AR039555A1 - Derivados n,n'-sustituidos de 1,3-diamino-2-hidroxipropano - Google Patents
Derivados n,n'-sustituidos de 1,3-diamino-2-hidroxipropanoInfo
- Publication number
- AR039555A1 AR039555A1 ARP020104299A ARP020104299A AR039555A1 AR 039555 A1 AR039555 A1 AR 039555A1 AR P020104299 A ARP020104299 A AR P020104299A AR P020104299 A ARP020104299 A AR P020104299A AR 039555 A1 AR039555 A1 AR 039555A1
- Authority
- AR
- Argentina
- Prior art keywords
- group
- oxide
- alkoxy
- optionally substituted
- alkyl
- Prior art date
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
- C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/36—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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- C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/40—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C07C233/78—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
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- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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- C07C235/50—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
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- C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
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- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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Abstract
Estos compuestos tienen actividad como inhibidores de la b-secretasa y, en consecuencia, son útiles para el tratamiento de varios trastornos como el mal de Alzheimer. Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable de los mismos, donde R1 es: (I) alquilo C1-6, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en alquilo C1-3, cicloalquilo C1-8 (opcionalmente sustituido por alquilo C1-3 y alcoxi C1-3), -F, -Cl, -Br, -I, -OH, -SH, -CsN, -CF3, alcoxi C1-3, -NR1-aR1-b, y -OC=O-NR1-aR1-b, donde R1-a y R1-b son, independientemente en cada caso, -H ó alquilo C1-6, (II) -CH2-S(O)0-2-(alquilo C1-6), (III) -CH2-CH2-S(O)0-2-(alquilo C1-6), (IV) alquenilo C2-6 con uno ó dos enlaces dobles, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, -NR1-aR1-b donde R1-a y R1-b son -H ó alquilo C1-6, (V) alquinilo C2-6 con uno ó dos enlaces triples, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, -NR1-aR1-b donde R1-a y R1-b son -H ó alquilo C1-6, (VI) -(CH2)n1-(R1-arilo) donde n1 es cero ó uno y donde R1-arilo es fenilo, naftilo, indanilo, indenilo, dihidronaftilo, ó tetralinilo cada uno de los cuales está opcionalmente sustituido por uno, dos, tres, cuatro, ó cinco de los siguientes sustituyentes en el anillo arilo: (A) alquilo C1-6 opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en alquilo C1-3, -F, -Cl, -Br, -I, -OH, -SH, -NR1-aR1-b, -CsN, -CF3, y alcoxi C1-3, (B) alquenilo C2-6 opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y NR1-aR1-b, (C) alquinilo C2-6 opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (D) -F, Cl, -Br e -I, (E) haloalcoxi C1-6, (F) alcoxi C1-6, (G) -NRN-2RN-3, (H) -OH, (I) -CsN, (J) cicloalquilo C3-7, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (K) -CO-(alquilo C1-4), (L) -SO2-NR1-aR1-b, (M) -CO-NR1-aR1-b, (N) -SO2-(alquilo C1-4), (VII) -(CH2)n1-(R1-heteroarilo), donde R1-heteroarilo está seleccionado del grupo que consiste en piridinilo, pirimidinilo, quinolinilo, benzotienilo, indolilo, indolinilo, piridazinilo, pirazinilo, isoindolilo, isoquinolilo, quinazolinilo, quinoxalinilo, ftalazinilo, imidazolilo, isoxazolilo, pirazolilo, oxazolilo, tiazolilo, indolizinilo, indazolilo, benzotiazolilo, bencimidazolilo, benzofuranilo, furanilo, tienilo, pirrolilo, oxadiazolilo, tiadiazolilo, triazolilo, tetrazolilo, oxazolopiridinilo, imidazopiridinilo, isotiazolilo, naftiridinilo, cinnolinilo, carbazolilo, beta-carbolinilo, isocromanilo, cromanilo, tetrahidroisoquinolinilo, isoindolinilo, isobenzotetrahidrofuranilo, isobenzotetrahidrotienilo, isobenzotienilo, benzoxazolilo, piridopiridinilo, benzotetrahidrofuranilo, benzotetrahidrotienilo, purinilo, benzodioxolilo, triazinilo, fenoxazinilo, fenotiazinilo, pteridinilo, benzotiazolilo, imidazopiridinilo, imidazotiazolilo, dihidrobencisoxazinilo, bencisoxazinilo, benzoxazinilo, dihidrobencisotiazinilo, benzopiranilo, benzotiopiranilo, cumarinilo, isocumarinilo, cromonilo, cromanonilo, tetrahidroquinolinilo, dihidroquinolinilo, dihidroquinolinonilo, dihidroisoquinolinonilo, dihidrocumarinilo, dihidroisocumarinilo, isoindolinonilo, benzodioxanilo, benzoxazolinonilo, piridinilo N-óxido, pirrolilo N-óxido, pirimidinilo N-óxido, piridazinilo N-óxido, pirazinilo N-óxido, quinolinilo N-óxido, indolilo N-óxido, indolinilo N-óxido, isoquinolilo N-óxido, quinazolinilo N-óxido, quinoxalinilo N-óxido, ftalazinilo N-óxido, imidazolilo N-óxido, isoxazolilo N-óxido, oxazolilo N-óxido, tiazolilo N-óxido, indolizinilo N-óxido, indazolilo N-óxido, benzotiazolilo N-óxido, bencimidazolilo N-óxido, pirrolilo N-óxido, oxadiazolilo N-óxido, tiadiazolilo N-óxido, triazolilo N-óxido, tetrazolilo N-óxido, benzotiopiranilo S-óxido, y benzotiopiranilo S,S-dióxido, donde el grupo R1-heteroarilo está enlazado con -(CH2)n1- mediante cualquier átomo del anillo del grupo RN-heteroarilo principal sustituido por hidrógeno, de modo tal que el nuevo enlace con el grupo R1-heteroarilo reemplace el átomo de hidrógeno y su enlace, donde el heteroarilo está opcionalmente sustituido por uno, dos, tres, cuatro, ó cinco de: (1) alquilo C1-6 opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en alquilo C1-3, -F, -Cl, -Br, -I, -OH, -SH, -NR1-aR1-b, -CsN, -CF3, y alcoxi C1-3, (2) alquenilo C2-6 con uno ó dos enlaces dobles, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y NR1-aR1-b, (3) alquinilo C2-6 con uno ó dos enlaces triples, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (4) -F, -Cl, -Br y -I, (5) haloalcoxi C1-6, (6) alcoxi C1-6, (7) -NRN-2RN-3, (8) -OH, (9) -CsN, (10) cicloalquilo C3-7, opcionalmente sustituido por uno, dos ó tres sustituyentes independientemente seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (11) -CO-(alquilo C1-4), -SO2-NR1-aR1-b, (13)-CO-NR1-aR1-b, (14) -SO2-(alquilo C1-4), con la condición de que, cuando n1 es cero, R1-heteroarilo no está enlazado con la cadena de carbonos por medio del nitrógeno, (VIII) -(CH2)n1-(R1-heterociclo) donde n1 es tal como se definió con anterioridad y R1-heterociclo está seleccionado del grupo que consiste en morfolinilo, tiomorfolinilo, tiomorfolinilo S-óxido, tiomorfolinilo S,S-dióxido, piperazinilo, homopiperazinilo, pirrolidinilo, pirrolinilo, tetrahidropiranilo, piperidinilo, tetrahidrofuranilo, tetrahidrotienilo, homopiperidinilo, homomorfolinilo, homotiomorfolinilo, homotiomorfolinilo S,S-dióxido, oxazolidinonilo, dihidropirazolilo, dihidropirrolilo, dihidropirazinilo, dihidropiridinilo, dihidropirimidinilo, dihidrofurilo, dihidropiranilo, tetrahidrotienilo S-óxido, tetrahidrotienilo S,S-dióxido, homotiomorfolinilo S-óxido, ditianilo, piranilo, dihidrofuranilo, pirrolidinonilo, imidazolidinonilo, imidazolidinondionilo, donde cada uno de los anteriores está fusionado opcionalmente con un anillo de benceno, piridina o pirimidina, y donde el grupo R1-heterociclo está enlazado con cualquier átomo del grupo R1-heterociclo principal sustituido por hidrógeno, de modo tal que el nuevo enlace con el grupo R1-heterociclo reemplaza el átomo de hidrógeno y su enlace, donde el heterociclo está opcionalmente sustituido por uno, dos, tres ó cuatro: (1) alquilo C1-6 opcionalmente sustituido con uno, dos ó tres sustituyentes independientemente seleccionados del grupo que consiste en alquilo C1-3, -F, -Cl, -Br, -I, -OH, -SH, -NR1-aR1-b, -CsN, -CF3, y alcoxi C1-3, (2) alquenilo C2-6 opcionalmente sustituido con uno, dos ó tres sustituyentes seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, -NR1-aR1-b, (3) alquinilo C2-6 opcionalmente sustituido con uno, dos ó tres sustituyentes independientemente seleccionados del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y NR1-aR1-b, (4) -F, -Cl, -Br y -I, (5) alcoxi C1-6, (6) haloalcoxi C1-6, (7) -NRN-2RN-3, (8) -OH, (9) -CsN, (10) cicloalquilo C3-7, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en -F, -Cl, -OH, -SH, -CN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (11) -CO-(alquilo C1-4), (12) -SO2-NR1-aR1-b, (13) -CO-NR1-aR1-b, (14) -SO2-(alquilo C1-4), (15) =O, con la condición de que, cuando n1 es cero, R1-heterociclo no está enlazado con la cadena de carbonos por medio del nitrógeno; donde R2 está seleccionado del grupo que consiste en: (I) -H, (II) alquilo C1-6, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en alquilo C1-3, -F, -Cl, -Br, -I, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (III) -(CH2)0-4-R30, donde R30 es R1-arilo, R1-heteroarilo, ó R1-heterociclo, (IV) alquenilo C2-6 con uno ó dos enlaces dobles, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (V) alquinilo C2-6 opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y NR1-aR1-b, (VI) -(CH2)0-4-cicloalquilo C3-7, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, donde R3 está seleccionado del grupo que consiste en: (I) -H, (II) alquilo C1-6, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados del grupo que consiste en alquilo C1-3, -F, -Cl, -Br, -I, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, (III) -(CH2)0-4-R30, (IV) alquenilo C2-6, (V) alquinilo C2-6, (VI) -(CH2)0-4-cicloalquilo C3-7, opcionalmente sustituido por uno, dos ó tres sustituyentes seleccionados independientemente entre sí del grupo que consiste en -F, -Cl, -OH, -SH, -CsN, -CF3, alcoxi C1-3, y -NR1-aR1-b, ó R2 y R3 se toman juntos con el átomo de carbono al que están unidos para formar un carbociclo de tres, cuatro, cinco, seis, y siete átomos de carbono, donde opcionalmente un átomo de carbono está reemplazado por un heteroátomo seleccionado del grupo que consiste en -O-, -S-, -SO2-, -NRN-2-; RN es: (I) RN-1-XN-donde XN está seleccionado del g
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PCT/US2002/036072 WO2003040096A2 (en) | 2001-11-08 | 2002-11-08 | N, n'-substituted-1,3-diamino-2-hydroxypropane derivatives |
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CO5640093A2 (es) | 2006-05-31 |
ECSP045100A (es) | 2006-06-27 |
EP1453789A2 (en) | 2004-09-08 |
GEP20074171B (en) | 2007-07-25 |
AU2002359376B8 (en) | 2003-05-19 |
KR20050044407A (ko) | 2005-05-12 |
BR0214035A (pt) | 2005-04-26 |
TNSN04082A1 (en) | 2006-06-01 |
OA12846A (en) | 2006-09-15 |
NZ533107A (en) | 2007-04-27 |
EA200400648A1 (ru) | 2005-04-28 |
US20070213316A1 (en) | 2007-09-13 |
IL161881A0 (en) | 2005-11-20 |
US20040171881A1 (en) | 2004-09-02 |
WO2003040096A2 (en) | 2003-05-15 |
RS50504A (en) | 2007-04-10 |
IL161881A (en) | 2011-01-31 |
JP2005520791A (ja) | 2005-07-14 |
US7727997B2 (en) | 2010-06-01 |
CA2466284A1 (en) | 2003-05-15 |
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