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AR102651A1 - IMMUNOMODULATORS - Google Patents

IMMUNOMODULATORS

Info

Publication number
AR102651A1
AR102651A1 ARP150103712A ARP150103712A AR102651A1 AR 102651 A1 AR102651 A1 AR 102651A1 AR P150103712 A ARP150103712 A AR P150103712A AR P150103712 A ARP150103712 A AR P150103712A AR 102651 A1 AR102651 A1 AR 102651A1
Authority
AR
Argentina
Prior art keywords
methyl
independently selected
hydrogen
ring
optionally substituted
Prior art date
Application number
ARP150103712A
Other languages
Spanish (es)
Inventor
R Langley David
Michael Scola Paul
P Gillis Eric
Mull Eric
Zhao Qian
Sun Li
A Qiang - Poss Michael
Mapelli Claudio
Zhang Yunhui
M Boy Kenneth
Goodrich Jason
W Gillman Kevin
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 AR102651A1 publication Critical patent/AR102651A1/en

Links

Classifications

    • 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

Landscapes

  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

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 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; n es 0 ó 1; m es 1 ó 2; m es 0 ó 1; w es 0, 1 ó 2; RX se selecciona de hidrógeno, amino, hidroxi y metilo; R¹⁴ y R¹⁵ se seleccionan independientemente de hidrógeno y metilo; R¹⁶ᵃ se selecciona de hidrógeno y C₁₋₆ alquilo; R¹⁶ se selecciona de -(C(R¹⁷ᵃ)₂)₂-X-R³⁰, -C(R¹⁷ᵃ)₂C(O)N(R¹⁶ᵃ)C(R¹⁷ᵃ)₂-X-R³¹, -C(R¹⁷ᵃ)₂[C(O)N(R¹⁶ᵃ)C(R¹⁷ᵃ)₂]ʷ-X-R³¹, -(C(R¹⁷ᵃ)(R¹⁷)C(O)NR¹⁶ᵃ)ₙ-H; y -(C(R¹⁷ᵃ)(R¹⁷)C(O)NR¹⁶ᵃ)ₘ-C(R¹⁷ᵃ)(R¹⁷)-CO₂H; en donde: w es 2 ó 3; n es 1 - 6; m es 0 - 5; X es una cadena de 1 a 172 átomos, en donde los átomos se seleccionan de carbono y oxígeno, y en donde la cadena puede contener 1, 2, 3 ó 4 grupos seleccionados de -NHC(O)NH- y -C(O)NH- incrustado; y en donde la cadena se sustituye opcionalmente con 1 a 6 grupos seleccionados independientemente de -CO₂H, -C(O)NH₂, -CH₂C(O)NH₂ y -(CH₂)CO₂H; X es una cadena de 1 a 172 átomos, en donde los átomos se seleccionan de carbono y oxígeno, y en donde la cadena puede contener 1, 2, 3 ó 4 grupos seleccionados de -NHC(O)NH- y -C(O)NH- incrustado; y en donde la cadena se sustituye opcionalmente con 1 a 6 grupos seleccionados independientemente de -CO₂H, -C(O)NH₂ y -CH₂CO₂H, siempre que X no sea PEG no sustituido; R³⁰ se selecciona de -CO₂H, -C(O)NRʷRˣ y -CH₃, en donde Rʷ y Rˣ se seleccionan independientemente de hidrógeno y C₁₋₆ alquilo, siempre que, cuando X es carbono, R³⁰ no sea -CH₃; R³¹ es -CO₂H, -C(O)NRʷRˣ, -CH₃, alexa-5-SDP y biotina; cada R¹⁷ᵃ se selecciona independientemente de hidrógeno, C₁₋₆ alquilo, -CH₂OH, -CH₂CO₂H, -(CH₂)₂CO₂H, cada R¹⁷ se selecciona independientemente de hidrógeno, -CH₃, (CH₂)ᶻN₃, -(CH₂)ᶻNH₂, -X-R³¹, -(CH₂)ᶻCO₂H, -CH₂OH, CH₂C=CH y -(CH₂)ᶻ-triazolil-X-R³⁵, en donde z es 1 - 6, y R³⁵ de selecciona de -CO₂H, -C(O)NRʷRˣ, CH₃, biotina, -2-fluropiridina, -C(O)-(CH₂)₂-C(O)O-vitamina E, -C(O)O-vitamina E; y un compuesto de fórmula (3), siempre que al menos un R¹⁷ no sea hidrógeno, -CH₃ o -CH₂OH; Rᶜ, Rᶠ, Rʰ, Rⁱ, Rᵐ y Rⁿ son hidrógeno; Rᵃ, Rᵉ, Rʲ y Rᵏ se seleccionan independientemente de hidrógeno y metilo; 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 forman 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, pirolidina, 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, pirolidina, 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; 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, pirolidina, 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, pirolidina, 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, benciloxi, ciano, ciclohexilo, metilo, halo, hidroxi, isoquinoliniloxi opcionalmente sustituido con un grupo metoxi, quinolíniloxi 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 pirolidina, en donde cada anillo se sustituye opcionalmente con uno a cuatro grupos seleccionados independientemente de amino, ciano, metilo, halo e hidroxi. Reivindicación 26: Un método para mejorar, estimular y/o aumentar la respuesta inmunitaria en un sujeto que lo necesita, caracterizado porque comprende administrarle al sujeto una cantidad terapéuticamente eficaz de un compuesto de acuerdo con la reivindicación 1 o una sal de este terapéuticamente aceptable. Reivindicación 31: Un método para inhibir el crecimiento, la proliferación o la metástasis de células cancerosas en un sujeto que lo necesita, caracterizado porque comprende administrarle al sujeto una cantidad terapéuticamente eficaz de un compuesto de acuerdo con la reivindicación 1 o una sal de este terapéuticamente aceptable. Reivindicación 34: El método de acuerdo con la reivindicación 33, caracterizado porque la enfermedad infecciosa es causada por un virus.Claim 1: A compound, characterized in that it has the formula (1), or a pharmaceutically acceptable salt thereof, wherein: A is selected from the group of formulas (2), wherein: the wavy line * indicates the point of attachment to the carbonyl group and the wavy line indicates the point of attachment to the nitrogen atom; n is 0 or 1; m is 1 or 2; m is 0 or 1; w is 0, 1 or 2; RX is selected from hydrogen, amino, hydroxy and methyl; R¹⁴ and R¹⁵ are independently selected from hydrogen and methyl; R¹⁶ᵃ is selected from hydrogen and C₁₋₆ alkyl; R¹⁶ is selected from - (C (R¹⁷ᵃ) ₂) ₂-X-R³⁰, -C (R¹⁷ᵃ) ₂C (O) N (R¹⁶ᵃ) C (R¹⁷ᵃ) ₂-X-R³¹, -C (R¹⁷ᵃ) ₂ [C ( O) N (R¹⁶ᵃ) C (R¹⁷ᵃ) ₂] ʷ-X-R³¹, - (C (R¹⁷ᵃ) (R¹⁷) C (O) NR¹⁶ᵃ) ₙ-H; and - (C (R¹⁷ᵃ) (R¹⁷) C (O) NR¹⁶ᵃ) ₘ-C (R¹⁷ᵃ) (R¹⁷) -CO₂H; where: w is 2 or 3; n is 1-6; m is 0-5; X is a chain of 1 to 172 atoms, where the atoms are selected from carbon and oxygen, and where the chain can contain 1, 2, 3 or 4 groups selected from -NHC (O) NH- and -C (O ) Embedded NH-; and wherein the chain is optionally substituted with 1 to 6 groups independently selected from -CO₂H, -C (O) NH₂, -CH₂C (O) NH₂ and - (CH₂) CO₂H; X is a chain of 1 to 172 atoms, where the atoms are selected from carbon and oxygen, and where the chain can contain 1, 2, 3 or 4 groups selected from -NHC (O) NH- and -C (O ) Embedded NH-; and wherein the chain is optionally substituted with 1 to 6 groups independently selected from -CO₂H, -C (O) NH₂ and -CH₂CO₂H, provided that X is not unsubstituted PEG; R³⁰ is selected from -CO₂H, -C (O) NRʷRˣ and -CH₃, where Rʷ and Rˣ are independently selected from hydrogen and C₁₋₆ alkyl, provided that, when X is carbon, R³⁰ is not -CH₃; R³¹ is -CO₂H, -C (O) NRʷRˣ, -CH₃, alexa-5-SDP and biotin; each R¹⁷ᵃ is independently selected from hydrogen, C₁₋₆ alkyl, -CH₂OH, -CH₂CO₂H, - (CH₂) ₂CO₂H, each R¹⁷ is independently selected from hydrogen, -CH₃, (CH₂) ᶻN₃, - (CH₂) ᶻNH₂, -X- R³¹, - (CH₂) ᶻCO₂H, -CH₂OH, CH₂C = CH and - (CH₂) ᶻ-triazolyl-X-R³⁵, where z is 1 - 6, and R³⁵ is selected from -CO₂H, -C (O) NRʷRˣ, CH₃, biotin, -2-fluropyridine, -C (O) - (CH₂) ₂-C (O) O-vitamin E, -C (O) O-vitamin E; and a compound of formula (3), provided that at least one R¹⁷ is not hydrogen, -CH₃ or -CH₂OH; Rᶜ, Rᶠ, Rʰ, Rⁱ, Rᵐ and Rⁿ are hydrogen; Rᵃ, Rᵉ, Rʲ and Rᵏ are independently selected from hydrogen and methyl; R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² and R¹³ are independently selected from a natural amino acid side chain and an unnatural amino acid side chain or form a ring with the group Corresponding next R, as described below; Rᵉ and Rᵏ can each form a ring with the corresponding nearby R group and the atoms to which they are attached, selected from azetidine, pyrolidine, morpholine, piperidine, piperazine and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo and hydroxy; Rᵇ is methyl, or Rᵇ and R², together with the atoms to which they are attached, form a ring selected from azetidine, pyrolidine, morpholine, piperidine, piperazine and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo and hydroxy; Rᵈ is hydrogen or methyl, or Rᵈ and R⁴, together with the atoms to which they are attached, can form a ring selected from azetidine, pyrolidine, morpholine, piperidine, piperazine and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, hydroxy and phenyl; Rᵍ is hydrogen or methyl, or Rᵍ and R⁷, together with the atoms to which they are attached, can form a ring selected from azetidine, pyrolidine, morpholine, piperidine, piperazine and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, benzyl optionally substituted with a halo, benzyloxy, cyano, cyclohexyl, methyl, halo, hydroxy, isoquinolinyloxy group optionally substituted with a methoxy group, quinolinyloxy optionally substituted with a halo group, and tetrazolyl; and wherein the pyrrolidine and piperidine rings are optionally fused with a cyclohexyl, phenyl or indole group; and Rˡ is methyl, or Rˡ and R¹², together with the atoms to which they are attached, form a ring selected from azetidine and pyrolidine, where each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo and hydroxy. Claim 26: A method for improving, stimulating and / or increasing the immune response in a subject in need thereof, characterized in that it comprises administering to the subject a therapeutically effective amount of a compound according to claim 1 or a therapeutically acceptable salt thereof. Claim 31: A method of inhibiting the growth, proliferation or metastasis of cancer cells in a subject in need thereof, characterized in that it comprises administering to the subject a therapeutically effective amount of a compound according to claim 1 or a therapeutically salt thereof. acceptable. Claim 34: The method according to claim 33, characterized in that the infectious disease is caused by a virus.

ARP150103712A 2014-11-14 2015-11-13 IMMUNOMODULATORS AR102651A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201462079944P 2014-11-14 2014-11-14

Publications (1)

Publication Number Publication Date
AR102651A1 true AR102651A1 (en) 2017-03-15

Family

ID=58688528

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP150103712A AR102651A1 (en) 2014-11-14 2015-11-13 IMMUNOMODULATORS

Country Status (2)

Country Link
AR (1) AR102651A1 (en)
MA (1) MA40303B1 (en)

Also Published As

Publication number Publication date
MA40303B1 (en) 2020-01-31
MA40303A1 (en) 2018-08-31

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