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

717975

Sigma-Aldrich

Methanol, suitable for NMR (reference standard)

82762

Supelco

Methanol, analytical standard

322415

Sigma-Aldrich

Methanol, anhydrous, 99.8%

151874

Sigma-Aldrich

Dimethyl sulfoxide-d₆, 99.9 atom % D

34885

Sigma-Aldrich

Methanol, suitable for HPLC, gradient grade, ≥99.9%

34860

Sigma-Aldrich

Methanol, suitable for HPLC, ≥99.9%

646377

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Methanol, HPLC Plus, ≥99.9%

PHR1372

Supelco

Methanol, Pharmaceutical Secondary Standard; Certified Reference Material

154903

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Methanol, ACS spectrophotometric grade, ≥99.9%

M1775

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Methanol, Absolute - Acetone free

179337

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Methanol, ACS reagent, ≥99.8%

239313

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Sodium sulfate, ACS reagent, ≥99.0%, anhydrous, granular

238597

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Sodium sulfate, ACS reagent, ≥99.0%, anhydrous, powder

793604

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Potassium bromide, anhydrous, free-flowing, Redi-Dri^™, ReagentPlus^®, ≥99%

221864

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Potassium bromide, ≥99% trace metals basis

24229

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Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)

494437

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Methanol, BioReagent, ≥99.93%

1424109

USP

Methyl alcohol, United States Pharmacopeia (USP) Reference Standard

PHR1557

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34856

Sigma-Aldrich

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

650463

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

34858

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Ethyl acetate, suitable for HPLC, ≥99.7%

439169

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Ethyl acetate, suitable for HPLC, ≥99.8%

EDS

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

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Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder

E9884

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

W241407

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Ethyl acetate, ≥99%, FCC, FG

03609

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Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)

270997

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

48600

Supelco

Dichloromethane solution, certified reference material, 200 μg/mL in methanol