AR103182A1 - Inmunomoduladores - Google Patents

Inmunomoduladores

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Publication number
AR103182A1
AR103182A1 ARP150104203A ARP150104203A AR103182A1 AR 103182 A1 AR103182 A1 AR 103182A1 AR P150104203 A ARP150104203 A AR P150104203A AR P150104203 A ARP150104203 A AR P150104203A AR 103182 A1 AR103182 A1 AR 103182A1
Authority
AR
Argentina
Prior art keywords
ring
hydrogen
methyl
independently selected
optionally substituted
Prior art date
Application number
ARP150104203A
Other languages
English (en)
Inventor
Michael Scola Paul
Mull Eric
Patrick Allen Martin
Matthew Miller Michael
P Gillis Eric
Zhao Qian
Sun Li-Qiang
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 AR103182A1 publication Critical patent/AR103182A1/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10Peptides having 12 to 20 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/16Antivirals for RNA viruses for influenza or rhinoviruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/20Antivirals for DNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/20Antivirals for DNA viruses
    • A61P31/22Antivirals for DNA viruses for herpes viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702Regulators; Modulating activity
    • C07K14/4703Inhibitors; Suppressors
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64Cyclic peptides containing only normal peptide links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against 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)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Proporciona péptidos macrocíclicos que inhiben las interacciones proteína/proteína PPD-1/PD-L1 y PD-L1/CD80, y por ende, son útiles para la mejora de varias enfermedades, que incluyen el cáncer y las enfermedades infecciosas. Reivindicación 1: Un compuesto, caracterizado porque tiene la fórmula (1), o una sal de este aceptable desde el punto de vista farmacéutico, en donde: A se selecciona de un enlace, o un compuesto del grupo de fórmulas (2); en donde: la línea ondulada * indica el punto de unión al grupo carbonilo y la línea ondulada indica el punto de unión al átomo de nitrógeno; z es 0, 1 ó 2; w es 1 ó 2; n es 0 ó 1; m es 1 ó 2; m es 0 ó 1; p es 0, 1 ó 2; Rˣ se selecciona de hidrógeno, amino, hidroxi y metilo; R¹⁴ y R¹⁵ se seleccionan independientemente de hidrógeno y metilo; y Rᶻ se selecciona de hidrógeno y -C(O)NHR¹⁶; en donde R¹⁶ se selecciona de hidrógeno, -CHR¹⁷C(O)NH₂, -CHR¹⁷C(O)NHCHR¹⁸C(O)NH₂ y -CHR¹⁷C(O)NHCHR¹⁸C(O)NHCH₂C(O)NH₂; en donde R¹⁷ se selecciona de hidrógeno y -CH₂OH, y en donde R¹⁸ se selecciona de hidrógeno y metilo; Rᵛ es hidrógeno o una cadena lateral de aminoácido natural; Rᶜ, Rᶠ, Rʰ, Rⁱ y Rᵐ son hidrógeno; Rⁿ es hidrógeno o metilo, o Rᵛ y Rⁿ forman un anillo de pirrolidina; Rᵃ, Rᵉ, Rʲ y Rᵏ se seleccionan independientemente de hidrógeno y metilo; cada R²⁰ se selecciona independientemente de hidrógeno y C₁₋₆alquilo; cada R²¹ se selecciona independientemente de hidrógeno y C₁₋₆alquilo; R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² y R¹³ se seleccionan independientemente de una cadena lateral de aminoácido natural y una cadena lateral de aminoácido no natural, o cada uno puede formar independientemente un anillo carbocíclico de tres a seis miembros o un anillo de seis miembros que contiene un átomo de oxígeno o de nitrógeno con un grupo R²⁰ germinal correspondiente, en donde el anillo se sustituye opcionalmente con uno, dos o tres sustituyentes seleccionados independientemente de C₁₋₃alcoxi, C₁₋₃alquilo, C₂₋₄alquenilo, halo, hidroxi y amino y en donde el anillo de cinco y seis miembros se fusiona opcionalmente a un anillo de fenilo; o R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² y R¹³ pueden formar, cada uno independientemente, un anillo con el grupo R próximo correspondiente como se describe más adelante; Rᵉ y Rᵏ pueden formar, cada uno, un anillo con el grupo R próximo correspondiente y los átomos a los que están unidos, seleccionado de azetidina, pirrolidina, morfolina, piperidina, piperazina y tetrahidrotiazol; en donde cada anillo se sustituye opcionalmente con uno a cuatro grupos seleccionados independientemente de amino, ciano, metilo, halo e hidroxi; Rᵇ es metilo, o Rᵇ y R², junto con los átomos a los que están unidos, forman un anillo seleccionado de azetidina, pirrolidina, morfolina, piperidina, piperazina y tetrahidrotiazol; en donde cada anillo se sustituye opcionalmente con uno a cuatro grupos seleccionados independientemente de amino, ciano, metilo, halo e hidroxi; o cuando R² y el R²⁰ germinal no son hidrógeno, Rᵇ es hidrógeno; Rᵈ es hidrógeno o metilo, o Rᵈ y R⁴, junto con los átomos a los que están unidos, pueden formar un anillo seleccionado de azetidina, pirrolidina, morfolina, piperidina, piperazina y tetrahidrotiazol; en donde cada anillo se sustituye opcionalmente con uno a cuatro grupos seleccionados independientemente de amino, ciano, metilo, halo, hidroxi y fenilo; Rᵍ es hidrógeno o metilo, o Rᵍ y R⁷, junto con los átomos a los que están unidos, pueden formar un anillo seleccionado de azetidina, pirrolidina, morfolina, piperidina, piperazina y tetrahidrotiazol; en donde cada anillo se sustituye opcionalmente con uno a cuatro grupos seleccionados independientemente de amino, bencilo opcionalmente sustituido con un grupo halo, bencìloxi, ciano, ciclohexilo, metilo, halo, hidroxi, isoquinoliniloxi opcionalmente sustituido con un grupo metoxi, quinoliniloxi opcionalmente sustituido con un grupo halo, y tetrazolilo; y en donde los anillos de pirrolidina y piperidina están opcionalmente fusionados con un grupo ciclohexilo, fenilo o indol; y Rˡ es metilo, o Rˡ y R¹², junto con los átomos a los que están unidos, forman un anillo seleccionado de azetidina y pirrolidina, en donde cada anillo se sustituye opcionalmente con uno a cuatro grupos seleccionados independientemente de amino, ciano, metilo, halo e hidroxi; siempre que el compuesto de la fórmula (1) contenga al menos un carbono en la estructura principal del anillo que tiene cuatro sustituyentes que no son hidrógeno y no es un anillo sustituido con a-metilo.
ARP150104203A 2014-12-19 2015-12-18 Inmunomoduladores AR103182A1 (es)

Applications Claiming Priority (1)

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US201462094281P 2014-12-19 2014-12-19

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AR103182A1 true AR103182A1 (es) 2017-04-19

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US (1) US9944678B2 (es)
EP (1) EP3233887B1 (es)
JP (1) JP6705823B2 (es)
KR (1) KR102590776B1 (es)
CN (1) CN107223129B (es)
AR (1) AR103182A1 (es)
AU (1) AU2015364573A1 (es)
BR (1) BR112017012704A2 (es)
CA (1) CA2971266A1 (es)
CY (1) CY1121571T1 (es)
DK (1) DK3233887T3 (es)
EA (1) EA033721B1 (es)
ES (1) ES2719135T3 (es)
HR (1) HRP20190575T1 (es)
HU (1) HUE044027T2 (es)
IL (1) IL252896A0 (es)
LT (1) LT3233887T (es)
MX (1) MX2017008160A (es)
PL (1) PL3233887T3 (es)
PT (1) PT3233887T (es)
RS (1) RS58580B1 (es)
SG (1) SG11201704821VA (es)
SI (1) SI3233887T1 (es)
TR (1) TR201906470T4 (es)
TW (1) TW201629087A (es)
WO (1) WO2016100608A1 (es)

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