AR121846A1 - Derivado de arilo o heteroarilo - Google Patents
Derivado de arilo o heteroariloInfo
- Publication number
- AR121846A1 AR121846A1 ARP210100992A ARP210100992A AR121846A1 AR 121846 A1 AR121846 A1 AR 121846A1 AR P210100992 A ARP210100992 A AR P210100992A AR P210100992 A ARP210100992 A AR P210100992A AR 121846 A1 AR121846 A1 AR 121846A1
- Authority
- AR
- Argentina
- Prior art keywords
- group
- optionally substituted
- alkyl
- alkoxy
- halogen atoms
- Prior art date
Links
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
[Problema] Se proporcionan agentes terapéuticos o profilácticos para enfermedades relacionadas con TRPC6, tales como síndrome nefrótico, nefropatía membranosa, insuficiencia renal aguda, sepsis, insuficiencia renal crónica, nefropatía diabética, hipertensión pulmonar, lesión pulmonar aguda, insuficiencia cardíaca, tumor maligno o distrofia muscular. [Solución] Un compuesto representado por la siguiente fórmula (1), o una sal farmacéuticamente aceptable de este (en donde, Ar¹, Ar², X¹ a X³, R¹, R³, R⁷, R⁸, L¹ y L² son como se define en la memoria descriptiva). Reivindicación 1: Un compuesto representado por la fórmula (1), o una sal farmacéuticamente aceptable de este, [en donde, X¹, X² y X³ son independientemente CH, N o CY; al menos uno de X¹, X² y X³ es CH o CY; Y es un átomo de halógeno, o un grupo alquilo C₁₋₃ opcionalmente sustituido con 1 a 3 átomos de halógeno; R¹ es un grupo ciano, un átomo de flúor o un átomo de cloro; L¹ es -O-, -S-, -SO-, -CH(R¹¹)-, -C(=CH₂)-, -CO-, un grupo 1,1-ciclopropilideno o -NR¹²-; R¹¹ es un átomo de hidrógeno, un grupo hidroxi, un grupo alquilo C₁₋₃ opcionalmente sustituido con 1 a 3 átomos de halógeno o un grupo alcoxi C₁₋₃ opcionalmente sustituido con 1 a 2 grupos ciano; R¹² es un átomo de hidrógeno, o un grupo alquilo C₁₋₃ opcionalmente sustituido con 1 a 3 átomos de halógeno; Ar¹ es un anillo heteroarilo que contiene nitrógeno opcionalmente sustituido con 1 a 3 R²; R² es independientemente un átomo de halógeno, un grupo ciano, o un grupo alquilo C₁₋₄ opcionalmente sustituido con 1 a 3 átomos de halógeno; R³ es un átomo de hidrógeno, un átomo de halógeno, un grupo amino, un grupo ciano, un grupo carboxi, un grupo (alquilcarbonil C₁₋₃)amino, un grupo (alquilamino C₁₋₆)carbonilo, un grupo di(alquil C₁₋₃)aminocarbonilo, un grupo (alcoxi C₁₋₃)carbonilo, un grupo (cicloalquil C₃₋₈)amino, un grupo (heterocicloalquil C₃₋₈)amino, un grupo cicloalquilo C₃₋₈, un grupo heterocicloalquiloxi de 3 a 8 miembros, un grupo cicloalquiloxi C₃₋₈ opcionalmente sustituido con 1 a 6 R³¹, un grupo alquilo C₁₋₆ opcionalmente sustituido con 1 a 6 R³¹, un grupo alcoxi C₁₋₆ opcionalmente sustituido con 1 a 6 R³¹, un grupo di(alquil C₁₋₆)amino opcionalmente sustituido con 1 a 6 R³¹, un grupo (alquil C₁₋₆)amino opcionalmente sustituido con 1 a 6 R³¹, un grupo heterocicloalquilo de 3 a 8 miembros opcionalmente sustituido con 1 a 4 R³², un grupo arilo opcionalmente sustituido con 1 a 4 R³², o un grupo heteroarilo opcionalmente sustituido con 1 a 4 R³²; R³¹ es independientemente un átomo de halógeno, un grupo hidroxi, un grupo ciclopropilideno, un grupo cicloalquilo C₃₋₈ opcionalmente sustituido con 1 a 3 átomos de halógeno, un grupo heterocicloalquilo de 3 a 8 miembros, un grupo oxetanilideno, un grupo alcoxi C₁₋₄, o un grupo cicloalquiloxi de 3 a 8 miembros; R³² es independientemente un átomo de halógeno, un grupo hidroxi, un grupo acetilamino, un grupo alquilo C₁₋₃ opcionalmente sustituido con 1 a 3 átomos de halógeno, un grupo alcoxi C₁₋₃ opcionalmente sustituido con 1 a 3 átomos de halógeno, un grupo oxo, un grupo ciano, un grupo carboxi, un grupo (alcoxi C₁₋₃)carbonilo, un grupo (alquil C₁₋₃)sulfonilo, un grupo carboxamida o un grupo benciloxi; cuando R² y R³ están unidos a átomos adyacentes entre sí en Ar¹, R² y R³ pueden estar unidos a través de un enlace simple o -O- para formar un anillo de 5 a 7 miembros junto con los átomos de Ar¹ a los cuales están unidos; Ar² es un anillo arilo opcionalmente sustituido con 1 a 4 R⁴, o un anillo heteroarilo opcionalmente sustituido con 1 a 4 R⁴; R⁴ es independientemente un átomo de halógeno, un grupo hidroxi, un grupo carboxi, un grupo ciano, un grupo cianometilo, un grupo amino, un grupo di(alquil C₁₋₃)amino, un grupo alquilo C₁₋₃ opcionalmente sustituido con 1 a 3 átomos de halógeno, o grupo alcoxi C₁₋₃; L² es un enlace simple, un grupo alquileno C₁₋₆ opcionalmente sustituido con 1 a 3 R²¹, un grupo cicloalquileno C₃₋₈ opcionalmente sustituido con 1 a 3 R²¹, o un grupo heterocicloalquileno de 4 a 8 miembros opcionalmente sustituido con 1 a 3 R²¹; L² pueden estar unidos en cualquier posición a Ar² o -NR⁷R⁸ que está ubicado en cualquiera de sus extremos; un átomo de carbono sp³ en cualquier posición de L² puede ser reemplazado por una estructura de -O- o -NR²²-; R²¹ es independientemente un átomo de halógeno, un grupo hidroxi, un grupo oxo, un grupo ciano, un grupo 1,1-ciclopropilideno, un grupo oxetanilideno, un grupo carboxi, un grupo carboxamida, un grupo alquilo C₁₋₆ opcionalmente sustituido con 1 a 3 átomos de halógeno, un grupo cicloalquilo C₃₋₈, un grupo alcoxi C₁₋₆, un grupo (alcoxi C₁₋₃)alquilo C₁₋₃, un grupo (alcoxi C₁₋₃)alcoxi C₁₋₃, un grupo (hidroxi) alquilo C₁₋₆, un grupo (carboxi)alquilo C₁₋₃, un grupo (carboxi)alcoxi C₁₋₃, un grupo (alcoxi C₁₋₃)carbonilo, un grupo (alcoxicarbonil C₁₋₃)alquilo C₁₋₃, un grupo (alquilamino C₁₋₆)carbonilo, un grupo di(alquil C₁₋₃) aminocarbonilo, un grupo fenilo opcionalmente sustituido con 1 a 3 átomos de halógeno, un grupo heteroarilo opcionalmente sustituido con 1 a 3 átomos de halógeno, o un grupo fenoxi opcionalmente sustituido con 1 a 3 átomos de halógeno; R²² es un átomo de hidrógeno o un grupo alquilo C₁₋₃; L² y R⁷ pueden estar unidos a través de un enlace simple, -O-, -S(=O)ₙ- o -NR²³-, para formar un anillo de 4 a 8 miembros que contiene un átomo de nitrógeno al cual L² y R⁷ están unidos, y el anillo es opcionalmente sustituido con 1 a 3 átomos de halógeno o 1 a 2 grupos hidroxi; n representa un número entero de 0 a 2; R²³ es un átomo de hidrógeno o un grupo alquilo C₁₋₃; cuando L² y R⁴ están unidos a átomos adyacentes entre sí en Ar², pueden estar unidos a través de un enlace simple o -O- para formar un anillo de 5 a 8 miembros junto con los átomos de Ar² a los cuales están unidos; R⁷ es un átomo de hidrógeno, o un grupo alquilo C₁₋₃; R⁷ y un átomo de Ar² pueden estar unidos a través de un enlace simple para formar un anillo de 5 a 8 miembros; R⁸ es un átomo de hidrógeno, un grupo alquilo C₁₋₆, un grupo adamantilo, un grupo cicloalquilo C₁₋₆, un grupo cianometilo, un grupo oxetanilo, un grupo (alquilamino C₁₋₃)carbonilmetilo, un grupo di(alquil C₁₋₃)aminocarbonilmetilo, un grupo (alquilamino C₁₋₃)alquilo C₁₋₈, un grupo di(alquil C₁₋₃)aminoalquilo C₁₋₈, un grupo (hidroxi)alquilo C₁₋₈, un grupo (carboxi)alquilo C₁₋₃, un grupo (alcoxicarbonil C₁₋₃)alquilo C₁₋₃, o un grupo (alcoxi C₁₋₃)alquilo C₁₋₃; R⁷ y R⁸ pueden estar unidos entre sí a través de un enlace simple, -O-, -S(=O)ₘ- o -NR⁴¹- para formar un anillo de 3 a 8 miembros, y además, el anillo está opcionalmente sustituido con un grupo amino, un grupo oxo o un grupo alquilo C₁₋₃; m representa un número entero de 0 a 2; R⁴¹ es un átomo de hidrógeno o un grupo alquilo C₁₋₃.]
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WO2014192865A1 (ja) * | 2013-05-30 | 2014-12-04 | 大日本住友製薬株式会社 | フェニルピペラジン誘導体 |
CN104292233B (zh) | 2014-10-09 | 2016-03-16 | 武汉大学 | 一种吡唑并[1,5-a]嘧啶衍生物及其抗肿瘤用途 |
CN106317050B (zh) | 2016-08-24 | 2018-11-23 | 烟台大学 | 一种苯基噻唑衍生物及其制备方法与应用 |
CN107253952B (zh) | 2017-08-01 | 2019-07-30 | 烟台大学 | 具有抗胃癌活性的trpc6抑制剂及其制备方法和用途 |
CN111417394B (zh) | 2017-10-19 | 2023-11-07 | 帝人制药株式会社 | 苯并咪唑衍生物及其用途 |
SI3700902T1 (sl) | 2017-10-27 | 2023-10-30 | Boehringer Ingelheim International Gmbh | Inhibitorji trpc6 |
EP3723754A4 (en) * | 2017-12-13 | 2021-05-19 | Merck Sharp & Dohme Corp. | IMIDAZO [1,2-C] QUINAZOLIN-5-AMINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES |
US11485740B2 (en) | 2018-02-15 | 2022-11-01 | Boehringer Ingelheim International Gmbh | Inhibitors of TRPC6 |
US11370771B2 (en) | 2018-02-16 | 2022-06-28 | Boehringer Ingelheim International Gmbh | Inhibitors of TRPC6 |
EP3789383B9 (en) * | 2018-04-27 | 2024-02-28 | Osaka University | Inhibitors of the trpc3 or trpc6 channel |
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2021
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- 2021-04-15 US US17/919,186 patent/US20230167073A1/en active Pending
- 2021-04-15 BR BR112022020245A patent/BR112022020245A2/pt unknown
- 2021-04-15 WO PCT/JP2021/015607 patent/WO2021210650A1/ja active Application Filing
- 2021-04-15 CN CN202180043070.3A patent/CN115996910A/zh active Pending
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- 2021-04-15 PE PE2022002232A patent/PE20221837A1/es unknown
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EP4137481A1 (en) | 2023-02-22 |
BR112022020245A2 (pt) | 2022-11-22 |
PE20221837A1 (es) | 2022-11-29 |
KR20220154773A (ko) | 2022-11-22 |
CO2022014517A2 (es) | 2022-12-30 |
MX2022012769A (es) | 2022-11-08 |
EP4137481A4 (en) | 2023-08-23 |
JPWO2021210650A1 (es) | 2021-10-21 |
AU2021255088A1 (en) | 2022-11-10 |
CR20220518A (es) | 2023-05-16 |
CN115996910A (zh) | 2023-04-21 |
ECSP22078861A (es) | 2023-01-31 |
IL296200A (en) | 2022-11-01 |
CA3172425A1 (en) | 2021-10-21 |
TW202204321A (zh) | 2022-02-01 |
WO2021210650A1 (ja) | 2021-10-21 |
US20230167073A1 (en) | 2023-06-01 |
CL2022002838A1 (es) | 2023-07-07 |
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