AR107004A1 - INDOLINE COMPOUNDS REPLACED AS PHOSPHODESTERASE INHIBITORS - Google Patents

INDOLINE COMPOUNDS REPLACED AS PHOSPHODESTERASE INHIBITORS

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Publication number
AR107004A1
AR107004A1 ARP160103948A ARP160103948A AR107004A1 AR 107004 A1 AR107004 A1 AR 107004A1 AR P160103948 A ARP160103948 A AR P160103948A AR P160103948 A ARP160103948 A AR P160103948A AR 107004 A1 AR107004 A1 AR 107004A1
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Argentina
Prior art keywords
alkyl
alkylene
nhs
cycloalkyl
unsubstituted
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ARP160103948A
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Spanish (es)
Inventor
Dr Hesslinger Christian
Welbers Andr
Dr Wagener Markus
Dr Jakob Florian
Dr Konetzki Ingo
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Gruenenthal Gmbh
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Publication of AR107004A1 publication Critical patent/AR107004A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Uso como medicamentos, en particular como medicamentos para el tratamiento de patologías y enfermedades que pueden tratarse mediante la inhibición de la enzima PDE4. Reivindicación 1: Un compuesto de acuerdo con la fórmula (1), caracterizado porque A, B y C representan en forma independiente CH o N; R¹ y R² junto con el átomo de carbono al cual están unidos forman un cicloalquilo de 3 a 6 miembros, que no está sustituido o está sustituido con uno, dos, tres o cuatro sustituyentes Y; G representa un fenilo o heteroarilo de 5 ó 6 miembros, donde dicho fenilo o dicho heteroarilo de 5 ó 6 miembros no está sustituido o está sustituido con uno, dos, tres o cuatro sustituyentes Z; R³ es -L-R⁴; L se selecciona de una unión, S(=O), S(=O)₂, P(=O)(R⁴), C(H)(OH) o C(CH₃)(OH); R⁴ se selecciona de OH, CN, R¹³, OR¹³, NH₂, NH(R¹³) o N(R¹³)₂, donde cada R¹³ independientemente uno de otro denota C₁₋₆-alquilo, no sustituido o mono- o polisustituido; o cicloalquilo C₃₋₆ o heterocicloalquilo de 3 a 7 miembros, en cada caso insustituido o mono- o polisustituido; o C₃₋₆-cicloalquilo o heterocicloalquilo de 3 a 7 miembros, en cada caso no sustituido o mono- o polisustituido, y en cada caso conectado por medio de un grupo alifático C₁₋₄, no sustituido, o mono- o polisustituido; Y en cada ocurrencia es independientemente de otra seleccionado del grupo que consiste en OH, =O, CN, NO₂, halógeno, C₁₋₆-alquilo, C₁₋₆-hidroxialquilo, C₁₋₆-alcoxi, S(C₁₋₆-alquilo), S(O)(C₁₋₆-alquilo), S(O)₂(C₁₋₆-alquilo), C₁₋₆-haloalquilo, S(C₁₋₆-haloalquilo), C₁₋₆-haloalcoxi, C₁₋₆-cianoalquilo, C₃₋₆-cicloalquilo, NH₂, NH(C₁₋₆-alquilo), N(C₁₋₆-alquil)₂, NHCO(C₁₋₆-alquilo), NHSO(C₁₋₆-alquilo), NHS(O)₂(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-CO(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-SO(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-SO₂(C₁₋₆-alquilo), NHCONH₂, NHCONH(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-CON(C₁₋₆-alquil)₂, CO₂H, CO₂(C₁₋₆-alquilo), CONH₂, CONH(C₁₋₆-alquilo) y CON(C₁₋₆-alquil)₂; Z en cada ocurrencia se selecciona independientemente del grupo que consiste en halógeno, OH, CN, SH, NO₂, C₁₋₆-alquilo, C₂₋₆-alquenilo, C₂₋₆-alquinilo, C₁₋₆-hidroxialquilo, C₁₋₆-cianoalquilo, C₁₋₆-alcoxi, C₁₋₆-tioalquilo, C₁₋₆-haloalquilo, C₁₋₆-tiohaloalquilo, C₁₋₆-haloalcoxi, (C₁₋₆-alquileno)-S-(C₁₋₆-alquilo), C₃₋₆-cicloalquilo, (C₃₋₆-cicloalquil)-(C₁₋₃-alquilenoilo), heterocicloalquilo de 3 a 7 miembros y dicho heterocicloalquilo de 3 a 7 miembros en cada caso no está sustituido o está mono- o polisustituido, NH₂, NH(C₁₋₆-alquilo), N(C₁₋₆-alquil)₂, NHCO(C₁₋₆-alquilo), NHCO₂(C₁₋₆-alquilo), NHC(O)NH₂, NHCONH(C₁₋₆-alquilo), NHCON(C₁₋₆-alquil)₂, (C₁₋₆-alquileno)NH₂, (C₁₋₆-alquileno)NH(C₁₋₆-alquilo), (C₁₋₆-alquileno)N(C₁₋₆-alquil)₂, (C₁₋₆-alquileno)NHCO(C₁₋₆-alquilo), (C₁₋₆-alquileno)NHCO₂(C₁₋₆-alquilo), (C₁₋₆-alquileno)NHC(O)NH₂, (C₁₋₆-alquileno)NHCONH(C₁₋₆-alquilo), (C₁₋₆-alquileno)NHCON(C₁₋₆-alquil)₂, NH(C₁₋₆-alquileno)-CO₂(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-CONH₂, NH(C₁₋₆-alquileno)-CONH(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-CON(C₁₋₆-alquil)₂, NHS(O)₂OH, NHS(O)₂(C₁₋₆-alquilo), NHS(O)₂O(C₁₋₆-alquilo), NHS(O)₂NH₂, NHS(O)₂NH(C₁₋₆-alquilo), NHS(O)₂N(C₁₋₆-alquil)₂, NH(C₁₋₆-alquileno)-S(O)₂OH, NH(C₁₋₆-alquileno)-S(O)₂(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-S(O)₂O(C₁₋₆-alquilo), NH(C₁₋₆-alquileno)-S(O)₂NH₂, NH(C₁₋₆-alquileno)-S(O)₂NH(C₁₋₆-alquilo), CO₂H, CO(C₁₋₆-alquilo), CO₂(C₁₋₆-alquilo), O-CO(C₁₋₆-alquilo), O-CO₂(C₁₋₆-alquilo), CONH₂, CONH(C₁₋₆-alquilo), CON(C₁₋₆-alquil)₂, OCONH(C₁₋₆-alquilo), OCON(C₁₋₆-alquil)₂, OS(O)₂(C₁₋₆-alquilo), OS(O)₂OH, OS(O)₂O(C₁₋₆-alquilo), OS(O)₂NH₂, OS(O)₂NH(C₁₋₆-alquilo), OS(O)₂N(C₁₋₆-alquil)₂, S(O)(C₁₋₆-alquilo), S(O)₂(C₁₋₆-alquilo), S(O)₂OH, S(O)₂O(C₁₋₆-alquilo), S(O)₂NH₂, S(O)₂NH(C₁₋₆-alquilo), y S(O)₂N(C₁₋₆-alquil)₂; opcionalmente en la forma de un estereoisómero individual o una mezcla de estereoisómeros, en la forma del compuesto libre y/o una sal fisiológicamente aceptable y/o un solvato fisiológicamente aceptable de los anteriores.Use as medicines, in particular as medicines for the treatment of pathologies and diseases that can be treated by inhibiting the PDE4 enzyme. Claim 1: A compound according to formula (1), characterized in that A, B and C independently represent CH or N; R¹ and R² together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl, which is unsubstituted or substituted with one, two, three or four substituents Y; G represents a 5 or 6 membered phenyl or heteroaryl, wherein said phenyl or said 5 or 6 membered heteroaryl is not substituted or substituted with one, two, three or four substituents Z; R³ is -L-R⁴; L is selected from a union, S (= O), S (= O) ₂, P (= O) (R⁴), C (H) (OH) or C (CH₃) (OH); R⁴ is selected from OH, CN, R¹³, OR¹³, NH₂, NH (R¹³) or N (R¹³) ₂, where each R¹³ independently of each other denotes C₁₋₆-alkyl, unsubstituted or mono- or polysubstituted; or C₃₋₆ cycloalkyl or 3- to 7-membered heterocycloalkyl, in each case unsubstituted or mono- or polysubstituted; or C₃₋₆-cycloalkyl or heterocycloalkyl of 3 to 7 members, in each case unsubstituted or mono- or polysubstituted, and in each case connected by means of a C₁₋₄ aliphatic group, unsubstituted, or mono- or polysubstituted; And in each occurrence it is independently of another selected from the group consisting of OH, = O, CN, NO₂, halogen, C₁₋₆-alkyl, C₁₋₆-hydroxyalkyl, C₁₋₆-alkoxy, S (C₁₋₆-alkyl ), S (O) (C₁₋₆-alkyl), S (O) ₂ (C₁₋₆-alkyl), C₁₋₆-haloalkyl, S (C₁₋₆-haloalkyl), C₁₋₆-haloalkoxy, C₁₋ ₆-cyanoalkyl, C₃₋₆-cycloalkyl, NH₂, NH (C₁₋₆-alkyl), N (C₁₋₆-alkyl) ₂, NHCO (C₁₋₆-alkyl), NHSO (C₁₋₆-alkyl), NHS (O) ₂ (C₁₋₆-alkyl), NH (C₁₋₆-alkylene) -CO (C₁₋₆-alkyl), NH (C₁₋₆-alkylene) -SO (C₁₋₆-alkyl), NH ( C₁₋₆-alkylene) -SO₂ (C₁₋₆-alkyl), NHCONH₂, NHCONH (C₁₋₆-alkyl), NH (C₁₋₆-alkylene) -CON (C₁₋₆-alkyl) ₂, CO₂H, CO₂ ( C₁₋₆-alkyl), CONH₂, CONH (C₁₋₆-alkyl) and CON (C₁₋₆-alkyl) ₂; Z at each occurrence is independently selected from the group consisting of halogen, OH, CN, SH, NO₂, C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₁₋₆-hydroxyalkyl, C₁₋₆- cyanoalkyl, C₁₋₆-alkoxy, C₁₋₆-thioalkyl, C₁₋₆-haloalkyl, C₁₋₆-thiohaloalkyl, C₁₋₆-haloalkoxy, (C₁₋₆-alkylene) -S- (C₁₋₆-alkyl), C₃₋₆-cycloalkyl, (C₃₋₆-cycloalkyl) - (C₁₋₃-alkyleneoyl), 3- to 7-membered heterocycloalkyl and said 3 to 7-membered heterocycloalkyl in each case is unsubstituted or mono- or polysubstituted, NH₂ , NH (C₁₋₆-alkyl), N (C₁₋₆-alkyl) ₂, NHCO (C₁₋₆-alkyl), NHCO₂ (C₁₋₆-alkyl), NHC (O) NH₂, NHCONH (C₁₋₆- alkyl), NHCON (C₁₋₆-alkyl) ₂, (C₁₋₆-alkylene) NH₂, (C₁₋₆-alkylene) NH (C₁₋₆-alkyl), (C₁₋₆-alkylene) N (C₁₋₆ -alkyl) ₂, (C₁₋₆-alkylene) NHCO (C₁₋₆-alkyl), (C₁₋₆-alkylene) NHCO₂ (C₁ ₆-alkyl), (C₁₋₆-alkylene) NHC (O) NH₂, (C₁₋₆-alkylene) NHCONH (C₁₋₆-alkyl), (C₁₋₆-alkylene) NHCON (C₁₋₆-alkyl) ₂ , NH (C₁₋₆-alkylene) -CO₂ (C₁₋₆-alkyl), NH (C₁₋₆-alkylene) -CONH₂, NH (C₁₋₆-alkylene) -CONH (C₁₋₆-alkyl), NH ( C₁₋₆-alkylene) -CON (C₁₋₆-alkyl) ₂, NHS (O) ₂OH, NHS (O) ₂ (C₁₋₆-alkyl), NHS (O) ₂O (C₁₋₆-alkyl), NHS (O) ₂NH₂, NHS (O) ₂NH (C₁₋₆-alkyl), NHS (O) ₂N (C₁₋₆-alkyl) ₂, NH (C₁₋₆-alkylene) -S (O) ₂OH, NH (C₁ ₋₆-alkylene) -S (O) ₂ (C₁₋₆-alkyl), NH (C₁₋₆-alkylene) -S (O) ₂O (C₁₋₆-alkyl), NH (C₁₋₆-alkylene) - S (O) ₂NH₂, NH (C₁₋₆-alkylene) -S (O) ₂NH (C₁₋₆-alkyl), CO₂H, CO (C₁₋₆-alkyl), CO₂ (C₁₋₆-alkyl), O- CO (C₁₋₆-alkyl), O-CO₂ (C₁₋₆-alkyl), CONH₂, CONH (C₁₋₆-alkyl), CON (C₁₋₆-alkyl) ₂, OCONH (C₁₋₆-alkyl), OCON (C₁₋₆-alkyl) ₂, OS (O) ₂ (C₁₋₆-alkyl), OS (O) ₂OH, OS (O) ₂O (C₁₋₆-alkyl), OS (O) ₂NH₂, OS (O) ₂NH (C₁₋₆-alkyl), OS (O) ₂N (C₁₋₆-alkyl) ₂, S (O) (C₁₋₆-alkyl), S (O) ₂ (C₁₋₆-alkyl), S (O) ₂OH, S (O) ₂O (C₁₋₆-alkyl), S (O) ₂NH₂, S (O) ₂NH (C₁₋₆-alkyl), and S (O) ₂N (C₁₋₆-alkyl) ₂; optionally in the form of an individual stereoisomer or a mixture of stereoisomers, in the form of the free compound and / or a physiologically acceptable salt and / or a physiologically acceptable solvate of the foregoing.

ARP160103948A 2015-12-22 2016-12-21 INDOLINE COMPOUNDS REPLACED AS PHOSPHODESTERASE INHIBITORS AR107004A1 (en)

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EP15003643 2015-12-22

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WO (1) WO2017108203A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112334192A (en) 2018-07-12 2021-02-05 Ucb生物制药有限责任公司 Spirocyclic indane analogs as IL-17 modulators
CN109180648B (en) * 2018-11-02 2020-01-17 郑州大学 7-alkyl-N-pyrimidine indoline compound and synthetic method thereof
CN113292477B (en) * 2021-06-01 2023-06-02 四川大学 Method for synthesizing isoindole-1-ketone compound through iridium-catalyzed hydrocarbon activation reaction

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EP1958947A1 (en) * 2007-02-15 2008-08-20 Ranbaxy Laboratories Limited Inhibitors of phosphodiesterase type 4
HUE035967T2 (en) * 2013-08-09 2018-06-28 Gruenenthal Gmbh Novel substituted condensed pyrimidine compounds
AR101196A1 (en) * 2014-07-16 2016-11-30 Gruenenthal Gmbh SUBSTITUTED PYRIMIDINE COMPOUNDS

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