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PE20231987A1 - Inhibidores de molecula pequena de la funcion de slc6a19 de mamifero - Google Patents

Inhibidores de molecula pequena de la funcion de slc6a19 de mamifero

Info

Publication number
PE20231987A1
PE20231987A1 PE2023002500A PE2023002500A PE20231987A1 PE 20231987 A1 PE20231987 A1 PE 20231987A1 PE 2023002500 A PE2023002500 A PE 2023002500A PE 2023002500 A PE2023002500 A PE 2023002500A PE 20231987 A1 PE20231987 A1 PE 20231987A1
Authority
PE
Peru
Prior art keywords
alkyl
slc6a19
absent
cycloalkyl
mammal
Prior art date
Application number
PE2023002500A
Other languages
English (en)
Inventor
Dean G Brown
Jaclyn L Henderson
Giovanni Muncipinto
Joshua E Zweig
Long V Nguyen
Nicholas Pullen
Mitchell T Antalek
Ryan A Hollibaugh
Original Assignee
Jnana 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 Jnana Therapeutics Inc filed Critical Jnana Therapeutics Inc
Publication of PE20231987A1 publication Critical patent/PE20231987A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • C07D401/02—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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • 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
    • C07D211/36—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
    • C07D211/56—Nitrogen atoms
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    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A—HUMAN NECESSITIES
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    • A61K31/445—Non condensed piperidines, e.g. piperocaine
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    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • 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
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    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • 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
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Abstract

Esta referido a un compuesto de Formula I, en donde n es 0, 1, o 2; L1 esta ausente o es alquilo, hidroxialquilo, cicloalquilo, heteroaril-CH2-; L2 esta ausente o es -CH2-; L3 esta ausente o es -C(O)-; X1 y X2 son H, alquilo, haloalquilo, cicloalquilo, alquil-cicloalquilo, heterociclilo; Y1 es arilo, heteroarilo; Y2 es alquilo, alquenilo, alquinilo, alcoxi, entre otros; Y3, Y4, Y5 son H, OH, haluro, alquilo, entre otros. Entre los compuestos preferidos tenemos los siguientes: 3-[(4-cloro-2-fluoro-5-metilfenil)metil]-1-ciclopropil-1-[(3R)-1-(piridazin3-il)piperidin-3-il]urea; 1-ciclopropil-3-[(3-fenil-1,2-oxazol-5- il)metil]-1-[(3R)-1-(piridazin-3- il)piperidin-3-il]urea; entre otros. Estos compuestos modulan el transporte de SLC6A19 y se emplean para tratar o prevenir una enfermedad o trastorno asociado con un defecto genetico en la fenilalanina hidroxilasa como fenilcetonuria, hiperfenilalaninemia, tirosinemia, hiperglicinemia no cetosica, entre otras.
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