboard Cite

Platinum-based metallodrugs candidates are extensively evaluated as antineoplastic agents against several tumoral cell lines, representing a considerable advance in cancer treatment. On the other hand, the hostile off-site toxicity has been limited their potential uses in clinical step. Thus, the search for novel active and selective antitumor drugs is a leading issue in the medicinal inorganic chemistry. As follow, the research focused on less toxic metals has strategic importance and several copper complexes have revealed promising activity. In addition, copper is an essential metal, which can increase the chances of reduced side effects. This review brings some copper complexes that showed highlighted anticancer activity as drug prototypes from the last ten years (2010-2019), involving phosphine and isatin ligands, different redox states, modes of action and the study of structure-activity relationship (SAR).

show abstract

“…Regarding the C-6 position, it is known that the substituent at this site has a great impact on modulating the biological activity in the benzopyran KCOs . In particular, it has been postulated that the C-6 substituent could contribute to receptor affinity either by a direct interaction with the receptor site or indirectly by withdrawing electrons from the benzene moiety of the benzopyran nucleus, thus increasing charge transfer interactions of the aromatic moiety with the receptor . In early investigations, optimum substitution was attributed to small, electron-withdrawing substituents such as NO 2 , CF 3 , and CN .…”

Section: Introductionmentioning

confidence: 99%

1,4-Benzothiazine ATP-Sensitive Potassium Channel Openers: Modifications at the C-2 and C-6 Positions

et al. 2013

View full text Add to dashboard Cite

ATP-sensitive potassium (KATP) channels play a prominent role in controlling cardiovascular function. In this paper, a novel series of 4-(1-oxo-2-cyclopentenyl)-1,4-benzothiazine derivatives modified at the C-2, and C-6 positions were synthesized as openers of vascular KATP channels. Most of the tested compounds evoked vasorelaxing effects on rat aortic rings and membrane hyperpolarization in human vascular smooth muscle cells, with potency similar or superior to that of the reference levcromakalim (LCRK). The selective KATP blocker glibenclamide antagonized the above vascular effects, confirming that KATP channels are closely involved in the mechanism of action. The experimental results confirmed the 1,4-benzothiazine nucleus as an optimal scaffold for activators of vascular KATP channels; moreover, the high level of potency exhibited by the 6-acetyl substituted benzothiazine 8, along with the lack of any significant interference with insulin secretion from pancreatic β-cells, paves the way to further develop a new series of potent activators of vascular KATP channels.

show abstract

Molecular modeling and QSAR studies on KATP channel openers of the benzopyran type

Cited by 5 publications

References 28 publications

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of K_ATP Channels

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of K_ATP Channels

Phosphine- and Isatin-Copper Complexes: Anticancer Activity, Mechanisms of Action and Structure-Activity Relationship Examples from the Last Ten Years

1,4-Benzothiazine ATP-Sensitive Potassium Channel Openers: Modifications at the C-2 and C-6 Positions

Contact Info

Product

Resources

About

Molecular modeling and QSAR studies on KATP channel openers of the benzopyran type

Cited by 5 publications

References 28 publications

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of KATP Channels

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of KATP Channels

Phosphine- and Isatin-Copper Complexes: Anticancer Activity, Mechanisms of Action and Structure-Activity Relationship Examples from the Last Ten Years

1,4-Benzothiazine ATP-Sensitive Potassium Channel Openers: Modifications at the C-2 and C-6 Positions

Contact Info

Product

Resources

About

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of K_ATP Channels

Synthesis of Modified 4H‐1,2,4‐Benzothiadiazine‐1,1‐dioxides and Determination of their Affinity and Selectivity for Different Types of K_ATP Channels