AR103232A1 - ANTAGONISTAS DE TGFbR - Google Patents

ANTAGONISTAS DE TGFbR

Info

Publication number
AR103232A1
AR103232A1 ARP150104241A ARP150104241A AR103232A1 AR 103232 A1 AR103232 A1 AR 103232A1 AR P150104241 A ARP150104241 A AR P150104241A AR P150104241 A ARP150104241 A AR P150104241A AR 103232 A1 AR103232 A1 AR 103232A1
Authority
AR
Argentina
Prior art keywords
hydrogen
3alkyl
6alkyl
halogen
independently
Prior art date
Application number
ARP150104241A
Other languages
English (en)
Inventor
G Kamau Muthoni
S Kim Kyoung
Zhang Liping
M Borzilleri Robert
Zhao Yufen
E Fink Brian
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 AR103232A1 publication Critical patent/AR103232A1/es

Links

Classifications

    • 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
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/495—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • 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
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Abstract

Compuestos que modulan la actividad de TGFbR-1 y TGFbR-2, composiciones farmacéuticas que contienen esos compuestos y métodos para el tratamiento de trastornos proliferativos y trastornos de apoptosis desregulada, tal como cáncer, mediante el uso de los compuestos. Reivindicación 1: El compuesto caracterizado porque tiene la fórmula (1) en donde: R es un resto de fórmula (2) o un grupo heterocíclico o heterobicíclico sustituido con 0 - 4 R²; X¹, X², X³ y X⁴ son independientemente -CR⁴ o -N-, en donde al menos uno es -N-; R¹ es hidrógeno, C₁₋₆alquilo, C₃₋₈cicloalquilo, -CONHR⁹, -COOR⁹, -COR⁹ o -SO₂R⁹, cualquiera de ellos, excepto hidrógeno, se sustituye con 0 - 3 Rˣ; Rˣ es hidrógeno, halógeno, -OH, halo-C₁₋₃alquilo, hidroxi-C₁₋₃alquilo, -amino-C₁₋₃alquilo o -CN; R² es independientemente uno o más de hidrógeno, -CD₃, OCD₃, halógeno, -CF₃, -CHF₂, -CN, C₁₋₆alquilo, C₁₋₆alcoxi o -SO₂-C₁₋₆alquilo; R³ es independientemente uno o más de hidrógeno, CD₃, OCD₃, halógeno, -CN, C₁₋₆alquilo, C₂₋₆alquenilo, C₁₋₆alcoxi, C₃₋₈cicloalquilo, hidroxi-C₁₋₃alquilo, C₁₋₆alquilamino-, C₁₋₆alquilamino-C₁₋₆alquilo, heteroarilo de 5 - 6 miembros, heterociclilo, O-heterociclilo, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁴, -COR⁴, -SO₂R⁴, -CHCF₂COOCH₂OH o -CHCF₂CONH₂, cualquiera de ellos, excepto hidrógeno, se sustituye con 0 - 4 Rʸ; Rʸ es hidrógeno, halógeno, -OH, C₁₋₃alquilo, halo-C₁₋₃alquilo, hidroxi-C₁₋₃alquilo, -amino-C₁₋₃alquilo, -NHCOOH o -CN; R⁴ es hidrógeno o C₁₋₆alquilo; R⁵ y R⁶ son independientemente hidrógeno, -C(O)alquilo o C₁₋₆alquilo; o R⁵ y R⁶ se pueden tomar junto con el átomo de nitrógeno al que están unidos para formar un anillo de heterociclo de 5 - 7 miembros; R⁷ es independientemente uno o más de hidrógeno, halógeno, halo-C₁₋₆alquilo o -CN; R⁸ es hidrógeno, C₁₋₆alquilo, C₃₋₈cicloalquilo, -CONHR⁹, -COOR⁹, -COR⁹ o -SO₂R⁹; R⁹ es hidrógeno, C₁₋₆alquilo, C₃₋₈cicloalquilo, heterociclilalquil-, heterociclil-C₁₋₃alquilamino-C₁₋₃alquil- o C₁₋₃alquilamino-C₁₋₃alquilo; m es 0, 1, 2, 3 ó 4; n es 0, 1, 2 ó 3; y/o una sal, un tautómero o un estereoisómero de aquel aceptables desde el punto de vista farmacéutico.
ARP150104241A 2014-12-22 2015-12-21 ANTAGONISTAS DE TGFbR AR103232A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201462095328P 2014-12-22 2014-12-22

Publications (1)

Publication Number Publication Date
AR103232A1 true AR103232A1 (es) 2017-04-26

Family

ID=55135542

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP150104241A AR103232A1 (es) 2014-12-22 2015-12-21 ANTAGONISTAS DE TGFbR

Country Status (7)

Country Link
US (1) US9708316B2 (es)
EP (1) EP3237415A1 (es)
JP (1) JP2018501315A (es)
CN (1) CN107257798A (es)
AR (1) AR103232A1 (es)
TW (1) TW201630907A (es)
WO (1) WO2016106266A1 (es)

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Also Published As

Publication number Publication date
TW201630907A (zh) 2016-09-01
JP2018501315A (ja) 2018-01-18
EP3237415A1 (en) 2017-11-01
US9708316B2 (en) 2017-07-18
US20160176871A1 (en) 2016-06-23
CN107257798A (zh) 2017-10-17
WO2016106266A1 (en) 2016-06-30

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