Design and synthesis of sulfonamide derivatives of pyrrolidine and piperidine as anti-diabetic agents.

Design and synthesis of sulfonamide derivatives of pyrrolidine and piperidine as anti-diabetic agents.

European journal of medicinal chemistry (2014-12-02)

Radhika Sharma, Shubhangi S Soman

ABSTRACT

Type 2 diabetes (T2D) is a lifestyle disease affecting millions of people worldwide. Various therapies are available for the management of T2D and dipeptidyl peptidase-IV (DPP-IV) inhibition has emerged as a promising therapy for the treatment of type 2 diabetes (T2D). Here we report design, synthesis and in vitro efficacy of sulfonamide derivatives of pyrrolidine and piperidine as anti-diabetic agents. Amongst all the compounds synthesized in this series, 9a, is the most potent (IC50 = 41.17 nM).

MATERIALS

Product Number

Brand

Product Description

PHR1481

Supelco

Ethyl Acetate, Pharmaceutical Secondary Standard; Certified Reference Material

PHR1557

Supelco

Methylene Chloride, Pharmaceutical Secondary Standard; Certified Reference Material

1424109

USP

Methyl alcohol, United States Pharmacopeia (USP) Reference Standard

34856

Sigma-Aldrich

Dichloromethane, suitable for HPLC, ≥99.8%, contains amylene as stabilizer

650463

Sigma-Aldrich

Dichloromethane, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains 50-150 ppm amylene as stabilizer

34858

Sigma-Aldrich

Ethyl acetate, suitable for HPLC, ≥99.7%

650528

Sigma-Aldrich

Ethyl acetate, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%

439169

Sigma-Aldrich

Ethyl acetate, suitable for HPLC, ≥99.8%

676853

Sigma-Aldrich

Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer

676810

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

D65100

Sigma-Aldrich

Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%

24233

Sigma-Aldrich

Dichloromethane, puriss., meets analytical specification of Ph. Eur., NF, ≥99% (GC)

494453

Sigma-Aldrich

Dichloromethane, biotech. grade, 99.9%, contains 40-150 ppm amylene as stabilizer

494518

Sigma-Aldrich

Ethyl acetate, biotech. grade, ≥99.8%

33211

Sigma-Aldrich

Ethyl acetate, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)

319902

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

320269

Sigma-Aldrich

Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer

27227

Sigma-Aldrich

Ethyl acetate, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99.5% (GC)

32222

Sigma-Aldrich

Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)

W241407

Sigma-Aldrich

Ethyl acetate, ≥99%, FCC, FG

W241415

Sigma-Aldrich

Ethyl acetate, natural, ≥99%, FCC, FG

721956

Sigma-Aldrich

Methanol solution, suitable for NMR (reference standard), 4% in methanol-d₄ (99.8 atom % D), NMR tube size 3 mm × 8 in.

270997

Sigma-Aldrich

Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer

270989

Sigma-Aldrich

Ethyl acetate, anhydrous, 99.8%

431788

Sigma-Aldrich

Ethylenediaminetetraacetic acid, 99.995% trace metals basis

439223

Sigma-Aldrich

Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer

03690

Sigma-Aldrich

Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, pH 8.0, ~0.5 M in H₂O

03609

Sigma-Aldrich

Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)

03620

Sigma-Aldrich

Ethylenediaminetetraacetic acid, ≥98.0% (KT)

02575

Supelco

Dichloromethane, analytical standard