8-azabicyclo[3.2.1]octane-8-carboxamide derivative

A technology of cycloalkyl and A-1, which is applied in the field of pharmaceutical compositions, and can solve problems such as having different structures and not having 8-azabicycles

Inactive Publication Date: 2012-07-18
SUMITOMO DAINIPPON PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the compounds disclosed in Patent Document 1 do not have an 8-azabicyclo[3.2.1]octane-8-carboxamide skeleton, so they are structurally different from the present invention

Method used

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  • 8-azabicyclo[3.2.1]octane-8-carboxamide derivative
  • 8-azabicyclo[3.2.1]octane-8-carboxamide derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[1126]The present invention is illustrated in more detail by the following Reference Examples, Examples and Experiments, but it is not intended that the present invention be limited thereto. In addition, the compound nomenclature used in the following Reference Examples and Examples is not necessarily based on IUPAC nomenclature.

[1127] The following abbreviations are used in the Examples and Reference Examples.

[1128] THF: Tetrahydrofuran

[1129] NaBH(OAc) 3 : Sodium Triacetoxyborohydride

[1130] (Boc) 2 O: di-tert-butyl dicarbonate

[1131] DMF: N,N-Dimethylformamide

[1132] DIAD: Diisopropyl azodicarboxylate

[1133] Me: methyl

[1134] Et: ethyl

[1135] Bu: butyl

[1136] Ph: phenyl

[1137] Bn: benzyl

[1138] Ms: Methanesulfonyl

[1139] Ac: Acetyl

[1140] Boc: tert-butoxycarbonyl

[1141] Cbz or Z: benzyloxycarbonyl

[1142] Tf: Trifluoromethanesulfonyl

[1143] N: equivalent (for example, 2N HCl refers to 2 equivalents of hydrochloric acid)

...

Embodiment 2

[1208] (3-endo)-3-(Benzyloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate tert-butyl

[1209]

[1210] Step (i):

[1211] Compound I (4.23 g) was dissolved in DMF (100 ml), and benzyl bromide (3.32 ml) and sodium hydride (1.62 g) were added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with diisopropyl ether. The organic layer was dried over sodium sulfate, then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate=3 / 1) to obtain the title compound II (4.98 g).

[1212]

Embodiment 3

[1214] (3-endo)-3-phenoxy-8-azabicyclo[3.2.1]octane-8-carboxylate tert-butyl

[1215]

[1216] Step (i):

[1217] Compound I (490.6 mg) was dissolved in THF (4 mL), and then DIAD (0.66 ml), triphenylphosphine (869 mg) and phenol (312 mg) were added thereto, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate and washed with 1N aqueous sodium hydroxide solution and brine. The organic layer was dried over sodium sulfate, then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate=9 / 1) to give the title compound II (451 mg).

[1218]

[1219] Reference Example 4:

[1220] (3-endo)-3-(Benzenesulfonyl)-8-azabicyclo[3.2.1]octane-8-carboxylate tert-butyl

[1221]

[1222] Step (i):

[1223] Compound I (13.4 g) was dissolved in dichloromethane (600 ml), and then methanesulfonyl chlorid...

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Abstract

Disclosed is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. (In the formula, A represents a group that is represented by formula (A-1); R1a and R1b may be the same or different and each independently represents a C1-6 alkyl group which may be substituted by one to three halogen atoms; m and n each independently represents an integer of 0-5; X1 represents a hydroxyl group or an aminocarbonyl group; Z1 represents a single bond or the like; and R2 represents an optionally substituted C1-6 alkyl group, an optionally substituted C6-10 aryl group or the like.)

Description

technical field [0001] The present invention relates to 8-azabicyclo[3.2.1]octane-8-carboxamide derivatives, or pharmaceutically acceptable salts thereof, which can be used as medicines. The present invention also relates to a pharmaceutical composition, including 8-azabicyclo[3.2.1]octane-8-carboxamide derivative or a pharmaceutically acceptable salt thereof. The present invention also relates to a therapeutic or preventive agent for glucocorticoid-related diseases, or an inhibitor of 11β hydroxysterol dehydrogenase type I enzyme (hereinafter referred to as 11βHSD1 ) comprising the compound. Background technique [0002] Glucocorticoids regulate peripheral glucose metabolism and amino acid metabolism. In humans, glucocorticoids are produced in the adrenal glands, and additionally, it is metabolized in peripheral tissues such as adipose tissue or liver. Because 11βHSD1 is an enzyme that converts inactive cortisol into activated cortisol and is mainly expressed in adipose t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D451/02A61K31/46A61K31/497A61K31/501A61K31/506A61K31/5377A61P1/14A61P1/16A61P3/02A61P3/04A61P3/06A61P3/08A61P3/10A61P5/14A61P5/18A61P5/50A61P7/04A61P9/00A61P9/10A61P9/12A61P9/14A61P11/00A61P13/02A61P17/00A61P19/10A61P21/04A61P25/00A61P25/04A61P25/06A61P25/08A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/36A61P27/02A61P27/06A61P31/00A61P31/10A61P35/00A61P37/02A61P39/02A61P43/00C07D451/04C07D451/06
CPCC07D451/06A61P1/14A61P1/16A61P3/00A61P3/02A61P3/04A61P3/06A61P3/08A61P3/10A61P5/14A61P5/18A61P5/48A61P5/50A61P7/04A61P9/00A61P9/10A61P9/12A61P9/14A61P11/00A61P13/02A61P17/00A61P19/10A61P21/04A61P25/00A61P25/04A61P25/06A61P25/08A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/36A61P27/02A61P27/06A61P31/00A61P31/10A61P35/00A61P37/02A61P39/02A61P43/00A61K31/46C07D451/04C07D451/10
Inventor 堀内良浩泽村洁人藤原广阳
Owner SUMITOMO DAINIPPON PHARMA CO LTD
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