Perfluoro-N-[4-(1H-tetrazol-5-ylmethyl)phenyl]alkanamides. A new class of oral antidiabetic agents

Kees, Kenneth L.; Cheeseman, Robert S.; Prozialeck, D. H.; Steiner, Kurt

doi:10.1021/jm00121a003

Cited by 39 publications

(26 citation statements)

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“…[34, 35] In ob/ob mice, the perfluorocarbons C 7 and C 8 perfluoroacyl chains C 8 (PFOA) and C 9 PFNA), respectively, demonstrated the greatest glucose lowering and insulin lowering after the 75 gram oral glucose tolerance test. With the exception of C 6 (PFHxS), which was not investigated, longer and shorter length chain perfluorocarbons did not eliminate hyperglycemia in this mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…With the exception of C 6 (PFHxS), which was not investigated, longer and shorter length chain perfluorocarbons did not eliminate hyperglycemia in this mouse model. [34] Kees et at found the strongest glucose lowering effect for PFOA in the ob/ob mouse, but there was also the possible suggestion of liver toxicity associated with this perfluorocarbon. [35] In the db/db mouse model of Type 2 diabetes, perfluorocarbon treatment attenuated polydipsia; treatment with PFOA and PFNA completely eliminated it in this mouse model, providing further evidence of the greater anti-diabetic effect of perfluorocarbons of these chain lengths.…”

Section: Discussionmentioning

confidence: 99%

“…[35] In the db/db mouse model of Type 2 diabetes, perfluorocarbon treatment attenuated polydipsia; treatment with PFOA and PFNA completely eliminated it in this mouse model, providing further evidence of the greater anti-diabetic effect of perfluorocarbons of these chain lengths. [34]…”

Section: Discussionmentioning

confidence: 99%

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Perfluoroalkyl substances and beta cell deficient diabetes

Conway

Innes

Long

2016

Journal of Diabetes and its Complications

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Aims Perfluoroalkyl Substances (PFAS) are synthetic hydrocarbons shown to preserve pancreatic islet cell viability and reduce islet cell hypoxia and apoptosis. We investigated the relationship of serum PFAS with diabetes, and whether this varied by diabetes type. Methods 6,460 individuals with and 60,439 without diabetes from the C8 Health Project, were categorized into three groups: Type 1 (n=820), Type 2 (n=4,291), or Uncategorized diabetes (n=1,349, missing data on diabetes type or diabetes based on blood sugar at study entry). Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluoroctanoic acid (PFOA), perfluoroctane sulfonate (PFOS), and perfluorononaoic acid (PFNA). Results PFAS levels were significantly lower in those with diabetes, and lowest in those with Type 1 diabetes. In age and sex adjusted analyses, ORs (CI) for Type 1, Type 2, and Uncategorized diabetes compared to no diabetes were 0.59 (0.54–0.64), 0.74 (0.71–0.77), 0.84 (0.78–0.90) respectively for PFHxS; 0.69 (0.65–0.74), 0.87 (0.89–0.91), 0.92 (0.88–0.97) respectively for PFOA; 0.65 (0.61–0.70), 0.86 (0.82–0.90), 0.93 (0.86–1.03) respectively for PFOS; and 0.65 (0.57–0.74), 0.94 (0.88–1.00), 0.95 (0.85–1.06), respectively for PFNA. Further adjustment for eGFR and other covariates did not eliminate these inverse associations. Conclusions PFAS levels were negatively associated with diabetes. This inverse relationship was strongest for Type 1 diabetes, suggesting the relationship with serum PFAS may vary with the severity of islet cell deficiency.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Perfluoroalkyl substances and beta cell deficient diabetes

Conway

Innes

Long

2016

Journal of Diabetes and its Complications

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“…For applications of benzamide derivatives, see: Ashwood et al (1990); Kees et al (1989); Ragavan et al (2010); Carmellino et al (1994); Rauko et al (2001). For a related structure, see: Cronin et al (2000).…”

Section: Related Literaturementioning

confidence: 99%

“…Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 A number of benzamide derivatives were reported to possess anti-hypertensive (Ashwood et al, 1990), anti-diabetic (Kees et al, 1989), anti-bacterial (Ragavan et al, 2010), anti-fungal (Carmellino et al, 1994) and anti-cancer (Rauko et al, 2001) activities. As a part of our study on the synthesis of new fluorine-containing compounds with possible biological activities, we report here the crystal structure of the title compound, (I).…”

Section: Data Collectionmentioning

confidence: 99%

N,N′-[4,4′-Methylenebis(4,1-phenylene)]bis(2,6-difluorobenzamide)

et al. 2011

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The complete molecule of the title compound, C27H18F4N2O2, is generated by crystallographic twofold symmetry, with one C atom lying on the rotation axis. The dihedral angle between fluoro-substituted phenyl ring and the adjacent benzene ring is 10.37 (5)°. In the crystal, molecules are connected by N—H⋯O and C—H⋯F hydrogen bonds, resulting in supramolecular chains propagating along the c direction.

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Synthesis and Functionalization of 5‐Substituted Tetrazoles

2012

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Tetrazoles are synthetic heterocycles with numerous applications in organic chemistry, coordination chemistry, the photographic industry, explosives, and, in particular, medicinal chemistry. In organic chemistry, 5‐substituted tetrazoles are used as advantageous intermediates in the synthesis of other heterocycles and as activators in oligonucleotide synthesis. In drug design, 5‐monosubstituted tetrazoles are the most important tetrazole derivatives because they represent non‐classical bioisosteres of carboxylic acids, with similar acidities but higher lipophilicities and metabolic resistance. In this review we focus on the preparation and further functionalization of these heterocycles. Firstly, the role of 5‐substituted tetrazoles in medicinal chemistry is described, including examples of their effects on pharmacokinetics, pharmacodynamics, and metabolism of the associated drugs. Then, the main synthetic approaches to 5‐substituted tetrazoles – consisting of methods based on acidic media/proton catalysis, Lewis acids, and organometallic or organosilicon azides – are presented, from the early procedures to the most recent ones, with special attention paid to the reaction mechanisms. Functionalization of 5‐substituted tetrazoles is a challenging task because it usually leads to the formation of two isomers, 1,5‐ and 2,5‐disubstituted tetrazoles, in various ratios. In this overview, reactions with high or unusual regioselectivities are described, with comments on the possible mechanisms. Microwave‐assisted approaches to the synthesis and functionalization of 5‐substituted tetrazoles are also included.

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Perfluoro-N-[4-(1H-tetrazol-5-ylmethyl)phenyl]alkanamides. A new class of oral antidiabetic agents

Cited by 39 publications

References 0 publications

Perfluoroalkyl substances and beta cell deficient diabetes

Perfluoroalkyl substances and beta cell deficient diabetes

N,N′-[4,4′-Methylenebis(4,1-phenylene)]bis(2,6-difluorobenzamide)

Synthesis and Functionalization of 5‐Substituted Tetrazoles

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