AR105575A1 - COMPUESTOS DE QUINOLINA COMO MODULADORES DE TNFa - Google Patents

COMPUESTOS DE QUINOLINA COMO MODULADORES DE TNFa

Info

Publication number
AR105575A1
AR105575A1 ARP160102357A ARP160102357A AR105575A1 AR 105575 A1 AR105575 A1 AR 105575A1 AR P160102357 A ARP160102357 A AR P160102357A AR P160102357 A ARP160102357 A AR P160102357A AR 105575 A1 AR105575 A1 AR 105575A1
Authority
AR
Argentina
Prior art keywords
alkyl
substituted
aryl
heterocyclyl
independently
Prior art date
Application number
ARP160102357A
Other languages
English (en)
Inventor
Tino Joseph
J Pitts William
Ngu Khehyong
Lu Zhonghui
Jiang Bin
Duan Jingwu
Li Ning
G Murali Dhar T
Xiao Hai-Yun
Original Assignee
Bristol Myers Squibb Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of AR105575A1 publication Critical patent/AR105575A1/es

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • A61P37/02—Immunomodulators
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Abstract

También métodos para usar tales compuestos como moduladores de TNFa, y composiciones farmacéuticas que comprenden tales compuestos. Estos compuestos son útiles para tratar enfermedades inflamatorias y autoinmunitarias. Reivindicación 1: Un compuesto caracterizado por la fórmula (1) o una sal de aquel, en donde: A es CR¹ o N; B es CR³ o N; D es CR⁴ o N; X es un enlace, -O-, -S- o -NR⁸-; L¹ es (CR⁷R⁷)ₘ; L² es -(CR⁷R⁷)ₙ-; Z es un grupo cíclico seleccionado de carbociclilo, heterociclilo, arilo y heteroarilo, en donde el grupo cíclico se sustituye con 0 a 3 Rᵃ; R¹ es H, halo, -CN, C₁₋₄ alquilo, C₁₋₆ haloalquilo o C₁₋₃ alcoxi; R² es H, R¹ᵃ, C₁₋₆ haloalquilo, C₂₋₆ alquenilo sustituido con 0 a 6 R¹ᵃ, C₂₋₆ alquinilo sustituido con 0 a 4 R¹ᵃ, -(CRᵍRᵍ)ʳ(carbociclilo de 3 a 14 miembros sustituido con 0 a 3 R¹ᵃ), -(CRᵍRᵍ)ʳ(arilo sustituido con 0 a 3 R¹ᵃ), -(CRᵍRᵍ)ʳ(heterociclilo de 5 a 7 miembros sustituido con 0 a 3 R¹ᵃ) o -(CRᵍRᵍ)ʳ(heteroarilo mono- o bicíclico sustituido con 0 a 3 R¹ᵃ); R³ es H, halo, -CN, -CF₃, -OCF₃, -NO₂, C₁₋₆ alquilo sustituido con 0 a 6 R¹ᵃ, -(CRᵍRᵍ)ʳORᵉ, (CRᵍRᵍ)ʳNRᶜRᶜ, -(CRᵍRᵍ)ʳS(O)ₚRᵇ, -(CRᵍRᵍ)ʳ(carbociclilo de 3 a 14 miembros sustituido con 0 a 3 R¹ᵃ), -(CRᵍRᵍ)ʳ(arilo sustituido con 0 a 3 R¹ᵃ), -(CRᵍRᵍ)ʳ(heterociclilo de 5 a 7 miembros sustituido con 0 a 3 R¹ᵃ) o -(CRᵍRᵍ)ʳ(heteroarilo monocíclico sustituido con 0 a 3 R¹ᵃ); R⁴ es H, halo, -CN, C₁₋₄ alquilo, C₁₋₆ haloalquilo o C₁₋₃ alcoxi; R⁵ y R⁶ son independientemente H, halo, -OH, -CN, C₁₋₅ alquilo sustituido con 0 a 6 Rᵃ, C₃₋₆ cicloalquilo sustituido con 0 a 6 Rᵃ, C₁₋₅ alquiltio sustituido con 0 a 6 Rᵃ, ariltio sustituido con 0 a 6 Rᵃ, C₁₋₅ alcoxi sustituido con 0 a 6 Rᵃ, ariloxi sustituido con 0 a 6 Rᵃ, -C(O)ORʰ, -C(O)NRʰRʰ, -NRʰRʰ, -NRᵇC(O)NRᶜRᶜ, -NRʰC(O)Rʸ, -NRᵇC(O)ORᵇ, -NRᵇS(O)₂NRᶜRᶜ o -NRʰS(O)₂Rʸ; o R⁵ y R⁶, junto con los carbonos a los que están unidos, forman un anillo carbocíclico o heterocíclico de 5 a 7 miembros; cada R⁷ es independientemente H, -OH, C₁₋₃ alquilo, C₁₋₃ fluoroalquilo, C₁₋₃ hidroxialquilo, C₁₋₂ aminoalquilo, -CH₂CH=CH₂, C₃₋₆ cicloalquilo, fenilo o -NRʰRʰ; o dos R⁷, junto con el átomo de carbono al que están unidos, forman un grupo espirocarbociclilo o espiroheterociclilo de 3 a 7 miembros; R⁸ es H o C₁₋₃ alquilo; cada R¹ᵃ es independientemente F, Cl, Br, -CN, C₁₋₆ alquilo sustituido con 0 a 6 Rᵃ, C₃₋₆ cicloalquilo sustituido con 0 a 6 Rᵃ, C₁₋₃ alcoxi sustituido con 0 a 7 Rᵃ, heterociclilo sustituido con 0 a 6 Rᵃ, arilo sustituido con 0 a 6 Rᵃ, heteroarilo mono- o bicíclico sustituido con 0 a 6 Rᵃ, -C(O)Rᵇ, -C(O)ORᵇ, -C(O)NRᶜRᶜ, -OC(O)Rᵇ, -OC(O)NRᶜRᶜ, -OC(O)ORᵈ, -NRᶜRᶜ, -NRᵇC(O)Rᵈ, -NRᵇC(O)ORᵈ, NRᵇS(O)ₚRᵈ, -NRᵇC(O)NRᶜRᶜ, -NRᵇS(O)ₚNRᶜRᶜ, S(O)ₚRᵇ, -S(O)ₚNRᶜRᶜ o -C(O)NRᵇ(CH₂)₁₋₃NRᶜRᶜ; cada Rᵃ es independientemente halo, -CN, -OH, -NO₂, -NH₂, -N₃, C₁₋₇ alquilo sustituido con 0 a 6 Rʷ; C₂₋₄ alquenilo, C₂₋₄ alquinilo, C₁₋₃ alcoxi, C₁₋₃ fluoroalcoxi, C₁₋₃ hidroxialcoxi, -O(CH=CH₂), -(CH₂)ʳC(O)OH, -O(CH₂)ʳC(O)OH, -(CH₂)ʳC(O)(C₁₋₆ alquilo), -C(O)O(C₁₋₄ alquilo), -OC(O)(C₁₋₃ alquilo), -NH(C₁₋₆ alquilo), -N(C₁₋₃ alquilo)₂, -(CH₂)₀₋₂C₍O₎NH₂, -(CH₂)₀₋₂C₍O₎NH₍C₁₋₃ alquilo), -(CH₂)₀₋₂C₍O₎N₍C₁₋₃ alquilo)₂, -OC(O)NH(C₁₋₃ alquilo), -C(O)CH(NH₂)(CH₂)₁₋₂C₍O₎OH, ₋C₍O₎CH₍NH₂)(CH₂)₁₋₂OH, -C(O)(CH₂)₁₋₂C(O)OH, -C(O)(C₂₋₄ alquenilo), -C(O)(C₂₋₄ alquinilo), -CºCH, -CºC(fenilo), -NHC(O)NH₂, -NHC(O)NH(C₁₋₃ alquilo), -CH=NOH, -C(=NH)(NH₂), C₃₋₇ carbociclilo, arilo, heterociclilo de 5 a 7 miembros, heteroarilo monocíclico o bicíclico, -(CH₂)ʳ(arilo), -(CH₂)ʳ(heteroarilo), -O(arilo), -O(bencilo), -O(heterociclilo), -O(heteroarilo), -S(O)₂NH₂, -S(O)₂CH₂CH₂C(O)O(C₁₋₃ alquilo), -S(O)ₚ(C₁₋₃ alquilo), -S(O)ₚ(arilo), -S(O)ₚ(heterociclilo), -NHS(O)₂(arilo), -NHS(O)₂(heterociclilo), -NHS(O)₂NH(arilo), -NHS(O)₂NH(heterociclilo), -NH(arilo sustituido con 0 a 3 Rˣ), -NH(heterociclilo), -NHC(O)(arilo), -NHC(O)(C₁₋₃ alquilo), -NHC(O)(heterociclilo), -OC(O)(arilo), -OC(O)(heterociclilo), -NHC(O)NH(arilo), -NHC(O)NH(heterociclilo), -OC(O)O(C₁₋₃ alquilo), -OC(O)O(arilo), -OC(O)O(heterociclilo), -OC(O)NH(arilo), -OC(O)NH(heterociclilo), -NHC(O)O(arilo), -NHC(O)O(heterociclilo), -NHC(O)O(C₁₋₄ alquilo), -C(O)NH(arilo), -C(O)NH(heterociclilo), -C(O)O(arilo), C(O)O(heterociclilo), -N(C₁₋₃ alquil)S(O)₂(arilo), -N(C₁₋₃ alquil)S(O)₂(heterociclilo), -N(C₁₋₃ alquil)S(O)₂NH(arilo), -N(C₁₋₃ alquil)S(O)₂NH(heterociclilo), -N(C₁₋₃ alquil)(arilo), -N(C₁₋₃ alquil)(heterociclilo), -N(C₁₋₃ alquil)C(O)(arilo), -N(C₁₋₃ alquil)C(O)(heterociclilo), -N(C₁₋₃ alquil)C(O)NH(arilo), -(CH₂)₀₋₃C₍O₎NH₍ₕₑₜₑʳₒᶜⁱᶜₗⁱₗₒ₎, ₋OC₍O₎N₍C₁₋₃ alquil)(arilo), -OC(O)N(C₁₋₃ alquil)(heterociclilo), -N(C₁₋₃ alquil)C(O)O(arilo), -N(C₁₋₃ alquil)C(O)O(heterociclilo), -C(O)N(C₁₋₃ alquil)(arilo), -C(O)N(C₁₋₃ alquil)(heterociclilo), -NHS(O)₂N(C₁₋₃ alquil)(arilo), -NHS(O)₂N(C₁₋₃ alquil)(heterociclilo), -NHP(O)₂N(C₁₋₃ alquil)(arilo), -NHC(O)N(C₁₋₃ alquil)(arilo), -NHC(O)N(C₁₋₃ alquil)(heterociclilo), -N(C₁₋₃ alquil)S(O)₂N(C₁₋₃ alquil)(arilo), -(CH₂)₀₋₂C₍O₎NHS₍O₎₂(C₁₋₃ alquilo), -N(C₁₋₃ alquil)S(O)₂N(C₁₋₃ alquil)(heterociclilo), -N(C₁₋₃ alquil)C(O)N(C₁₋₃ alquil)(arilo), -N(C₁₋₃ alquil)C(O)N(C₁₋₃ alquil)(heterociclilo) o -Si(C₁₋₃ alquilo)₃, en donde cada uno de carbociclilo, arilo, heterociclilo y heteroarilo se sustituye con 0 a 4 Rᶻ; o dos Rᵃ, unidos al mismo átomo de carbono, forman =O; cada Rᵇ es independientemente H, C₁₋₆ alquilo sustituido con 0 a 6 Rᶠ, C₃₋₇ cicloalquilo sustituido con 0 a 6 Rᶠ, heterociclilo sustituido con 0 a 6 Rᶠ, arilo sustituido con 0 a 3 Rᶠ o heteroarilo mono- o bicíclico sustituido con o a 3 Rᶠ; cada Rᶜ es independientemente H, C₁₋₆ alquilo sustituido con 0 a 6 Rᶠ, C₃₋₇ cicloalquilo sustituido con 0 a 6 Rᶠ, heterociclilo sustituido con 0 a 6 Rᶠ, arilo sustituido con 0 a 3 Rᶠ o heteroarilo mono- o bicíclico sustituido con 0 a 3 Rᶠ; o dos Rᶜ, unidos al mismo átomo de nitrógeno, forman un anillo heterocíclico de 4 a 8 miembros sustituido con 0 a 3 Rᵍ; cada Rᵈ es independientemente H, C₁₋₆ alquilo sustituido con 0 a 6 Rᶠ, C₃₋₇ cicloalquilo sustituido con 0 a 6 Rᶠ, heterociclilo sustituido con 0 a 6 Rᶠ, arilo sustituido con 0 a 3 Rᶠ o heteroarilo mono- o bicíclico sustituido con 0 a 3 Rᶠ; cada Rᵉ es independientemente H, C₁₋₆ alquilo sustituido con 0 a 7 Rᶠ, C₃₋₇ cicloalquilo sustituido con 0 a 6 Rᶠ, heterociclilo sustituido con 0 a 6 Rᶠ, arilo sustituido con 0 a 3 Rᶠ o heteroarilo mono- o bicíclico sustituido con 0 a 3 Rᶠ; cada Rᶠ es independientemente H, halo, -OH, -CN, -NH₂, C₁₋₆ alquilo sustituido con 0 a 6 Rᵃ, C₁₋₃ alcoxi sustituido con 0 a 7 Rᵃ, C₃₋₇ cicloalquilo sustituido con 0 a 6 Rᵃ, heterociclilo sustituido con 0 a 6 Rᵃ, arilo sustituido con 0 a 3 Rᵃ o heteroarilo mono- o bicíclico sustituido con 0 a 3 Rᵃ; cada Rᵍ es independientemente H, F, -OH, -CN, C₁₋₃ alquilo, -CF₃ o fenilo; cada Rʰ es independientemente H, C₁₋₅ alquilo sustituido con 0 a 2 Rˣ, C₃₋₇ cicloalquilo sustituido con 0 a 2 Rˣ, heterociclilo mono- o bicíclico sustituido con o a 2 Rˣ, arilo sustituido con 0 a 2 Rˣ o heteroarilo mono- o bicíclico sustituido con 0 a 2 Rˣ; cada Rʷ es independientemente F, -OH, -CN, -NH₂, -C(O)OH, -C(O)(C₁₋₃ alquilo), -C(O)NH₂, -C(O)NH(C₁₋₃ alquilo), -NHC(O)(C₁₋₃ alquilo) o -C(O)NHS(O)₂(C₁₋₃ alquilo); cada Rˣ es independientemente H, halo, -CN, C₁₋₄ alquilo, C₁₋₆ haloalquilo o C₁₋₃ alcoxi; cada Rʸ es independientemente C₁₋₅ alquilo; cada Rᶻ es independientemente H, halo, -CN, C₁₋₄ alquilo, C₁₋₄ hidroxialquilo, C₁₋₆ haloalquilo, C₁₋₃ alcoxi, -NH₂, -NH(C₁₋₃ alquilo), -N(C₁₋₃ alquilo)₂, -OC(O)(C₁₋₄ alquilo), -C(O)OH, -CH₂C(O)OH, -CH₂(fenilo), -CH₂CH₂(morfolinilo), C(O)(morfolinilo), C₃₋₆ cicloalquilo y morfolinilo; o dos Rᶻ, unidos al mismo átomo de carbono, forman =O; m es 0, 1, 2, 3 ó 4; n es 0, 1, 2, 3 ó 4; cada p es independientemente 0, 1 ó 2; y cada r es independientemente 0, 1, 2, 3 ó 4; siempre que cuando al menos uno de R⁵ y R⁶ es H, entonces X sea -O-, -S- o -NR⁸-, uno de m y n sea 1, 2, 3 ó 4, y el otro de m y n sea 0, 1, 2, 3 ó 4.
ARP160102357A 2015-08-03 2016-08-02 COMPUESTOS DE QUINOLINA COMO MODULADORES DE TNFa AR105575A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201562200424P 2015-08-03 2015-08-03

Publications (1)

Publication Number Publication Date
AR105575A1 true AR105575A1 (es) 2017-10-18

Family

ID=56618285

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP160102357A AR105575A1 (es) 2015-08-03 2016-08-02 COMPUESTOS DE QUINOLINA COMO MODULADORES DE TNFa

Country Status (22)

Country Link
US (1) US10865191B2 (es)
EP (1) EP3331871A1 (es)
JP (1) JP6955482B2 (es)
KR (1) KR20180031772A (es)
CN (1) CN108137547B (es)
AR (1) AR105575A1 (es)
AU (1) AU2016302144B2 (es)
BR (1) BR112018001960A2 (es)
CA (1) CA2994717A1 (es)
CL (1) CL2018000293A1 (es)
CO (1) CO2018002061A2 (es)
EA (1) EA033686B1 (es)
HK (1) HK1252623A1 (es)
IL (1) IL257154A (es)
MA (1) MA43512A (es)
MX (1) MX2018001054A (es)
PE (1) PE20181366A1 (es)
SG (1) SG10201911831RA (es)
TW (1) TW201718536A (es)
UY (1) UY36838A (es)
WO (1) WO2017023905A1 (es)
ZA (1) ZA201800716B (es)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201710257A (zh) 2015-04-17 2017-03-16 艾伯維有限公司 Ｔｎｆ信號傳遞之三環調節劑
US9879016B2 (en) 2015-04-17 2018-01-30 Abbvie Inc. Indazolones as modulators of TNF signaling
US20160304496A1 (en) 2015-04-17 2016-10-20 Abbvie Inc. Indazolones as modulators of tnf signaling
GB201510758D0 (en) 2015-06-18 2015-08-05 Ucb Biopharma Sprl Novel TNFa structure for use in therapy
GB201513742D0 (en) 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
NZ739228A (en) 2015-08-03 2019-11-29 Glenmark Pharmaceuticals Sa Novel compounds as ror gamma modulators
GB201621907D0 (en) 2016-12-21 2017-02-01 Ucb Biopharma Sprl And Sanofi Antibody epitope
JOP20190257A1 (ar) 2017-04-28 2019-10-28 Novartis Ag مركبات أريل غير متجانسة ثنائية الحلقة مندمجة 6-6 واستخدامها كمثبطات lats
CA3090788A1 (en) * 2018-02-09 2019-08-15 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Heterocyclic p2y14 receptor antagonists
CN108658977A (zh) * 2018-04-12 2018-10-16 苏州康润医药有限公司 一种7-溴-1,5-萘啶-3-甲酸的合成方法
BR112022023550A2 (pt) 2020-05-19 2023-01-03 Bayer Cropscience Ag (tio)amidas azabicíclicas como compostos fungicidas
BR112022024413A2 (pt) 2020-06-10 2023-02-07 Bayer Ag Heterociclos substituídos com azabiciclila como fungicidas inovadores
EP4167982A1 (en) 2020-06-22 2023-04-26 PMV Pharmaceuticals, Inc. Methods and compounds for restoring mutant p53 function
IL303965A (en) * 2020-12-22 2023-08-01 Mekanistic Therapeutics Llc Transmuted heteroaryl aminobenzyl compounds as EGFR and/or PI3K inhibitors
WO2023067546A1 (en) * 2021-10-21 2023-04-27 Satyarx Pharma Innovations Pvt Ltd Novel bicyclic heteroaryl derivatives as sos1:kras proteinprotein interaction inhibitors
CN114605409B (zh) * 2022-04-01 2024-04-02 苏州睿尔思科技有限公司 一种4-羟基-1,5-萘啶类配体的生产制备方法
CN114751858B (zh) * 2022-04-20 2023-09-12 沈阳药科大学 含有喹啉基的氨甲环酸衍生物及其制备与应用

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US856095A (en) * 1906-09-01 1907-06-04 Railway Safety Signal Company Electric semaphore.
IL85741A (en) 1987-03-17 1996-05-14 Hoechst Roussel Pharma Transformed Tetra-Hydroacridines Process for their preparation and pharmaceutical preparations containing A-amino-Tetra-Transformed Hydroacridines
DE3917232A1 (de) * 1989-05-26 1990-11-29 Basf Ag 4-arylmethamino-2,3-dialkyl-chinoline, ihre verwendung und daraus hergestellte arzneimittel
PL366516A1 (en) * 2001-05-31 2005-02-07 Sanofi-Synthelabo Aminoquinoline and aminopyridine derivatives and their use as adenosine a3 ligands
EP1427408A4 (en) * 2001-09-17 2005-10-26 Bristol Myers Squibb Co CYCLIC HYDROXAMINE ACIDS AS INHIBITORS OF MATRIX METALLOPROTEINASES AND / OR TNF-a-CONVERTASE (TACE TNF-a-CONVERTING ENZYM)
US7294624B2 (en) 2001-12-20 2007-11-13 Bristol Myers Squibb Company Barbituric acid derivatives as inhibitors of TNF-α converting enzyme (TACE) and/or matrix metalloproteinases
HUP0105406A3 (en) * 2001-12-21 2003-12-29 Sanofi Aventis Imidazo[1,2-a]quinolin derivatives, process for their preparation, pharmaceutical compositions thereof and intermediates
DE602004010284T2 (de) * 2003-07-31 2008-10-02 Sanofi-Aventis Aminochinolinderivate und deren verwendung als adenosin-a3-liganden
TW200815447A (en) 2006-06-14 2008-04-01 Astrazeneca Ab Novel compounds IV
WO2009155121A2 (en) 2008-05-30 2009-12-23 Amgen Inc. Inhibitors of pi3 kinase
WO2012016082A1 (en) * 2010-07-30 2012-02-02 Oncotherapy Science, Inc. Quinoline derivatives and melk inhibitors containing the same
CN104428293B (zh) 2012-06-11 2018-06-08 Ucb生物制药私人有限公司 调节TNFα的苯并咪唑类
ES2689429T3 (es) * 2012-07-13 2018-11-14 Ucb Biopharma Sprl Derivados de imidazopiridina como moduladores de actividad de TNF
GB201212513D0 (en) 2012-07-13 2012-08-29 Ucb Pharma Sa Therapeutic agents
PT2914296T (pt) 2012-11-01 2018-10-30 Infinity Pharmaceuticals Inc Tratamento de cancros utilizando moduladores de isoformas de pi3-quinase
CN105407894A (zh) * 2013-03-14 2016-03-16 康威基内有限公司 用于抑制含布罗莫结构域的蛋白质的方法和组合物
NZ739228A (en) 2015-08-03 2019-11-29 Glenmark Pharmaceuticals Sa Novel compounds as ror gamma modulators
GB201513742D0 (en) 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
AR105556A1 (es) 2015-08-03 2017-10-18 Hoffmann La Roche Derivados de etinilo
WO2017167993A1 (en) 2016-04-01 2017-10-05 Ucb Biopharma Sprl Fused pentacyclic imidazole derivatives as modulators of tnf activity

Also Published As

Publication number Publication date
ZA201800716B (en) 2019-07-31
EA201890165A1 (ru) 2018-07-31
CN108137547B (zh) 2021-11-12
CL2018000293A1 (es) 2018-07-13
KR20180031772A (ko) 2018-03-28
AU2016302144A1 (en) 2018-03-22
MA43512A (fr) 2018-11-07
AU2016302144B2 (en) 2020-10-08
US20180222883A1 (en) 2018-08-09
CO2018002061A2 (es) 2018-06-20
CN108137547A (zh) 2018-06-08
JP2018525379A (ja) 2018-09-06
JP6955482B2 (ja) 2021-10-27
UY36838A (es) 2017-01-31
EP3331871A1 (en) 2018-06-13
IL257154A (en) 2018-03-29
BR112018001960A2 (pt) 2018-09-18
CA2994717A1 (en) 2017-02-09
EA033686B1 (ru) 2019-11-15
HK1252623A1 (zh) 2019-05-31
SG10201911831RA (en) 2020-02-27
US10865191B2 (en) 2020-12-15
WO2017023905A1 (en) 2017-02-09
PE20181366A1 (es) 2018-08-27
TW201718536A (zh) 2017-06-01
MX2018001054A (es) 2018-07-06

Similar Documents

Publication Publication Date Title
AR105575A1 (es) COMPUESTOS DE QUINOLINA COMO MODULADORES DE TNFa
AR105845A1 (es) Compuestos de heteroarilo bicíclicos fusionados como moduladores de la función irak4
AR108838A1 (es) Ácidos de carbamoiloximetil triazol ciclohexilo como antagonistas de lpa
AR100809A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR111419A1 (es) Compuestos fusionados de indazol piridona como antivirales
AR106798A1 (es) Inhibidores pirazol de acc y usos de los mismos
AR105648A1 (es) Métodos para la preparación de ácidos biliares y derivados de los mismos
AR095359A1 (es) Compuestos heteroaromáticos y su uso como ligandos d1 de dopamina
AR100033A1 (es) Compuestos y composiciones para inhibir la actividad de shp2
AR102177A1 (es) Compuestos de heteroarilo como inhibidores de btk y usos de los mismos
AR104884A1 (es) Compuestos de 4-hidroxi-3-(heteroaril)piridin-2-ona como agonistas de apj
AR111407A1 (es) Compuestos inhibidores de ask1 y usos de los mismos
AR095430A1 (es) Compuestos de pirimidina y piridina y su uso como inhibidores de la actividad de fgfr
AR100808A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR107061A1 (es) Heteroarilhidroxipirimidinonas como agonistas del receptor de apj
AR092869A1 (es) Alcoxipirazoles como activadores de guanilato ciclasa soluble
AR089143A1 (es) Triazolopiridinas sustituidas con actividad inhibidora de ttk
AR106604A1 (es) Compuestos de criptoficina y productos conjugados, su preparación y su uso terapéutico
AR106297A1 (es) Compuestos macrocíclicos modificados como inhibidores selectivos de la quinasa cdk9
AR103170A1 (es) Compuestos y composiciones farmacéuticas de los mismos para el tratamiento de desordenes inflamatorios y osteoartritis
AR099890A1 (es) Inhibidores de histona demetilasas
AR106185A1 (es) Compuestos macrocíclicos de sulfondiimina
AR104555A1 (es) SULFONAS TRICÍCLICAS COMO MODULARES DE RORg
AR108010A1 (es) Derivados de indolina y su uso como inhibidores de ews-fli1
AR100439A1 (es) Derivados de carboxamida

Legal Events

Date Code Title Description
FB Suspension of granting procedure