AR126754A1 - HETEROCYCLIC COMPOUNDS AND METHODS OF USE - Google Patents
HETEROCYCLIC COMPOUNDS AND METHODS OF USEInfo
- Publication number
- AR126754A1 AR126754A1 ARP220102150A ARP220102150A AR126754A1 AR 126754 A1 AR126754 A1 AR 126754A1 AR P220102150 A ARP220102150 A AR P220102150A AR P220102150 A ARP220102150 A AR P220102150A AR 126754 A1 AR126754 A1 AR 126754A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkylene
- alkyl
- cycloalkyl
- hydroxyl
- halogen
- Prior art date
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 8
- 229910020008 S(O) Inorganic materials 0.000 abstract 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 7
- 229910052736 halogen Inorganic materials 0.000 abstract 6
- 150000002367 halogens Chemical class 0.000 abstract 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 4
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 4
- -1 -N(Rz)2 Chemical group 0.000 abstract 3
- 125000001072 heteroaryl group Chemical group 0.000 abstract 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 3
- 125000004043 oxo group Chemical group O=* 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 3
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 abstract 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 2
- 125000003118 aryl group Chemical group 0.000 abstract 2
- 201000011510 cancer Diseases 0.000 abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 102000008300 Mutant Proteins Human genes 0.000 abstract 1
- 108010021466 Mutant Proteins Proteins 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical group 0.000 abstract 1
- 102200006539 rs121913529 Human genes 0.000 abstract 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Reivindicación 1: Un compuesto de fórmula (1) o una sal farmacéuticamente aceptable de dicho compuesto, en dónde; - - - es un enlace sencillo o un enlace doble; W es C, CH o N, donde cuando W es CH o N, - - - es un enlace sencillo ;X es O, S, S(O), S(O)(NRᶻ), S(O)₂, CH₂ o CH=CH; n es 0, 1 o 2; m es 0, 1 o 2; p es 2, 3 o 4; dos Rˣ tomados junto con el mismo átomo de carbono forman un cicloalquilo C₃₋₇ o un heterocicloalquilo de 4 a 7 miembros, donde cada cicloalquilo C₃₋₇ o heterocicloalquilo de 4 a 7 miembros está sustituido adicionalmente con 0 - 3 apariciones de Rʸ y cuando p es 3 o 4, cada Rˣ restante es hidroxilo, halógeno, oxo, ciano, -N(Rᶻ)₂, alquilo C₁₋₄, alcoxilo C₁₋₄, haloalquilo C₁₋₄, haloalcoxilo C₁₋₄, cicloalquilo C₃₋₆, heteroarilo de 5 a 7 miembros; L es alquileno C₁₋₆, -O-alquileno C₁₋₆, -S-alquileno C₁₋₆, NRᶻ, O o S, en donde cada cadena alquileno C₁₋₆, -O-alquileno C₁₋₆ y -S-alquileno C₁₋₆ se sustituye con 0 - 2 apariciones de R²; R¹ es hidroxilo, arilo, heteroarilo, cicloalquilo C₃₋₈ o heterocicloalquilo sustituido con 0 - 3 apariciones de R⁵; R² es halógeno, hidroxilo, alquilo C₁₋₄, o dos R² en los mismos átomos de carbono o átomos adyacentes, se pueden tomar conjuntamente para formar un cicloalquilo C₃₋₇; R³ es arilo o heteroarilo sustituido con 0 - 3 apariciones de R⁶; R⁴ es hidrógeno, hidroxilo, halógeno, alquilo C₁₋₄, alcoxi C₁₋₄, haloalquilo C₁₋₄, alquenilo C₂₋₄, alquinilo C₂₋₄, cicloalquilo C₃₋₇ o ciano; cada R⁵ es halógeno, oxo, hidroxilo, ciano, amino o alquilo C₁₋₄; cada R⁶ es halógeno, hidroxilo, ciano, -N(Rᶻ)₂, alquilo C₁₋₄, alcoxi C₁₋₄, haloalquilo C₁₋₄, haloalcoxi C₁₋₄, alquinilo C₂₋₄ o cicloalquilo C₃₋₆; T es alquileno C₁₋₄, -S(O)₂-, -C(O)-, -alquileno C₁₋₄-C(O)-, -N(H)-C(O)-, -N(H)-S(O)₂-, alquileno C₁₋₄-S(O)₂- o - S-; Rʸ es halógeno, oxo, alquilo C₁₋₄, alcoxilo C₁₋₄, haloalquilo C₁₋₄, hidroxilo, ciano, -S(O)₂-alquilo C₁₋₄, =NRᶻ o -N(Rᶻ)₂; y Rᶻ es hidrógeno o alquilo C₁₋₄. Reivindicación 32: Un compuesto de acuerdo con una cualquiera de las reivindicaciones 1 - 29 o una sal farmacéuticamente aceptable del mismo, o la composición farmacéutica de acuerdo con la reivindicación 31 para su uso en el tratamiento del cáncer. Reivindicación 33: Un compuesto de acuerdo con una cualquiera de las reivindicaciones 1 - 29 o una sal farmacéuticamente aceptable del mismo, o la composición farmacéutica de acuerdo con la reivindicación 31 para su uso en el tratamiento del cáncer, en donde una o más células expresan la proteína mutante KRAS G12D.Claim 1: A compound of formula (1) or a pharmaceutically acceptable salt of said compound, wherein; - - - is a single bond or a double bond; W is C, CH or N, where when W is CH or N, - - - is a single bond ;X is O, S, S(O), S(O)(NRᶻ), S(O)₂, CH₂ or CH=CH; n is 0, 1 or 2; m is 0, 1 or 2; p is 2, 3 or 4; two Rˣ taken together with the same carbon atom form a C₃₋₇ cycloalkyl or a 4- to 7-membered heterocycloalkyl, where each C₃₋₇ cycloalkyl or 4- to 7-membered heterocycloalkyl is additionally substituted with 0 - 3 occurrences of Rʸ and when p is 3 or 4, each remaining Rˣ is hydroxyl, halogen, oxo, cyano, -N(Rᶻ)₂, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, C₃₋₆ cycloalkyl, 5- to 7-membered heteroaryl; L is C₁₋₆ alkylene, -O-C₁₋₆ alkylene, -S-C₁₋₆ alkylene, NRᶻ, O or S, wherein each chain C₁₋₆ alkylene, -O-C₁₋₆ alkylene and -S-alkylene C₁₋₆ is replaced with 0 - 2 occurrences of R²; R¹ is hydroxyl, aryl, heteroaryl, C₃₋₈ cycloalkyl or substituted heterocycloalkyl with 0-3 occurrences of R⁵; R² is halogen, hydroxyl, C₁₋₄ alkyl, or two R² on the same or adjacent carbon atoms can be taken together to form a C₃₋₇ cycloalkyl; R³ is aryl or substituted heteroaryl with 0-3 occurrences of R⁶; R⁴ is hydrogen, hydroxyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₃₋₇ cycloalkyl or cyano; each R⁵ is halogen, oxo, hydroxyl, cyano, amino or C₁₋₄ alkyl; each R⁶ is halogen, hydroxyl, cyano, -N(Rᶻ)₂, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, C₂₋₄ alkynyl or C₃₋₆ cycloalkyl; T is C₁₋₄ alkylene, -S(O)₂-, -C(O)-, -C₁₋₄ alkylene-C(O)-, -N(H)-C(O)-, -N(H )-S(O)₂-, C₁₋₄ alkylene-S(O)₂- or -S-; Rʸ is halogen, oxo, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, hydroxyl, cyano, -S(O)₂-C₁₋₄ alkyl, =NRᶻ or -N(Rᶻ)₂; and Rᶻ is hydrogen or C₁₋₄ alkyl. Claim 32: A compound according to any one of claims 1 - 29 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 31 for use in the treatment of cancer. Claim 33: A compound according to any one of claims 1 - 29 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 31 for use in the treatment of cancer, wherein one or more cells express the KRAS G12D mutant protein.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063299667P | 2020-01-14 | 2020-01-14 | |
| US202063289578P | 2020-12-14 | 2020-12-14 | |
| US202163231543P | 2021-08-10 | 2021-08-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR126754A1 true AR126754A1 (en) | 2023-11-08 |
Family
ID=89061593
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP220102150A AR126754A1 (en) | 2020-01-14 | 2022-08-10 | HETEROCYCLIC COMPOUNDS AND METHODS OF USE |
Country Status (1)
| Country | Link |
|---|---|
| AR (1) | AR126754A1 (en) |
-
2022
- 2022-08-10 AR ARP220102150A patent/AR126754A1/en unknown
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