ECSP034709A - Derivados de eteres utiles como agentes inhibidores de las isozimas pde4 - Google Patents
Derivados de eteres utiles como agentes inhibidores de las isozimas pde4Info
- Publication number
- ECSP034709A ECSP034709A EC2003004709A ECSP034709A ECSP034709A EC SP034709 A ECSP034709 A EC SP034709A EC 2003004709 A EC2003004709 A EC 2003004709A EC SP034709 A ECSP034709 A EC SP034709A EC SP034709 A ECSP034709 A EC SP034709A
- Authority
- EC
- Ecuador
- Prior art keywords
- alkyl
- substituted
- nr22a
- nr16r17
- nhs
- Prior art date
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- 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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Abstract
Compuestos útiles como inhibidores de las PDE en el tratamiento de enfermedades reguladas por la activación y desgranulación de eosonofilos, especialmente asma, bronquitis crónica y enfermedad pulmonar obstructiva crónica, de la fórmula (gráfico) en la que j es 0 ó 1, con la condición de que cuando j es 0, n debe ser 2; k es 0 ó 1; m es 1,2ó 3; n es 1 ó 2; W1 y W2 son -0-0; -S(=O),-. en que t es 0 , 1 ó 2, ó,N(R3)-; Y es =C(R1a)-ó-[N (O)k-en que k es 0 ó 1; R1a es -H, - F, -CI, -CN, -N=2, alquilo (C1 -C4), alquinilo (C2-C4). alquilo (C1-C3) Fluorado, alcoxi (C1-C3) fluorado, - OR16, ó -C(=o= NR22a R22b; R y RB son -H, -F. -CF3, alquilo (c1-C4), cicloalquilo (C3-C7), fenilo ó bencilo sustituido con 0-3 R10; ó RA y RB se toman juntos paraformar un resto espiro en que r y s son 0-4 con la condición de que r + s ha de ser >1 pero no > 5; XA es -CH2-, -CHF, -CF2, -NR15-. -0-, ó -S(=Oh-, en que t es 0,1; Rc y RD son los mismos que RA y RB excepto que uno de ellos debe ser -H; R1 yR2 son -H, -F, -CI, -CN, -N02, alquilo (C1-C4). alquilo (C1-C4), alquilo (C1-C3) fluorado, -OR16 ó -C(=0) NR22a R22b; R3 es -H, alquilo (C1-C4) fenilo, bencilo ó -OR16; R4, R5 y R6 son (a) -H, -F, -CI, alquilo (C2-C4) -R16, OR16. -S(=0)p R16, -S(0)R16, -OC(=0)OR16, -OC(=0)R16, -CN _NO2 -C (=0)NR16R17 -C (=0)NR16R17 -NR22 aC (=0)NR16R17 -NR22 aC(=NR12)NR16R17, - NR22aC(=NCN)NR16R17, -NR22aC(=N-N02)NR'6R'7 -C(=NR22a)NR16R'7, -CH2C(=NR22a) NR'6R'7, -OC(=NR22a)NR16R17, -OC(=N-N02)N R16R17, -NR16R17, CH2N R16R17, -NR22aC(=O)R16.-NR22aC(=O)OR16, -NR22aS(=O)R17, -S(=O)pN R16 R17; ó -CH2C(=NR22a)NR16 R17; en que p es 0,1ó 2; (b) alquilo (C1-C4) o alcoxi (C1-C4) sustituido con 0-3 de -F ó -CI; o 0 ó 1 de alcoxi (C1-C2)-carbonilo, alquil (C1-C2) -carbonilo ó alquil (C1-C2) -carboniloxi; ó (c) fenilo, bencilo. furanilo, tetrahidrofuranilo, oxetanilo, tienilo, tetrahidrotienilo, pirrolilo, pirrolidinilo, oxazolilo, oxazolidinilo, isoxazolilo, isoxazolidinilo, tiazolilo, tiazolidinilo, isotiazolilo, isotiaozolidinilo, isotiazolilo, isotiazolidinilo, pirazolilo, pirazolidinilo, oxadiazolilo, tiadiazolilo, imidazolilo, imidazolidinilo, piridinilo, pirazinilo, pirimidinilo, ptridazinilo, piperidinilo, piperazinilo, triazolilo, trizinilo, tetrazolilo, piranilo, azetidinilo, morfoliniJo, paratiazinilo, indolilo, indolinilo, benzo [b] furanilo, 2,3 -dihidro-benzofuranilo, 2- h-cromenilo, cromanilo, benzotienilo, 1-H-indazolilo, bencimidazolilo, benzoxazolilo, benzoisoxazolilo, benzotiazolilo, benzotiazolilo, quinolinilo, isoquinolinilo, fta 1 azinilo, quinazolinilo, quinoxalinilo ó purinilo, todos ellos sustituidos con 0-2 de R14, 0 (d) R5 y R6 se toman conjuntamente para formar un resto de fórmulas parciales (1.3.1) hasta (1.3.15), D es un grupo de fórmular parciales (1.1.1.) hasta (1.1.9.): (gráfico) en que es 1-3, con la condición de que cuando q es 2 ó 3, R9 ha de ser -H; v es 0-1; W3 es -0-, -N(R9)- ó -OC(=O)-; R7 es (a) -H; (b) alquilo (C1-C6), alquenilo (C2-C6) ó alquinilo (C2-C6), Todos ellos sustituidos con 0-3 de R10; (c) -(CH2)u-cicloalquilo (C3-C7) en que u es 0-2, sustituido con 0-3 de R10; o (d) fenilo o bencilo sustituido con 0-3 de R10; R8 es (a) tetrazol-5-ilo, 1,2,4-triazol-3-ilo, 1,2,3-triazol-3-on-5-ilo, 1,2,3-triazol-5-ilo, imidazol-2-ilo, imidazol-4-ilo, imidazol-4-ilo, imidazolidin-2-2on-4ilo, 1,2,4-oxadiazol-3-ilo, 1,2,4- oxadiazol- 5-on-3-ilo, 1,2,4-ozadiazol-3-on-5-ilo, 1,3,4-oxadiazolilo, 1,3,4-oxadiazol-2-on-5-ilo, oxazolilo, isoxazolilo, pirrolilo, pirazolilo, succinimidilo, glutarimidilo, pirrolidonilo, 2-piridonilo, 4-piridonilo, piridazin-3-onilo, tiadiazolilo, paratiazinilo; (b) indolilo, indolinilo, isoindolinilo, benzo [b] furanilo, 2,3-dihidro-benzofuranilo, 2-H-cromenilo, cromanilo, benzotienilo, 1 H-indazolilo,bencimidazolilo, benzoxazolilo, benzoisoxazolilo, benzotiazolilo, benzotriazolilo, benzotriazinilo, quinazolinilo, quinoxalinilo, pirazolo [3,4-d] pirimidinilo, pirimido [4,5-d]pirimidinilo, imidazo [1,2-a] piridinilo, pirido-piridinilo, pteridinilo ó purinilo, todos ellos opcionalmente sustituidos en un átomo de carbono con R14, en un átomo de nitrógeno con R15 y todas sus formas tautómeras, ó en un átomo azufre con 0-2 átomos de oxígeno; R9 es -H, alquilo (C1-C4), cicloalquilo (C3-C7), fenilo, bencilo, - (C=O)OR16, -C(=O)R16, OR16, alquil (C1-C2)-OR16 ó alquil (C1-C2)-OR16 ó alquil (C1-C2)-C(=O)OR16;ó (c) -O-P(=O)(OHh (fosfórico), -PH(=O)OH (fosfinico), -P(=O)(OHh (fosfónico), [P(=O)(OH)-O-alquilo (C1-C4)] (alquilo-fosfono), -P(=O) (OH)-O-alquilo (C1-C4) (alquil-fosfinilo), -P(=O(OH)NH2 (fosforamido), -P (=O) (OH)NHR25 (fosforamido sustituido), -O-S(=O)2OH (sulfurico), -S(=O)2OH (sulfónico), -S(=O)2NHR26 ó -NHS(=O)2R26 (sulfonamido) en que R26 es -CH#, CF3, u otoluilo, y acil-sulfonamido seleccionado entre el grupo que consta de -C(=O)NHS(=O)2R25, -C(=O)NHS(=O)2NH2, -C(=O)NHS(=O)2-alquilo (C1-C4), -C(=O)NHS(=O)2NH-alquilo (C1-C4), -C(=O)NHS(=O)2N[alquilo (C1-C4)2 -S(=O)2NHC(=O)alquilo (1-C4). -S(=O)2NHC(=O)NH2, -S(=O)2 NHC(=O)NH-alquilo (C1-C4), -S(O)2NHC(=O)N[alquilo (C1-C4)]2, -S(=O)2 NHC(=O)R25, -S(=O)2 NHCN, -S(=O2)NHC{=S)NH2, -S(=OhNHC(=S)NH-alquilo (C1-C4), -S(=O)2 NHC(=S)N[alquilo(C1-C4)2, ó -S(O)2 NHS(=O)2R25, en que R25 es _H, -alquilo (C1-C4), fenilo ó -OR16; J1 y J2 son un resto que comprende un sistema anular de carbonos saturado ó insaturado que es monocíclico de 3 a 7 miembros, ó que es policiclico condesado ó discontinuo de 7 a 12 miembros; en que opcionalmente un átomo de carbono de dicho sistema anular de carbonos puede ser reeempazado por un heeroátomo seleccionado entre N, O y S; y cuando se selecciona N, opcionalmente un segundo átomo de carbono de este puede ser reemplazado por un heteroátomo seleccionado entre N, ó y S; 0 una sal farmacéuticamente aceptable de este.
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- 2003-07-17 CR CR7025A patent/CR7025A/es not_active Application Discontinuation
- 2003-07-21 MA MA27241A patent/MA26983A1/fr unknown
- 2003-07-28 BG BG108038A patent/BG108038A/xx unknown
- 2003-07-30 NO NO20033397A patent/NO20033397L/no not_active Application Discontinuation
- 2003-07-31 EC EC2003004710A patent/ECSP034710A/es unknown
- 2003-07-31 EC EC2003004709A patent/ECSP034709A/es unknown
Also Published As
Publication number | Publication date |
---|---|
US20040048903A1 (en) | 2004-03-11 |
IL156413A0 (en) | 2004-01-04 |
ZA200304894B (en) | 2004-06-24 |
CZ20031895A3 (cs) | 2004-08-18 |
CN1518542A (zh) | 2004-08-04 |
EP1355884A1 (en) | 2003-10-29 |
KR20030074761A (ko) | 2003-09-19 |
WO2002060875A8 (en) | 2003-07-31 |
CR7025A (es) | 2003-11-25 |
CA2436535A1 (en) | 2002-08-08 |
OA12540A (en) | 2006-06-05 |
NZ526453A (en) | 2005-01-28 |
JP2004520386A (ja) | 2004-07-08 |
MXPA03006887A (es) | 2003-11-13 |
HUP0400637A2 (hu) | 2004-06-28 |
US20020193612A1 (en) | 2002-12-19 |
US6953810B2 (en) | 2005-10-11 |
EA200300621A1 (ru) | 2003-12-25 |
ECSP034710A (es) | 2003-09-24 |
SK8792003A3 (en) | 2004-09-08 |
IS6846A (is) | 2003-06-16 |
US6649633B2 (en) | 2003-11-18 |
WO2002060875A1 (en) | 2002-08-08 |
NO20033397D0 (no) | 2003-07-30 |
MA26983A1 (fr) | 2004-12-20 |
NO20033397L (no) | 2003-09-19 |
BG108038A (en) | 2004-07-30 |
PL364135A1 (en) | 2004-12-13 |
BR0116852A (pt) | 2004-02-25 |
EE200300360A (et) | 2003-12-15 |
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