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AR081252A1 - COMPOUNDS FOR THE TREATMENT OF METABOLIC SYNDROME - Google Patents

COMPOUNDS FOR THE TREATMENT OF METABOLIC SYNDROME

Info

Publication number
AR081252A1
AR081252A1 ARP110101820A ARP110101820A AR081252A1 AR 081252 A1 AR081252 A1 AR 081252A1 AR P110101820 A ARP110101820 A AR P110101820A AR P110101820 A ARP110101820 A AR P110101820A AR 081252 A1 AR081252 A1 AR 081252A1
Authority
AR
Argentina
Prior art keywords
alkyl
halo
optionally substituted
cycloalkyl
heteroaryl
Prior art date
Application number
ARP110101820A
Other languages
Spanish (es)
Original Assignee
Prosidion Ltd
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
Priority claimed from GBGB1008985.2A external-priority patent/GB201008985D0/en
Priority claimed from GBGB1019547.7A external-priority patent/GB201019547D0/en
Priority claimed from GB1103283.6A external-priority patent/GB2488360A/en
Application filed by Prosidion Ltd filed Critical Prosidion Ltd
Publication of AR081252A1 publication Critical patent/AR081252A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/14Heterocyclic 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 three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Obesity (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

Composición farmacéutica y usos como agonistas de GPR119. Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo, en donde A es un fenilo para sustituido o un anillo heteroarilo de 6 miembros para sustituido que contienen uno a tres átomos de nitrógeno; R1 es hidrógeno, halo, ciano, alquilo C1-4, haloalquilo C1-4, alcoxi C1-4 o alcoxialquilo C2-6; R2 es: un resto de fórmula (2), fenilo opcionalmente sustituido con uno o más grupos halo, metilo, halometilo o metoxi, o piridilo, N-piridonilo o N-pirazolilo, opcionalmente sustituido con uno o más grupos halo, alquilo C1-2 o halometilo; R3 es independientemente halo, metilo o halometilo; Z es -C(O)OR4, -C(O)R4, -S(O)2R4, -S(O)2N(alquil C1-3)R4, heteroarilo o -CH2-heteroarilo, y cuando p y q son ambos 0, Z también puede ser -CH2-fenilo, dicho fenilo está opcionalmente sustituido con uno o dos grupos independientemente seleccionados de alquilo C1-4, haloalquilo C1-4 y halo; R4 es arilo, heteroarilo, alquilo C2-6, cicloalquilo C3-6, heterociclilo C4-6, heterociclilalquilo C1-4, alcoxialquilo C2-6, arilalquilo C1-4, heteroarilalquilo C1-4 o cicloalquil C4-6alquilo C1-4, dicho cicloalquilalquilo C1-4 está opcionalmente sustituido con alquilo C1-4; en donde cuando Z es o incluye heteroarilo o cuando R4 es o incluye arilo o heteroarilo, dicho arilo o heteroarilo puede estar opcionalmente sustituido con uno o dos grupos seleccionados de halo, ciano, SF5, alquilo C1-4, haloalquilo C1-4, hidroxialquilo C1-5, alcoxi C1-4, alcoxialquilo C2-4, heterociclilo, heterociclilalquilo C1-4, heteroarilalquilo C1-4, alquilamino C1-4, alquilamino C1-4alquilo C1-4, cicloalquilo C3-6 y -(alquil C1-3)-(cicloalquilo C3-6), en donde los grupos cicloalquilo y alquilo están cada uno opcionalmente sustituidos con uno o dos grupos independientemente seleccionados de alquilo C1-4, hidroxi o halo; X se selecciona de CR5H, O, y NR6 en los cuales R5 y R6 son independientemente hidrógeno o alquilo C1-2; Y es Y1 o W-Y1, donde W es un anillo heteroarilo de 5 miembros que contiene uno o más heteroátomos seleccionados de N, O y S, e Y1 se seleccione de CR7H, O y NR8, en los cuales R7 es hidrógeno, alquilo C1-2, alcoxialquilo C2-6 o heterociclilo; en donde dicho alquilo C1-2 puede estar opcionalmente sustituido con ciano, hidroxi o halo y R8 es alquilo C1-4 o cicloalquilo C1-4, siempre que cuando Y es W-Y1, X es O y Y1 es CR7H, cuando Y1 es O ó NR8, X es CR5H y cuando X es O ó NR6, Y1 es CR7H; cada uno de R9 y R10 es independientemente H, halo, alquilo C1-2, haloalquilo C1-2, alcoxi C1-3 o hidroxi; o R9 y R10 se unen para formar un azabiciclo[3.3.1]nonano, un 3-oxa-7-azabiciclo[3.3.1]nonano o un azabiciclo[3.2.1]octano; R11 es H, halo, alquilo C1-2, haloalquilo C1-2 o alcoxi C1-3; m es 0, 1 ó 2; n es 0 ó 1; p y q son cada uno 0, 1 ó 2, siempre que 0 L p + q L 2; y r es 1 ó 2.Pharmaceutical composition and uses as agonists of GPR119. Claim 1: A compound of the formula (1) or a pharmaceutically acceptable salt thereof, wherein A is a substituted phenyl or a 6-membered heteroaryl ring containing one to three nitrogen atoms; R1 is hydrogen, halo, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy or C2-6 alkoxyalkyl; R2 is: a moiety of formula (2), phenyl optionally substituted with one or more halo, methyl, halomethyl or methoxy groups, or pyridyl, N-pyridonyl or N-pyrazolyl, optionally substituted with one or more halo groups, C1- alkyl 2 or halomethyl; R3 is independently halo, methyl or halomethyl; Z is -C (O) OR4, -C (O) R4, -S (O) 2R4, -S (O) 2N (C1-3 alkyl) R4, heteroaryl or -CH2-heteroaryl, and when p and q are both 0 , Z may also be -CH2-phenyl, said phenyl is optionally substituted with one or two groups independently selected from C1-4 alkyl, C1-4 haloalkyl and halo; R 4 is aryl, heteroaryl, C 2-6 alkyl, C 3-6 cycloalkyl, C 4-6 heterocyclyl, C 1-4 heterocyclylalkyl, C 2-6 alkoxyalkyl, C 1-4 arylalkyl, C 1-4 heteroarylalkyl or C 1-4 alkyl cycloalkyl, said C1-4 cycloalkylalkyl is optionally substituted with C1-4 alkyl; wherein when Z is or includes heteroaryl or when R4 is or includes aryl or heteroaryl, said aryl or heteroaryl may be optionally substituted with one or two groups selected from halo, cyano, SF5, C1-4 alkyl, C1-4 haloalkyl, hydroxyalkyl C1-5, C1-4 alkoxy, C2-4 alkoxyalkyl, heterocyclyl, C1-4 heterocyclylalkyl, C1-4 heteroarylalkyl, C1-4 alkylamino, C1-4 alkylamino C1-4 alkyl, C3-6 cycloalkyl and - (C1-3 alkyl ) - (C3-6 cycloalkyl), wherein the cycloalkyl and alkyl groups are each optionally substituted with one or two groups independently selected from C1-4 alkyl, hydroxy or halo; X is selected from CR5H, O, and NR6 in which R5 and R6 are independently hydrogen or C1-2 alkyl; Y is Y1 or W-Y1, where W is a 5-membered heteroaryl ring containing one or more heteroatoms selected from N, O and S, and Y1 is selected from CR7H, O and NR8, in which R7 is hydrogen, alkyl C1-2, C2-6 alkoxyalkyl or heterocyclyl; wherein said C1-2 alkyl may be optionally substituted with cyano, hydroxy or halo and R8 is C1-4 alkyl or C1-4 cycloalkyl, provided that when Y is W-Y1, X is O and Y1 is CR7H, when Y1 is O or NR8, X is CR5H and when X is O or NR6, Y1 is CR7H; each of R9 and R10 is independently H, halo, C1-2 alkyl, C1-2 haloalkyl, C1-3 alkoxy or hydroxy; or R9 and R10 join to form an azabicyclo [3.3.1] nonane, a 3-oxa-7-azabicyclo [3.3.1] nonane or an azabicyclo [3.2.1] octane; R11 is H, halo, C1-2 alkyl, C1-2 haloalkyl or C1-3 alkoxy; m is 0, 1 or 2; n is 0 or 1; p and q are each 0, 1 or 2, provided that 0 L p + q L 2; and r is 1 or 2.

ARP110101820A 2010-05-28 2011-05-27 COMPOUNDS FOR THE TREATMENT OF METABOLIC SYNDROME AR081252A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB1008985.2A GB201008985D0 (en) 2010-05-28 2010-05-28 Novel compounds
GBGB1019547.7A GB201019547D0 (en) 2010-11-19 2010-11-19 Novel compounds
GB1103283.6A GB2488360A (en) 2011-02-25 2011-02-25 Heterocyclic GPCR agonists

Publications (1)

Publication Number Publication Date
AR081252A1 true AR081252A1 (en) 2012-07-18

Family

ID=44227954

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP110101820A AR081252A1 (en) 2010-05-28 2011-05-27 COMPOUNDS FOR THE TREATMENT OF METABOLIC SYNDROME

Country Status (3)

Country Link
AR (1) AR081252A1 (en)
TW (1) TW201209054A (en)
WO (1) WO2011147951A1 (en)

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Also Published As

Publication number Publication date
TW201209054A (en) 2012-03-01
WO2011147951A1 (en) 2011-12-01
WO2011147951A8 (en) 2012-03-15

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