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AR095339A1 - Compuestos moduladores alostericos de la hemoglobina - Google Patents

Compuestos moduladores alostericos de la hemoglobina

Info

Publication number
AR095339A1
AR095339A1 ARP140101043A ARP140101043A AR095339A1 AR 095339 A1 AR095339 A1 AR 095339A1 AR P140101043 A ARP140101043 A AR P140101043A AR P140101043 A ARP140101043 A AR P140101043A AR 095339 A1 AR095339 A1 AR 095339A1
Authority
AR
Argentina
Prior art keywords
optionally substituted
alkyl
ring
independently
aryl
Prior art date
Application number
ARP140101043A
Other languages
English (en)
Inventor
Li Zhe
L Gwaltney Stephen
Xu Qing
Original Assignee
Global Blood Therapeutics 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 Global Blood Therapeutics Inc filed Critical Global Blood Therapeutics Inc
Publication of AR095339A1 publication Critical patent/AR095339A1/es

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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
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    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur atoms
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
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    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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    • 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
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
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    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
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    • 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
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    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D335/02—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
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    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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  • General Health & Medical Sciences (AREA)
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  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
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Abstract

Reivindicación 1: Un compuesto de fórmula (1) o uno de sus tautómeros o sal farmacéuticamente aceptable de cada uno de ellos o una sal farmacéuticamente aceptable de ellos, donde: R³ es alquilo C₁₋₆, cicloalquilo C₃₋₈, alcoxi C₁₋₆, cicloalcoxi C₃₋₈ o -NR¹R²; cada R¹ y R² es, independientemente, hidrógeno, alquilo C₁₋₆, cicloalquilo C₃₋₈, arilo C₆₋₁₀, un heterociclo de 4 - 10 miembros o heteroarilo de 5 - 10 miembros y cada uno comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, donde cada alquilo, cicloalquilo, heterociclo, arilo o heteroarilo está opcionalmente sustituido, o R¹ y R² junto con el átomo de nitrógeno al que están unidos forman un heterociclo de 4 - 7 miembros opcionalmente sustituido; o R³ es arilo C₆₋₁₀, o un heteroarilo de 5 - 10 miembros, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, donde cada arilo o heteroarilo está opcionalmente sustituido por 1 - 4 alquilo C₁₋₆; L¹ es un enlace o es NR⁷⁰, O, S, o (CR⁷¹R⁷²)ᵈ; donde cada R⁷⁰, R⁷¹, y R⁷² es, independientemente, hidrógeno o alquilo C₁₋₆; d es 1, 2 ó 3: L² es C=O o SO₂; el anillo B es arilo C₆₋₁₀ opcionalmente sustituido, un heteroarilo de 5 - 10 miembros opcionalmente sustituido que tiene de 1 - 3 átomos de nitrógeno o formas oxidadas de N, o un heterociclo de 4 - 10 miembros opcionalmente sustituido que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S; o el anillo B es un heterociclo de 4 - 10 miembros opcionalmente sustituido que contiene hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S y formas oxidadas de N y S; cada Y y Z es, independientemente, CR¹⁰R¹¹, O, S, SO, SO₂, o NR¹⁰; cada R¹⁰ y R¹¹ es, independientemente, hidrógeno o alquilo C₁₋₃ opcionalmente sustituido por 1 - 3 halo, OH, o alcoxi C₁₋₆ o CR¹⁰R¹¹ es C=O, siempre y cuando, si uno de Y y Z es O, S, SO, SO₂, entonces el otro no es CO, e Y y Z ambos no son heteroátomos o formas oxidadas de ellos; donde Y es a o b sustituido con respecto a -L¹L²R³; donde Z y CV¹V²H se unen a los átomos adyacentes en el anillo C; el anillo C es un arilo C₆₋₁₀ opcionalmente sustituido o un heteroarilo de 5 - 10 miembros opcionalmente sustituido que comprende de 1 - 3 átomos de nitrógeno o una forma oxidada de N; o el anillo C es arilo C₆₋₁₀ o un heteroarilo de 5 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S, cada uno de los cuales está opcionalmente sustituido por 1 - 4 halo, oxo, -OR¹⁹, alquilo C₁₋₆, y/o alcoxi C₁₋₆, donde el alquilo C₁₋₆ está opcionalmente sustituido por 1 - 5 halo, alcoxi C₁₋₆ y/o un heterociclo de 4 - 10 miembros que comprende hasta 5 heteroátomos en el anillo, donde el heteroátomo se selecciona entre el grupo que comprende O, N, S, y formas oxidadas de N y S; y R¹⁹ es hidrógeno o una parte del profármaco R; V¹ y V² son, independientemente, alcoxi C₁₋₆; o V¹ y V² junto con el átomo de carbono al que están unidos forman un anillo de fórmula (2), en la cual cada V³ y V⁴ son, independientemente, O, S, o NH, siempre que cuando uno de V³ y V⁴ es S, el otro sea NH, y siempre que V³ y V⁴ ambos no sean NH; q es 1 ó 2; cada V⁵ es, independientemente, alquilo C₁₋₆ o CO₂R⁶⁰, donde cada R⁶⁰ es, independientemente, alquilo C₁₋₆ o hidrógeno; t es 0, 1, 2, ó 4; o CV¹V² es C=V, donde V es O, NOR⁸⁰, o NNR⁸¹R⁸²; R⁸⁰ es alquilo C₁₋₆ opcionalmente sustituido; R⁸¹ y R⁸² se seleccionan, independientemente, entre el grupo que comprende hidrógeno, alquilo C₁₋₆ opcionalmente sustituido, COR⁸³ y CO₂R⁸⁴; R⁸³ es hidrógeno o alquilo C₁₋₆ opcionalmente sustituido; y R⁸⁴ es alquilo C₁₋₆ opcionalmente sustituido.
ARP140101043A 2013-03-15 2014-03-14 Compuestos moduladores alostericos de la hemoglobina AR095339A1 (es)

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BR112015021986A2 (pt) 2013-03-15 2017-07-18 Global Blood Therapeutics Inc compostos e seus usos para a modulação de hemoglobina
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US9776960B2 (en) 2017-10-03
US20140275008A1 (en) 2014-09-18
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US10315991B2 (en) 2019-06-11

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