AR061273A1 - THERAPY USING CITOCINE INHIBITORS - Google Patents

THERAPY USING CITOCINE INHIBITORS

Info

Publication number
AR061273A1
AR061273A1 ARP070102483A ARP070102483A AR061273A1 AR 061273 A1 AR061273 A1 AR 061273A1 AR P070102483 A ARP070102483 A AR P070102483A AR P070102483 A ARP070102483 A AR P070102483A AR 061273 A1 AR061273 A1 AR 061273A1
Authority
AR
Argentina
Prior art keywords
attached
forming
target protein
orientation
variables
Prior art date
Application number
ARP070102483A
Other languages
Spanish (es)
Inventor
Constance A Crowley
Bernard King
Bonnie Hepburn
Nancy G J Delaet
Stephen Miller
Carrie Gail Grove
Christopher J Larson
Kent Pryor
Lewis J Shuster
Justin Ernst
Original Assignee
Kemia Inc
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 Kemia Inc filed Critical Kemia Inc
Publication of AR061273A1 publication Critical patent/AR061273A1/en

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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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and 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
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Métodos para tratar, prevenir, modificar y manejar las enfermedades mediadas con citocina o las enfermedades relacionadas, que comprenden la administracion de un compuesto, tal como un inhibidor de citocina, solo o en combinacion con terapéuticos conocidos. Composiciones farmacéuticas y regímenes de dosis usando los compuestos descritos. Uso de compuestos como se describen en este documento, opcionalmente en conjuncion con otras terapias, para el tratamiento de enfermedades autoinmunes, enfermedades inflamatorias, enfermedades cardiovasculares y cáncer. Reivindicacion 1: Un método para tratar un trastorno mediado por una o más citocinas, caracterizado porque comprende administrar a un sujeto en necesidad de tal tratamiento una cantidad terapéuticamente efectiva de un compuesto, en donde el compuesto se selecciona de: a) G-N(H)X-Ar-L-Q en donde las variables G, X, Ar, L, y Q son como se definieron en las Listas II, III o IV; b) G-X-N(H)Ar-L-Q en donde las variables G, X, Ar, L, y Q son como se definieron en las Listas V, VI, o VII; c) G-anillo-Ar-L-Q, en donde las variables G, anillo, Ar, L, y Q son como se definieron en la Lista VIII; d) formula (2) en donde las variables G, X', Ar, L, y Q son como se definieron en la Lista IX, e) formula (3) en donde las variables G, L1, L2, L3, A, Ar, y Q son como se definieron en la Lista X; f) formula (4) en donde las variables G, X, Y, L1, L2, A, B, D, E y Q son como se definieron en la Lista XI, g) un compuesto que comprende: una porcion de direccion, TM que comprende por lo menos un grupo amida que tiene un NH amida, la porcion de direccion capaz de formar uno o más enlaces de hidrogeno con una proteína objetivo, y en donde la porcion de direccion no es un grupo urea; una porcion de expansion de cavidad, PEM unida directamente a la porcion de direccion, la porcion de expansion de cavidad comprende una porcion plana unida a una porcion hidrofobica no plana voluminosa, la porcion no plana forma interacciones hidrofobicas con la proteína objetivo; y una porcion de orientacion, OM que comprende una porcion hidrofobica plana y unida a un átomo diferente de la porcion de direccion que la porcion de expansion de cavidad, la porcion de orientacion capaz de formar una interaccion aromática p-p o borde a cara con la proteína objetivo; h) un compuesto que comprende una porcion de direccion, TM, que comprende un grupo amida que tiene un NH amida y carbonilo, la porcion de direccion capaz de formar uno o más enlaces de hidrogeno con una proteína objetivo; una porcion de expansion de cavidad, PEM, unida directamente a la porcion de direccion, la porcion de expansion de cavidad comprende una porcion plana unida a una porcion hidrofobica no plana voluminosa, en donde la porcion no plana es capaz de formar interacciones hidrofobicas con la proteína objetivo; una porcion de orientacion, OM, que comprende un anillo piridilo y unida a un átomo diferente de la porcion de direccion que la porcion de expansion de cavidad, en donde la porcion de orientacion es capaz de formar interacciones hidrofobicas con la proteína objetivo; y una porcion de anclaje, AM, unida indirectamente a la porcion de orientacion por una porcion conectora, L, en donde la porcion de anclaje es capaz de formar por lo menos una interaccion de enlace de hidrogeno con una cavidad de union a ATP de la proteína objetivo; i) un compuesto que comprende: una porcion de direccion, TM, que comprende un NH amida y carbonilo, la porcion de direccion capaz de formar uno o más enlaces de hidrogeno con una proteína objetivo; una porcion de expansion de cavidad, PEM, unida directamente al carbonilo de la porcion de direccion, la porcion de expansion de cavidad comprende una porcion plana unida a una porcion hidrofobica no plana voluminosa, en donde la porcion no plana capaz de formar interacciones hidrofobicas con la proteína objetivo; una porcion de orientacion, OM, que comprende un anillo arilo o heteroarilo de 6 miembros y unida al NH de la porcion de direccion, en donde la porcion de orientacion es capaz de formar interacciones hidrofobicas con la proteína objetivo; una porcion conectora, L, unida a un átomo diferente de la porcion de orientacion que la porcion de direccion, en donde la porcion conectora comprende una porcion heteroarilo de 5 miembros y el punto de union en la porcion heteroarilo es un átomo de carbono; y una porcion de anclaje, AM, unida a la porcion de orientacion por la porcion conectora, L, en donde la porcion de anclaje es capaz de formar por lo menos una interaccion de enlace de hidrogeno con una cavidad de union a ATP de la proteína objetivo; o un estereoisomero, tautomero, solvato, profármaco, o sales farmacéuticamente aceptable de cualquiera de uno o más de (a)-(i).Methods for treating, preventing, modifying and managing cytokine-mediated diseases or related diseases, which comprise the administration of a compound, such as a cytokine inhibitor, alone or in combination with known therapeutics. Pharmaceutical compositions and dose regimens using the compounds described. Use of compounds as described herein, optionally in conjunction with other therapies, for the treatment of autoimmune diseases, inflammatory diseases, cardiovascular diseases and cancer. Claim 1: A method of treating a disorder mediated by one or more cytokines, characterized in that it comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound, wherein the compound is selected from: a) GN (H) X-Ar-LQ where the variables G, X, Ar, L, and Q are as defined in Lists II, III or IV; b) G-X-N (H) Ar-L-Q where the variables G, X, Ar, L, and Q are as defined in Lists V, VI, or VII; c) G-ring-Ar-L-Q, where the variables G, ring, Ar, L, and Q are as defined in List VIII; d) formula (2) where the variables G, X ', Ar, L, and Q are as defined in List IX, e) formula (3) where the variables G, L1, L2, L3, A, Ar, and Q are as defined in List X; f) formula (4) wherein the variables G, X, Y, L1, L2, A, B, D, E and Q are as defined in List XI, g) a compound comprising: a direction portion, TM comprising at least one amide group having an NH amide, the address portion capable of forming one or more hydrogen bonds with a target protein, and wherein the address portion is not a urea group; a cavity expansion portion, PEM attached directly to the direction portion, the cavity expansion portion comprises a flat portion attached to a bulky non-planar hydrophobic portion, the non-plane portion forms hydrophobic interactions with the target protein; and an orientation portion, OM comprising a flat hydrophobic portion and attached to an atom different from the direction portion than the cavity expansion portion, the orientation portion capable of forming a pp or edge-to-face aromatic interaction with the protein objective; h) a compound comprising a direction portion, TM, comprising an amide group having an NH amide and carbonyl, the direction portion capable of forming one or more hydrogen bonds with a target protein; a cavity expansion portion, PEM, directly attached to the direction portion, the cavity expansion portion comprises a flat portion attached to a bulky non-planar hydrophobic portion, wherein the non-plane portion is capable of forming hydrophobic interactions with the target protein; an orientation portion, OM, comprising a pyridyl ring and attached to an atom different from the direction portion than the cavity expansion portion, wherein the orientation portion is capable of forming hydrophobic interactions with the target protein; and an anchor portion, AM, indirectly attached to the orientation portion by a connector portion, L, wherein the anchor portion is capable of forming at least one hydrogen bonding interaction with an ATP binding cavity of the target protein; i) a compound comprising: a direction portion, TM, comprising an NH amide and carbonyl, the direction portion capable of forming one or more hydrogen bonds with a target protein; a cavity expansion portion, PEM, directly attached to the carbonyl of the steering portion, the cavity expansion portion comprises a flat portion attached to a bulky non-planar hydrophobic portion, wherein the non-flat portion capable of forming hydrophobic interactions with the target protein; an orientation portion, OM, comprising a 6-membered aryl or heteroaryl ring and attached to the NH of the address portion, wherein the orientation portion is capable of forming hydrophobic interactions with the target protein; a connecting portion, L, attached to an atom different from the orientation portion than the steering portion, wherein the connecting portion comprises a 5-membered heteroaryl portion and the point of attachment in the heteroaryl portion is a carbon atom; and an anchor portion, AM, attached to the orientation portion by the connector portion, L, wherein the anchor portion is capable of forming at least one hydrogen bonding interaction with an ATP binding cavity of the protein objective; or a stereoisomer, tautomer, solvate, prodrug, or pharmaceutically acceptable salts of any one or more of (a) - (i).

ARP070102483A 2006-06-09 2007-06-08 THERAPY USING CITOCINE INHIBITORS AR061273A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US81226806P 2006-06-09 2006-06-09
US83307806P 2006-07-24 2006-07-24
US83527006P 2006-08-03 2006-08-03

Publications (1)

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AR061273A1 true AR061273A1 (en) 2008-08-13

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Country Status (8)

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EP (1) EP2035005A4 (en)
AR (1) AR061273A1 (en)
AU (1) AU2007257959A1 (en)
CA (1) CA2691214A1 (en)
CL (1) CL2007001670A1 (en)
PE (1) PE20080935A1 (en)
TW (1) TW200814998A (en)
WO (1) WO2007146712A2 (en)

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JP2004530690A (en) * 2001-05-16 2004-10-07 ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド Diaryl urea derivatives useful as anti-inflammatory drugs
CN102060806A (en) * 2003-09-11 2011-05-18 iTherX药品公司 Cytokine inhibitors

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