AR101976A1 - DERIVATIVES OF PIRIDIN-2 (1H) -ON QUINOLINONE AS INHIBITORS OF MUTANT DEHYDROGENASE ISOCITRATE - Google Patents
DERIVATIVES OF PIRIDIN-2 (1H) -ON QUINOLINONE AS INHIBITORS OF MUTANT DEHYDROGENASE ISOCITRATEInfo
- Publication number
- AR101976A1 AR101976A1 ARP150103022A ARP150103022A AR101976A1 AR 101976 A1 AR101976 A1 AR 101976A1 AR P150103022 A ARP150103022 A AR P150103022A AR P150103022 A ARP150103022 A AR P150103022A AR 101976 A1 AR101976 A1 AR 101976A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- cycloalkyl
- alkoxy
- heterocyclyl
- elements
- Prior art date
Links
- 101710088194 Dehydrogenase Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 title 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title 1
- 229930185107 quinolinone Natural products 0.000 title 1
- 229910052736 halogen Inorganic materials 0.000 abstract 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 11
- 125000000623 heterocyclic group Chemical group 0.000 abstract 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 10
- 125000001072 heteroaryl group Chemical group 0.000 abstract 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 8
- 125000003118 aryl group Chemical group 0.000 abstract 7
- 150000002367 halogens Chemical class 0.000 abstract 7
- 125000005843 halogen group Chemical group 0.000 abstract 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 5
- 125000000217 alkyl group Chemical group 0.000 abstract 5
- 229910052757 nitrogen Inorganic materials 0.000 abstract 4
- 229910052760 oxygen Inorganic materials 0.000 abstract 4
- 229910052717 sulfur Inorganic materials 0.000 abstract 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 4
- 125000004429 atom Chemical group 0.000 abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract 3
- 125000001424 substituent group Chemical group 0.000 abstract 3
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 abstract 2
- 125000000304 alkynyl group Chemical group 0.000 abstract 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- 229910052805 deuterium Inorganic materials 0.000 abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
- -1 -S (O) 2NHR7 Proteins 0.000 abstract 1
- SHENXRCDBJGWNU-GOSISDBHSA-N 6-(1,3-benzothiazol-6-ylamino)-4-(cyclopropylamino)-n-[(2r)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound CC(C)(O)[C@H](F)CNC(=O)C1=CN=C(NC=2C=C3SC=NC3=CC=2)C=C1NC1CC1 SHENXRCDBJGWNU-GOSISDBHSA-N 0.000 abstract 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 abstract 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 abstract 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 abstract 1
- 101710134866 Quinone reductase Proteins 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
- WCYWZMWISLQXQU-FIBGUPNXSA-N trideuteriomethane Chemical compound [2H][C]([2H])[2H] WCYWZMWISLQXQU-FIBGUPNXSA-N 0.000 abstract 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Reivindicación 1: Un compuesto de fórmula (1), o sal farmacéutica, enantiómero, hidrato, solvato, profármaco, isómero, o tautómero del mismo, caracterizado porque: cada W¹ y W² es independientemente CH, CF o N; W³ es independientemente, CR² o N; U es N o CR⁶; A se selecciona a partir del grupo que consiste de H, D, halógeno, CN, -CHO, -COOH, -COOR, -C(O)NH₂, -C(O)NHR, RS(O)₂-, -O(CH₂)ₙC(O)R, RS(O)-, heteroarilo, -SOMe, -SO₂Me, o un resto del grupo de fórmulas (2); en donde X e Y son independientemente en cada caso C, N, NR, S, y O, siempre que el anillo que contiene X e Y no puede tener más de 4 N o NH átomos o más de un átomo de S u O, y en donde el S y O no son contiguos; R y R en cada caso son independientemente seleccionados a partir del grupo que consiste de H, OH, CN, -CH₂CN, halógeno, -NR⁷R⁸, CHCF₂, CF₃, alquilo C₁₋₆, R⁷S(O)₂-, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquilalquilo C₃₋₈, heterociclilo, arilo, y heteroarilo de 3 a 8 elementos, en donde cada R es opcionalmente sustituido con uno o más sustituyentes seleccionados a partir del grupo que consiste de OH, halógeno, alcoxi C₁₋₆, NH₂, R⁷S(O)₂-, CN, cicloalquilo C₃₋₈, heterociclilo, arilo, heteroarilo 3 a 8 elementos y R⁷S(O)-; R¹ es independientemente OH, CN, halógeno, CHCF₂, CF₃, alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquenilo C₂₋₆, cicloalquilo C₃₋₈, heterociclilo, arilo, o heteroarilo 3 a 8 elementos, en donde cada alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, heterociclilo, arilo, o heteroarilo 3 a 8 elementos es opcionalmente sustituido una o más veces con sustituyentes seleccionados a partir del grupo que consiste de halógeno, OH, NH₂, CN, alquilo C₁₋₆, y alcoxi C₁₋₆; cada R² es independientemente H, OH, CN, halógeno, CF₃, CHF₂, bencilo, alquilo C₁₋₆, alcoxi C₁₋₆, NH₂, -O(CH₂)ₙR, -O(CH₂)ₙC(O)NHR, -O(CH₂)ₙC(O)R, NHR⁷, -N(R⁷)(R⁸), NHC(O)R⁷, NHS(O)R⁷, NHS(O)₂R⁷, NHC(O)OR⁷, NHC(O)NHR⁷, -S(O)₂NHR⁷, NHC(O)N(R⁸)R⁷, OCH₂R⁷, CHRR o OCHRR⁷, en donde alquilo C₁₋₆, alcoxi C₁₋₆ es opcionalmente sustituido con uno o más sustituyentes seleccionados a partir del grupo que consiste de alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, cicloalquilo C₃₋₈ sustituido con uno o más halógenos, heterociclilo, arilo 3 a 8 elementos -heteroarilo-C(O)NH₂, y heteroarilo; o R¹ y R² se pueden combinar para formar un cicloalquilo C₄₋₆ o un heterociclilo de 3 a 8 elementos que contiene al menos un átomo seleccionado a partir del grupo que consiste de N, O, y S; R³ es H, alquilo C₁₋₆, o -OH; R⁴ y R⁵ son independientemente H, halógeno, CH₂OH, alquilo C₁₋₃, o alquilo C₁₋₃ sustituido con halógeno, o R⁴ y R⁵ cuando se combinan pueden formar un cicloalquilo C₃₋₆ o heterociclilo C₃₋₆; cada R⁶ es H, halógeno, alquilo C₁₋₆, alquilo C₁₋₆ sustituido con halógeno, alcoxi C₁₋₆, alcoxi C₁₋₆ sustituido con uno o más halógenos, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, heterociclilo, arilo, o heteroarilo 3 a 8 elementos; R⁷ y R⁸ son independientemente H, alquilo C₁₋₆, alcoxi C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₈, heterociclilo, arilo, y heteroarilo de 3 a 8 elementos; o cuando se combinan R⁷ y R⁸ pueden formar un anillo elementos heterociclilo o heteroarilo de 3 a 8 elementos; R⁹ es independientemente H, D, CD₃, CF₃, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₃₋₆, cicloalquilo C₃₋₈, en donde el alquilo, alquenilo, alquinilo, y cicloalquilo es opcionalmente sustituido con amino, OH, halo, o alcoxi; n es 0, 1, ó 2; y r es 0, 1, ó 2; con la condición que cuando A sea H, entonces R¹ no es alquilo C₁₋₆ o alcoxi C₁₋₆ y R¹ y R² no se pueden combinar para formar un heterociclilo de 3 a 8 elementos.Claim 1: A compound of formula (1), or pharmaceutical salt, enantiomer, hydrate, solvate, prodrug, isomer, or tautomer thereof, characterized in that: each W¹ and W² is independently CH, CF or N; W³ is independently, CR² or N; U is N or CR⁶; A is selected from the group consisting of H, D, halogen, CN, -CHO, -COOH, -COOR, -C (O) NH₂, -C (O) NHR, RS (O) ₂-, -O (CH₂) ₙC (O) R, RS (O) -, heteroaryl, -SOMe, -SO₂Me, or a remainder of the group of formulas (2); where X and Y are independently in each case C, N, NR, S, and O, provided that the ring containing X and Y cannot have more than 4 N or NH atoms or more than one atom of S or O, and where S and O are not contiguous; R and R in each case are independently selected from the group consisting of H, OH, CN, -CH₂CN, halogen, -NR⁷R⁸, CHCF₂, CF₃, C₁₋₆ alkyl, R⁷S (O) ₂-, C₁₋₆ alkoxy , C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl of 3 to 8 elements, wherein each R is optionally substituted with one or more substituents selected from the group consisting of OH, halogen, C₁₋₆ alkoxy, NH₂, R⁷S (O) ₂-, CN, C₃₋₈ cycloalkyl, heterocyclyl, aryl, heteroaryl 3 to 8 elements and R⁷S (O) -; R¹ is independently OH, CN, halogen, CHCF₂, CF₃, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₂₋₆ alkenyl, C₂₋₆ alkenyl, C₃₋₈ cycloalkyl, heterocyclyl, aryl, or heteroaryl 3 to 8 elements, in wherein each C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₈ cycloalkyl, heterocyclyl, aryl, or heteroaryl 3 to 8 elements is optionally substituted one or more times with substituents selected from the group consisting of halogen , OH, NH₂, CN, C₁₋₆ alkyl, and C₁₋₆ alkoxy; each R² is independently H, OH, CN, halogen, CF₃, CHF₂, benzyl, C₁₋₆ alkyl, C₁₋₆ alkoxy, NH₂, -O (CH₂) ₙR, -O (CH₂) ₙC (O) NHR, -O (CH₂) ₙC (O) R, NHR⁷, -N (R⁷) (R⁸), NHC (O) R⁷, NHS (O) R⁷, NHS (O) ₂R⁷, NHC (O) OR⁷, NHC (O) NHR⁷, -S (O) ₂NHR⁷, NHC (O) N (R⁸) R⁷, OCH₂R⁷, CHRR or OCHRR⁷, wherein C alquilo alkyl, C₁₋₆ alkoxy is optionally substituted with one or more substituents selected from the group consisting of C₁₋₆ alkyl, C₁₋₆ alkoxy, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ substituted cycloalkyl, substituted with one or more halogens, heterocyclyl, aryl 3 to 8 elements -heteroaryl-C (O) NH₂, and heteroaryl; or R¹ and R² can be combined to form a C₄₋₆ cycloalkyl or a heterocyclyl of 3 to 8 elements containing at least one atom selected from the group consisting of N, O, and S; R³ is H, C₁₋₆ alkyl, or -OH; R⁴ and R⁵ are independently H, halogen, CH₂OH, C₁₋₃ alkyl, or halogen substituted C con alkyl, or R⁴ and R⁵ when combined can form a C₃₋₆ cycloalkyl or C₃₋₆ heterocyclyl; each R⁶ is H, halogen, C₁₋₆ alkyl, halogen substituted C con alkyl, C₁₋₆ alkoxy, C₁₋₆ alkoxy substituted with one or more halogens, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₈ cycloalkyl , heterocyclyl, aryl, or heteroaryl 3 to 8 elements; R⁷ and R⁸ are independently H, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₈ cycloalkyl, heterocyclyl, aryl, and heteroaryl of 3 to 8 elements; or when R⁷ and R⁸ are combined, heterocyclyl or heteroaryl elements of 3 to 8 elements can form a ring; R⁹ is independently H, D, CD₃, CF₃, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₃₋₆ alkynyl, C₃₋₈ cycloalkyl, wherein the alkyl, alkenyl, alkynyl, and cycloalkyl is optionally substituted with amino, OH, halo, or alkoxy; n is 0, 1, or 2; and r is 0, 1, or 2; with the proviso that when A is H, then R¹ is not C alquilo alkyl or C₁₋₆ alkoxy and R¹ and R² cannot be combined to form a heterocyclyl of 3 to 8 elements.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462053006P | 2014-09-19 | 2014-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR101976A1 true AR101976A1 (en) | 2017-01-25 |
Family
ID=58698665
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP150103022A AR101976A1 (en) | 2014-09-19 | 2015-09-18 | DERIVATIVES OF PIRIDIN-2 (1H) -ON QUINOLINONE AS INHIBITORS OF MUTANT DEHYDROGENASE ISOCITRATE |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR101976A1 (en) |
| HR (1) | HRP20182176T1 (en) |
| MA (1) | MA46064B1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107556366A (en) * | 2016-06-30 | 2018-01-09 | 上海海和药物研究开发有限公司 | Compound, preparation method and the usage with saltant type isocitric dehydrogenase inhibitory activity |
| WO2022262784A1 (en) * | 2021-06-15 | 2022-12-22 | 微境生物医药科技(上海)有限公司 | Idh mutant inhibitor and use thereof |
-
2015
- 2015-09-18 AR ARP150103022A patent/AR101976A1/en active IP Right Grant
- 2015-09-18 MA MA46064A patent/MA46064B1/en unknown
-
2018
- 2018-12-21 HR HRP20182176TT patent/HRP20182176T1/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107556366A (en) * | 2016-06-30 | 2018-01-09 | 上海海和药物研究开发有限公司 | Compound, preparation method and the usage with saltant type isocitric dehydrogenase inhibitory activity |
| WO2022262784A1 (en) * | 2021-06-15 | 2022-12-22 | 微境生物医药科技(上海)有限公司 | Idh mutant inhibitor and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| MA46064A (en) | 2019-07-03 |
| HRP20182176T1 (en) | 2019-02-22 |
| MA46064B1 (en) | 2020-04-30 |
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