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

09-0730

Sigma-Aldrich

Ethyl acetate, suitable for HPLC

723851

Supelco

Dichloromethane solution, contains 10 % (v/v) methanol

09-1320

Sigma-Aldrich

Ethylenediaminetetraacetic acid, SAJ special grade, ≥99.0%

09-0680

Sigma-Aldrich

Ethyl acetate, JIS special grade, ≥99.5%

09-0690

Sigma-Aldrich

Ethyl acetate, SAJ first grade, ≥99.0%

09-0702

Sigma-Aldrich

Ethyl acetate, JIS 1000, ≥99.5%, suitable for residue analysis

07-2190

Sigma-Aldrich

Dichloromethane, SAJ first grade, ≥99.0%

09-0700

Sigma-Aldrich

Ethyl acetate, JIS 300, ≥99.5%, suitable for residue analysis

07-2180

Sigma-Aldrich

Dichloromethane, JIS special grade, ≥99.0%

03620

Sigma-Aldrich

Ethylenediaminetetraacetic acid, ≥98.0% (KT)

66742

Supelco

Dichloromethane, Selectophore^™, ≥99.5%

W241407

Sigma-Aldrich

Ethyl acetate, ≥99%, FCC, FG

270563

Supelco

Dichloromethane, ≥99.9%

W241415

Sigma-Aldrich

Ethyl acetate, natural, ≥99%, FCC, FG

E6758

Sigma-Aldrich

Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture

Sigma-Aldrich

Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder

EDS

Sigma-Aldrich

Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)

E9884

Sigma-Aldrich

Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder

E8008

Sigma-Aldrich

Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture

03690

Sigma-Aldrich

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

437549

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

431788

Sigma-Aldrich

Ethylenediaminetetraacetic acid, 99.995% trace metals basis

537446

Sigma-Aldrich

Ethyl acetate, ReagentPlus^®, ≥99.8%

02575

Supelco

Dichloromethane, analytical standard

58958

Supelco

Ethyl acetate, analytical standard

270997

Sigma-Aldrich

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

270989

Sigma-Aldrich

Ethyl acetate, anhydrous, 99.8%

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.

439223

Sigma-Aldrich

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

PHR1557

Supelco

Methylene Chloride, Pharmaceutical Secondary Standard; Certified Reference Material