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AR059726A1 - Moduladores de 11 beta hidroxil esteroide deshidrogenasa de tipo 1, composiciones farmaceuticas de los mismos, y metodos de uso de los mismos - Google Patents

Moduladores de 11 beta hidroxil esteroide deshidrogenasa de tipo 1, composiciones farmaceuticas de los mismos, y metodos de uso de los mismos

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Publication number
AR059726A1
AR059726A1 ARP070100887A ARP070100887A AR059726A1 AR 059726 A1 AR059726 A1 AR 059726A1 AR P070100887 A ARP070100887 A AR P070100887A AR P070100887 A ARP070100887 A AR P070100887A AR 059726 A1 AR059726 A1 AR 059726A1
Authority
AR
Argentina
Prior art keywords
heterocycloalkyl
cycloalkyl
alkyl
haloalkyl
heteroaryl
Prior art date
Application number
ARP070100887A
Other languages
English (en)
Inventor
Wenqing Yao
Yung-Long Li
Original Assignee
Incyte Corp
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Filing date
Publication date
Application filed by Incyte Corp filed Critical Incyte Corp
Publication of AR059726A1 publication Critical patent/AR059726A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/10—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/23—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—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
    • 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
    • C07D213/60—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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/14—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • C07D451/06—Oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (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)

Abstract

Composiciones farmacéuticas que los contienen. Reivindicacion 1: Un compuesto de formula (1) o (2) o sal aceptable para uso farmacéutico o prodroga del mismo, caracterizado porque: Cy es arilo, heteroarilo, cicloalquilo o heterocicloalquilo, cada uno opcionalmente sustituido con 1, 2, 3, 4 o 5 -W-X-Y-Z; R1 es H, F, CN, OR5 , SR5, alquilo C1-6, haloalquilo C1-6, alcoxialquilo C2-12, haloalcoxialquilo C2-12, cicloalquilo, heterocicloalquilo, cicloalquilalquilo o heterocicloalquilalquilo; R2 es H, F, CN, alquilo C1-6, haloalquilo C1-6, alcoxialquilo C2-12, haloalcoxialquilo C2-12, cicloalquilo, heterocicloalquilo, cicloalquilalquilo o heterocicloalquilalquilo; en donde al menos uno de R1 y R2 es distinto de H; R3 es H, alquilo C1-6, cicloalquilo o heterocicloalquilo, en donde cada uno de los alquilo C1-6, cicloalquilo, y heterocicloalquilo está opcionalmente sustituido por 1, 2, 3, 4 o 5 -W'-X'-Y'-Z'; R4 es alquilo C1-6, arilo, cicloalquilo, heteroarilo o heterocicloalquilo, cada uno opcionalmente sustituido con 1, 2, 3, 4 o 5 -W'-X'-Y'-Z'; o R3 y R4 junto con el átomo de N a! cual están unidos forman a un grupo heterocicloalquilo de 4 a 20 miembros opcionalmente sustituido por 1, 2, 3, 4 o 5 -W'-X'-Y'-Z'; cada R5 es independientemente H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, cicloalquilalquilo, heteroarilalquilo o heterocicloalquilalquilo, en donde cada uno de los alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, cicloalquilalquilo, heteroarilalquilo y heterocicloalquilalquilo está opcionalmente sustituido por 1, 2, 3, 4 o 5 sustituyentes seleccionados en forma independiente entre halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRCRd, NRcC(O)Rb, NRcC(O)ORa, NRcS(O)2Rb, S(O)Rb, S(O)NRcRd, S(O)2Rb, y S(O)2NRcRd; L es SO2, (CR6R7)n1O(CR6R7)n2, (CR6R7)n1S(CR6R7)n2, o (CR6R7)n3; R6 y R7 se seleccionan en forma independiente entre H, halo, alquilo C1-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, CN, NO2, ORa', SRa', C(O)Rb', C(O)NRc'Rd', C(O)ORa', OC(O)Rb', OC(O)NRc'Rd', NRc'Rd', NRc'C(O)Rd', NRc'C(O)ORa, S(O)Rb', S(O)NRc'Rd', S(O)2Rb', y S(O)2NRc'Rd', n1 es 0, 1, 2 o 3; n2 es 0, 1, 2 o 3; n3 es 1, 2, 3 o 4; W, W' y Wö se seleccionan en forma independiente entre ausente, alquilenilo C1-6, alquenilenilo C2-6, alquinilenilo C2-6, O, S, NRe, CO, COO, CONRe, SO, SO2, SONRe y NReCONRf, en donde cada uno de los alquilenilo C1-6, alquenilenilo C2-6 y alquinilenilo C2-6, está opcionalmente sustituido por 1, 2 o 3 sustituyentes seleccionados en forma independiente entre halo, OH, alcoxi C1-6, haloalcoxi C1-6, amino, alquilamino C1-6, y dialquilamino C2-8; X, X' y Xö se seleccionan en forma independiente entre ausente, alquilenilo C1-6, alquenilenilo C2-6, alquinilenilo C2-6, arilo, cicloalquilo, heteroarilo y heterocicloalquilo, en donde cada uno de los alquilenilo C1-6, alquenilenilo C2-6, alquinilenilo C2-6, cicloalquilo, heteroarilo y heterocicloalquilo está opcionalmente sustituido por 1, 2 o 3 sustituyentes seleccionados en forma independiente entre halo, CN, NO2, OH, alquilo C1-6, haloalquilo C1-6, alcoxialquilo C2-8, alcoxi C1-6, haloalcoxi C1-6, alcoxialcoxi C2- 8, cicloalquilo, heterocicloalquilo, C(O)ORa, C(O)NRcRd, amino, alquilamino C1-6, y dialquilamino C2-8; Y, Y' y Yö se seleccionan en forma independiente entre ausente, alquilenilo C1-6, alquenilenilo C2-6, alquinilenilo C2-6, O, S, NRe, CO, COO, CONRe, SO, SO2, SONRe, y NReCONRf, en donde cada uno de los alquilenilo C1-6, alquenilenilo C2-6 y alquinilenilo C2-6, está opcionalmente sustituido por 1, 2 o 3 sustituyentes seleccionados en forma independiente entre halo, OH, alcoxi C1-6, haloalcoxi C1-6, amino, alquilamino C1-6 y dialquilamino C2-8; Z, Z' y 7ö se seleccionan en forma independiente entre H, halo, CN, NO2, OH, alcoxi C1-6, haloalcoxi C1-6, amino, alquilamino C1-6, dialquilamino C2-8, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo y heterocicloalquilo, en donde cada uno de los alquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo y heterocicloalquilo, está opcionalmente sustituido por 1, 2 o 3 sustituyentes seleccionados en forma independiente entre halo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, haloalquilo C1-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcS(O)2Rb, S(O)Rb, S(O)NRcRd, S(O)2Rb, y S(O)2NRcRd; en donde dos -W-X-Y-Z unidos al mismo átomo opcionalmente forman un grupo cicloalquilo de 3 a 14 miembros o heterocicloalquilo de 3 a 14 miembros opcionalmente sustituido por 1, 2 o 3 -Wö-Xö-Yö-Zö; en donde dos -W'-X'-Y'-Z' unidos al mismo átomo opcionalmente forman un grupo cicloalquilo de 3 a 14 miembros o heterocicloalquilo de 3 a 14 miembros opcionalmente sustituido por 1, 2 o 3 -Wö-Xö-Yö-Zö; en donde - W-X-Y-Z es distinto de H; en donde -W'-X'-Y'-Z' es distinto de H; en donde -Wö-Xö-Yö-Zö es distinto de H; cada Ra y Ra' se selecciona en forma independiente entre H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo y heterocicloalquilo, en donde cada uno de los alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo y heterocicloalquilo, está opcionalmente sustituido por OH, amino, halo, alquilo C1-6, haloalquilo C1-6, arilo, arilalquilo, heteroariIo, heteroarilalquilo, cicloalquilo o heterocicloalquilo; cada Rb y Rb' se selecciona en forma independiente entre H, alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo cicloalquilalquilo y heterocicloalquilalquilo en donde cada uno de los alquilo C1-6, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, cicloalquilo, heteroarilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo está opcionalmente sustituido por OH, amino, halo, alquilo C1-6, haloalquilo C1-6, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo o heterocicloalquilo; Rc y Rd se selecciona en forma independiente entre H, alquilo C1-10, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo, en donde cada uno de los alquilo C1-10, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo está opcionalmente sustituido por OH, amino, halo, alquilo C1-6, haloalquilo C1-6, haloalquilo C1-6, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo o heterocicloalquilo; o Rc y Rd junto con el átomo de N al cual están unidos forman un grupo heterocicloalquilo de 4, 5, 6 o 7 miembros; Rc' y Rd' se seleccionan en forma independiente entre H, alquilo C1-10, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo, en donde cada uno de los alquilo C1-10, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo está opcionalmente sustituido por OH, amino, halo, alquilo C1-6, haloalquilo C1-6, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo o heterocicloalquilo; o Rc' y Rd' junto con el átomo de N al cual están unidos forman un grupo heterocicloalquilo de 4, 5, 6 o 7 miembros; y Re y Rf se seleccionan en forma independiente entre H, alquilo C1-10, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo, en donde cada uno de los alquilo C1-10, haloalquilo C1-6, alquenilo C2-6, alquinilo C2-6, arilo, heteroarilo, cicloalquilo, heterocicloalquilo, arilalquilo, heteroarilalquilo, cicloalquilalquilo y heterocicloalquilalquilo está opcionalmente sustituido por OH, amino, halo, alquilo C1-6, haloalquilo C1-6, haloalquilo C1-6, arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilo o heterocicloalquilo; con la salvedad de que cuando R2 es alquilo C1-6 o haloalquilo C1-6, luego R1 es distinto de alquilo C1-6 o haloalquilo C1-6.
ARP070100887A 2006-03-02 2007-03-02 Moduladores de 11 beta hidroxil esteroide deshidrogenasa de tipo 1, composiciones farmaceuticas de los mismos, y metodos de uso de los mismos AR059726A1 (es)

Applications Claiming Priority (2)

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US77831206P 2006-03-02 2006-03-02
US80903506P 2006-05-26 2006-05-26

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US (1) US20070213311A1 (es)
AR (1) AR059726A1 (es)
TW (1) TW200808807A (es)
WO (1) WO2007101270A1 (es)

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