Cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-1,3-diazaspiro[4.5]decan-2-one derivatives
Cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-1,3-diazaspiro4,5-dec-2-one derivatives offer a novel therapeutic solution for neurological disorders, neurodegenerative diseases, and neuropsychiatric disorders, enhancing treatment efficacy.
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- GRUNENTHAL GMBH
- Filing Date
- 2026-05-12
- Publication Date
- 2026-07-10
AI Technical Summary
Current treatments for neurological disorders, neurodegenerative diseases, neuroinflammatory diseases, and neuropsychiatric disorders are inadequate, and there is a need for more effective therapeutic agents to address these conditions.
The development of cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-1,3-diazaspiro4,5-dec-2-one derivatives for use in medicine to treat these disorders.
The derivatives provide a novel therapeutic approach with potential efficacy in treating pain, neurodegenerative diseases, neuroinflammatory diseases, and neuropsychiatric disorders, offering improved treatment options.
Abstract
Description
Invention Title: cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-1,3-diazaspiro4,5-dec-2-one Derivatives Abstract: This invention relates to cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-1,3-diazaspiro4,5-dec-2-one derivatives, their preparation, and their use in medicine, particularly in various neurological disorders, including but not limited to pain, neurodegenerative diseases, neuroinflammatory diseases, neuropsychiatric disorders, and substance abuse / dependence.
Claims
Patent claims1. A compound according to general formula (I)whereinAl represents N or CR1;A2 represents N or C;A3 represents N or CH;A4 represents N or CH;A5 represents N or C; with the proviso that one or two of Al, A2, A3, A4 and A5 mean N, whereas the remaining three or four of Al, A2, A3, A4, and A5 do not mean N;R1 represents -H, -CH3 or =0;R2 represents-Ci-Ce-alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently selected from -F and -OH;-Cs-Cv-heterocycloalkyl, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently selected from -F, -OH and -CH3;-S(O)2-Ci-C4-alkyl, linear, branched or cyclic, unsubstituted or substituted with one, two or three substituents -F;-O-Ci-Ce-alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently selected from -F, -OH and -OCH3;-O-Cs-Cs-cycloalkyl, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently selected from -F, -OH and -CH3; or-O-Cs-Cv-heterocycloalkyl, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently selected from -F and -OH; or R1 and R2 together with Al and A2 form a ring and mean -CH=CN-NH-;R3 represents -H or -CH3;R4 and R5 both represent either each -H or together mean =0; or a physiologically acceptable salt thereof.
2. The compound according to claim 1, wherein(i) one of Al, A2, A3, A4 and A5 represents N, whereas the remaining four of Al, A2, A3, A4, and A5 do not represent N; or(ii) two of Al, A2, A3, A4 and A5 represent N, whereas the remaining three of Al, A2, A3, A4, and A5 do not represent N.
3. The compound according to claim 1 or 2, wherein Al represents CR1; A2 represents C; A3 represents CH; A4 represents N; and A5 represents C.
4. The compound according to claim 1 or 2, wherein Al represents N; A2 represents C; A3 represents CH; A4 represents CH; and A5 represents C5. The compound according to claim 1 or 2, wherein Al represents CR1; A2 represents C; A3 represents N; A4 represents N; and A5 represents C.
6. The compound according to claim 1 or 2, wherein Al represents N; A2 represents C; A3 represents N; A4 represents CH; and A5 represents C.
7. The compound according to claim 1 or 2, wherein Al represents CR1 with R1 meaning =0; A2 represents N; A3 represents CH; A4 represents CH; and A5 represents C.
8. The compound according to claim 1 or 2, wherein Al represents N; A2 represents C; A3 represents CH; A4 represents N; and A5 represents C.
9. The compound according to claim 1 or 2, wherein Al represents CR1 with R1 meaning =0; A2 represents C; A3 represents CH; A4 represents CH; and A5 represents N.
10. The compound according to any of the preceding claims, wherein R1 (if present) represents -H, or -CH3.
11. The compound according to any of the preceding claims, wherein R2 is selected from -CH3, -CF3, -C(CH3)2OH, and -C(CH3)(OH)CF3.
12. The compound according to any of claims 1 to 10, wherein R2 represents 3-fluorooxetan-3-yl.
13. The compound according to any of claims 1 to 10, wherein R2 is selected from -S(O)2CH3 and -S(O)2CH2CH3.
14. The compound according to any of claims 1 to 10, wherein R2 is selected from -OCH3, -OCHF2, -OCH2CHF2, -OCF2CH3, -OCF3, -OCH2CH2OCH3, -O-cyclopropyl, and 3-hydroxy-3- methylcyclobutoxy.
15. The compound according to any of claims 1 to 10, wherein R2 represents oxetan-3-yloxy.
16. The compound according to any of claims 1 to 10, wherein R1 and R2 together with Al and A2 form a ring and mean -CH=CN-NH-.
17. The compound according to any of the preceding claims, wherein R3 represents -CH3.
18. The compound according to any of the preceding claims, wherein R4 and R5 both mean -H.
19. The compound according to any of the preceding claims, which is selected from the group consisting of:EX-I-01 cis-3 -(5 -cyclopropoxy-3 -methylpyridin-2-yl)-8-(3 ,5 -difluorophenyl)-8-(dimethyl- amino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-02 cis-8-(3,5-difhiorophenyl)-8-(dimethylamino)-3-(2-methoxy-4-methylpyrimidin-5 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-03 cis-8-(3 ,5 -difluorophenyl)-8-(dimethylamino)-3 -(5 -(2-hydroxypropan-2-yl)-3 - methylpyridin-2-yl)- 1 ,3 -diazaspiro [4.5] decan-2 -oneEX-I-04 cis-3 -(5 -(difluoromethoxy)-3 -methylpyridin-2-yl)-8-(3 ,5 -difluorophenyl)-8-(dime- thylamino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-06 cis-8-(3 ,5 -difluorophenyl)-3 -(5 -(2-hydroxypropan-2-yl)-3 -methylpyridin-2-yl)-8- (methylamino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-07 cis-8-(3 ,5 -difluorophenyl)-8-(dimethylamino)-3 -(3 -methyl-5 -(trifluorometh- oxy)pyridin-2-yl)-l,3-diazaspiro[4.5]decan-2-oneEX-I-08 cis-8-(3,5-difhiorophenyl)-8-(dimethylamino)-3-(4-methyl-6-(trifluorometh- oxy)pyridazin-3 -yl)- 1 , 3 -diazaspiro [4.5] decan-2 -oneEX-I-09 cis-8-(3 ,5 -difluorophenyl)-8-(dimethylamino)-3 -(5 -(3 -hydroxy-3 -methylcyclobu- toxy)-3-methylpyridin-2-yl)-l,3-diazaspiro[4.5]decan-2-oneEX-I-10 cis-8-(3 ,5 -difluorophenyl)-8-(dimethylamino)-3 -(3 -methyl-5 -(methylsulfonyl)pyr- idin-2-yl)- 1 , 3 -diazaspiro [4.5] decan-2 -oneEX-I-11 cis-8-(3 ,5 -difluorophenyl)-8-(dimethylamino)-3 -(5 -(ethylsulfonyl)-3 -methylpyri- din-2-yl)-l,3-diazaspiro[4.5]decan-2-oneEX-I-12 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(2-methyl-6-(trifluoromethyl)pyr- idin-3 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-13 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(2,6-dimethylpyridin-3-yl)-l,3- diazaspiro [4.5] decan-2-oneEX-I-14 cis-8-(3,5-difluorophenyl)-8-(dirnethylarnino)-3-(2-methyl-6-(trifluorometh- oxy)pyridin-3 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-15 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(4-methyl-2-(oxetan-3-yloxy)py- rimidin-5 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-16 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(2-(2-methoxyethoxy)-4- methylpyrimidin-5 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-17 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(2-methyl-6-(methylsulfonyl)pyr- idin-3 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-18 cis-3-(2-cyclopropoxy-4-methylpyrimidin-5-yl)-8-(3,5-difluorophenyl)-8-(dime- thylamino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-19 cis-8-(3,5-difluorophenyl)-3-(l,3-dimethyl-2 -oxo-1, 2-dihydropyridin-4-yl)-8-(di- methylamino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-20 cis-8-(3 ,5 -difluorophenyl)-8-(dimethylamino)-3 -(5 -(2-hydroxypropan-2-yl)-3 - methylpyrazin-2-yl)-l,3-diazaspiro[4.5]decan-2-oneEX-I-21 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(2-(3-fluorooxetan-3-yl)-4- methylpyrimidin-5 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-22 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(2-(2-hydroxypropan-2-yl)-4- methylpyrimidin-5 -yl)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-23 cis-3 -(5 -(1,1 -difluoroethoxy)- 1 -methyl-6-oxo- 1 ,6-dihydropyridin-2-yl)-8-(3 ,5 - difluorophenyl)-8-(dimethylamino)-l,3-diazaspiro[4.5]decan-2-oneEX-I-24 cis-8-(3,5-difluorophenyl)-8-(dimethylamino)-3-(3-methyl-5-((S)-l, 1, 1-trifluoro-2-hydroxypropan-2-yl)pyridin-2-yl)-l,3-diazaspiro[4.5]decan-2-oneEX-I-25 cis-3 -(5 -cyclopropoxy-3 -methylpyridin-2-yl)-8-(3 ,5 -difluorophenyl)-8-(methyla- mino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-26 cis 1 -3 -(5 -(2,2-difluoroethoxy)-3 -methylpyridin-2-yl)-8-(3 ,5 -difluorophenyl)-8- (dimethylamino)- 1 ,3 -diazaspiro [4.5] decan-2 -oneEX-I-27 cis-3-(6-(2,2-difluoroethoxy)-4,5-dimethylpyridazin-3-yl)-8-(3,5-difluorophenyl)- 8 -(dimethylamino)- 1 , 3 -diazaspiro [4.5] decan-2-oneEX-I-28 cis-3-(5-(difluoromethoxy)-3-methylpyridin-2-yl)-8-(3,5-difluorophenyl)-8-(dime- thylamino)-l,3-diazaspiro[4.5]decane-2, 4-dione and the physiologically acceptable salts thereof.
20. A medicament comprising a compound according to any of the preceding claims.
21. A compound according to any of claims 1 to 13 for use in the treatment of pain.