Sulfonamide derivatives for the treatment of diseases

A technology of acetamide and methylsulfonyl, applied in the field of β2 agonists, to achieve excellent efficacy

Inactive Publication Date: 2009-10-14
PFIZER INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] However, none of the above-mentioned sulfonamide derivatives has shown β2 agonist activity and pharmacological properties, making them useful as therapeutic agents for β2-mediated diseases and / or physical disorders (especially allergic and non-allergic airway diseases or Effective drug use for other diseases such as those previously listed)

Method used

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  • Sulfonamide derivatives for the treatment of diseases
  • Sulfonamide derivatives for the treatment of diseases
  • Sulfonamide derivatives for the treatment of diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-38

[0725] The appropriate protected alcohol (0.075 mmol) was dissolved in ethanol (4 mL) and the solution was treated with ammonium fluoride (16 mg, 0.43 mmol) in water (300 μL). The reaction mixture was then stirred at 50°C for 18 hours and allowed to cool to room temperature. If a solid product precipitated, the reaction mixture was filtered and washed with methanol:water (2 mL, 1:1 by volume) to yield the title compound. If no product precipitated, the reaction mixture was concentrated in vacuo and purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia 98:2:0 to 95:5:0.5 to 90:10:1 residue to give the title product.

Embodiment 1

[0728] Example 1: 2-(3-{2-[((2R)-2-hydroxyl-2-[4-hydroxyl-3-[(methylsulfonyl)amino]phenyl}ethyl)amino]-2 -Methylpropyl}phenyl)-N-(4-hydroxy-3-methoxybenzyl)acetamide

[0729]

[0730] Preparation 18 (0.075 mmol) was dissolved in ethanol (4 mL) and the solution was treated with a solution of ammonium fluoride (16 mg, 0.43 mmol) in water (300 μL). The reaction mixture was then stirred at 50°C for 18 hours and allowed to cool to room temperature. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia 98:2:0 to 95:5:0.5 to 90:10:1 to give the title product of colorless solid.

[0731] 1 HNMR (CD 3 OD, 400MHz) δ: 1.04(s, 3H), 1.06(s, 3H), 2.68-2.90(m, 7H), 3.53(s, 2H), 3.74(s, 3H), 4.23(m, 2H), 4.62 (m, 1H), 6.67 (m, 2H), 6.77 (m, 1H), 6.85 (d, 1H), 7.01-7.22 (m, 6H), 7.37 (m, 1H) ppm.

[0732] MS (electrospray) m / z 572[M+H] +

Embodiment 2

[0733] Example 2: N-[(4'-hydroxybiphenyl-4-yl)methyl]-2-(3-{2-[((2R)-2-hydroxyl-2-{4-hydroxyl-3- [(methylsulfonyl)amino]phenyl}ethyl)amino]-2-methylpropyl}phenyl)acetamide

[0734]

[0735] Preparation 19 (0.075 mmol) was dissolved in ethanol (4 mL) and the solution was treated with a solution of ammonium fluoride (16 mg, 0.43 mmol) in water (300 μL). The reaction mixture was then stirred at 50°C for 18 hours and allowed to cool to room temperature. The reaction mixture was filtered and the solid was washed with methanol:water (2 mL, 1:1 by volume) to give the title compound as a colorless solid.

[0736] 1 HNMR (400MHz, DMSO d6 )δ: 0.90(s, 3H), 0.92(s, 3H), 2.56(s, 2H), 2.62-2.65(m, 2H), 2.88(s, 3H), 3.43(s, 2H), 4.25(2H , d), 4.40-4.43(m, 1H), 6.80-6.82(m, 3H), 6.96-7.01(m, 2H), 7.07-7.10(m, 2H), 7.14-7.18(m, 2H), 7.23 (d, 2H), 7.42-7.48 (m, 4H), 8.47 (t, 1H).

[0737] MS (electrospray) m / z 618[M+H] +

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PUM

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Abstract

The present invention relates to compounds of formula (1) and processes for the preparation of these derivatives, compositions comprising these derivatives and uses of these derivatives. The compounds according to the invention are useful in the treatment of a wide variety of diseases, disorders and ailments, especially inflammatory, allergic and respiratory diseases, conditions and ailments.

Description

technical field [0001] The present invention relates to beta2 agonists of the general formula: [0002] [0003] where R 1 , R 2 , n and Q 1 Has the meaning shown below, and relates to processes for the preparation of these derivatives, compositions comprising these derivatives and uses of these derivatives. Background technique [0004] Adrenergic receptors are members of the large superfamily of G-protein coupled receptors. The adrenoceptor subfamily itself is divided into alpha and beta subfamilies, and the beta subfamily consists of at least three receptor subtypes: beta1, beta2 and beta3. These receptors exhibit different expression patterns in tissues of various systems and organs of mammals. β2-adrenergic (β2) receptors are predominantly expressed in smooth muscle cells (e.g., vascular, bronchial, uterine, or intestinal smooth muscle), whereas β3-adrenergic receptors are predominantly expressed in adipose tissue (so β3 agonists may be able to treat obesity tr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C311/08A61K31/165A61K31/395A61P5/38
Inventor A·D·布朗M·E·邦纳吉P·A·格罗索普K·詹姆斯C·A·L·雷恩R·A·鲁斯外特I·B·莫西斯D·A·普莱斯N·M·汤姆森
Owner PFIZER INC
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