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New analogs as androgen receptor and glucocorticoid receptor modulators

A compound, the technology of halogen atoms, applied in the field of dihydropyridine derivatives, can solve problems such as the treatment of cancer that has not been mentioned

Active Publication Date: 2020-08-04
ONCOSTELLAE SL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no mention of these compounds being useful in the treatment of cancer

Method used

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  • New analogs as androgen receptor and glucocorticoid receptor modulators
  • New analogs as androgen receptor and glucocorticoid receptor modulators
  • New analogs as androgen receptor and glucocorticoid receptor modulators

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[1410] Preparation of dihydropyridine

[1411] Method A (Rampa, A et al., Forsch. 1992, 42, 1284).

Embodiment A1

[1412] Example A1: Methyl 5-acetyl-4-(benzo[b]thiophen-3-yl)-2,6-dimethyl-1,4-dihydro-pyridine-3-carboxylate

[1413]

[1414] 3-(Benzo[b]thiophen-3-ylmethylene)pentane-2,4-dione (0.24g, 0.98mmol, 1eq), methyl 3-oxobutyrate (0.158ml, 1.47mmol, 1.5eq) and 30% aqueous ammonium (0.62ml, 9.8mmol, 10eq) in i-PrOH (2ml) was heated for 12 hours. The solvent was removed under reduced pressure. The residue was taken up in water and extracted with dichloromethane and ethyl acetate. The combined organic layers were washed with brine, dried (Na 2 SO 4 ), filtered and concentrated, and used CH 2 Cl 2 The crude product was purified by flash column chromatography on silica gel with MeOH (1%) as eluent to give the title compound (114 mg, 25%) as a yellow solid.

[1415] 1 H-NMR (300MHz, CDCl 3 )δ=8.10(d, J=8.0Hz, 1H), 7.79(d, J=7.9Hz, 1H), 7.34(dt, J=24.0, 7.1Hz, 2H), 7.13(s, 1H), 6.27( bs, 1H), 5.47(s, 1H), 3.64(s, 3H), 2.34(s, 3H), 2.27(s, 3H), 2.14(s, 3H).

[1416] C 19 h 19...

Embodiment A4

[1418] Example A4: 5-Acetyl-4-(benzo[b]thiophen-3-yl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxamide

[1419] Method A yielded the title compound (73 mg, 22%) as a yellow solid.

[1420] 1 H-NMR (300MHz, CDCl 3 )δ=8.05(d, J=7.7Hz, 1H), 7.76(d, J=7.6Hz, 1H), 7.29(dt, J=15.0, 7.0Hz, 2H), 7.09(s, 1H), 6.76( s, 1H), 5.65 (bs, 2H), 5.34 (s, 1H), 2.25 (s, 3H), 2.08 (s, 6H).

[1421] C 18 h 18 N 2 o 2 HRMS (IE) m / z calculated for S: 326.0910, found: 326.1011.

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Abstract

The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improveby modulation of androgen receptor and / or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases,cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.

Description

technical field [0001] The present invention relates to novel pharmaceutically useful, optionally substituted dihydropyridine derivatives useful as modulators of nuclear receptors, such as receptors selected from the group consisting of androgen receptor and glucocorticoid receptor body. The compounds have potential use in the treatment of diseases and conditions mediated by nuclear receptors selected from androgen receptor and glucocorticoid receptor, such as cancer. The invention also relates to the use of such compounds as medicines, pharmaceutical compositions containing them and synthetic routes for their production. Background technique [0002] Nuclear receptors constitute a large superfamily of ligand-dependent transcription factors that are involved in many physiological and developmental processes and are associated with a variety of human diseases. This makes them attractive targets for drug discovery. In fact, approximately 13% of all FDA-approved drugs act on...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04A61P35/00A61P5/00A61K31/4422
CPCA61P5/00A61P35/00C07D495/04A61K31/4422A61K45/06C07D409/04C07D409/14
Inventor G·库兹J·卡马乔戈麦斯
Owner ONCOSTELLAE SL