Preparation and pharmacological evaluation of the R - and S -enantiomers of 3-(2′-butylamino)-4 H - and 3-(3′-methyl-2′-butylamino)-4 H -pyrido[4,3- e ]-1,2,4-thiadiazine 1,1-dioxide, two tissue selective ATP-sensitive potassium channel openers

Khelili, Smail; Tullio, Pascal De; Lebrun, Philippe; Fillet, Marianne; Antoine, Marie-Hélène; Ouedraogo, R.; Dupont, L.; Fontaine, Jeanine; Felekidis, Apostolos; Leclerc, G.; Delarge, J.; Pirotte, Bernard

doi:10.1016/s0968-0896(99)00082-6

Cited by 21 publications

(31 citation statements)

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“…For drugs exhibiting a stereogenic center on the 3-alkylamino side chain, only the racemates were introduced in the study and built as the R -enantiomeric structure. This necessary arbitrary choice was driven by classical SAR deduced from the comparison of biological data obtained with ( R )- and ( S )-BPDZ 42 and -BPDZ 44 enantiomers …”

Section: Computational Detailsmentioning

confidence: 99%

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (K_ATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

et al. 2006

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Recent studies have demonstrated that selective activation of pancreatic ATP-sensitive potassium (KATP) channels could be of clinical value in the treatment of type I and type II diabetes, obesity, and hypersinsulinemia. Taking into account these promising therapeutic opportunities, we have explored the 3-alkylamino-4H-1,2,4-pyrido- and 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide families. Among these series, numerous drugs were identified as highly potent and selective openers of either the pancreatic or the aortic KATP channels. Thanks to comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), quantitative structure-activity relationship approaches using more than 100 compounds, pharmacophoric models explaining the activity and selectivity of the drugs have been elaborated. These models highlighted the importance of several chemical regions for KATP channel activation and could be very helpful for future improvement of drug potency, selectivity, or both. Moreover, an original CoMSIA analysis, using a selectivity index (SI) as a dependent variable, was also performed with the aim of identifying the structural parameters influencing tissue selectivity.

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Section: Computational Detailsmentioning

confidence: 99%

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (K_ATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

et al. 2006

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“…13 Four polymorphs of (S)-naproxen have been claimed, but three of them have been obtained under extreme crystallization conditions. Four naproxen cocrystals [14][15][16][17] and eight salts [18][19][20][21][22][23][24][25] have been recorded in the Cambridge Structural Database (CSD), 26 underlining the interest for this compound in solid-state studies. To diversify the structural study, we considered all possible chiral combinations between both partners as shown in Table 1.…”

Section: Introductionmentioning

confidence: 99%

On the influence of using a zwitterionic coformer for cocrystallization: structural focus on naproxen–proline cocrystals

et al. 2013

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“…We previously synthesized 3-alkylamino-4Hpyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides, with different aminoalkyl side-chains in the 3-position (Pirotte et al 1993(Pirotte et al , 1994de Tullio et al 1996;Lebrun et al 1996), which can be regarded as hybrid compounds between diazoxide and pinacidil ( Figure 1). Pharmacological investigation has recently shown that compounds such as BPDZ 42 (3-(2 H -butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide) and BPDZ 44 (3-(3 H -methyl-2 Hbutylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1dioxide) have the pharmacological pro®les of K ATP -channel openers (Pirotte et al 1994;Khelili et al 1999). In contrast with diazoxide, which is devoid of tissue selectivity, these two pyridothiadiazine dioxides seemed to be more active on endocrine pancreatic tissue (inhibition of insulin release) than on vascular tissue.…”

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confidence: 99%

Synthesis and Biological Effects of New 3-Alkylamino-4<I>H</I>- 1,2,4-Benzothiadiazine 1,1-Dioxides on Insulin-secreting Cells

Somers¹,

Tullio²,

Boverie³

et al. 2000

Pharmacy and Pharmacology Communications

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3‐Alkylamino‐4H‐1,2,4‐benzothiadiazine 1,1‐dioxides with nitro, amino or acetylamino groups in the 7‐position have been synthesized in an attempt to discover new tissue‐selective KATP‐channel openers. The compounds were tested as putative pancreatic β‐cells KATP‐channel openers by measuring their inhibitory activity on the insulin releasing process. The influence of the substituent in the 7‐position on the acidic character (pKa) and on biological activity is discussed. The nitrobenzene derivatives were biologically active, but less so than the un‐derivatized parent pyridothiadiazine dioxides.

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Preparation and pharmacological evaluation of the R - and S -enantiomers of 3-(2′-butylamino)-4 H - and 3-(3′-methyl-2′-butylamino)-4 H -pyrido[4,3- e ]-1,2,4-thiadiazine 1,1-dioxide, two tissue selective ATP-sensitive potassium channel openers

Cited by 21 publications

References 11 publications

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (K_ATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (K_ATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

On the influence of using a zwitterionic coformer for cocrystallization: structural focus on naproxen–proline cocrystals

Synthesis and Biological Effects of New 3-Alkylamino-4<I>H</I>- 1,2,4-Benzothiadiazine 1,1-Dioxides on Insulin-secreting Cells

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Preparation and pharmacological evaluation of the R - and S -enantiomers of 3-(2′-butylamino)-4 H - and 3-(3′-methyl-2′-butylamino)-4 H -pyrido[4,3- e ]-1,2,4-thiadiazine 1,1-dioxide, two tissue selective ATP-sensitive potassium channel openers

Cited by 21 publications

References 11 publications

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (KATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (KATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

On the influence of using a zwitterionic coformer for cocrystallization: structural focus on naproxen–proline cocrystals

Synthesis and Biological Effects of New 3-Alkylamino-4<I>H</I>- 1,2,4-Benzothiadiazine 1,1-Dioxides on Insulin-secreting Cells

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Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (K_ATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families

Three-Dimensional Quantitative Structure−Activity Relationships of ATP-Sensitive Potassium (K_ATP) Channel Openers Belonging to the 3-Alkylamino-4H-1,2,4-benzo- and 3-Alkylamino-4H-1,2,4-pyridothiadiazine 1,1-Dioxide Families