ES2270438T3 - Derivados amino biciclicos y agonista de pgd2 que contienen los mismos. - Google Patents

Derivados amino biciclicos y agonista de pgd2 que contienen los mismos. Download PDF

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ES2270438T3
ES2270438T3 ES96918841T ES96918841T ES2270438T3 ES 2270438 T3 ES2270438 T3 ES 2270438T3 ES 96918841 T ES96918841 T ES 96918841T ES 96918841 T ES96918841 T ES 96918841T ES 2270438 T3 ES2270438 T3 ES 2270438T3
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meoh
no2a
chcl
300mhz
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Mitsuaki Ohtani
Akinori Arimura
Tatsuo Tsuri
Junji Kishino
Tsunetoshi Honma
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Shionogi and Co Ltd
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Shionogi and Co Ltd
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Abstract

SE PRESENTA UN COMPUESTO DE FORMULA (I): DONDE ES O POR EJEMPLO, EL COMPUESTO REPRESENTADO DEBAJO: DONDE R SUB,1} ES CH SUB,3}, H O NA; Y X1 - X2 - X3 ES O UNA SAL O HIDRATO DEL MISMO, ES UTIL COMO ANTAGONISTA DE PGD SUB,2} Y SE PUEDE UTILIZAR COMO MEDICAMENTO PARA EL TRATAMIENTO DE ENFERMEDADES EN LAS CUALES ESTA IMPLICADA UNA DISFUNCION DE UNA CELULA CEBADA, POR EJEMPLO, MASTOCITOSIS SISTEMICA Y ALTERACION DE LA ACTIVACION DE LAS CELULAS CEBADAS SISTEMICAS, ASI COMO CONTRACCION TRAQUEAL, ASMA, RINITIS ALERGICA, CONJUNTIVITIS ALERGICA, URTICARIA, LESION DEBIDA A REPERFUSION ISQUEMICA Y TAMBIEN COMO AGENTE ANTIINFLAMATORIO. DICHO COMPUESTO ES ESPECIALMENTE UTIL PARA EL TRATAMIENTO DE LA OCLUSION NASAL.

Description

Derivados amino bicíclicos y agonista de PGD_{2} que contienen los mismos.
Campo de la invención
La presente invención se refiere a derivados amino bicíclicos y agonista de prostaglandina D_{2} (en adelante denominada PDG_{2}) que los contienen.
Antecedentes de la invención
Se sabe que algunos derivados amino bicíclicos son útiles como antagonistas de tromboxano A_{2} (TXA_{2}) (publicación de patente japonesa Nº JP63-139161). No obstante, la publicación de patente japonesa Nº JP 63-139161 describe únicamente los compuestos como útiles como antagonistas de TXA_{2}, y no sugiere su utilidad como antagonistas de PDG_{2}.
En concreto, se sabe que TXA_{2} posee actividades, como por ejemplo acción contra la aglutinación de plaquetas, trombogenesis, etc. Por consiguiente, se ha considerado que el antagonista de TXA_{2} es útil como agente anti-trombótico, y también en el tratamiento de infarto de miocardio o asma por antagonización contra TXA_{2}.
En EP-A-608847 se describen sulfonamidas carbocíclicas como agonistas o antagonistas de PGEZ.
EP-A-312906 describe derivados de sulfonamida, que se pueden utilizar como antagonistas TXA_{2}.
EP-A-0226346 describe derivados de sulfonamida bicíclicos que se pueden utilizar como fármacos antitrombóticos, anti-vasoconstrictores y anti-broncoconstrictores.
EP-A-0150709 describe análogos de 7-oxabicicloheptano prostaglandina como agentes cardiovasculares, que son útiles en el tratamiento de enfermedad trombolítica.
EP-A-0290285 describe derivados de sulfonamida bicílicos y su uso en el tratamiento de enfermedades como angina de pecho, infarto de miocardio e infarto cerebral.
En Int. Arc. Allergy Immunol. (1992) 98, 239-246, Arimura y cols., "Antiasthmatic Activity of a Novel Thromboxane A2 Antagonist, S-1452, in Guinea Pigs" (XP 00 291 6327) se describe un antagonista de receptor TXA_{2}, "S-1452".
Por otra parte, el antagonista de PGD_{2} de la presente invención es útil para mejorar estados patológicos debidos a una producción excesiva de PGD_{2}. Específicamente, es útil como fármaco para el tratamiento de enfermedades en las que participa una disfunción de la célula cebadora, como por ejemplo, mastocitosis sistémica y trastorno de la activación de célula cebadora sistémica, así como contracción traqueal, asma, rinitis alérgica, conjuntivitis alérgica, urticaria, lesión como consecuencia de reperfusión isquémica e inflamación.
Tal como se puede deducir de lo anterior, el antagonista TXA_{2} y el antagonista de PGD_{2} son completamente diferentes entre sí en lo que se refiere a los sitios activos, el mecanismo de acción, y aplicación, y además tienen características bastante diferentes. Por consiguiente, nunca se ha esperado que ningún compuesto pudiera poseer estas actividades simultáneamente.
PGD_{2} se produce a través de PGG_{2} y PGH_{2} a partir de ácido araquidónico mediante la acción de ciclooxigenasa activada por estimulación inmunológica o no inmunológica y es el principal prostanoide que se produce y libera desde células cebadoras. PGD_{2} posee diversas potentes actividades fisiológicas y patológicas. Por ejemplo, PGD_{2} puede causar una fuerte contracción traqueal, que conduce a asma bronquial y, en un estado alérgico sistémico, puede dilatar los vasos periféricos, lo que lleva a un ataque anafiláptico. Especialmente, gran parte de la atención ha estado dirigida a la idea de que PGD_{2} es una de las sustancias causales responsables del inicio de la oclusión nasal en la rinitis alérgica. Por consiguiente, se ha propuesto el desarrollo de un inhibidor contra la biosíntesis de PGD_{2} o un antagonista de receptor de PGD_{2} como fármaco para la reducción de oclusión nasal. No obstante, el inhibidor de la biosíntesis de PGD_{2} posiblemente afecte sobre todo a la síntesis de prostaglandinas en otros organismos y, por lo tanto, es deseable desarrollar un antagonista (agente de bloqueado) específico para el receptor
PGD_{2}.
Descripción de la invención
Los autores de la presente invención han realizado exhaustivos estudios para desarrollar antagonistas de receptor PGD_{2} (agentes de bloqueo) específicos para receptor PGD_{2}, y han observado que los compuestos de la fórmula (Ib) que se muestra a continuación, o su sal, poseen una potente actividad como antagonistas de receptor PGD_{2} y son químicamente y bioquímicamente estables.
\newpage
Por consiguiente, la presente invención proporciona un antagonista de PGD_{2} que comprende un compuesto de fórmula (Ib):
1
en la que:
2
es
3
en la que A es alquileno que opcionalmente está sustituido por heteroátomo o fenileno, contiene grupo oxo, y/o tiene un enlace insaturado;
B es hidrógeno, alquilo, aralquilo o acilo;
R es COOR_{1}, CH_{2}OR_{2} ó CON(R_{3})R_{4};
R_{1} es hidrógeno o alquilo;
R_{2} es hidrógeno o alquilo;
R_{3} y R_{4} son cada uno de ellos independientemente hidrógeno, alquilo, hidroxi o alquilsulfonilo;
X_{1} es un enlace simple, fenileno, naftileno, tiofenediilo, indolediilo u oxazolediilo;
X_{2} es un enlace simple; -N=N-, -N=CH-, -CH=N-, -CH=N-N-, -CH=N-O; -C=NNHCSNH-, -C=NNHCONH-,
-CH=CH-, -CH(OH)-, -C(Cl)=C(Cl)-, -(CH_{2})_{n}-, etinileno, -N(R_{5})-, -N(R_{51})CO-, -N(R_{52})SO_{2}-, -N(R_{53})CON(R_{54})-,
-CON(R_{55})-, -SO_{2}N(R_{56})-, -O-, -S-, -SO-, -SO_{2}-, -CO-, oxadiazolediilo, tiadiazolediilo o tetrazolediilo;
X_{3} es alquilo, alquenilo, alquinilo, arilo, aralquilo, grupo heterocíclico, cicloalquilo, cicloalquenilo, tiazolinilidenmetilo, tiazolidinilidenmetilo, -CH=NR_{6} ó -N=C(R_{7})R_{8};
R_{5}, R_{51}, R_{52}, R_{53}, R_{54}, R_{55} y R_{56} son cada uno de ellos hidrógeno o alquilo;
R_{6} es hidrógeno, alquilo, hidroxi, alcoxi, carbamoíloxi, tiocarbamoiloxi, ureido o tioureido;
R_{7} y R_{8} son cada uno de ellos independientemente alquilo, alcoxi o arilo; y
n es 1 ó 2;
pudiendo ser tener un sustituyente cíclico de uno a tres sustituyentes seleccionados del grupo que consiste en nitro, alcoxi, sulfamoílo, amino sustituido o sin sustituir, acilo, aciloxi, hidroxi, halógeno, alquilo, alquinilo, carboxi, alcoxicarbonilo, aralcoxicarbonilo, ariloxicarbonilo, mesiloxi, ciano, alqueniloxi, hidroxialquilo, trifluorometilo, alquiltio, -N=PPh_{3}, oxo, tioxo, hidroxiimino, alcoxiimino, fenilo y alquilendioxi, o su sal o hidrato del mismo; siempre y cuando se excluyan los compuestos (a) en los que X_{1} y X_{2} son un enlace simple y X_{3} es fenilo; (b) en los que X_{1} es un enlace simple, X_{2} es -O-, y X_{3} es bencilo;
4 
\vskip1.000000\baselineskip
5
Se excluyen los compuestos representados por las fórmulas:
6 
\vskip1.000000\baselineskip
7 
\vskip1.000000\baselineskip
8 
\vskip1.000000\baselineskip
9
del alcance de la reivindicación 1 de la presente solicitud/patente por medio de las renuncias que se introdujeron en la memoria descriptiva tras el registro de la solicitud. En los documentos EP-A-226346, EP-A-290285 y Chem. Pharm. Bull., 37(6), 1524-1533, K. Seno, S. Hagishita, “Thromboxane A2 Receptor Antagonists III aparecen uno o más de estos compuestos. La síntesis y actividad farmacológica de los derivados de 6,6-dimetilbiciclo[3.1.1]heptano con un grupo C-2 sulfonilamino sustituido”, XP2058537. Estos compuestos han sido descartados de las reivindicaciones como anticipaciones accidentales con arreglo a las decisiones G1/03 y G2/03.
Entre los ejemplos de los compuestos que se prefieren sobre todo se incluyen aquellos de fórmula (Ib) en los que R es COOR_{1} (R_{1} es tal como se ha definido antes) o una sal o hidrato del mismo.
De manera similar, entre los ejemplos de los compuestos de la presente invención se incluyen aquellos de fórmula (Ib) en los que X_{1} es un fenileno o tiofenediilo, X_{2} es un enlace simple, -N-N-, CH=CH-, etinileno, -O-, -S-, -CO-, -CON(R_{55})- (R_{55} es tal como se ha definido antes), -N(R_{51})CO- (R_{51} es como se ha definido antes) y X_{3} es fenilo, o una sal o hidrato del mismo.
Entre los ejemplos de modos de realización más preferibles se incluyen aquellos en los que B es hidrógeno, tanto X_{1} como X_{2} son un enlace simple, X_{3} es tienilo, tiazolilo, tiadiazolilo, isotiazolilo, pirrolilo, piridilo, benzofurilo, bencimidazolilo, benzotienilo, dibenzofurilo, dibenzotienilo, quinolilo o indolilo o una sal o hidrato del mismo. De manera similar, entre los ejemplos se incluyen aquellos en los que X_{1} es fenileno, tiofenediilo, indolediilo u oxazolediilo, X_{2}
es un enlace simple, -N=N-, etinileno, -S-, ó -O-, y X_{3} es arilo o un grupo heterocíclico o una sal o hidrato del mismo.
Los compuestos de fórmula general (Ib) son compuestos nuevos sintetizados por los autores de la presente invención.
Los términos utilizados a lo largo de la presente memoria descriptiva son tal como se definen a continuación.
El término "alquileno" significa alquileno de cadena lineal o ramificada de C_{1}-C_{9}, como por ejemplo metileno, metilmetileno, dimetilmetileno, metiletilmetileno, etileno, trimetileno, tetrametileno, pentametileno, hexametileno, heptametileno, octametileno, nonametileno o similares. El alquileno anterior puede estar sustituido por un heterátomo(s) (átomo de oxígeno, azufre, nitrógeno o similar) o fenileno (v.g., 1,4-fenileno, 1,3-fenileno, 1,2-fenileno, o similares), puede contener un grupo oxo, y/o tener uno o más enlaces dobles o triples en cualquiera de las posiciones de la cadena. Entre los ejemplos se incluyen -(CH_{2})_{2}-O-CH_{2}-, -(CH_{2})_{2}-O(CH_{2})_{2}-, -(CH_{2})_{2}-O(CH_{2})_{3}-, -(CH_{2})_{2}-
O-(CH_{2})_{4}-, -(CH_{2})_{2}-O-(CH_{2})_{5}-, -(CH_{2})_{2}-O-(CH_{2})_{6}-, -(CH_{2})_{2}-S-(CH_{2})_{2}-, -(CH_{2})_{3}-S-(CH_{2})_{2}-, -CH_{2}-S-CH_{2}, -CH_{2}-S-
(CH_{2})_{4}-, -CH_{2}-N(CH_{3})-CH_{2}, -CH_{2}-NH-(CH_{2})_{2}-, -(CH_{2})_{2}-N(CH_{2}CH_{3})-(CH_{2})_{3}-, -(CH_{2})_{2}-1,4-fenileno-CH_{2}, -(CH_{2})_{2}-O-1,3-fenileno-CH_{2}, -(CH_{2})_{2}-O-1,2-fenileno-CH_{2}, -(CH_{2})_{2}-O-1,4-fenileno-CH_{2}-, -CH=CH-S-CH_{2}-1,4-fenileno-CH_{2},
-CH=CH-S-1,3-fenileno-(CH_{2})_{2}-, 2-oxopropileno, 3-oxopentileno, 5-oxohexileno, vinileno, 1-propenileno, 2-propenileno, 1-butenileno, 2-butenileno, 3-butenileno, 1,2-butadienileno, 1,3-butadienileno, 1-pentenileno, 2-pentenileno, 3-pentenileno, 4-pentenileno, 1,2-pentadienileno, 1,3-pentadienileno, 1,4-pentadienileno, 2,3-pentadienileno, 2,4-pentadienileno, 1-hexienileno, 2-hexenileno, 3-hexenileno, 4-hexenileno, 5-hexenileno, 1,2-hexadienileno, 1,3-hexadienileno, 1,4-hexadienileno, 1,5-hexadienileno, 2,3-hexadienileno, 2,4-hexadienileno, 2,5-hexadienileno, 3,4-hexadienileno, 3,5-hexadienileno, 4,5-hexadienileno, 1,1-dimetil-4-hexenileno, 1-heptenileno, 2-heptenileno, 3-heptenileno, 4-heptenileno, 5-heptenileno, 2,2-dimetil-5-heptenileno, 6-heptenileno, 1,2-heptadienileno, 1,3-hetadienileno, 1,4-heptadienileno, 1,5-heptadienileno, 1,6-heptadienileno, 2,3-heptadienileno, 2,4-heptadienileno, 2,5-heptadienileno, 2,6-heptadienileno, 3,4-heptadienileno, 3,5-heptadienileno, 3,6-heptadienileno, 4,5-heptadienileno, 4,6-heptadienileno o 5,6-heptadienileno, 1-propinileno, 3-butinileno, 2-pentinileno, 5-hexinileno, 6-heptinileno, -(CH_{2})-CH=CH-O-
(CH_{2})_{2}-, -CH_{2}-S-(CH_{2})_{3}-, -CH_{2}-cis-CH=CH-1,2-fenileno-CH_{2}-, -CH=CH-1,4-fenileno-(CH_{2})_{2}-, 4-oxo-4,5-hexenileno y similares.
El término "alquilo" significa alquilo de cadena lineal o ramificada de C_{1}-C_{20}, como por ejemplo metilo, etilo, n-propilo, i-propilo, n-butilo, i-butilo, s-butilo, t-butilo, n-pentilo, i-pentilo, neopentilo, t-pentilo, hexilo, heptilo, octilo, nonilo, decilo, undecilo, dodecilo, tridecilo, tetradecilo, pentadecilo, hexadecilo, heptadecilo, octadecilo, nonadecilo, icosilo, y similares.
El término "arilo" significa un anillo condensado o monocíclico de C_{6}-C_{14} como por ejemplo fenilo, naftilo (v.g. 1-naftilo, 2-naftilo), antrilo (v.g. 1-antrilo, 2-antrilo, 9-antrilo), fenantrilo (v.g., 2-fenantrilo, 3-fenantrilo, 9-fenantrilo), fluorenilo (v.g., 2-fluorenilo) y similares. Se prefiere especialmente fenilo.
El término "aralquilo" significa un grupo formado al sustituir un alquilo tal como se ha definido anteriormente con un arilo como los citados en una posición adecuada del alquilo. Entre los ejemplos se incluyen bencilo, fenetilo, fenil propilo (v.g., 3-fenilpropilo), naftilmetilo (v.g., \alpha-naftilmetilo), antrimetilo (v.g., 9-antrilmetilo, fenantrilmetilo (v.g., 3-fenantrilmetilo) y similares.
El término "acilo" significa acilo de C_{1}-C_{9} derivado de ácido carboxílico alifático, como por ejemplo formilo, acetilo, propionilo, butirilo, valerilo y similares.
El término "alquilsulfonilo" significa un grupo formado al sustituir un sulfonilo con un alquilo como los citados, como por ejemplo metilsulfonilo, etilsulfonilo, propilsulfonilo y similares.
El término "alquenilo" es alquenilo de cadena lineal o ramificada de C_{2}-C_{20}, que corresponde a un alquilo como los citados que contiene uno o más enlaces dobles. Entre los ejemplos se incluyen vinilo, 1-propenilo, 2-propenilo, 1-butenilo, 2-butenilo, 3-butenilo, 1,2-butadienilo, 1-pentenilo, 1,2-pentadienilo, 2-hexienilo, 1,2-hexadienilo, 3-heptenilo, 1,5-heptadienilo y similares.
El término "alquinilo" es alquilino de cadena lineal o ramificada de C_{2}-C_{20} que corresponde a un alquilo como los citados que contiene uno o más enlaces triples. Entre los ejemplos se incluyen etinilo, 1-propinilo, 2-propinilo, 1-butinilo, 2-butinilo, 3-butinilo y similares.
El término "grupo heterocíclico" significa un grupo cíclico de 5 a 7 eslabones que contiene uno o más heteroátomos seleccionado independientemente del grupo que consiste en un átomo de oxígeno, azufre y/o nitrógeno en el anillo, y opcionalmente, está condensado con un anillo de carbono u otro grupo heterocíclico en cualquier posición sustituible. Entre los ejemplos se incluyen pirrolilo (v.g., 1-pirrolilo, 3-pirrolilo), indolilo (v.g., 2-indolilo, 3-indolilo, 6-indolilo), carbazolilo (v.g., 2-carbazolilo, 3-carbazolilo), imidazolilo (v.g., 1-imidazolilo, 4-imidazolilo), pirazolilo (v.g., 1-pirazolilo, 3-pirazolilo), bencimidazolilo (v.g. 2-bencimidazolilo, 5-bencimidazolilo), indazolilo (v.g., 3-indazolilo), indolicinilo (v.g., 6-indolicinilo), piridilo (v.g., 2-piridilo, 3-piridilo, 4-piridilo), quinolilo (v.g., 8-quinolilo), isoquinolilo (v.g., 3-isoquinolilo), acridilo (v.g., 1-acridilo), fenantridinilo (v.g., 2-fenantridinilo, 3-fenantridinilo), piridacinilo (v.g., 3-piridacinilo), pirimidinilo (v.g., 4-pirimidinilo), piracinilo (v.g., 2-piracinilo), cinolinilo (v.g., 3-cinolinilo), ftaladinilo (v.g., 5-ftaladinilo), quinazolinilo (v.g., 2-quinazolinilo), isoxazolilo (v.g., 3-isoxazolilo, 4-isoxazolilo), bencisoxazolilo (v.g., 1,2-bencisoxazol-4-ilo, 2,1-bencisoxazol-3-ilo), oxazolilo (v.g., 2-oxazolilo, 4-oxazolilo, 5-oxazolilo), benzoxazolilo (v.g., 2-benzoxazolilo), benzoxadiazolilo (v.g., 4-benzoxadiazolilo), isotiazolilo (v.g., 3-isotiazolilo, 4-isotiazolilo), benzisotiazolilo (v.g., 1,2-benzisotiazol-3-il, 2,1-benzisotiazol-5-ilo), tiazolilo (v.g., 2-tiazolilo), benzotiazolilo (v.g., 2-benzotiazolilo), tiadiazolilo (v.g., 1,2,3-tiadiazol-4-ilo), oxadiazolilo (v.g., 1,3,4-oxadiazol-2-il), dihidroxadiazolilo (v.g., 4,5-dihidro-1,2,4-oxadiazol-3-il)-, furilo (v.g., 2-furilo, 3-furilo), benzofurilo (v.g., 3-benzofurilo), isobenzofurilo (v.g. 1-isobenzofurilo), tienilo (v.g., 2-tienilo, 3-tienilo), benzotienilo (1-benzotiofen-2-ilo, 2-benzotiofen-1-ilo), tetrazolilo (v.g., 5-tetrazolilo), benzodioxolilo (v.g., 1,3-benzodioxol-5-ilo), dibenzofurilo (v.g., 2-dibenzofurilo, 3-dibenzofurilo), dibenzoxepinilo (v.g., dibenz[b.f]oxepin-2-ilo), dihidrodibenzoxepinilo (v.g., dihidrodibenz[b.f]oxepin-2-ilo, cromenilo (v.g., 2H-cromen-3-ilo, 4H-cromen-2-ilo), dibenzotiepinilo (v.g., dibenzo[b.f]tiepin-3-ilo, dihidrodibenzo[b.f]tiepin-3-ilo), morfolinilo (v.g., 1,4-morfolin-4-ilo), fenotiadinilo (2-fenotiadinilo), ciclopentatienilo (v.g. ciclopenta[b]tiofen-3-il), ciclohexatienilo (v.g., ciclohexa[b]tiofen-3-ilo), cicloheptatienilo (v.g., ciclohepta[b]tiofen-3-ilo), dibenzotienilo (v.g., 2-dibenzotienilo), dibenzopiranilo (v.g., 2-dibenzopiranilo), dibenzo-p-dioxilo (v.g., 2-dibenzo-p-dioxilo), y similares.
El término "cicloalquilo" significa alquilo cíclico de C_{1}-C_{8}, como por ejemplo ciclopropilo, ciclobutilo, ciclopentilo, ciclohexilo y similares.
El término "cicloalquenilo" significa alquenilo cíclico de C_{3}-C_{8}, como por ejemplo ciclopropenilo (v.g., 1-ciclopropenilo), ciclobutenilo (v.g., 2-ciclobuten-1-ilo), ciclopentenilo (1-ciclopenten-1-ilo), ciclohexenilo (1-ciclohexen-1-ilo) y similares.
El término "alcoxi" significa alcoxi de C_{1}-C_{6}, como por ejemplo, metoxi, etoxi, n-propoxi, i-propoxi, n-butoxi y similares.
Entre los ejemplos de amino sustituido en la definición de "amino sustituido o sin sustituir" se incluyen amino mono- o di-sustituido como por ejemplo metilamino, etilamino, dimetilamino, ciclohexilamino, fenilamino, difenilamino o amino cíclico como piperidino, piperadino o morfolino.
El término "aciloxi" significa un aciloxi derivado del "acilo" mencionado, como por ejemplo acetiloxi, propioniloxi, butiriloxi, valeriloxi y similares.
El término "halógeno" significa flúor, cloro, bromo y yodo.
El término "alcoxicarbonilo" significa un grupo alcoxicarbonilo, derivado del "alcoxi" mencionado, como por ejemplo metoxicarbonilo, etoxicarbonilo, feniloxicarbonilo y similares.
El término "aralquiloxicarbonilo" significa un grupo aralquiloxicarbonilo derivado del "aralquilo" mencionado, como por ejemplo benciloxicarbonilo, fenetiloxicarbonilo y similares.
El término "ariloxicarbonilo" significa un grupo ariloxicarbonilo derivado del "arilo" anterior, como por ejemplo, feniloxicarbonilo, naftiloxicarbonilo y similares.
El término "alqueniloxi" significa un grupo alqueniloxi derivado del "alquenilo" anterior, como por ejemplo, viniloxi, 1-propeniloxi, 2-buteniloxi y similares.
El término "hidroxialquilo" significa un grupo hidroxialquilo derivado del "alquilo" anterior, como por ejemplo hidroximetilo, hidroxietilo, hidroxipropilo, y similares.
El término "alquiltio" significa un grupo alquiltio derivado del "alquilo" anterior, como por ejemplo, metiltio, etiltio, propiltio y similares.
El término "alquilendioxi" significa alquilendioxi de C_{1}-C_{3} como por ejemplo metilendioxi, etilendioxi, propilendioxi y similares.
En el caso de "fenileno", "naftileno", "tiofenediilo", "indolediilo", "oxazolediilo", "oxadiazolediilo" y "tetrazolediilo", dicho grupo se puede unir a los grupos colindantes en dos sitios cualquiera sustituibles.
En la definición anterior, cuando un sustituyente(s) es cíclico puede estar sustituido por uno a tres sustituyentes seleccionados entre nitro, alcoxi, sulfamoílo, amino sustituido o sin sustituir, acilo, aciloxi, hidroxi, halógeno, alquilo, alquinilo, carboxi, alcoxicarbonilo, aralcoxicarbonilo, ariloxicarbonilo, mesiloxi, ciano, alqueniloxi, hidroxialquilo, trifluorometilo, alquiltio, -N=PPh3, oxo, tioxo, hidroxiimino, alcoxiimino, fenilo y alquilendioxi. El (los) sustituyente(s)
pueden unirse a cualquier posición sustituible del anillo.
Entre los ejemplos de sales del compuesto (Ib) se incluyen aquellas formadas con un metal alcalino (v.g., litio, sodio o potasio), un metal alcalinotérreo (v.g., calcio), una base orgánica (v.g., trometamina, trimetilamina, trietilamina, 2-aminobutano, t-butilamina, diisopropiletilamina, n-butilmetilamina, ciclohexilamina, diciclohexilamina, N-isopropilciclohexilamina, furfurilamina, bencilamina, metilbencilamina, dibencilamina, N,N-dimetilbencilamina, 2-clorobencilamina, 4-metoxibencilamina, 1-naftilenmetilamina, difenilbencilamina, trifenilamina, 1-naftilamina, 1-aminoantraceno, 2-aminoantraceno, dehidroabietilamina, N-metilmorfolina o piridina), un amino ácido (v.g., lisina, o arginina) y similares.
El término "hidrato" significa un hidrato de un compuesto de fórmula (Ib) o su sal. Entre los ejemplos se incluyen mono- y di-hidratos.
Los compuestos de la presente invención están representados por la fórmula (Ib) e incluyen la forma de cualquier tipo de estereoisómero (v.g., diastereómero, epímero, enantiómero) y compuestos racémicos.
Los compuestos de la fórmula general (Ib) se pueden preparar haciendo reaccionar un compuesto amino de fórmula general (II) con un derivado reactivo de ácido sulfónico o ácido carboxílico que corresponde a la estructura parcial: Z-X_{1}-X_{2}-X_{3} tal como se muestra a continuación:
10
en la que A, B, R, X_{1}, X_{2}, X_{3} e Y son como se han definido anteriormente y Z es -CO-, el ácido carboxílico que corresponde a dicha estructura parcial es un compuesto de fórmula general X_{3}-X_{2}-X_{1}-COOH. El derivado reactivo de estos ácidos carboxílicos significa un haluro correspondiente (v.g., cloro, bromo, yodo), anhídrido ácido (v.g., anhídrido de ácido mixto con ácido fórmico o ácido acético), éster activo (v.g., éster de succinimida) y entre los ejemplos de los mismos se incluyen generalmente agentes acilantes utilizados para la acilación de grupo amino. El ácido carboxílico X_{3}-X_{2}-X_{1}-COOH se puede utilizar en la reacción como tal sin convertirlo a un derivado activo, en presencia de un agente de condensación (v.g., diciclohexilcarbodiimida (DCC), 1-etil-3-(3-dimetilaminopropil)carbodiimida, N,N’-carbonildiimidazol) que se utilizan en la reacción de condensación entre amina y ácido carboxílico.
La reacción se puede llevar a cabo en las condiciones empleadas generalmente para la acilación de grupos amino. Por ejemplo, en el caso de condensación utilizando un haluro de ácido, se lleva a cabo la reacción utilizando un disolvente como por ejemplo un disolvente de éter (v.g., éter dietílico, tetrahidrofurano, dioxano), disolvente de benceno (v.g., benceno, tolueno, xileno), disolvente de hidrocarburo halogenado (v.g., diclorometano, dicloroetano, cloroformo), acetato de etilo, dimetilformamida, sulfóxido de dimetilo, acetonitrilo o similares, si es necesario, en presencia de una base (v.g., base orgánica, como trietilamina, piridina, N,N-dimetilaminopiridina, N-metilmorfolina; base inorgánica como hidróxido sódico, hidróxido potásico, carbonato potásico, o similar), con enfriamiento, a temperatura ambiente, o con calentamiento, preferiblemente a una temperatura comprendida entre -20ºC y una temperatura por debajo del enfriamiento, o entre la temperatura ambiente y la temperatura de reflujo del sistema de reacción, durante varios minutos a varias horas, preferiblemente durante 0,5 horas a 24 horas, más preferiblemente, durante 1 hora a 12 horas.
Las condiciones de reacción para la reacción entre otros derivados reactivos o un ácido libre y una amina (II) se pueden determinar según el modo convencional dependiendo de las características del derivado reactivo o ácido libre correspondiente.
El producto de reacción se puede purificar a través de métodos de purificación convencionales, como por ejemplo extracción con un disolvente, cromatografía, recristalización o similares.
Entre los ejemplos específicos del compuesto (II) como material de partida del método de la presente invención se incluyen los que se muestran a continuación. Entre los ejemplos de compuestos 3-amino[2.2.1]bicíclicos se incluyen ácido 7-(3-aminobiciclo[2.2.1]hept-2-il)-5-heptenoico, ácido 7-(3-aminobiciclo[2.2.1]hept-2-il)-2,2-dimetil-5-heptenoico, ácido 7-(N-metil-3-aminobiciclo[2.2.1]hept-2-il)-5-heptenoico, ácido 6-(3-aminobiciclo[2.2.1]hept-2-il)-5-hexenoico. Entre los ejemplos específicos de compuestos 2-amino-6,6-dimetil[3.1.1]bicíclicos se incluyen ácido 7-(2-amino-6,6-dimetilbiciclo[3.1.1]hept-3-il]-5-heptenoico. En estos compuestos de partida, la cadena de ácido heptenoico puede estar saturada para formar una cadena de ácido heptanoico, sustituida con un heteroátomo(s) o un hetero grupo como -O-, -S-, -NH- o fenileno(s) o sustituida con un grupo oxo. Entre los ejemplos de dichos compuestos se incluyen ácido 7-(3-aminobiciclo[2.2.1]hept-2-il)-heptanoico, ácido 4-[2-(2-aminobiciclo[3.1.1]hept-3-il)etoxifenil acético, ácido 7-(3-aminobiciclo[2.2.1]hept-2-il)-6-oxo-heptanoico. Estos compuestos de partida se describen en la publicación de patente japonesa Nº JP 63-139161 o JP 0-52751 o se pueden preparar con arreglo al método que se describe en dichos documentos.
El ácido carboxílico X_{3}-X_{2}-X_{1}-COOH que corresponde a la estructura parcial Z-X_{1}-X_{2}-X_{3} significa un ácido carboxílico que tiene sustituyentes que corresponden al Xs anterior. Es decir, entre los ejemplos se incluyen ácido alcano carboxílico, ácido alqueno carboxilo, ácido alquino carboxílico, ácido cicloalcano carboxílico, ácido cicloalqueno carboxílico, ácido aril carboxílico, ácido aralquiloxi carboxílico, ácido carboxílico sustituido heterocílico, ácido heteroarilalquilo carboxílico y ácido amino carboxílico sustituido. Cada uno de los ácidos carboxílico pueden tener un sustituyente como los mencionados. Estos ácidos carboxílicos son asequibles en el comercio o se pueden sintetizar fácilmente a partir de un compuesto(s) conocido(s) de acuerdo con un método conocido. Tras la reacción, se puede convertir el ácido carboxílico a un derivado reactivo correspondiente, como los mencionados, si es necesario. Por ejemplo, cuando es necesario un haluro ácido, se hace reaccionar el compuesto con haluro de tionilo (v.g., cloruro de tionilo), haluro de fósforo (v.g., tricloruro de fósforo, pentacloruro de fósforo), haluro de oxalilo (v.g., cloruro de oxalilo) de acuerdo con un método conocido como por ejemplo los descritos en la bibliografía (v.g., Shin-Jikken-Kagaku-Koza, vol., 14, pp. 1787 (1978), Synthesis, 852-854 (1986); Shin-Jikken-Kagaku-Koza, vol., 22, pp. 115 (1992)). Se pueden preparar también otros derivados reactivos con arreglo a métodos conocidos.
Entre los compuestos objetivo (Ib), aquellos en los que la cadena lateral A contiene un enlace insaturado, especialmente un enlace doble, se pueden preparar también haciendo reaccionar un derivado de aldehído de fórmula general (III), tal como se muestra más adelante, con un compuesto iluro que corresponde al resto de la cadena lateral A-R en las condiciones de la reacción de Wittig
11
en la que A, B, R, X_{1}, X_{2}, X_{3} e Y son como se han definido anteriormente, y Z es -CO-.
El compuesto de partida (III) se puede preparar con arreglo al método descrito por ejemplo en la publicación de patente japonesa Nº JP 02-256650. Por otra parte, se puede sintetizar un compuesto iluro que corresponde al resto de la cadena lateral A-R, haciendo reaccionar trifenilfosfina con un ácido alcanoico halogenado correspondiente o un derivado de éster, un derivado de éter o un derivado amina del mismo en presencia de una base con arreglo a un método conocido.
Entre los compuestos objetivo (Ib), se pueden convertir aquellos en los que R es COOH al correspondiente derivado de éster, derivado alcohol, derivado de éter, derivado amida, si se desea. Por ejemplo, se pueden preparar derivados de éster por esterificación de un ácido carboxílico según un modo convencional. Un derivado de éster, cuando se reduce, da un derivado de alcohol, y cuando se amida, da un derivado de amida. Se puede obtener un derivado de éter por O-alquilación de un derivado de alcohol.
El compuesto (Ib) de la presente invención presenta un efecto antagonista contra PGD_{2} in vitro a través de la unión con receptor PGD_{2}, y es útil como fármaco para el tratamiento de enfermedades en las que participa una disfunción de las células cebadoras como consecuencia de una excesiva producción de PGD_{2}. Por ejemplo, el compuesto (Ib) es útil como fármaco para el tratamiento de enfermedades, como por ejemplo mastocitosis sistémica y trastornos de la activación de células cebadoras sistémica, así como contracción traqueal, asma, rinitis alérgica, conjuntivitis alérgica, urticaria, lesión debida a reperfusión isquémica e inflamación. El compuesto (Ib) posee un efecto preventivo sobre la oclusión nasal in vivo y, por consiguiente, es particularmente útil como fármaco para su tratamiento.
Cuando se utiliza un compuesto (Ib) de la presente invención en tratamiento, se puede formular según las formulaciones habituales para administración oral y parenteral. Una composición farmacéutica que contiene un compuesto (Ib) según la presente invención puede presentarse en una forma para administración oral y parenteral. Específicamente se puede formular en formulaciones para administración oral, como tabletas, cápsulas, granulados, polvos, siropes y similares; las formas para administración parenteral como, por ejemplo, soluciones inyectables o suspensiones para inyección intravenosa, intramuscular o subcutánea, inhaladores, gotas oculares, gotas nasales, supositorios o formulaciones percutáneas como pomadas.
En la preparación de las formulaciones, se pueden utilizar vehículos, excipientes, disolventes y bases conocidas entre las personas especializadas en este campo. En el caso de las tabletas, se preparan comprimiendo o formulando un ingrediente activo junto con componentes auxiliares. Entre los ejemplos de componentes auxiliares se incluyen excipientes farmacéuticamente aceptables como aglutinantes (v.g., almidón de maíz), cargas (v.g., lactosa, celulosa microcristalina), disgregantes (v.g., glicolato sódico de almidón) o lubricantes (v.g. estearato de magnesio). Las tabletas pueden recubrirse de manera apropiada. En el caso de formulaciones líquidas, como por ejemplo siropes, soluciones o suspensiones, pueden contener agentes de suspensión (v.g., metil celulosa), emulsionantes (v.g., lecitina), conservantes y similares. En el caso de formulaciones inyectables, pueden presentarse en forma de solución o suspensión, o en forma de emulsión oleosa o acuosa, que puede contener un agente de suspensión-estabilizante o un agente de dispersión y similares. En el caso de un inhalador, se formula en una formulación líquida aplicable a la persona que inhala. En el caso de gotas oculares, se formula en una solución o en una suspensión. Especialmente, en el caso de un fármaco nasal para el tratamiento de oclusión nasal, se puede utilizar como una solución o una solución preparada a través de un método de formulación convencional, o como un polvo formulado utilizando un agente de formación de polvo (v.g., hidroxipropil celulosa, carbopol) que se administra en la cavidad nasal. Alternativamente, se puede utilizar en forma de aerosol tras la carga en un contenedor especial junto con un disolvente de bajo punto de ebullición.
Si bien la dosis del compuesto (Ib) apropiada varía dependiendo de la ruta de administración, la edad, el peso corporal, el sexo o el estado del paciente y el tipo de fármaco(s) utilizado(s) a la vez, cuando es así, y deberá ser determinada por el médico de cabecera, en último término, en el caso de administración oral, la dosis diaria puede estar comprendida generalmente entre aproximadamente 0,01 y 100 mg, preferiblemente entre aproximadamente 0,01 y 10 mg, más preferiblemente entre aproximadamente 0,1 y 10 mg, por kg de peso corporal. En el caso de administración parenteral, la dosis diaria puede estar comprendida generalmente entre aproximadamente 0,001 y 100 mg, preferiblemente entre aproximadamente 0,001 y 1 mg, más preferiblemente entre aproximadamente 0,01 y 1 mg, por kg de peso corporal. La dosis diaria se puede administrar en 1 a 4 divisiones.
Los ejemplos que se exponen a continuación servirán para ilustrar mejor la presente invención, no pretendiéndose por ello que se consideren como limitativos del alcance de la misma.
Ejemplo 1 
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12 
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Se disolvió (Z)-7-[(1-S,2R,3R,4R)-3-aminobiciclo[2.2.1]hept-2-il]-5-heptenoato trifluoroacetato de metilo (II-2) (232 mg, 0,636 mmoles), que se había preparado a través del método descrito en el ejemplo de referencia 4 de la publicación de patente japonesa Nº JP 63-139161, en cloruro de metileno (5 ml). Se añadió a la solución trietilamina (0,279 ml, 2,00 mmoles) y cloruro de 4-bifenilcarbonilo con enfriamiento con hielo y se agitó durante 7 horas a la misma temperatura. Se purificó la mezcla de reacción por cromatografía de columna sobre gel de sílice (acetato de etilo/n-hexano (1:4) para producir (Z)-7-[(1-S,2R,3R,4R)-3-(4-bifenil)carbonilaminobiciclo[2.2.1]hept-2-il]-5-heptenoato de metilo (1k-11) (221 mg, 0,512 mmoles). Se disolvió el compuesto (1k-11) (190 mg, 0,440 mmoles) en metanol (6 ml). Se añadió a la solución KOH 1N (1,10 ml, 1,10 mmoles) con enfriado con hielo y se agitó durante 15 horas a temperatura ambiente. Se concentró la mezcla de reacción al vacío. Se extrajo el residuo, tras la adición de agua (20 ml) y HCl 1N (2 ml), se extrajo con acetato de etilo. Se lavó la capa orgánica con salmuera saturada, se secó sobre sulfato sódico anhidro y se concentró. Se purificó el residuo por cromatografía de columna sobre gel de sílice (acetato de etilo/hexano (1:1) que contenía ácido acético al 0,3%) para producir ácido (Z)-7-[(1S,2R,3R,4R)-3-(4-bifenil)carbonilaminobiciclo[2.2.1]hept-2-il]-5-heptenoico (1k-12) (172 mg, 0,412 mmoles). Rendimiento 94%.
Se prepararon los siguientes compuestos también según el mismo procedimiento.
Los compuestos preparados con arreglo al método descrito en el ejemplo anterior son los que se muestran en las tablas a continuación.
TABLA 1k
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
TABLA 2b
43 
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TABLA 2c
44
TABLA 2d
45 
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TABLA 2e
46
TABLA 2f
47 
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TABLA 2g
48
TABLA 2h
49 
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TABLA 2i
50
51
TABLA 2j
52
TABLA 2k 
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53 
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Las propiedades físico-químicas de estos compuestos son las que se muestran a continuación. El número de compuesto a continuación se corresponde con el descrito en las tablas anteriores.
Nº1k-1
[\alpha]_{D} = -25,4º (CHCl_{3}, c=1,08, 23ºC)
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Nº1k-2
CDCl_{3} 200MHz
1,07-2,28 (4H, m), 2,32 (2H, t, J = 7,4 Hz), 2,63 (1H, m), 3,63 (3H, s), 3,93 (1H, m), 5,30,5,52 (2H, m), 6,35 (1H, d, J = 7,0 Hz), 7,48 -7,60 (3H, m), 7,88 -8,02 (6H, m).
IR (CHCl_{3}): 3438, 3002, 2946,2868,1727,1652, 1514, 1485, 1363, 1310, 1245, 1154/cm
[\alpha]_{D} = 80,4º (CHCl_{3}, c = 1,01, 24,0ºC)
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Nº1k-3
CDCl_{3} 200MHz
1,10-2,26 (14H, m), 2,37 (2H, t, J = 7,2 Hz), 2,60 (1H, m), 3,93 (1H, m), 5,30 -5,50 (2H, m), 6,33 (1H, d, J = 7,5 Hz), 7,48 -7,58 (3H, m), 7,88-7,99 (6H,m).
IR (CHCl_{3}): 3446, 3004, 2952, 2874, 1709, 1652, 1515, 1485, 1305, 1153 /cm
[\alpha]_{D} = -96,4º (CHCl_{3}, c = 1,05, 23,0ºC)
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Nº1k-4
CDCl_{3} 300MHz
1,05-2,17 (14H, m), 2,38 (2H, t, J = 7,2 Hz), 2,52 (1H, m), 3,81 (1H, m), 5,33 -5,50 (2H, m), 6,08 (1H, d, J = 7,6 Hz), 7,39 -7,53 (3H, m), 7,57 -7,62 (6H, m).
IR (CHCl_{3}): 3420, 3250, 3008, 2948, 2870, 2660, 2208, 1735(sh), 1705, 1640, 1500/cm
[\alpha]_{D} = 21,9\pm0,6º (CHCl_{3}, c = 1,02, 22ºC).
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Nº1k-5
CDCl_{3} 300MHz
1,05-2,14 (14H, m), 2,38 (2H, t, J = 7,2Hz), 2,51 (1H, m), 3,81 (1H, m), 5,34-5,46 (2H, m), 6,07 (1H, d, J = 7,6 Hz), 7,33-7,56 (5H, m).
IR (CHCl_{3}): 3422, 3250, 3010, 2950, 2876, 2664, 2558, 2210, 1735(sh), 1705, 1645, 1502,1441, 1410, 1307, 1276 /cm
[\alpha]_{D} = -63,6\pm1,9º (CHCl_{3}, c = 0,56, 22ºC)
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Nº1k-6
CDCl_{3} 300MHz
1,04-2,24 (14H, m), 2,36 (2H, t, J = 7,5 Hz), 2,58 (1H, m), 3,88 (1H, m), 5,30 -5,43 (2H, m), 6,21 (1H, d, J = 7,2 Hz), 7,41-7,49 (3H, m), 7,73-7,77 (2H, m).
IR (CHCl_{3}): 3447, 3011, 2955, 1708, 1653, 1603, 1578, 1515, 1486, 1457, 1312, 1211, 1164 /cm
[\alpha]_{D} = -60,3º (CHCl_{3}, c = 1,00, 23ºC)
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Nº1k-7
CDCl_{3} 300MHz
1,04-2,22 (14H, m), 2,36 (2H, t, J = 7,2 Hz), 2,57 (1H, m), 3,87 (1H, m), 5,30-5,44 (2H, m), 6,17 (1H, d, J = 8,7 Hz), 6,99 -7,40 (7H, m), 7,73 (2H, d, J = 7,5 Hz).
IR (CHCl_{3}): 3449, 3013, 2955, 1739, 1708, 1651, 1609, 1588, 1522, 1487, 1234, 1227, 1169/cm
[\alpha]_{D} = -60,2º (CHCl_{3}, c = 0,92, 23ºC)
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Nº1k-8
CDCl_{3} 300MHz
1,04-2,25 (14H, m), 2,34 (2H, t, J = 7,5 Hz), 2,56 (1H, m), 3,87 (1H, m), 5,30 -5,44 (2H, m), 6,19 (1H, d, J = 7,5 Hz), 6,83-6,94 (6H, m), 7,69 (2H, d, J = 8,7Hz).
IR (CHCl_{3}): 3599, 3455, 3012, 2955, 1711, 1644, 1604, 1577, 1524, 1507, 1492, 1290, 1236, 1197, 1170/cm
[\alpha]_{D} = 47,7º (CHCl_{3}, c = 1,01, 22ºC)
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Nº1k-9
CDCl_{3} 300MHz
1,04-2,20 (14H, m), 2,31 (3H, s), 2,36 (2H, t, J = 7,2Hz), 2,56 (1H, m), 3,86 (1H, m), 5,30-5,43 (2H, m); 6,16 (1H, d, J = 7,2 Hz), 7,00-7,11 (6H, m), 7,74 (2H, d, J = 8,7 Hz).
IR (CHCl_{3}): 3450, 3010, 2955, 1750, 1709, 1651, 1609, 1596, 1523, 1489, 1370, 1247, 1227, 1183 /cm
[\alpha]_{D} = -54,7º (CHCl_{3}, c =1,01, 22ºC)
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Nº1k-10
CDCl_{3} 300MHz
1,04-2,22 (14H, m), 2,35 (2H, t, J = 7,2Hz), 2,56 (1H, m), 3,82 (3H, s), 3,86 (1H, m), 5,30-5,43 (2H, m), 6,17 (1H, d, J = 6,9 Hz), 6,89-7,01 (6H, m), 7,70 (2H, d, J = 8,7 Hz).
IR (CHCl_{3}): 3023, 2955, 1742, 1708, 1649, 1613, 1602, 1577, 1522, 1507, 1490, 1227, 1210, 1170/cm
[\alpha]_{D} = 58,1º (CHCl_{3}, c =1,01, 22ºC)
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Nº1m-1
CDCl_{3} 300MHz
1,06-2,25 (14H, m), 2,32 (2H, t, J = 7,4 Hz), 2,61 (1H, m), 3,63 (3H, s), 3,91 (1H, m), 5,33-5,47 (2H, m), 6,24 (1H, d, J = 6,9 Hz), 7,35 -7,38 (3H, m), 7,53 -7,60 (4H, m), 7,75 -7,78 (2H, m).
IR (CHCl_{3}): 3438, 3008, 2946, 2875, 2212, 1732, 1650, 1605, 1519, 1496/cm.
[\alpha]_{D} = +76º (CHCl_{3}, c =1,39, 24ºC)
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Nº1m-2
CDCl_{3} 300MHz
1,05-2,20 (14H, m), 2,36 (2H, t, J = 6,2 Hz), 2,59 (1H, m), 3,89 (1H, m), 5,29 -5,48 (2H, m), 6,26 (1H, d, J = 7,0Hz), 7,26-7,38 (3H, m), 7,52-7,60 (4H, m), 7,73-7,77 (2H, m).
IR (CHCl_{3}): 3444, 3012, 2952, 2874, 2664, 2214, 1718(sh), 1708, 1649, 1605, 1520, 1498 /cm.
[\alpha]_{D} = +81,4º (CHCl_{3}, c = 1,01, 23ºC)
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Nº1m-3
CDCl_{3} 300MHz
1,06-2,23 (14H, m), 2,32 (2H, t, J = 7,0 Hz), 2,62 (1H, m), 3,63 (3H, s), 3,93 (1H, m), 5,30-5,50 (2H, m), 6,28 (1H, d, J = 7,0Hz), 7,38-7,51 (3H, m), 7,58-7,67 (4H, m), 7,83-7,88 (2H, m).
IR (CHCl_{3}): 3438, 3008, 2948, 2875, 1783(w), 1727, 1650, 1608, 1580 (w), 1523, 1501, 1482 /cm
[\alpha]_{D} = +59º (CHCl_{3}, c =1,49, 25ºC)
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Nº1m-4
CDCl_{3} 300MHz
1,08-2,25 (14H, m), 2,36 (2H, t, J = 7,4Hz), 2,59 (1H, m), 3,91 (1H, m), 5,28-5,48 (3H, m), 6,29 (1H, d, J = 7,4 Hz), 7,38-7,50 (3H, m), 7,61-7,67 (4H, m), 7,81-7,86 (2H, m).
IR (CHCl_{3}): 3436, 3010, 2948, 2868, 1727, 1715(sh), 1649, 1615(w), 1524, 1502, 1482, 1372/cm.
[\alpha]_{D} = +72º (CHCl_{3}, c =0,98, 25ºC)
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Nº1m-5
CDCl_{3} 300MHz
1,09-2,20 (14H, m), 2,32 (2H, t, J = 7,2 Hz), 2,63 (1H, m), 3,63 (3H, m), 3,92 (1H, m), 5,31-5,51 (2H, m), 6,35 (1H, d, J = 7,0 Hz), 7,51-7,60 (3H, m), 7,92-7,97 (6H, m).
IR (CHCl_{3}): 3436, 3008, 2946, 2875, 1727, 1652, 1608(w), 1515, 1484/cm
[\alpha]_{D} = +82º (CHCl_{3}, c =0,99, 25ºC)
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Nº1m-6
CDCl_{3} 300MHz
1,09-2,23 (14H, m), 2,37 (2H, t, J = 7,2Hz), 2,60 (1H, m), 3,92 (1H, m), 5,30-5,49 (2H, m), 6,32 (1H, d, J = 7,4 Hz), 7,51-7,55 (3H, m), 7,85 -7,98 (6H, m).
IR (CHCl_{3}):3436, 3010, 2950, 2875, 2670, 1727, 1715(sh), 1650, 1605(w), 1515, 1484/cm.
[\alpha]_{D} = +84º (CHCl_{3}, c =1,54, 25ºC)
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Nº1m-7
CDCl_{3} 300MHz
1,03-2,18 (14H, m), 2,32 (2H, t, J = 7,4 Hz), 2,59 (1H, m), 3,64 (3H, s), 3,89 (1H, m), 5,29-5,49 (2H, m), 6,16 (1H, d, J = 7,8 Hz), 6,98 -7,06 (4H, m), 7,14-7,20 (1H, m), 7,34-7,41 (2H, m), 7,73-7,78 (2H, m).
IR (CHCl_{3}): 3438, 3008, 2946, 2868, 1727, 1648, 1610, 1586, 1519, 1485 /cm.
[\alpha]_{D} = +54º (CHCl_{3}, c =1,29, 25ºC)
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Nº1m-8
CDCl_{3} 300MHz
1,06-2,21 (14H, m), 2,36 (2H, t, J = 7,5 Hz), 2,58 (1H, m), 3,88 (1H, m), 5,31-5,46 (2H, m), 6,17 (1H, d, J = 6,9 Hz), 6,99-7,05 (4H, m), 7,15-7,21 (1H, m), 7,36-7,41 (2H, m), 7,72-7,75 (2H, m).
IR (CHCl_{3}): 3436, 3010, 2948, 2868, 2675, 1730 (sh), 1709, 1647, 1608, 1586, 1520, 1485 /cm
[\alpha]_{D} = +56º (CHCl_{3}, c =0,97, 25ºC)
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Nº1m-9
CDCl_{3} 300MHz
1,05-2,18 (14H, m), 2,29-2,34 (5H, m), 2,59 (1H, m), 3,64 (3H, s), 3,89 (1H, m), 5,32-5,46 (2H, m), 6,16 (1H, d, J = 7,5 Hz), 7,00-7,11 (6H, m), 7,74-7,77 (2H, m).
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IR (CHCl_{3}): 3440, 3010, 2946, 2868, 1729, 1649, 1595, 1519, 1488/cm
[\alpha]_{D} = +47º (CHCl_{3}, c =0,82, 25ºC).
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Nº1m-10
CDCl_{3} 300MHz
1,04-2,20 (14H, m), 2,31-2,39 (5H, m), 2,57 (1H, m), 3,87 (1H, m), 5,28-5,47 (2H, m), 6,17 (1H, d, J = 7,0 Hz), 6,99 -7,12 (6H, m), 7,72 -7,76 (2H, m).
IR (CHCl_{3}): 3674, 3572, 3438, 3010, 2948, 2868, 2626, 1748, 1710, 1648, 1615, 1595, 1520, 1489 /cm.
[\alpha]_{D} = +51º (CHCl_{3}, c =0,91, 25ºC)
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Nº1m-11
CDCl_{3} 300MHz
1,04-2,16 (14H, m), 2,31 (2H, t, J = 7,2Hz), 2,59 (1H, m), 3,63 (3H, s), 3,89 (1H, m), 5,29-5,49 (2H, m), 6,24 (1H, d, J = 7,4 Hz), 6,54 (1H, s), 6,83-6,93 (6H, m), 7,69-7,73 (2H, m).
IR (CHCl_{3}): 3674, 3588, 3438, 3296, 3010, 2946, 2868, 1725, 1646, 1603, 1520, 1504, 1489 /cm.
[\alpha]_{D} = +51º (CHCl_{3}, c =0,91, 25ºC)
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Nº1m-12
CDCl_{3} 300MHz
1,04-2,21 (14H, m), 2,33 (2H, t, J = 8,0 Hz), 2,56 (1H, m), 3,87 (1H, m), 5,28-5,48 (2H, m), 6,23 (1H, d, J = 8,0 Hz), 6,75 (1H, m), 6,87-6,94 (6H, m), 7,66-7,71 (2H, m), 9,63 (1H, ancho s).
IR (CHCl_{3}): 3674, 3582, 3436, 3275, 3010, 2950, 2868, 2675, 1727, 1710(sh), 1643, 1603, 1522, 1504, 1490/cm.
[\alpha]_{D} = +30º (CHCl_{3}, c = 0,97, 25ºC)
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Nº1m-13
CDCl_{3} 300MHz
1,01-2,18 (14H, m), 2,31 (2H, t, J = 7,4 Hz), 2,58 (1H, m), 3,63 (3H, s), 3,82 (3H, s), 3,89 (1H, m), 5,29-5,48 (2H, m), 6,14 (1H, d, J = 7,0 Hz), 6,88-7,02 (6H, m), 7,70-7,74 (2H, m).
IR (CHCl_{3}): 3442, 3402, 3004, 2946, 2868, 1727, 1648, 1600, 1518, 1499 /cm.
[\alpha]_{D} = +42º (CHCl_{3}, c =1,82, 26ºC)
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Nº1m-14
CDCl_{3} 300MHz
1,05-2,21 (14H, m), 2,35 (2H, t, J = 7,2 Hz), 2,55 (1H, m), 3,82 (3H, s), 3,88 (1H, m), 5,27-5,46 (2H, m), 6,16 (1H, d, J = 7,2 Hz), 6,88 -7,02 (6H, m), 7,68-7,73 (2H, m).
IR (CHCl_{3}): 3438, 3012, 2948, 2870, 2650, 1730 (sh), 1709, 1647, 1615(sh), 1601, 1519, 1492/cm.
[\alpha]_{D} = +64º (CHCl_{3}, c =0,70, 25ºC).
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Nº1m-15
CDCl_{3} 300MHz
1,05-2,20 (14H, m), 2,29-2,36 (5H, m), 2,62 (1H, m), 3,63 (3H, s), 3,92 (1H, m), 5,30-5,50 (2H, m), 6,25 (1H, d, J = 7,2Hz), 7,16-7,21 (2H, m), 7,59-7,64 (4H, m), 7,83-7,87 (2H, m).
IR (CHCl_{3}): 3446, 3010, 2946, 2868, 1745 (sh), 1728, 1650, 1615, 1525, 1507, 1486/cm.
[\alpha]_{D} = +65,0º (CHCl_{3}, c = 1,02, 23ºC)
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Nº1m-16
CDCl_{3} 300MHz
1,08-2,21 (14H, m), 2,34-2,40 (5H, m), 2,59 (1H, m), 3,90 (1H, m), 5,29-5,48 (2H, m), 6,29 (1H, d, J = 7,0Hz), 7,18 (2H, d, J = 8,6 Hz), 7,58-7,64 (4H, m), 7,83 (2H, d, J = 8,2 Hz).
IR (CHCl_{3}): 3438, 3012, 2948, 2870, 2622, 1749, 1710, 1649, 1610, 1526, 1508, 1487/cm.
[\alpha]_{D} = +66º (CHCl_{3}, c =1,21, 24ºC)
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Nº1m-17
CDCl_{3} 300MHz
1,06-2,19 (14H, m), 2,32 (2H, t, J = 7,2Hz), 2,62 (1H, m), 3,63 (3H, s), 3,93 (1H, m), 5,30-5,50 (2H, m), 6,32 (1H, d, J = 7,6Hz), 6,41 (1H, s), 6,94 (2H, d, J = 9,0Hz), 7,47 (2H, d, J = 9,0 Hz), 7,58 (2H, d, J = 8,6Hz), 7,81 (2H, d, J = 8,6 Hz).
IR (CHCl_{3}): 3580, 3434, 3284, 3010, 2946, 2868, 1726, 1646, 1606, 1528, 1490/cm
[\alpha]_{D} = +62,4º (CHCl_{3}, c =1,01, 23ºC)
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Nº1m-18
CDCl_{3} 300MHz
1,11-2,18 (14H, m), 2,32 (2H, t, J = 7,4Hz), 2,59 (1H, m), 3,88 (1H, m), 5,30-5,49 (2H, m), 6,55 (1H, d, J = 7,0Hz), 6,92 (2H, d, J = 8,6 Hz), 7,47 (2H, d, J = 8,6 Hz), 7,59 (2H, d, J = 8,6 Hz), 7,79 (2H, d, J = 8,2 Hz).
IR (nujol): 3398, 3175, 2725, 1696, 1635, 1601, 1531, 1510/cm
[\alpha]_{D} = +99,5º (CHCl_{3}, c =1,011, 25ºC)
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Nº1m-19
CDCl_{3} 300MHz
1,05-2,20 (14H, m), 2,32 (2H, t, J = 7,4 Hz), 2,61 (1H, m), 3,63 (3H, s), 3,86 (3H, s), 3,94 (1H, m), 5,30-5,50 (2H, m), 6,24 (1H, d, J = 7,0 Hz), 6,99 (2H, d, J = 8,6 Hz), 7,53-7,63 (4H, m), 7,82 (2H, d, J = 8,6 Hz).
IR (CHCl_{3}): 3440, 3006, 2946, 2875, 1726, 1649, 1606, 1527, 1510, 1489/cm.
[\alpha]_{D} = +68º (CHCl_{3}, c =0,88, 26ºC)
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Nº1m-20
CDCl_{3} 300MHz
1,09-2,20 (14H, m), 2,35 (2H, t, J = 7,3 Hz), 2,58 (1H, m), 3,85 (3H, s), 3,89 (1H, m), 5,28-5,48 (2H, m), 6,35 (1H, d, J = 7,2 Hz), 6,98 (2H, d, J = 8,8 Hz), 7,51-7,61 (4H, m), 7,81 (2H, d, J = 8,4 Hz), 8,34 (1H, ancho s).
IR (CHCl_{3}): 3446, 3012, 2952, 2881, 2640, 1730(sh), 1707, 1647, 1606, 1527, 1510, 1489 /cm.
[\alpha]_{D} = +83º (CHCl_{3}, c = 1,00, 25ºC).
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Nº1m-21
CDCl_{3} 300MHz
1,05-2,14 (14H, m), 2,37 (2H, t, J = 7,2 Hz), 2,51 (1H, m), 3,81 (1H, m), 5,34-5,46 (2H, m), 6,11 (1H, d, J = 7,5 Hz), 7,33-7,48 (3H, m), 7,53 -7,55 (2H, m).
IR (CHCl_{3}): 3420, 3250, 3008, 2948, 2870, 2660, 2210, 1735 (sh), 1705, 1645, 1503, 1441, 1409/cm.
[\alpha]_{D} = +59,2\pm1,0º (CHCl_{3}, c =1,023, 22ºC).
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Nº1m-22
CDCl_{3} 300MHz
1,05-2,17 (14H, m), 2,37 (2H, t, J = 7,2 Hz), 2,52 (1H, m), 3,82 (1H, m), 5,32 -5,47 (2H, m), 6,20 (1H, d, J = 7,6 Hz), 7,38-7,53 (3H, m), 7,58-7,61 (6H, m), 9, 11 (1H, ancho s).
IR (CHCl_{3}): 3420, 3250, 3010, 2984, 2870, 2675, 2208, 1730 (sh), 1705, 1640, 1500, 1406 /cm.
[\alpha]_{D} = +57,4º (CHCl_{3}, c =1,83, 23ºC).
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Nº1m-23
CDCl_{3} 300MHz
1,05-2,18 (14H, m), 2,31 (2H, t, J = 7,5 Hz), 2,60 (1H, m), 3,63 (3H, s), 3,90 (1H, m), 5,32-5,47 (2H, m), 6,22 (1H, d, J = 6,9 Hz), 7,40 -7,49 (3H, m), 7,76 -7,79 (2H, m).
IR (CHCl_{3}): 3438, 3008, 2946, 2868, 1727, 1651, 1603, 1585, 1512, 1484/cm.
[\alpha]_{D} = +52º (CHCl_{3}, c =1,49, 25ºC).
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Nº1m-24
CDCl_{3} 300MHz
1,05-2,21 (14H, m), 2,36 (2H, t, J = 7,2Hz), 2,57 (1H, m), 3,89 (1H, m), 5,28-5,47 (2H, m), 6,22 (1H, d, J = 7,0 Hz), 7,39 -7,55 (3H, m), 7,73-7,79 (2H, m).
IR (CHCl_{3}): 3676, 3572, 3436, 3010, 2948, 2875, 1730(sh), 1709, 1650, 1600, 1580, 1514, 1484 /cm.
[\alpha]_{D} = +57º (CHCl_{3}, c = 0,97, 26ºC).
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Nº1m-25
CDCl_{3} 300MHz
1,04-2,18 (14H, m), 2,28 -2,35 (5H, m), 2,59 (1H, m), 3,62 (3H,s), 3,88 (1H, m), 5,29 -5,49 (2H, m), 6,20 (1H, d, J = 7,2 Hz), 7,15 (2H, d, J = 9,0 Hz), 7,80 (2H, d, J = 8,8 Hz).
IR (CHCl_{3}): 3436, 3010, 2946, 2868, 1752, 1727, 1653, 1602, 1519, 1491/cm.
[\alpha]_{D} = +53º (CHCl_{3}, c = 1,63, 25ºC).
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Nº1m-26
CDCl_{3} 300MHz
1,05-2,19 (14H, m), 2,32-2,38 (5H, m), 2,56 (1H, m), 3,88 (1H, m), 5,29-5,47 (2H, m), 6,25 (1H, d, J = 7,4 Hz), 7,15 (2H, d, J = 9,0 Hz), 7,78 (2H, d, J = 8,6 Hz).
IR (CHCl_{3}): 3434, 3016, 3006, 2948, 2880, 2622, 1752, 1730 (sh), 1710, 1651, 1605, 1520, 1492 /cm.
[\alpha]_{D} = +58º (CHCl_{3}, c = 3,68, 24ºC)
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Nº1m-27
CDCl_{3} 300MHz
1,05-2,16 (14H, m), 2,30 (2H, t, J = 7,5 Hz), 2,57 (1H, m), 3,62 (3H, s), 3,87 (1H, m), 5,27-5,47 (2H, m), 6,32 (1H, d, J = 7,4 Hz), 6,85 (2H, d, J = 8,6 Hz), 7,62 (2H, d, J = 8,6 Hz), 8,35 (1H, s).
IR (CHCl_{3}): 3580, 3450, 3216, 3010, 2946, 2868, 1726, 1640, 1608, 1584, 1528, 1496 /cm.
[\alpha]_{D} = +56,2º (CHCl_{3}, c = 0,713, 23ºC).
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Nº1m-28
CDCl_{3} 300MHz
1,10-2,25 (14H, m), 2,32 (2H, t, J = 7,2 Hz), 2,55 (1H, ancho s), 3,82 -3,93 (1H, m), 5,27-5,47 (2H, m), 6,25 (1H, d, J = 7,4 Hz), 6,86 (2H, d, J = 8,6 Hz), 7,62 (2H, d, J = 8,6 Hz).
IR (CHCl_{3}): 3438, 3242, 2675, 1730 (sh), 1708, 1639, 1607, 1585 /cm.
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Nº1m-29
CDCl_{3} 300MHz
1,05-2,18 (14H, m), 2,31 (2H, t, J = 7,4 Hz), 2,58 (1H, m), 3,64 (3H, s), 3,85 (3H, s), 3,89 (1H, m), 5,29 -5,48 (2H, m), 6,14 (1H, d, J = 6,6 Hz), 6,92 (2H, d, J = 9,0 Hz), 7,74 (2H, d, J = 9,0 Hz).
IR (CHCl_{3}): 3445, 3008, 2946, 2868, 1727, 1646, 1606, 1578, 1523, 1493/cm
[\alpha]_{D} = +53º (CHCl_{3}, c = 2,03, 24ºC)
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Nº1m-30
CDCl_{3} 300MHz
1,04-2,21 (14H, m), 2,36 (2H, t, J = 7,3 Hz), 2,56 (1H, m), 3,85 (3H, s), 3,88 (1H, m), 5,27-5,46 (2H, m), 6,15 (1H, d, J = 7,2 Hz), 6,92 (2H, d, J = 8,6 Hz), 7,73 (2H, d, J = 8,6 Hz).
IR (CHCl_{3}): 3440, 3010, 2950, 2870, 2645, 1727, 1710(sh), 1646, 1606, 1575, 1524, 1494/cm.
[\alpha]_{D} = +62º (CHCl_{3}, c =1,10, 24ºC).
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Nº1m-31
CDCl_{3} + CD_{3}OD 300MHz
1,16-2,20 (14H, m), 2,31 (2H, t, J = 7,2 Hz), 2,59 (1H, m), 3,85 (1H, m), 5,31-5,51 (2H, m), 7,13-7,21 (1H, m), 7,31-7,42 (2H, m), 7,68 -7,93 (6H, m).
IR (nujol): 3344, 3175, 2715, 2675, 1699, 1631, 1566/cm
[\alpha]_{D} = +67º (CHOH, c = 1,01, 24ºC).
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Nº1m-32
CDCl_{3} 200MHz
1,09-2,23 (14H, m), 2,33 (2H, t, J = 7,1 Hz), 2,57 (1H, ancho s), 3,40 -3,93 (9H, m), 4,41 (1H, ancho s), 5,29-5,48 (2H, m),6,44 (1H, d, J = 7,4 Hz), 7,43 (2H, d, J = 8,2 Hz), 7,80 (2H, d, J = 7,8 Hz).
IR (CHCl_{3}): 3434, 3354, 1726, 1720(sh), 1660 (sh), 1626 /cm
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Nº1m-33
CDCl_{3} 200MHz
1,14-2,25 (14H, m), 2,37 (2H, t, J = 7,3 Hz), 2,64 (1H, ancho s), 3,93 -4,01 (1H, m), 5,30-5,51 (2H, m), 6,47 (1H, d, J = 7,4 Hz), 7,63 -7,74 (2H, m), 7,79 (2H, s), 7,89 -7,93 (1H, m), 8,00 (1H, dd, J = 2,3, 1,0 Hz), 8,30 (1H, d, J = 1,0 Hz), 8,65-8,73 (2H, m).
IR (CHCl_{3}): 3450, 2675, 1728, 1707, 1649, 1528, 1509/cm.
[\alpha]_{D} = +82,8\pm1,2º (CHCl_{3}, c = 1,01, 23ºC).
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Nº2a-1
[\alpha]_{D} = +69,0º (MeOH, c = 1,01, 25ºC)
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Nº2a-2
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,15 y 1,24 (cada 3H, cada s), 1,50-2,50 (14H, m), 4,30 (1H, m), 5,35 -5,52 (2H, m), 6,32 (1H, d, J = 8,7 Hz), 7,36-7,49 (3H, m), 7,58 -7,62 (2H, m), 7,66 y 7,80 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3116, 3014, 2925, 2870, 2663, 1708, 1651, 1610, 1524, 1504, 1484, 1472 /cm.
[\alpha]_{D} = +64,1º (MeOH, c = 1,02, 25ºC)
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Nº2a-3
[\alpha]_{D} = 76,6º (MeOH, c = 1,18, 26ºC).
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Nº2a-4
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,15 y 1,25 (cada 3H, cada s), 1,64-2,51 (14H, m), 4,31 (1H, m), 5,36-5,53 (2H, m), 6,33 (1H, d, J = 8,4 Hz), 7,50 -7,56 (3H, m), 7,85-7,98 (6H, m).
IR (CHCl_{3}): 3515, 3452, 3014, 2925, 2870, 1740, 1708, 1654, 1517, 1486, 1470/cm.
[\alpha]_{D} = +79,5º (MeOH, c = 1,18, 22º).
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Nº2a-5
CD_{3}OD 300MHz
0,98 (1H, d, J = 9,9 Hz), 1,18 y 1,25 (cada 3H, cada s), 1,56 -1,71 (3H, m), 1,98-2,40 (11H, m), 4,17 (1H, m), 5,41-5,52 (2H, m), 7,52 -7,61 (3H, m), 7,91-8,01 (6H, m).
IR (KBr):3416, 3063, 2983, 2921, 2869, 1704, 1643, 1566, 1518, 1488, 1408 /cm.
[\alpha]_{D} = +62,0º (MeOH, c = 1,00, 25ºC)
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Nº2a-6
[\alpha]_{D} = +64,0º (MeOH, c = 1,01, 25ºC)
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Nº2a-7
[\alpha]_{D} = +65,3º (MeOH, c = 0,99, 25ºC)
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Nº2a-8
[\alpha]_{D} = +74,0º (MeOH, c = 1,01, 25ºC)
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Nº2a-9
[\alpha]_{D} = +71,0º (MeOH, c = 1,10, 25ºC)
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Nº2a-10
[\alpha]_{D} = +74,0º (MeOH, c = 1,00, 25ºC)
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Nº2a-11
[\alpha]_{D} = +72,1º (MeOH, c = 1,00, 25ºC)
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Nº2a-12
[\alpha]_{D} = +53,1º (MeOH, c = 1,01, 26ºC)
p.f. 155,0-156,0ºC
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Nº2a-13
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,8 y 1,25 (cada 3H, cada s), 1,63-2,40 (14H, m), 4,30 (1H, m), 5,46-5,58 (2H, m), 6,44 (1H, d, J = 8,4 Hz), 7,49 y 7,77 (cada 2H, cada d, J = 8,7 Hz), 7,54 (1H, s).
IR (CHCl_{3}): 3689, 3378, 3028, 3014, 2924, 1713, 1652, 1602, 1522, 1496 /cm.
[\alpha]_{D} = +78,3º (MeOH, c = 0,84, 25ºC)
p.f. 205,0-206,0ºC)
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Nº2a-14
[\alpha]_{D} = +72,5º (MeOH, c = 1,07, 25ºC)
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Nº2a-15
CDCl_{3} 300MHz
0,99 (1H, d, J = 9,9 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,55-2,44 (14H, m), 4,27 (1H, m), 5,30 -5,50 (2H, m), 6,29 (1H, d, J = 9,0 Hz), 7,11 y 7,20 (cada 1H, cada, J = 16,2Hz), 7,29-7,55 (5H, m), 7,57 y 7,72 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}):3453, 3083, 3022, 3013, 2925, 2870, 1708, 1650, 1607, 1560, 1522, 1496 /cm.
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[\alpha]_{D} = +72,3º (MeOH, c = 1,00, 27ºC)
p.f. 115,0-117,0ºC
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Nº2a-16
CDCl_{3} 300MHz
0,92 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,50 -2,48 (14H, m), 3,62 (3H, s), 4,29 (1H, m), 5,30-5,50 (2H, m), 6,20 (1H, d, J = 8,7 Hz), 6,59 y 6,68 (cada 1H, cada d, J = 12,3 Hz), 7,23 (5H, s), 7,29 y 7,59 (cada 2H, cada d, J = 8,1Hz).
IR (CHCl_{3}): 3453, 3024, 3016, 2924, 2870, 1730, 1651, 1607, 1520, 1495/cm.
[\alpha]_{D} = +56,8º (MeOH, c = 1,04, 24ºC)
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Nº2a-17
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,50 -2,38 (14H, m), 4,26 (1H, m), 5,30 -5,50 (2H, m), 6,23 (1H, d, J = 8,4 Hz), 6,59 y 6,70 (cada 1H, cada d, J = 12,3 Hz), 7,23 (5H, s), 7,30 y 7,57 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3452, 3081, 3019, 3014, 2925, 2870, 2665, 1708, 1650, 1607, 1521, 1495/cm.
[\alpha]_{D} = +61,1º (MeOH, c = 1,00, 27ºC)
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Nº2a-18
CDCl_{3} 300MHz
0,97 (1H, d, J = 1,02, Hz), 1,11 y 1,23 (cada 3H, cada, s), 1,50-2,50 (14H, m), 3,61 (3H, s), 4,31 (1H, m), 5,35-5,51 (2H, m), 6,33 (1H, d, J = 8,4 Hz), 7,48 -7,64 (4H, m), 7,79-7,83 (2H, m), 7,91 (1H, dt, J = 1,5 y 7,8 Hz), 8,01 (1H, dt, J = 1,5 y 7,8 Hz), 8,13 (1H, t, J = 1,5 Hz).
IR (CHCl_{3}): 3450, 3026, 3013, 2925, 2870, 1730, 1659, 1600, 1510/cm.
[\alpha]_{D} = +56,0º (MeOH, c = 1,01, 25ºC)
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Nº2a-19
CDCl_{3} 300MHz
0,95 (1H, d, J = 9,9 Hz), 1,4 y 1,21 (cada 3H, cada s), 1,53-2,60 (14H, m), 4,25 (1H, m), 5,35 -5,64 (2H, m), 7,21 (1H, d, J = 7,8 Hz), 7,49 -7,68 (4H, m), 7,76-7,84 (3H, m), 8,25 (1H, m), 8,43 (1H, m).
IR (CHCl_{3}): 3382, 3196, 3025, 3015, 2925, 2870, 1725, 1652, 1599, 1577, 1521/cm.
[\alpha]_{D} = +55,9º (MeOH, c = 1,00, 25ºC)
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Nº2a-20
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,3 y 1,24 (cada 3H, cada s), 1,50-2,50 (14H, m), 3,62 (3H, s), 4,31 (1H, m), 5,35-5,51 (2H, m), 6,24 (1H, d, J = 8,4Hz), 7,40-7,52 (3H, m), 7,71-7,76 (2H, m).
IR (CHCl_{3}): 3453, 3025, 3013, 2925, 2870, 1730, 1753, 1579, 1514, 1486/cm.
[\alpha]_{D} = +61,2º (MeOH, c = 1,04, 25ºC)
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Nº2a-21
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,3 y 1,23 (cada 3H, cada s), 1,52 -2,50 (14H, m), 4,28 (1H, m), 5,34-5,51 (2H, m), 6,27 (1H, d, J = 8,7 Hz), 7,41 -7,53 (3H, m), 7,71 -7,74 (2H, m).
IR (CHCl_{3}): 3452, 3063, 3027, 3014, 2925, 2871, 1708, 1652, 1578, 1515, 1486/cm.
[\alpha]_{D} = +62,0º (MeOH, c = 1,01, 27ºC)
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Nº2a-22
d_{6}DMSO 300MHz
0,86 (1H, d, J = 9,9 Hz), 1,10 y 1,16 (cada 3H, cada s), 1,42 -1,52 (3H, m), 1,85-2,46 (1H, m), 3,98 (1H, m), 5,32 -5,43 (2H, m), 7,41 (3H, m), 7,88 (2H, d, J = 6,6 Hz), 8,19 (1H, d, J = 6,6 Hz).
IR (KBr): 3367, 3060, 2984, 2922, 2868, 1634, 1563, 1529, 1487/cm.
[\alpha]_{D} = +47,7º (MeOH, c = 1,00, 25ºC)
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Nº2a-23
[\alpha]_{D} = +62,7º (MeOH, c = 1,01, 27ºC)
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Nº2a-24
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,14 y 1,25 (cada 3H, cada s), 1,52-2,50 (14H, m), 4,31 (1H, m), 5,36-5,52 (2H, m), 6,34 (1H, d, J = 8,4 Hz), 7,47 -7,52 (2H, m), 7,59 -7,63 (1H, m), 7,78-7,83 (6H, m).
IR (CHCl_{3}): 3449, 3027, 3013, 2925, 2869, 1708, 1656, 1599, 1518, 1493/cm.
[\alpha]_{D} = +63,1º (MeOH, c = 1,00, 25ºC)
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Nº2a-25
[\alpha]_{D} = +35,5º (MeOH, c = 1,00, 25ºC)
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Nº2a-26
[\alpha]_{D} = +35,5º (MeOH, c = 1,02, 25ºC)
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Nº2a-27
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,2 y 1,23 (cada 3H, cada s), 1,52-2,50 (14H, m), 3,63 (3H, s), 4,29 (1H, m), 5,36-5,51 (2H, m), 6,18 (1H, d, J = 8,4 Hz), 7,01 y 7,71 (cada 2H, cada d, J = 8,7 Hz), 6,98 -7,05 (2H, m), 7,16 (1H, t, J = 7,5 Hz), 7,34-7,41 (2H, m).
IR (CHCl_{3}): 3455, 3024, 3016, 2924, 2870, 1730, 1651, 1588, 1520, 1487 /cm.
[\alpha]_{D} = +56,4º (MeOH, c = 1,01, 25ºC)
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Nº2a-28
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,52-2,50 (14H, m), 4,26 (1H, m), 5,34 -5,51 (2H, m), 6,20 (1H, d, J = 9,0 Hz), 7,01 y 7,70 (cada 2H, cada d, J = 9,0 Hz), 6,98-7,15 (2H, m), 7,17 (1H, t, J = 7,5 Hz), 7,34-7,40 (2H, m).
IR (CHCl_{3}): 3454, 3031, 3018, 2925, 2870, 1708, 1650, 1588, 1523, 1487/cm.
[\alpha]_{D} = +56,2º (MeOH, c = 1,00, 25ºC)
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Nº2a-29
[\alpha]_{D} = +53,0º (MeOH, c = 1,03, 25ºC)
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Nº2a-30
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,0 y 1,23 (cada 3H, cada s), 1,52-2,50 (14H, m), 4,25 (1H, m), 5,30-5,50 (2H, m), 6,23 (1H, d, J = 8,7 Hz), 6,36 (1H, s), 7,26-7,39 (10H, m), 7,60 y 7,68 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3451, 3088, 3064, 3029, 3014, 2925, 2869, 1707, 1652, 1522, 1495 /cm.
[\alpha]_{D} = +54,2º (MeOH, c = 1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-31
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,50-2,50 (14H, m), 3,63 (3H, s), 4,31 (1H, m), 5,30-5,50 (2H, m), 6,26 (1H, d, J = 8,4 Hz), 6,90 (1H, t, J = 7,4 Hz), 7,13 (1H, d, J = 8,7 Hz), 7,29 (2H, t, J = 8,0 Hz), 7,67-7,75 (5H, m), 7,82 (1H, s).
IR (nujol): 3380, 3244, 1723, 1638, 1601, 1578, 1535, 1495 /cm.
[\alpha]_{D} = +73,6º (MeOH, c = 0,50, 26ºC)
p.f. 133,0-134,0ºC
\vskip1.000000\baselineskip
Nº2a-32
[\alpha]_{D} = +56,1º (MeOH, c = 1,02, 26ºC)
\vskip1.000000\baselineskip
Nº2a-33
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,2 Hz), 1,10 y 1,21 (cada 3H, cada s), 1,50-2,50 (14H, m), 4,25 (1H, m), 5,13 (2H, s), 5,30-5,70 (3H, m), 6,41 (1H, d, J = 8,2 Hz), 6,89 (1H, s), 7,09 (1H, s), 7,17 y 7,72 (cada 2H, cada d, J = 8,2 Hz), 7,62 (1H,
s).
IR (CHCl_{3}): 3450, 3125, 3031, 3013, 2925, 2870, 2467, 1917, 1708, 1654, 1615, 1575, 1523, 1497/cm.
[\alpha]_{D} = +55,2º (MeOH, c = 1,01, 26ºC)
\vskip1.000000\baselineskip
Nº2a-34
[\alpha]_{D} = +72,9º (MeOH, c = 1,03, 25ºC)
\vskip1.000000\baselineskip
Nº2a-35
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,13 y 1,24 (cada 3H, cada s), 1,52-2,48 (14H, m), 4,28 (1H, m), 5,35-5,51 (2H, m), 6,28 (1H, d, J = 8,7 Hz), 7,34-7,37 (3H, m), 7,52 -7,55 (2H, m), 7,58 y 7,71 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3515, 3452, 3030, 3012, 2925, 2870, 1739, 1708, 1652, 1607, 1555, 1521, 1497 /cm.
[\alpha]_{D} = +74,3º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-36
[\alpha]_{D} = +23,49º (MeOH, c = 1,07, 25ºC)
\vskip1.000000\baselineskip
Nº2a-37
CDCl_{3} 300MHz
0,83 (1H, d, J = 10,5 Hz), 0,95 y 1,18 (cada 3H, cada s), 1,44-2,46 (14H, m), 3,92 (1H, m), 5,34-5,52 (3H, m), 7,26-7,54 (9H, m), 7,62 (1H, s).
IR (CHCl_{3}): 3432, 3310, 3189, 3023, 3014, 2924, 2870, 1704, 1610, 1594, 1523, 1487/cm.
[\alpha]_{D} = +25,3º (MeOH, c = 1,00, 26ºC)
\vskip1.000000\baselineskip
Nº2a-38
[\alpha]_{D} = +70,9º (MeOH, c = 1,02, 25ºC)
\vskip1.000000\baselineskip
Nº2a-39
[\alpha]_{D} = +70,6º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-40
[\alpha]_{D} = +74,7º (MeOH, c = 1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-41
[\alpha]_{D} = +72,1º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-42
[\alpha]_{D} = +69,2º (MeOH, c = 1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-43
[\alpha]_{D} = +70,8º (MeOH, c = 1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-44
[\alpha]_{D} = +60,4º (MeOH, c = 1,00, 26ºC)
\vskip1.000000\baselineskip
Nº2a-45
CDCl_{3} 300MHz
0,97 (1H, d, J = 9,9 Hz), 1,13 y 1,23 (cada 3H, cada s), 1,55-2,52 (14H, m), 4,29 (1H, m), 5,34 -5,54 (2H, m), 6,33 (1H, d, J = 9,0 Hz), 7,10 (1H, t, J = 7,4 Hz), 7,34 (2H, t, J = 7,4 Hz), 7,52 (2H, m), 7,68 y 7,75 (cada 2H, cada d, J = 8,4 Hz), 7,80 (1H, s), 8,10 (1H, s), 10,09 (1H, s).
IR (CHCl_{3}): 3393, 3195, 3093, 3033, 3013, 2925, 2870, 1698, 1656, 1598, 1537, 1498 /cm.
[\alpha]_{D} = +59,4º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-46
[\alpha]_{D} = +63,5º (MeOH, c =1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-47
CDCl_{3} 300MHz
0,97 (1H, d, J = 9,9 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,54-2,48 (14H, m), 4,29 (1H, m), 5,35-5,52 (2H, m), 6,32 (1H, d, J = 8,7 Hz), 7,26 (1H, m), 7,41 (2H, t, J = 7,8 Hz), 7,64 (2H, d, J = 7,5 Hz), 7,73 y 7,77 (cada 2H, cada d, J = 8,4 Hz), 7,95 (1H, s), 9,20 (1H, s), 10,38 (1H, s).
IR (CHCl_{3}): 3450, 3339, 3003, 2992, 2925, 2870, 1706, 1653, 1596, 1523, 1495/cm.
[\alpha]_{D} = +63,3º (MeOH, c = 1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-48
[\alpha]_{D} = +63,8º (MeOH, c = 1,00, 24ºC)
\vskip1.000000\baselineskip
Nº2a-49
CDCl_{3} 300MHz
1,00 (1H, d, J = 10,5 Hz), 1,17 y 1,26 (cada 3H, cada s), 1,55-2,52 (14H, m), 4,34 (1H, m), 5,36-5,54 (2H, m), 6,35 (1H, d, J = 9,0 Hz), 7,50-7,62 (3H, m), 7,90 y 8,33 (cada 2H, cada d, J = 8,4 Hz), 8,21 (2H, m).
IR (CHCl_{3}): 3451, 3029, 3022, 3016, 2925, 2870, 1708, 1655, 1542, 1508, 1498, 1471, 1459/cm.
[\alpha]_{D} = +63,5º (MeOH, c = 1,02, 25ºC)
p.f. 135,0-137,0ºC
\vskip1.000000\baselineskip
Nº2a-50
[\alpha]_{D} = +68,9º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-51
D_{6}-DMSO 300MHz
0,87 (1H, d, J = 9,9 Hz), 1,10 y 1,17 (cada 3H, cada s), 1,40 -1,60 (3H, m), 1,90-2,40 (11H, m), 3,98 (1H, m), 5,35 -5,46 (2H, m), 7,64 (1H, s), 7,65 y 7,91 (cada 2H, cada d, J = 8,7 Hz), 8,06 (1H, d, J = 6,0 Hz), 9,32 (1H, ancho s).
IR (KBr): 3385, 2962, 1734, 1707, 1632, 1529, 1498 /cm.
[\alpha]_{D} = +68,4º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-52
[\alpha]_{D} = +76,2º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-53
[\alpha]_{D} = +73,9º (MeOH, c = 1,02, 24ºC)
\vskip1.000000\baselineskip
Nº2a-54
[\alpha]_{D} = +68,1º (MeOH, c = 1,00, 24ºC)
\vskip1.000000\baselineskip
Nº2a-55
[\alpha]_{D} = +67,8º (MeOH, c = 1,00, 24ºC)
\vskip1.000000\baselineskip
Nº2a-56
[\alpha]_{D} = +65,4º (MeOH, c = 1,03, 25ºC)
\vskip1.000000\baselineskip
Nº2a-57
[\alpha]_{D} = +63,4º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-58
[\alpha]_{D} = +66,6º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-59
[\alpha]_{D} = +65,5º (MeOH, c = 1,00, 24ºC)
\vskip1.000000\baselineskip
Nº2a-60
[\alpha]_{D} = +60,9º (MeOH, c = 1,02, 25ºC)
\vskip1.000000\baselineskip
Nº2a-61
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,0Hz), 1,10 y 1,22 (cada 3H, cada s), 1,50 -2,50 (14H, m), 4,26 (1H, m), 5,30-5,54 (2H, m), 6,28 (1H, d, J = 8,6 Hz), 6,60 y 6,82 (cada 1H, cada d, J = 12,4 Hz), 7,12 (2H, d, J =6,0 Hz), 7,25 y 7,62 (cada 2H, cada d, J = 8,6 Hz), 8,47 (2H, d, J = 6,0 Hz).
IR (CHCl_{3}): 3452, 3027, 3019, 3013, 2925, 2870, 2480, 1708, 1651, 1606, 1520, 1494/cm.
[\alpha]_{D} = +61,6º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-62
[\alpha]_{D} = +72,0º (MeOH, c = 0,93, 25ºC)
\vskip1.000000\baselineskip
Nº2a-63
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,50-2,50 (14H, m), 4,29 (1H, m), 5,36-5,55 (2H, m), 6,35 (1H, d, J = 9,1 Hz), 7,04 y 7,27 (cada 1H, cada d, J = 16,5 Hz), 7,37 (2H, d, J = 6,6 Hz), 7,56 y 7,76 (cada 2H, cada d, J = 8,4 Hz), 8,57 (2H, d, J = 6,6 Hz).
\newpage
IR (CHCl_{3}): 3452, 3024, 3018, 3014, 2925, 2870, 2470, 1933, 1708, 1652, 1605, 1521, 1496/cm.
[\alpha]_{D} = +69,2º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-64
[\alpha]_{D} = +56,9º (MeOH, c = 1,24, 25ºC)
\vskip1.000000\baselineskip
Nº2a-65
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,5 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,54 -2,46 (14H, m), 4,27 (1H, m), 5,23 (2H, s), 5,34 -5,52 (2H, m), 6,26 (1H, d, J = 8,4 Hz), 7,32-7,45 (5H, m), 7,64 y 7,71 (cada 2H, cada d, J = 8,4 Hz), 8,15 (1H,
s).
IR (CHCl_{3}): 3452, 3088, 3065, 3032, 3013, 2925, 2870, 1708, 1653, 1611, 1559, 1522, 1496/cm.
[\alpha]_{D} = +61,0º (MeOH, c =0,91, 25ºC)
\vskip1.000000\baselineskip
Nº2a-66
[\alpha]_{D} = +76,0º (MeOH, c =1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-67
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,4 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,54 -2,46 (14H, m), 4,28 (1H, m), 5,32-5,53 (2H, m), 6,27 (1H, d, J = 8,6 Hz), 6,92-7,31 (cada 1H, cada d, J = 16,4Hz), 7,02 (1H, d, J = 5,8 y 3,6 Hz), 7,12 (1H, d, J = 3,6 Hz), 7,24 (1H, d, J = 5,8 Hz), 7,51 y 7,70 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3453, 3029, 3013, 2925, 2870, 1739, 1650, 1604, 1524, 1515, 1494/cm
[\alpha]_{D} = +76,2 MeOH, c = 1,00, 24ºC)
p.f. 104,0-106,0ºC
\vskip1.000000\baselineskip
Nº2a-68
[\alpha]_{D} = +57,7º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-69
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,54-2,48 (14H, m), 4,28 (1H, m), 5,34-5,53 (2H, m), 6,29 (1H, d, J = 9,0 Hz), 6,54-6,74 (cada 1H, cada d, J = 12,0 Hz), 7,02 (1H, dd, J = 4,8 y 3,3 Hz), 6,97 (1H, dd, J = 3,3 y 1,2 Hz), 7,13 (1H, dd, J = 4,8 y 1,2 Hz), 7,44 y 7,70 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3453, 3025, 3010, 2925, 2870, 1708, 1650, 1607, 1559, 1523, 1493 /cm.
[\alpha]_{D} = +58,4º (MeOH, c =1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-70
[\alpha]_{D} = +48,6º (MeOH, c =1,00, 25ºC)
\newpage
Nº2a-71
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 2,31 (3H, s), 4,26 (1H, m), 5,33-5,52 (2H, m), 6,20 (1H, d, J = 9,3 Hz), 7,02-7,11 (6H, m), 7,70 (2H, d, J = 9,0 Hz).
IR (CHCl_{3}): 3460, 3031, 3022, 3011, 2925, 2870, 1750, 1708, 1650, 1608, 1597, 1523, 1490/cm.
[\alpha]_{D} = +48,9º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-72
[\alpha]_{D} = +51,2º (MeOH, c = 1,02, 25ºC)
\vskip1.000000\baselineskip
Nº2a-73
CDCl_{3} 300MHz
0,97 (1H, d, J = 9,9 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,54 -2,48 (14H, m), 4,27 (1H, m), 5,32-5,52 (2H, m), 6,24 (1H, d, J = 9,0 Hz), 6,83-6,94 (6H, m), 7,65 (2H, d, J = 9,0 Hz).
IR (CHCl_{3}): 3598, 3451, 3199, 3033, 3012, 2925, 2870, 1708, 1642, 1604, 1524, 1507, 1491 /cm.
[\alpha]_{D} = +52,2º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-74
[\alpha]_{D} = +51,5º (MeOH, c = 0,92, 25ºC)
\vskip1.000000\baselineskip
Nº2a-75
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,55-2,46 (14H, m), 3,82 (3H, s), 4,25 (1H, m), 5,32 -5,52 (2H, m), 6,19 (1H, d, J = 8,7 Hz), 6,89-7,01 (6H, m), 7,65-7,68 (2H, m).
IR (CHCl_{3}): 3450, 3025, 3008, 2925, 2870, 2837, 1741, 1649, 1612, 1521, 1505, 1490/cm.
[\alpha]_{D} = +51,1º (MeOH, c =1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-76
[\alpha]_{D} = +60,4º (MeOH, c =0,98, 25ºC)
\vskip1.000000\baselineskip
Nº2a-77
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,5 Hz), 1,15 y 1,24 (cada 3H, cada s), 1,54-2,48 (14H, m), 2,34 (3H, s), 4,29 (1H, m), 5,32 -5,54 (2H, m), 6,32 (1H, d, J = 8,4 Hz), 7,19 y 7,60 (cada 2H, cada d, J = 8,4 Hz), 7,63 y 7,79 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3452, 3027, 3012, 2925, 2870, 1751, 1709, 1651, 1611, 1560, 1527, 1509, 1489/cm.
[\alpha]_{D} = +61,2º (MeOH, c = 1,00, 25ºC)
\vskip1.000000\baselineskip
Nº2a-78
[\alpha]_{D} = +67,4º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-79
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,15 y 1,24 (cada 3H, cada s), 1,54-2,54 (14H, m), 4,31 (1H, m), 5,32-5,54 (2H, m), 6,36 (1H, d, J = 8,2 Hz), 6,93 y 7,48 (cada 2H, cada d, J = 8,6 Hz), 7,59 y 7,75 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3593, 3448, 3192, 3030, 3010, 2925, 2870, 1708, 1644, 1608, 1591, 1559, 1530, 1516, 1491/cm.
[\alpha]_{D} = +65,8º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-80
[\alpha]_{D} = +66,9º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-81
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,5 Hz), 1,15 y 1,24 (cada 3H, cada s), 1,54-2,48 (14H, m), 3,86 (3H, s), 4,29 (1H, m), 5,34-5,52 (2H, m), 6,20 (1H, d, J = 8,7 Hz), 6,99 y 7,55 (cada 2H, cada d, J = 9,0 Hz), 7,61 y 7,77 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3450, 3009, 2925, 2870, 2838, 1740, 1708, 1650, 1608, 1557, 1528, 1512, 1491/cm.
[\alpha]_{D} = +66,2º (MeOH, c =1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-82
[\alpha]_{D} = +57,7º (MeOH, c =1,02, 24ºC)
\vskip1.000000\baselineskip
Nº2a-83
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,54-2,48 (14H, m), 2,33 (3H, s), 4,26 (1H, m), 5,32-5,52 (2H, m), 6,25 (1H, d, J = 8,7 Hz), 7,16 y 7,75 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3452, 3030, 3022, 3012, 2925, 2870, 1754, 1709, 1654, 1604, 1585, 1522, 1493/cm.
[\alpha]_{D} = +57,4º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-84
[\alpha]_{D} = +57,8º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-85
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,2 Hz), 1,12 y 1,22 (cada 3H, cada s), 1,54-2,48 (14H, m), 4,25 (1H, m), 5,32-5,52 (2H, m), 6,28 (1H, d, J = 8,7Hz), 6,87 y 7,57 (cada 2H, cada d, J = 9,0 Hz).
IR (CHCl_{3}): 3590, 3450, 3166, 3019, 3012, 2925, 2871, 1708, 1637, 1608, 1583, 1531, 1498/cm.
[\alpha]_{D} = +56,0º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-86
[\alpha]_{D} = +59,3º (MeOH, c = 1,01, 22ºC)
\vskip1.000000\baselineskip
Nº2a-87
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,0 Hz), 1,13 y 1,23 (cada 3H, cada s), 1,54-2,48 (14H, m), 3,85 (3H, s), 4,25 (1H, m), 5,32-5,53 (2H, m), 6,19 (1H, d, J = 8,8Hz), 6,93 y 7,69 (cada 2H, cada d, J = 9,0 Hz).
IR (CHCl_{3}): 3450, 3030, 3017, 3012, 2925, 2870, 2840, 1740, 1708, 1647, 1606, 1575, 1525, 1496/cm.
[\alpha]_{D} = +58,2º (MeOH, c =0,99, 22ºC)
\vskip1.000000\baselineskip
Nº2a-88
[\alpha]_{D} = +50,9º (MeOH, c =1,02, 25ºC)
\vskip1.000000\baselineskip
Nº2a-89
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,18 y 1,26 (cada 3H, cada s), 1,56-2,48 (14H, m), 4,29 (1H, m), 5,36-5,54 (2H, m), 7,03 (1H, d, J = 8,7 Hz), 7,21 (1H, s), 7,43 (2H, m), 7,74 (1H, ddd, J = 1,8, 6,9 y 8,7 Hz), 8,22 (1H, dd, J = 1,8 y 8,1 Hz).
IR (CHCl_{3}): 3443, 3087, 3023, 3014, 2925, 2870, 1708, 1685, 1658, 1630, 1517, 1466/cm.
[\alpha]_{D} = +57,1º (MeOH, c = 1,01, 22ºC)
p.f. 117,0-118,0ºC
\vskip1.000000\baselineskip
Nº2a-90
[\alpha]_{D} = +54,1º (MeOH, c = 1,01, 22ºC)
\vskip1.000000\baselineskip
Nº2a-91
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,13 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 4,24 (1H, m), 5,34-5,52 (2H, m), 6,49-6,53 (2H, m), 7,11 (1H, dd, J = 0,9 y 3,6 Hz), 7,44 (1H, dd, J = 0,9 y 1,8 Hz).
IR (CHCl_{3}): 3437, 3033, 3022, 3014, 2925, 2870, 1739, 1708, 1655, 1595, 1520, 1472 /cm.
[\alpha]_{D} = +55,0º (MeOH, c = 1,00, 22ºC)
\vskip1.000000\baselineskip
Nº2a-92
[\alpha]_{D} = +50,3º (MeOH, c = 1,00, 22ºC)
\vskip1.000000\baselineskip
Nº2a-93
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,5 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 4,25 (1H, m), 5,34 -5,52 (2H, m), 6,12 (1H, d, J = 8,7 Hz), 7,07 (1H, dd, J = 3,9 y 5,1 Hz), 7,45 - 7,48 (2H, m).
IR (CHCl_{3}): 3450, 3023, 3011, 2925, 2870, 1739, 1708, 1645, 1531, 1501, 1471 /cm.
[\alpha]_{D} = +49,1º (MeOH, c = 1,02, 24ºC)
\vskip1.000000\baselineskip
Nº2a-94
[\alpha]_{D} = +51,5º (MeOH, c = 1,00, 24ºC)
\vskip1.000000\baselineskip
Nº2a-95
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 4,25 (1H, m), 5,34-5,56 (2H, m), 6,14 (1H, d, J = 8,7 Hz), 7,34 (2H, d, J = 2,0 Hz), 7,85 (1H, d, J = 2,0 Hz).
IR (CHCl_{3}): 3452, 3114, 3030, 3013, 2925, 2870, 1708, 1649, 1535, 1498, 1471/cm.
[\alpha]_{D} = +55,5º (MeOH, c = 1,00, 25ºC)
p.f. 87,0-88,0ºC
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Nº2a-96
CD_{3}OD 300MHz
0,94 (1H, d, J = 10,2 Hz), 1,13 y 1,22 (cada 3H, cada s), 1,50-1,76 (3H, m), 1,94-2,39 (11H, m), 4,11 (1H, m), 5,39-5,49 (2H, m), 7,43-7,51 (2H, m), 8,05 (1H, m).
IR (KBr): 3369, 3084, 2985, 2921, 2868, 1630, 1566, 1538, 1503/cm.
[\alpha]_{D} = +38,8º (MeOH, c = 1,01, 22ºC)
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Nº2a-97
CD_{3}OD 300MHz
0,93 (1H, d, J = 9,9Hz), 1,3 y 1,22 (cada 3H, cada s), 1,48-1,58 (3H, m), 1,96-2,36 (11H, m), 4,10 (1H, m), 5,35-5,50 (2H, m), 7,42 -7,51 (2H, m), 8,06 (1H, m).
IR (KBr): 3447, 3087, 2987, 2922, 2868, 1629, 1545, 1501/cm.
[\alpha]_{D} = +52,9º (MeOH, c = 1,01, 24ºC)
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Nº2a-98
[\alpha]_{D} = +53,2º (MeOH, c = 1,02, 23ºC)
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Nº2a-99
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,2 y 1,22 (cada 3H, cada s), 1,26-2,45 (24H, m), 4,25 (2H, m), 5,34 -5,52 (2H, m), 6,18 (1H, d, J = 8,7 Hz), 6,91 y 7,66 (cada 2H, cada d, J = 9,0 Hz).
IR (CHCl_{3}): 3455, 3029, 3019, 2939, 2862, 1738, 1709, 1645, 1605, 1523, 1494 /cm.
[\alpha]_{D} = +51,4º (MeOH, c = 1,00, 23ºC)
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Nº2a-100
[\alpha]_{D} = +49,3º (MeOH, c = 1,00, 24ºC)
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Nº2a-101
[\alpha]_{D} = +51,3º (MeOH, c =1,00, 24ºC)
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Nº2a-102
[\alpha]_{D} = +48,8º (MeOH, c = 1,01, 23ºC)
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Nº2a-103
CDCl_{3} 300MHz
0,94 (1H, d, J = 10,2 Hz), 1,12 y 1,22 (cada 3H, cada s), 1,52-2,46 (14H, m), 2,48 83H, d, J = 0,3 Hz), 4,20 (1H, m), 5,32-5,54 (2H, m), 6,46 (1H, ancho s), 7,12 (1H, d, J = 9,0 Hz).
IR (CHCl_{3}): 3415, 3144, 3029, 3011, 2926, 2871, 1708, 1671, 1598, 1538, 14564/cm.
[\alpha]_{D} = +49,6º (MeOH, c = 1,01, 23ºC)
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Nº2a-104
[\alpha]_{D} = +77,0º (MeOH, c = 1,02, 23ºC)
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Nº2a-105
CDCl_{3} 300MHz
93(1H, d, J = 9,9 Hz), 1,09 y 1,21 (cada 3H, cada s), 1,51-2,44 (14H, m), 3,90 (6H, s), 4,20 (1H, m), 5,38-5,50 (2H, m), 5,87 (1H, d, J = 9,0 Hz), 6,25 y 7,54 (cada 1H, cada d, J = 15,6 Hz), 6,84 (1H, d, J = 8,1 Hz), 7,03 (1H, d, J = 1,8 Hz), 7,09 (1H, dd, J = 1,8 Hz y 8,1 Hz).
IR (CHCl_{3}): 3439, 3028, 3012, 2937, 2871, 2841, 1739, 1708, 1661, 1620, 1600, 1513/cm.
[\alpha]_{D} = +77,3º (MeOH, c = 1,01, 23ºC)
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Nº2a-106
[\alpha]_{D} = +67,0º (MeOH, c = 1,00, 25ºC)
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Nº2a-107
[\alpha]_{D} = +66,6º (MeOH, c = 1,01, 24ºC)
p.f. 168,0-170,0ºC
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Nº2a-108
[\alpha]_{D} = +61,8º (MeOH, c = 1,00, 22ºC)
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Nº2a-109
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,10 y 1,22 (cada 3H, cada s), 1,51-2,45 (14H, m), 4,25 (1H, m), 5,33-5,49 (2H, m), 6,21 (1H, d, J = 8,7 Hz), 7,25 y 7,60 (cada 2H, cada d, J = 8,7 Hz), 7,33-7,41 (5H, s).
IR (CHCl_{3}): 3453, 3062, 3028, 3014, 2925, 2870, 1739, 1708, 1651, 1594, 1557, 1515, 1481/cm.
[\alpha]_{D} = +61,0º (MeOH, c = 1,01, 22ºC)
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Nº2a-110
CD_{3}OD 300MHz
0,94 (1H, d, J = 9,9 Hz), 1,13 y 1,22 (cada 3H, cada s), 1,54-2,37 (14H, m), 4,12 (1H, m), 5,38-5,49 (2H, m), 7,25 y 7,68 (cada 2H, cada d, J = 8,7 Hz), 7,41 (5H, s).
\newpage
IR (KBr): 3435, 3058, 2986, 2920, 2866, 1635, 1595, 1562, 1521, 1482, 1439, 1411/cm.
[\alpha]_{D} = +47,3º (MeOH, c = 1,01, 23ºC)
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Nº2a-111
[\alpha]_{D} = +65,6º (MeOH, c = 1,01, 24ºC)
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Nº2a-112
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2Hz), 1,12 y 1,23 (cada 3H, cada s), 1,51-2,46 (14H, m), 4,27 (1H, m), 5,35 -5,50 (2H, m), 6,22 (1H, d, J = 8,4 Hz), 7,40 y 7,66 (cada 2H, cada d, J = 9,0 Hz).
IR (CHCl_{3}): 3439, 3028, 3012, 2937, 2871, 2841, 1739, 1708, 1661, 1620, 1600, 1513 /cm.
[\alpha]_{D} = +65,6º (MeOH, c = 1,01, 22ºC)
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Nº2a-113
[\alpha]_{D} = +59,6º (MeOH, c = 1,00, 24ºC)
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Nº2a-114
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,12 y 1,24 (cada 3H, cada s), 1,52-2,46 (14H, m), 4,29 (1H, m), 5,35-5,51 (2H, m), 6,28 (1H, d, J = 8,4 Hz), 7,70 y 7,83 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3439, 3028, 3012, 2937, 2871, 2841, 1739, 1708, 1661, 1620, 1600, 1513/cm.
[\alpha]_{D} = +60,6º (MeOH, c = 1,01, 22ºC)
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Nº2a-115
[\alpha]_{D} = +59,7º (MeOH, c = 0,99, 24ºC)
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Nº2a-116
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 2,39 (3H, s), 4,27 (1H, m), 5,33-5,51 (2H, m), 6,24 (1H, d, J = 9,0 Hz), 7,23 y 7,62 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3439, 3028, 3012, 2937, 2871, 2841, 1739, 1708, 1661, 1620, 1600, 1513/cm.
[\alpha]_{D} = +59,7º (MeOH, c = 0,99, 24ºC)
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Nº2a-117
[\alpha]_{D} = +56,7º (MeOH, c = 1,00, 23ºC)
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Nº2a-118
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,53-2,44 (14H, m), 4,23 (1H, m), 5,34 -5,51 (2H, m), 6,02 (2H, s), 6,13 (1H, d, J = 8,7 Hz), 6,83 (1H, dd, J = 1,2 y 7,8 Hz), 7,22-7,25 (2H, m).
IR (CHCl_{3}): 3453, 3031, 3020, 3012, 2924, 2870, 1740, 1708, 1650, 1619, 1605, 1519, 1504, 1480/cm.
[\alpha]_{D} = +57,2º (MeOH, c = 1,02, 23ºC)
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Nº2a-119
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,07 y 1,23 (cada 3H, cada s), 1,51-2,44 (14H, m), 2,32 (3H, s), 4,26 (1H, m), 5,37 -5,52 (2H, m), 6,40 (1H, d, J = 9,0 Hz), 7,09 (1H, m), 7,30 (1H, m), 7,46 (1H, m), 7,66 (1H, m).
IR (CHCl_{3}): 3443, 3028, 3012, 2925, 2870, 1766, 1747, 1709, 1657, 1607, 1516, 1479/cm.
[\alpha]_{D} = +53,2º (MeOH, c = 0,99, 21ºC)
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Nº2a-120
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,53-2,44 (14H, m), 4,30 (1H, m), 5,35-5,52 (2H, m), 6,42 (1H, d, J = 8,7 Hz), 6,85 (1H, m), 6,99 (1H, dd, J = 1,2 y 8,4 Hz), 7,27 (1H, m), 7,39 (1H, m).
IR (CHCl_{3}): 3463, 3033, 3021, 3014, 2992, 2924, 2870, 1708, 1643, 1597, 1523, 1488/cm.
[\alpha]_{D} = +46,3º (MeOH, c = 1,01, 21ºC)
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Nº2a-121
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,14 y 1,23 (cada 3H, cada s), 1,47-2,47 (14H, m), 3,95 (3H, s), 4,31 (1H, m), 5,32 -5,50 (2H, m), 6,98 (1H, dd, J = 0,9 y 8,4 Hz), 7,09 (1H, ddd, J = 0,9, 7,7 y 8,4Hz), 7,45 (1H, m), 8,19 (1H, dd, J = 2,1 y 8,1 Hz), 8,32 (1H, d, J = 9,0 Hz).
IR (CHCl_{3}): 3400, 3078, 3028, 3020, 3007, 2924, 2870, 2842, 1736, 1708, 1640, 1600, 1536, 1483, 1470/cm.
[\alpha]_{D} = +38,1º (MeOH, c = 1,02, 23ºC)
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Nº2a-122
[\alpha]_{D} = +42,3º (MeOH, c = 0,99, 23ºC)
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Nº2a-123
[\alpha]_{D} = +38,7º (MeOH, c = 1,00, 21ºC)
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Nº2a-124
[\alpha]_{D} = +45,0º (MeOH, c = 1,01, 21ºC)
p.f. 119,0-120,0ºC
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Nº2a-125
[\alpha]_{D} = +49,8º (MeOH, c = 1,01, 22ºC)
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Nº2a-126
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,52-2,47 (14H, m), 4,26 (1H, m), 5,34-5,50 (2H, m), 6,22 (1H, d, J = 8,7 Hz), 7,55 -7,61 (4H, m).
IR (CHCl_{3}): 3400, 3078, 3028, 3020, 3007, 2924, 2870, 2842, 1736, 1708, 1640, 1600, 1536, 1483, 1470/cm.
[\alpha]_{D} = +63,0º (MeOH, c = 1,01, 23ºC)
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Nº2a-127
CDCl_{3} 300MHz
0,91 (1H, d, J = 10,2 Hz), 1,10 y 1,20 (cada 3H, cada s), 1,50-2,42 (14H, m), 4,23 (1H, m), 5,31-5,51 (2H, m), 6,45 (1H, d, J = 8,4 Hz), 7,01 (1H, t, J = 7,4 Hz), 7,22-7,27 (2H, m), 7,33-7,40 (4H, m), 7,53 (2H, d, J = 9,0 Hz), 8,30 y 8,48 (cada 1H, cada s)
IR (CHCl_{3}): 3452, 3028, 3022, 3015, 2925, 2870, 1708, 1654, 1590, 1514, 1478/cm.
[\alpha]_{D} = +59,5º (MeOH, c = 1,01, 23ºC)
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Nº2a-128
d_{6}-DMSO 300MHz
0,84 (1H, d, J = 9,9 Hz), 1,06 y 1,19 (cada 3H, cada s), 1,37-2,37 (14H, m), 3,79 (1H, m), 5,35-5,51 (2H, m), 6,08 (1H, d, J = 8,7 Hz), 6,85-6,90 (1H, m), 7,18-7,23 (2H, m), 7,35-7,38 (2H, m), 8,42 (1H, s), 12,00 (1H, s).
IR (Nujol): 3395, 3345, 2925, 2866, 2623, 2506, 1697, 1658, 1638, 1597, 1557 /cm.
[\alpha]_{D} = +26,0º (MeOH, c = 1,01, 23ºC)
p.f. 164,0-166,0ºC
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Nº2a-129
CDCl_{3} 300MHz
1,01 (1H, d, J = 10,0 Hz), 1,17 y 1,25 (cada 3H, cada s), 1,54-2,52 (14H, m), 4,34 (1H, m), 5,36-5,57 (2H, m), 6,42 (1H, d, J = 8,6 Hz), 7,51-7,60 (2H, m), 7,77 (1H, dd, J = 1,8 y 8,6 Hz), 7,85 -7,96 (3H, m), 8,24 (1H, ancho s).
IR (CHCl_{3}): 3451, 3060, 3028, 3010, 2925, 2870, 1708, 1652, 1629, 1600, 1517, 1502/cm.
[\alpha]_{D} = +68,6º (MeOH, c = 1,00, 22ºC)
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Nº2a-130
CDCl_{3} 300MHz
1,02 (1H, d, J = 10,2 Hz), 1,04 y 1,26 (cada 3H, cada s), 154-2,52 (14H, m), 4,41 (1H, m), 5,41 -5,58 (2H, m), 6,14 (1H, d, J = 9,0 Hz), 7,43-7,59 (4H, m), 7,85 -7,92 (2H, m), 8,27 (1H, dd, J = 1,8 y 7,2 Hz).
IR (CHCl_{3}): 3436, 3032, 3010, 2924, 2870, 2664, 1708, 1652, 1512, 1498/cm.
[\alpha]_{D} = +93,9º (MeOH, c = 1,00, 22ºC)
p.f. 94,0-96,0ºC
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Nº2a-131
[\alpha]_{D} = +50,2º (MeOH, c = 0,95, 21ºC)
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Nº2a-132
[\alpha]_{D} = +10,9º (MeOH, c = 0,92, 21ºC)
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Nº2a-133
[\alpha]_{D} = +60,4º (MeOH, c = 1,00, 21ºC)
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Nº2a-134
[\alpha]_{D} = +38,5º (MeOH, c = 1,01, 23ºC)
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Nº2a-135
[\alpha]_{D} = +52,5º (MeOH, c = 1,01, 23ºC)
p.f. 180,0-182,0ºC
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Nº2a-136
[\alpha]_{D} = +35,3º (MeOH, c = 1,02, 23ºC)
p.f. 79,0-80,0ºC
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Nº2a-137
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2Hz), 1,11 y 1,22 (cada 3H, cada s), 1,43 (3H, t, J = 6,9 Hz), 1,52-2,44 (14H, m), 4,03 (2H, q, J = 6,9 Hz), 4,26 (1H, m), 5,33-5,50 (2H, m), 6,19 (1H, d, J = 8,7 Hz), 6,88-7,00 (6H, m), 7,65 -7,68 (2H, m).
IR (CHCl_{3}): 3455, 3031, 3024, 3014, 2988, 2925, 2870, 1741, 1708, 1649, 1602, 1521, 1504, 1490/cm.
[\alpha]_{D} = +52,0º (MeOH, c = 1,01, 23ºC)
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Nº2a-138
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,22 (cada 3H, cada s), 1,35 (6H, d, J = 6,0 Hz), 1,53-2,46 (14H, m), 4,25 (1H, m), 4,51 (1H, m), 5,33-5,50 (2H, m), 6,12 (1H, d, J = 9,0 Hz), 6,87 -6,99 (6H, m), 7,65 -7,68 (2H, m).
IR (CHCl_{3}): 3454, 3031, 3014, 2980, 2925, 2870, 1741, 1708, 1649, 1602, 1522, 1490/cm.
[\alpha]_{D} = +50,0º (MeOH, c = 1,05, 22ºC)
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Nº2a-139
CDCl_{3} 300MHz
1,00 (1H, d, J = 10,2 Hz), 1,16 y 1,24 (cada 3H, cada s), 1,59 -2,52 (14H, m), 4,31 (1H, m), 5,40 -5,53 (2H, m), 6,36 (1H, d, J = 8,7 Hz), 6,70 (1H, d, J = 1,5 Hz), 7,12 (1H, m), 7,30 (1H, m), 7,47 (1H, dd, J = 0,6 y 8,1 Hz), 7,61 (1H, d, J = 8,4 Hz).
IR (CHCl_{3}): 3449, 3243, 3029, 3022, 3013, 2925, 2871, 1707, 1631, 1542, 1505 /cm.
[\alpha]_{D} = +63,4º (MeOH, c = 1,00, 23ºC)
p.f. 178,0-179,0ºC
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Nº2a-140
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,8 y 1,23 (cada 3H, cada s), 1,57 -2,50 (14H, m), 4,35 (1H, m), 5,32-5,55 (2H, m), 6,42 (1H, d, J = 8,7 Hz), 6,70 (1H, d, J = 1,5 Hz), 7,21 -7,24 (2H, m), 7,46 (1H, m), 7,76 (1H, m), 7,86 (1H, d, J = 3,0 Hz), 10,20 (1H, s).
IR (CHCl_{3}): 3465, 3010, 2924, 1739, 1604, 1546, 1504/cm.
[\alpha]_{D} = +39,4º (MeOH, c = 1,01, 22ºC)
p.f. 167,0-168,0
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Nº2a-141
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,55-2,44 (14H, m),3,84 (3H, s), 4,27 (1H, m), 5,34-5,52 (2H, m), 6,28 (1H, d, J = 9,0 Hz), 6,91 y 7,47 (cada 2H, cada d, J = 9,0 Hz), 6,98 y 7,14 (cada 1H, cada d, J = 16,5Hz), 7,54 y 7,70 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3453, 3025, 3015, 2925, 2870, 2839, 1740, 1708, 1649, 1602, 1510, 1493, 1470 /cm.
[\alpha]_{D} = +73,4º (MeOH, c = 1,02, 22ºC)
p.f. 155,0-157,0ºC
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Nº2a-142
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,52-2,45 (14H, m), 3,79 (3H, s), 4,27 (1H, m), 5,34-5,50 (2H, m), 6,24 (1H, d, J = 9,0 Hz), 6,49 y 6,62 (cada 1H cada d, J = 12,3 Hz), 6,77 y 7,16 (cada 2H, cada d, J = 8,7 Hz), 7,32 y 7,59 (cada 2H, cada d, J = 8,1 Hz).
IR (CHCl_{3}): 3453, 3025, 3014, 2925, 2870, 2839, 1739, 1708, 1649, 1606, 1510, 1494/cm.
[\alpha]_{D} = +60,7º (MeOH, c = 0,99, 22ºC)
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Nº2a-143
[\alpha]_{D} = +57,3º (MeOH, c = 1,01, 23ºC)
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Nº2a-144
[\alpha]_{D} = +12,2º (MeOH, c = 1,00, 23ºC)
p.f. 114,0-116,0ºC
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Nº2a-145
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,2 Hz), 1,10 y 1,21 (cada 3H, cada s), 1,52-2,44 (14H, m), 4,25 (1H, m), 5,33-5,49 (2H, m), 6,37 (1H, d, J = 8,7 Hz), 7,45 (3H, m), 7,62-7,66 (2H, m), 7,69 y 7,80 (cada 2H, cada d, J = 7,5 Hz).
IR (CHCl_{3}): 3449, 3058, 3027, 3012, 2925, 2870, 1708, 1655, 1513, 1481, 1043/cm.
[\alpha]_{D} = +61,0º (MeOH, c = 1,01, 23ºC)
\newpage
Nº2a-146
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,5 Hz), 1,09 y 1,21 (cada 3H, cada s), 1,50-2,41 (14H, m), 4,25 (1H, m), 5,33-5,49 (2H, m), 6,33 (1H, d, J = 8,4 Hz), 7,49 -7,61 (3H, m), 7,91-7,92 (2H, m), 7,82 y 7,97 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3447, 3029, 3023, 3015, 2925, 2870, 1708, 1660, 1514, 1484, 1321, 1161/cm.
[\alpha]_{D} = +62,0º (MeOH, c = 1,00, 22ºC)
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Nº2a-147
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 2,51 (3H, s), 4,26 (1H, m), 5,34-5,51 (2H, m), 6,23 (1H, d, J = 8,4 Hz), 7,26 y 7,64 (cada 2H, cada d, J = 8,4 Hz).
IR (CHCl_{3}): 3453, 3027, 3015, 2925, 2870, 2665, 1708, 1648, 1596, 1516, 1484 /cm.
[\alpha]_{D} = +67,7º (MeOH, c = 0,82, 22ºC)
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Nº2a-148
[\alpha]_{D} = +72,5º (MeOH, c = 1,01, 25ºC)
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Nº2a-149
[\alpha]_{D} = +67,8º (MeOH, c = 0,98, 25ºC)
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Nº2a-150
CDCl_{3} 300MHz
0,94 (1H, d, J = 10,2 Hz), 1,10 y 1,23 (cada 3H, cada s), 1,52-2,50 (14H, m), 4,22 (1H, m), 5,36-5,55 (2H, m), 6,48 (1H, d, J = 8,4 Hz), 8,35 (1H, s), 8,90 (1H, s).
IR (CHCl_{3}): 3443, 3374, 3091, 3024, 3012, 2925, 2871, 1709, 1652, 1525, 1494/cm.
[\alpha]_{D} = +58,1º (MeOH, c = 1,01, 23ºC)
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Nº2a-151
[\alpha]_{D} = +40,6º (MeOH, c = 1,01, 23ºC)
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Nº2a-152
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,10 y 1,24 (cada 3H, cada s), 1,50-2,50 (14H, m), 2,71 (3H, s), 4,26 (1H, m), 5,37 -5,51 (2H, m), 6,02 (1H, d, J = 9,0 Hz), 8,73 (1H, s).
IR (CHCl_{3}): 3463, 3435, 3087, 3025, 3014, 2925, 2870, 1708, 1649, 1523, 1503/cm.
[\alpha]_{D} = +54,1º (MeOH, c = 1,02, 22ºC)
\newpage
Nº2a-153
CDCl_{3} 300MHz
0,95 (1H, d, J = 9,9 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,50-2,50 (14H, m), 2,50 (3H, s), 4,26 (1H, m), 5,36-5,51 (2H, m), 6,01 (2H, m), 6,01 (1H, d, J = 8,4 Hz), 6,88 (1H, d, J = 5,1 Hz), 7,26 (1H, d, J = 5,1 Hz).
IR (CHCl_{3}): 3469, 3431, 3025, 3013, 2925, 2871, 2664, 1708, 1639, 1544, 1505/cm.
[\alpha]_{D} = +35,8º (MeOH, c = 1,03, 22ºC)
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Nº2a-154
CDCl_{3} 300MHz
0,95 (1H, d, J = 9,9 Hz), 1,10 y 1,22 (cada 3H, cada s), 1,52-2,46 (14H, m), 2,51 (3H, d, J = 1,2 Hz), 4,26 (1H, m), 5,34-5,50 (2H, m), 6,00 (1H, d, J = 8,4 Hz), 6,73 (1H, dd, J = 5,1 y 3,6 Hz), 7,29 (1H, d, J = 3,6 Hz).
IR (CHCl_{3}): 3450, 3431, 3026, 3011, 2925, 2869, 1739, 1708, 1639, 1547, 1508/cm.
[\alpha]_{D} = +50,5º (MeOH, c = 1,01, 22ºC)
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Nº2a-155
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,19 y 1,25 (cada 3H, cada s), 1,53-2,48 (14H, m), 4,31 (1H, m), 5,36-5,51 (2H, m)), 6,79 (1H, d, J = 9,3 Hz), 7,29 (1H, m), 7,41 (1H, m), 7,48 (1H, s), 7,51 (1H, m), 7,66 (1H, d, J = 8,1 Hz).
IR (CHCl_{3}): 3436, 3029, 3024, 3015, 2925, 2871, 2670, 1708, 1659, 1598, 1510/cm.
[\alpha]_{D} = +69,1º (MeOH, c = 1,01, 22ºC)
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Nº2a-156
CDCl_{3} : CD_{3}OD = 10:1 300MHz
0,99 (1H, d, J = 9,9 Hz), 1,11 y 1,21 (cada 3H, cada s), 1,56-2-58 (14H, m), 4,22 (1H, m), 5,35-5,59 (2H, m), 6,83 (1H, d, J = 8,4 Hz), 7,48 (1H, d, J = 8,4 Hz), 7,61 (1H, dd, J = 1,5 y 8,4 Hz), 8,09 (1H, d, J = 1,5 Hz), 8,12 (1H,
s).
IR (KBr): 3422, 3115, 2985, 2922, 2869, 2609, 1708, 1636, 1578, 1529, 1470/cm.
[\alpha]_{D} = +62,8º (MeOH, c = 1,01, 22ºC)
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Nº2a-157
[\alpha]_{D} = +40,0º (MeOH, c = 0,95, 22ºC)
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Nº2a-158
CDCl_{3} 300MHz
1,00 (1H, d, J = 10,5 Hz), 1,7 y 1,24 (cada 3H, cada s), 1,54-2,50 (14H, m), 4,34 (1H, m), 5,36-5,52 (2H, m), 7,80 (1H, d, J = 9,0 Hz), 9,30 (1H, s).
IR (CHCl_{3}): 3410, 3122, 3030, 3012, 2925, 2871, 2668, 1709, 1667, 1538, 1466/cm.
[\alpha]_{D} = +44,9º (MeOH, c = 0,99, 22ºC)
\newpage
Nº2a-159
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,13 y 1,22 (cada 3H, cada s), 1,55-2,43 (14H, m), 3,03 (6H, m), 4,23 (1H, m), 5,32-5,51 (2H, m), 6,16 (1H, d, J = 8,7 Hz), 6,87 y 7,63 (cada 2H, cada d, J = 8,7 Hz).
IR (CHCl_{3}): 3457, 3028, 3006, 2924, 2870, 2654, 1739, 1709, 1637, 1608, 1608, 1534, 1501/cm.
[\alpha]_{D} = +64,8º (MeOH, c = 1,01, 22ºC)
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Nº2a-160
d_{6}-DMSO 300MHz
0,83 (1H, d, J = 9,9 Hz), 1,02 y 1,19 (cada 3H, cada s), 1,38-1,61 (3H, m), 1,90-2,32 (11H, m), 3,90 (1H, m), 5,41-5,44 (2H, m), 7,32 (1H, dd, J = 0,9 y 7,2 Hz), 7,45-7,60 (2H, m), 7,77 (1H, dd, J = 0,9 y 7,8 Hz), 8,03 (1H, d, J = 6,9 Hz), 12,40 (1H, s).
IR (nujol): 3315, 2924, 2856, 2656, 2535, 1737, 1703, 1637, 1598, 1581, 1541/cm.
[\alpha]_{D} = +78,5º (MeOH, c = 1,01, 24ºC)
p.f. 161,0-162,0ºC
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Nº2a-161
[\alpha]_{D} = +65,3º (MeOH, c = 1,00, 22ºC)
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Nº2a-162
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,3 y 1,25 (cada 3H, cada s), 1,53-2,45 (14H, m), 4,30 (1H, m), 5,36 -5,51 (2H, m), 6,32 (1H, d, J = 8,4 Hz), 7,88 y 8,28 (cada 2H, cada d, J = 9,0 Hz).
IR (CHCl_{3}): 3448, 3029, 3016, 2925, 2870, 1708, 1664, 1602, 1527, 1484, 1347/cm.
[\alpha]_{D} = +72,7º (MeOH, c = 1,02, 22ºC)
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Nº2a-163
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,55-2,51 (14H, m), 4,26 (1H, m), 5,36-5,57 (2H, m), 6,68, (1H, d, J = 7,8 Hz), 7,41 (1H, dd, J = 4,8 y 8,1 Hz), 8,20 (1H, d, J = 8,1 Hz), 8,66 (1H, d, J = 4,8 Hz), 9,00 (1H, s).
IR (CHCl_{3}): 3448, 3026, 3013, 2925, 2870, 2534, 1709, 1658, 1590, 1515, 1471/cm.
[\alpha]_{D} = +71,3º (MeOH, c = 1,01, 22ºC)
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Nº2a-164
[\alpha]_{D} = +40,8º (MeOH, c = 0,98, 22ºC)
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Nº2a-165
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,11 y 1,24 (cada 3H, cada s), 1,55-2,52 (14H, m), 4,24 (1H, m), 5,37-5,57 (2H, m), 6,63 (1H, d, J 0 7,8 Hz), 7,59 y 8,63 (cada 2H, cada d, J = 6,0 Hz).
IR (CHCl_{3}): 3447, 3346, 3028, 3016, 2925, 2870, 2538, 1941, 1708, 1662, 1556, 1516/cm.
[\alpha]_{D} = +75,4º (MeOH, c = 1,01, 22ºC)
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Nº2a-166
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,22 (cada 3H, cada s), 1,51-2,44 (14H, m), 2,95 (6H, s), 4,25 (1H, m), 5,33-5,50 (2H, m), 6,19 (1H, d, J = 8,7 Hz), 6,77 y 6,97 (cada 2H, cada d, J = 8,4 Hz), 6,94 y 7,65 (cada 2H, cada d, J = 9,0 Hz).
IR (CHCl_{3}): 3453, 3024, 3016, 2924, 2871, 2806, 1739, 1708, 1647, 1612, 1604, 1515, 1490/cm.
[\alpha]_{D} = +51,3º (MeOH, c = 1,02, 23ºC)
p.f. 104,0-105,5ºC
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Nº2a-167
CDCl_{3} 300MHz
1,01 (1H, d, J = 9,9 Hz), 1,19 y 1,26 (cada 3H, cada s), 1,56-2,53 (14H, m), 4,37 (1H, m), 5,35-5,55 (2H, m), 6,47 (1H, d, J = 8,4 Hz), 7,61-7,71 (2H, m), 7,79 (2H, s), 7,89 -7,97 (2H, m), 8,27 (1H, d, J = 2,1 Hz), 8,66-8,73 (2H, m).
IR (CHCl_{3}): 3450, 3024, 3014, 2925, 2870, 2667, 1707, 1650, 1531, 1509/cm.
[\alpha]_{D} = +70,5º (MeOH, c = 1,00, 22ºC)
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Nº2a-168
CDCl_{3} 300MHz
1,02 (1H, d, J = 10,2 Hz), 1,20 y 1,26 (cada 3H, cada s), 1,56-2,50 (14H, m), 4,38 (1H, m), 5,36-5,56 (2H, m), 6,51 (1H, d, J = 8,4 Hz), 7,61-7,93 (7H, m), 8,74 (1H, d, J = 8,4 Hz), 9,15 (1H, s).
IR (CHCl_{3}): 3517, 3451, 3060, 3028, 3011, 2925, 2870, 2664, 1709, 1651, 1519, 1498/cm.
[\alpha]_{D} = +54,4º (MeOH, c = 1,00, 23ºC)
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Nº2a-169
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,09 y 1,21 (cada 3H, cada s), 1,50-2,44 (14H, m), 3,85 (3H, s), 4,24 (1H, m), 5,32-5,48 (2H, m), 6,19 (1H, d, J = 8,4 Hz), 6,94 y 7,45 (cada 2H, cada d, J = 9,0 Hz), 7,11 y 7,45 (cada 2H, cada d, J = 8,7
Hz).
IR (CHCl_{3}): 3516, 3453, 3029, 3009, 2925, 2870, 2840, 2665, 1708, 1650, 1593, 1515, 1493, 1482/cm.
[\alpha]_{D} = +57,8º (MeOH, c =1,00, 23ºC)
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Nº2a-170
CDCl_{3} 300MHz
0,98 (1H, d, J = 10,2 Hz), 1,5 y 1,24 (cada 3H, cada s), 1,52-2,50 (14H, m), 4,28 (1H, m), 5,33 -5,54 (2H, m), 6,25 (1H, d, J = 8,2 Hz), 7,38 -7,44 (2H, m), 7,74 (1H, s), 7,81-7,86 (2H, m).
IR (CHCl_{3}): 3517, 3448, 3427, 3024, 3013, 2925, 2870, 2669, 1708, 1650, 1562, 1535, 1500/cm.
[\alpha]_{D} = +61,6º (MeOH, c = 1,00, 23ºC)
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Nº2a-171
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,22 (cada 3H, cada s), 1,52-2,42 (14H, m), 2,48 (3H, s), 4,21 (1H, m), 5,31 -5,52 (2H, m), 6,06 (1H, d, J = 8,2 Hz), 6,97 y 7,59 (cada 1H, cada d, J = 1,2 Hz).
IR (CHCl_{3}): 3452, 3113, 3028, 3007, 2925, 2870, 2669, 1708, 1645, 1554, 1509/cm.
[\alpha]_{D} = +52,4º (MeOH, c = 1,00, 23ºC)
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Nº2a-172
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,09 y 1,28 (cada 3H, cada s), 1,50 -2,40 (14H, m), 2,69 (3H, s), 4,24 (1H, m), 5,35-5,51 (2H, m), 5,96 (1H, d, J = 8,7 Hz), 7,03 y 7,07 (cada 1H, cada d, J = 5,4 Hz).
IR (CHCl_{3}): 3451, 3031, 3013, 2925, 2870, 2666, 1708, 1647, 1542, 1497/cm.
[\alpha]_{D} = +51,2º (MeOH, c = 1,00, 23ºC)
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Nº2a-173
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,2 Hz), 1,10 y 1,23 (cada 3H, cada s), 1,50-2,45 (14H, m), 4,22 (1H, m), 5,35-5,49 (2H, m), 6,05 (1H, d, J = 8,4 Hz), 7,26 y 7,75 (cada 1H, cada d, J = 1,5 Hz).
IR (CHCl_{3}): 3451, 3011, 3029, 3011, 2925, 2870, 1708, 1652, 1538, 1500/cm.
[\alpha]_{D} = +50,6º (MeOH, c = 1,01, 23ºC)
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Nº2a-174
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,13 y 1,23 (cada 3H, cada s), 1,52 -2,50 (14H, m), 4,29 (1H, m), 5,35-5,51 (2H, m), 7,02 (1H, d, J = 8,4 Hz), 7,32 y 8,16 (cada 1H, cada d, J = 3,9 Hz).
IR (CHCl_{3}): 3417, 3115, 3023, 3014, 2925, 2870, 1708, 1645, 1530/cm.
[\alpha]_{D} = +48,8º (MeOH, c = 1,02, 23ºC)
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Nº2a-175
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,14 y 1,23 (cada 3H, cada s), 1,50-2,52 (14H, m), 2,52 (3H, s), 4,29 (1H, m), 5,34 -5,51 (2H, m), 7,78 (1H, d, J = 9,0 Hz), 7,24 y 7,52 (cada 1H, cada d, J = 5,4 Hz).
IR (CHCl_{3}): 3329, 3093, 3023, 3015, 2924, 2871, 1708, 1640, 1526/cm.
[\alpha]_{D} = +4,50º (MeOH, c = 1,01, 23ºC)
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Nº2a-176
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,5Hz), 1,09 y 1,23 (cada 3H, cada s), 1,52-2,46 (14H, m), 2,40 (3H, d, J = 0,9 Hz), 4,24 (1H, m), 5,35 -5,51 (2H, m), 6,05 (1H, d, J = 8,7 Hz), 6,95 (1H, m), 7,57 (1H, d, J = 3,3 Hz).
IR (CHCl_{3}): 3517, 3444, 3103, 3024, 3013, 2926, 2870, 1739, 1708, 1649, 1636, 1507/cm.
[\alpha]_{D} = +54,8º (MeOH, c = 1,01, 23ºC)
p.f. 97,0-99,0ºC
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Nº2a-177
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,52-2,45 (14H, m), 3,93 (3H, s), 4,27 (1H, m), 5,34-5,50 (2H, m), 6,35 (1H, d, J = 3,3 Hz), 7,80 (1H, d, J = 8,7 Hz), 8,10 (1H, d, J = 3,3 Hz).
IR (CHCl_{3}): 3395, 3121, 3031, 3019, 3012, 2925, 2871, 1739, 1709, 1640, 1557, 1533/cm.
[\alpha]_{D} = +22,8º (MeOH, c = 1,01, 23ºC)
p.f. 109,0-112,0ºC
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Nº2a-178
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,10 y 1,23 (cada 3H, cada s), 1,51-2,45 (14H, m), 4,24 (1H, m), 5,35-5,50 (2H, m), 6,09 (1H, d, J = 8,4 Hz), 7,17-7,31 (6H, m), 7,95 (1H, d, J = 1,5 Hz).
IR (CHCl_{3}): 3510, 3451, 3062, 3031, 3022, 3011, 2925, 2870, 2662, 1708, 1651, 1582, 1535, 1497, 1477/cm.
[\alpha]_{D} = +47,9º (MeOH, c = 1,01, 25ºC)
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Nº2a-179
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,52-2,48 (14H, m), 4,30 (1H, m), 5,36-5,52 (2H, m), 6,73 (1H, d, J = 9,0 Hz), 6,26 y 7,37 (cada 1H, cada d, J = 6,0 Hz)
IR (CHCl_{3}): 3509, 3429, 3115, 3094, 3025, 3014, 2925, 2871, 2666, 1708, 1649, 1529, 1510
[\alpha]_{D} = +51,0 (MeOH, c = 1,02, 25ºC)
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Nº2a-180
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,2 Hz), 1,14 y 1,24 (cada 3H, cada s), 1,52-2,46 (14H, m), 3,89 (3H, s), 4,21 (1H, m), 5,35 -5,50 (2H, m), 6,05 (1H, d, J = 8,4 Hz), 6,46 y 7,04 (cada 1H, cada d, J = 1,8 Hz).
IR (CHCl_{3}): 3516, 3450, 3114, 3031, 3010, 2925, 2871, 1708, 1648, 1546, 1511, 1477 /cm
[\alpha]_{D} = +49,1º (MeOH, c = 1,01, 25ºC)
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Nº2a-181
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,14 y 1,23 (cada 3H, cada s), 1,52-2,48 (14H, m), 2,42 (3H, s), 4,31 (1H, m), 5,34 -5,52 (2H, m), 8,07 (1H, d, J = 9,3 Hz), 7,27 y 8,17 (cada 1H, cada d, J = 3,3 Hz).
IR (CHCl_{3}): 3510, 3301, 3112, 3023, 3007, 2924, 2871, 2663, 1708, 1636, 1534/cm.
[\alpha]_{D} = +41,0º (MeOH, c = 0,96, 25ºC)
\newpage
Nº2a-182
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,53-2,46 (14H, m), 2,51 (3H, s), 4,21 (1H, m), 5,35-5,51 (2H, m), 6,05 (1H, d, J = 8,1 Hz), 7,26 y 7,78 (cada 1H, cada d, J = 1,8 Hz).
IR (CHCl_{3}): 3509, 3450, 3109, 3024, 3012, 2925, 2870, 2666, 1708, 1650, 1535, 1498, 1471/cm.
[\alpha]_{D} = +52,9º (MeOH, c = 0,95, 25ºC)
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Nº2a-183
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,12 y 1,22 (cada 3H, cada s), 1,52-2,46 (14H, m), 4,25 (1H, m), 5,33-5,51 (2H, m), 6,17 (1H, d, J = 8,7 Hz), 7,01 -7,05 (3H, m), 7,14 y 7,62 (cada 2H, cada d, J = 8,7 Hz), 7,27-7,34 (2H,
m).
IR (CHCl_{3}): 3428, 3026, 3015, 2925, 2870, 2666, 1739, 1708, 1643, 1613, 1594, 1526, 1499/cm.
[\alpha]_{D} = +64,8º (MeOH, c = 1,02, 23ºC)
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Nº2a-184
CDCl_{3} 300MHz
1,01 (1H, d, J = 10,2 Hz), 1,18 y 1,26 (cada 3H, cada s), 1,55-2,50 (14H, m), 4,35 (1H, m), 5,35 -5,55 (2H, m), 6,42 (1H, d, J = 8,7 Hz), 7,46 -7,52 (2H, m), 7,73 (1H, dd, J = 1,8 y 8,4 Hz), 7,83-7,89 (2H, m), 8,21 (1H, m), 8,59 (1H, d, J = 1,5 Hz).
IR (CHCl_{3}): 3451, 3031, 3014, 2925, 2870, 2660, 1739, 1708, 1650, 1604, 1513, 1463/cm.
[\alpha]_{D} = +58,3º (MeOH, c = 1,00, 23ºC)
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Nº2a-185
CDCl_{3} 300MHz
1,00 (1H, d, J = 10,2 Hz), 1,8 y 1,25 (cada 3H, cada s), 1,55-2,50 (14H, m), 4,34 (1H, m), 5,35-5,54 (2H, m), 6,36 (1H, d, J = 8,7 Hz), 7,37 (1H, d, J = 7,4 Hz), 7,50 (1H, m), 7,57 -7,59 (2H, m), 7,79 (1H, dd, J = 1,8 y 8,1 Hz), 7,99 (1H, d, J = 7,8 Hz), 8,39 (1H, d, J = 1,8 Hz).
IR (CHCl_{3}): 3451, 3030, 3020, 2870, 2665, 1708, 1652, 1632, 1603, 1586, 1514, 1469, 1448/cm.
[\alpha]_{D} = +59,4º (MeOH, c = 1,01, 24ºC)
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Nº2a-186
CDCl_{3} 300MHz
1,00 (1H, d, J = 10,5 Hz), 1,17 y 1,25 (cada 3H, cada s), 1,54-2,50 (14H, m), 4,33 (1H, m), 5,35-5,543 (2H, m), 6,37 (1H, d, J = 8,7 Hz), 7,37 (1H, d, J = 7,4 Hz), 7,51 (1H, t, J = 7,8 Hz), 7,56 (1H, m), 7,70 (1H, dd, J = 1,2 y 8,4 Hz), 7,97 (3H, m).
IR (CHCl_{3}): 3451, 3030, 3014, 2924, 2870, 2671, 1739, 1708, 1652, 1577, 1517, 1488, 1471/cm.
[\alpha]_{D} = +72,2º (MeOH, c = 1,00, 24ºC)
\newpage
Nº2a-187
CDCl_{3} 300MHz
1,00 (1H, d, J = 9,8 Hz), 1,18 y 1,25 (cada 3H, cada s), 1,54-2,53 (14H, m), 4,07 (3H, s), 4,37 (1H, m), 5,30-5,54 (2H, m), 7,34 (1H, m), 7,47 (1H, s), 7,47 -7,60 (2H, m), 7,93 (1H, d, J = 7,8 Hz), 8,43 (1H, s), 8,49 (1H, d, J = 9,0 Hz).
IR (CHCl_{3}): 3397, 3074, 3027, 3020, 3009. 2924, 1738, 1708, 1647, 1633, 1534, 1465, 1453/cm.
[\alpha]_{D} = +43,7º (MeOH, c = 1,01, 25ºC)
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Nº2a-188
CDCl_{3} 300MHz
0,97 (1H, d, J = 10,2 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,53-2,50 (14H, m), 4,23 (1H, m), 5,37-5,50 (2H, m), 6,10 (1H, d, J = 9,0 Hz), 6,20 (1H, m), 6,51 (1H, m), 6,97 (1H, m), 10,81 (1H, ancho s).
IR (CHCl_{3}): 3450, 3236, 3112, 3029, 3015, 2925, 2871, 1645, 1701, 1616, 1558, 1516/cm.
[\alpha]_{D} = +50,6º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-189
CDCl_{3} 300MHz
0,94 (1H, d, J = 9,9 Hz), 1,11 y 1,23 (cada 3H, cada s), 1,50 -2,46 (14H, m), 3,93 (3H, s), 4,18 (1H, m), 5,35-5,52 (2H, m), 6,03 (1H, d, J = 9,3 Hz), 6,09 (1H, m), 6,48 (1H, m), 6,73 (1H, m).
IR (CHCl_{3}): 3452, 3102, 3028, 3007, 2925, 2871, 2666, 1739, 1708, 1650, 1536, 1499, 1471/cm.
[\alpha]_{D} = +49,8º (MeOH, c = 1,01, 23ºC)
p.f. 101,5-103,5ºC
\vskip1.000000\baselineskip
Nº2a-190
CDCl_{3} 300MHz
0,94 (1H, d, J = 10,2 Hz), 1,11 y 1,21 (cada 3H, cada s), 1,54-2,47 (14H, m), 4,23 (1H, m), 5,33-5,52 (2H, m), 6,06 (1H, d, J = 9,0 Hz), 6,34 (1H, m), 6,75 (1H, m), 6,36 (1H, m), 9,71 (1H, ancho s).
IR (CHCl_{3}): 3470, 3215, 3030, 3020, 3010, 2925, 2871, 2664, 1709, 1613, 1564, 1510/cm.
[\alpha]_{D} = +43,3º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-191
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,22 (cada 3H, cada s), 1,55-2,44 (14H, m), 3,66 (3H, s), 4,20 (1H, m), 5,35-5,51 (2H, m), 5,93 (1H, d, J = 8,4 Hz), 6,27 (1H, dd, J = 1,8 y 2,7 Hz), 6,56 (1H, t, J = 2,7 Hz), 7,19 (1H, t, J = 1,8
Hz).
IR (CHCl_{3}): 3452, 3031, 3018, 3006, 2925, 2871, 2662, 1736, 1710, 1634, 1609, 1556, 1498/cm.
[\alpha]_{D} = +43,1º (MeOH, c = 1,01, 23ºC)
\newpage
Nº2a-192
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,11 y 1,21 (cada 3H, cada s), 1,43 (3H, t, J = 7,5 Hz), 1,54-2,44 (14H, m), 3,93 (2H, q, J = 7,5 Hz), 4,21 (1H, m), 5,33 -5,51 (2H, m), 5,94 (1H, d, J = 8,4 Hz), 6,27 (1H, dd, J = 1,8 y 2,7 Hz), 6,62 (1H, t, J = 2,7 Hz), 7,26 (1H, t, J = 1,8 Hz).
IR (CHCl_{3}): 3630, 3452, 3032, 3018, 3006, 2925, 2871, 2661, 1735, 1710, 1633, 1610, 1555, 1497/cm.
[\alpha]_{D} = +40,1º (MeOH, c = 1,00, 23ºC)
\vskip1.000000\baselineskip
Nº2a-193
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,2 Hz), 1,10 y 1,22 (cada 3H, cada s), 1,53-2,49 (14H, m), 2,58 (3H, s), 4,21 (1H, m), 5,35 -5,54 (2H, m), 6,15 (1H, d, J = 8,1 Hz), 6,52 (1H, dd, J = 1,8 y 3,6 Hz), 7,29 (1H, t, J = 3,6 Hz), 7,94 (1H, t, J = 1,8
Hz).
IR (CHCl_{3}): 3516, 3450, 3410, 3152, 3027, 3015, 2925, 2871, 2670, 1732, 1648, 1574, 1509/cm.
[\alpha]_{D} = +45,0º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-194
CDCl_{3} 300MHz
0,99 (1H, d, J = 10,2 Hz), 1,11 y 1,24 (cada 3H, cada s), 1,52-2,53 (14H, m), 4,34 (1H, m), 5,33 -5,57 (2H, m), 6,21 (1H, d, J = 8,6 Hz), 7,35-7,50 (2H, m), 7,83 (1H, s), 7,86 (1H, m), 8,31 (1H, m).
IR (CHCl_{3}): 3443, 3067, 3013, 2925, 2870, 2665, 1708, 1651, 1515, 1493/cm.
[\alpha]_{D} = +55,7º (MeOH, c = 1,01, 23ºC)
\vskip1.000000\baselineskip
Nº2a-195
CDCl_{3} 300MHz
1,01 (1H, d, J = 10,0 Hz), 1,06 y 1,26 (cada 3H, cada s), 1,50-2,64 (14H, m), 2,68 (3H, s), 4,40 (1H, m), 5,36-5,61 (2H, m), 6,02 (1H, d, J = 9,4 Hz), 7,30-7,42 (2H, m), 7,73-7,86 (2H, m).
IR (CHCl_{3}): 3510, 3434, 3062, 3029, 3014, 2924, 2871, 2669, 1708, 1650, 1563, 1539, 1500/cm.
[\alpha]_{D} = +72,4º (MeOH, c = 1,00, 23ºC)
p.f. 111,0-112,0ºC
\vskip1.000000\baselineskip
Nº2a-196
CDCl_{3} 300MHz
0,42 y 1,04 (cada 3H, cada s), 0,80 (1H, d, J = 10,0 Hz), 1,11-2,48 (14H, m), 2,24 (3H, s), 4,02 (1H, m), 5,23-5,44 (2H, m), 5,53 (1H, d, J = 8,8 Hz), 7,27-7,31 (2H, m), 7,42-7,48 (3H, m), 7,93 (1H, s).
IR (CHCl_{3}): 3419, 3114, 3025, 3006, 2924, 2871, 2662, 1737, 1709, 1636, 1540, 1519/cm.
[\alpha]_{D} = +43,7º (MeOH, c = 1,01, 23ºC)
\newpage
Nº2a-197
CDCl_{3} 300MHz
0,95 (1H, d, J = 10,0 Hz), 1,09 y 1,23 (cada 3H, cada s), 1,54-2,46 (18H, m), 2,77 (4H, ancho s), 4,21 (1H, m), 5,32-5,54 (2H, m), 6,02 (1H,d, J = 8,6 Hz), 7,43 (1H, s).
IR (CHCl_{3}): 3445, 3101, 3024, 3014, 2928, 2865, 2661, 1739, 1708, 1646, 1550, 1507/cm.
[\alpha]_{D} = +51,9º (MeOH, c = 1,01, 23ºC)
\vskip1.000000\baselineskip
Nº2a-198
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,22 (cada 3H, cada s), 1,50-2,44 (14H, m), 4,24 (1H, m), 4,42 (2H, s), 5,35-5,49 (2H, m), 6,25 (1H, d, J = 8,1 Hz), 7,33 (1H, m), 7,43 (1H, dd, J = 1,5 y 7,5 Hz), 7,49 (1H, d, J = 8,1 Hz), 7,60-7,63 (1H, m), 7,68 (1H, d, J = 1,8 y 7,8 Hz), 8,02 (1H, d, J = 1,8 Hz), 8,19 (1H, dd, J = 1,5 y 8,1 Hz).
IR (CHCl_{3}): 3448, 3030, 3012, 2925, 2870, 1739, 1708, 1671, 1588, 1559, 1514, 1472/cm.
[\alpha]_{D} = +56,9º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2a-199
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,11 y 1,22 (cada 3H, cada s), 1,51-2,46 (14H, m), 3,40 (1H, m), 3,76 (1H, m), 4,24 (1H, m), 5,33-5,51 (3H, m), 6,25 (1H, m), 7,16 (1H, m), 7,24-7,33 (2H, m), 7,46 (1H, d, J = 7,5 Hz), 7,52-7,60 (2H, m), 7,85 (1H, dd, J = 1,8 y 4,5 Hz).
IR (CHCl_{3}): 3583, 3447, 3062, 3028, 3013, 2924, 2871, 2663, 1708, 1651, 1600, 1557, 1514, 1471/cm.
[\alpha]_{D} = +54,8º (MeOH, c = 1,00, 23ºC)
\vskip1.000000\baselineskip
Nº2a-200
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz), 1,12 y 1,23 (cada 3H, cada s), 1,51-2,46 (14H, m), 4,25 (1H, m), 5,34-5,51 (2H, m), 6,25 (1H, d, J = 8,4 Hz), 7,02 y 7,10 (cada 1H, cada d, J = 12,3 Hz), 7,23-7,33 (4H, m), 7,50 (1H, m), 7,64 (1H, dd, J = 1,8 y 7,8 Hz), 7,82 (1H, d, J = 1,8 Hz).
IR (CHCl_{3}): 3450, 3060, 3025, 3014, 2925, 2871, 2662, 1708, 1653, 1596, 1542, 1513, 1473/cm.
[\alpha]_{D} = +62,5º (MeOH, c = 1,00, 24ºC)
\vskip1.000000\baselineskip
Nº2a-201
CDCl_{3} 300MHz
0,95 (1H, d, J = 9,9 Hz), 1,5 y 1,22 (cada 3H, cada s), 1,55-2,60 (14H, m), 4,26 (1H, m), 5,35-5,63 (2H, m), 7,14 (1H, d, J = 9,9 Hz), 7,34 y 7,40 (cada 1H, cada d, J = 12,9 Hz), 7,62-7,73 (4H, m), 8,25-8,30 (2H, m), 8,72 (1H, d, J = 1,5 Hz).
IR (CHCl_{3}): 3443, 3389, 3297, 3061, 3030, 3016, 2925, 2870, 1726, 1708, 1652, 1603, 1521, 1483, 1472, 1309/cm.
[\alpha]_{D} = +61,1º (MeOH, c = 1,01, 23ºC)
\newpage
Nº2a-202
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,2 Hz),1,09 y 1,22 (cada 3H, cada s), 1,52-2,43 (14H, m), 2,63 (3H, s), 4,25 (1H, m), 5,33-5,49 (2H, m), 6,19 (1H, d, J = 8,4 Hz), 7,10 y 7,58 (cada 2H, cada d, J = 9,0 Hz), 7,21 (1H, m), 7,30-7,32 (2H, m), 7,46 (1H, d, J = 7,5 Hz).
IR (CHCl_{3}): 3511, 3453, 3062, 3032, 3014, 2925, 2870, 1739, 1708, 1650, 1595, 1556, 1516, 1482, 1471/cm.
[\alpha]_{D} = +60,2º (MeOH, c = 1,01, 25ºC)
\vskip1.000000\baselineskip
Nº2a-203
CDCl_{3} 300MHz
0,96 (1H, d, J = 10,5 Hz), 1,09 y 1,23 (cada 3H, cada s), 1,52-2,43 (14H, m), 4,23 (1H, m), 5,35-5,51 (2H, m), 5,93 (1H, d, J = 8,7 Hz), 6,56 (1H, dd, J = 0,9 y 1,8 Hz), 7,43 (1H, d, J = 1,8 Hz), 7,92 (1H, dd, J = 0,9 y 1,8 Hz).
IR (CHCl_{3}): 3517, 3450, 3134, 3031, 3008, 2925, 2870, 2667, 1708, 1656, 1588, 1570, 1514/cm.
[\alpha]_{D} = +46,7º (MeOH, c = 0,92, 25ºC)
\vskip1.000000\baselineskip
Nº2b-1
[\alpha]_{D} = +25,6º (MeOH, c = 1,01, 23ºC)
\vskip1.000000\baselineskip
Nº2b-2
[\alpha]_{D} = +38,9º (MeOH, c = 1,01, 24ºC)
\vskip1.000000\baselineskip
Nº2c-1
[\alpha]_{D} = +60,5º (MeOH, c = 1,01, 22ºC)
\vskip1.000000\baselineskip
Nº2c-2
[\alpha]_{D} = +55,8º (MeOH, c = 0,92, 22ºC)
\vskip1.000000\baselineskip
Nº2c-3
[\alpha]_{D} = +54,7º (MeOH, c = 1,01, 22ºC)
\vskip1.000000\baselineskip
Nº2d-1
[\alpha]_{D} = -6,2º (MeOH, c = 1,00, 21ºC)
\vskip1.000000\baselineskip
Nº2d-2
[\alpha]_{D} = +15,8º (MeOH, c = 0,34, 22ºC)
\vskip1.000000\baselineskip
Nº2d-3
[\alpha]_{D} = +31,6º (MeOH, c = 1,01, 22ºC)
\vskip1.000000\baselineskip
Nº2e-1
[\alpha]_{D} = -9,4º (MeOH, c = 1,00, 22ºC)
\vskip1.000000\baselineskip
Nº2e-2
[\alpha]_{D} = -1,8º (MeOH, c =1,02, 23ºC)
\vskip1.000000\baselineskip
Nº2e-3
[\alpha]_{D} = -6,7º (MeOH, c = 1,01, 23ºC)
\vskip1.000000\baselineskip
Nº2f-1
[\alpha]_{D} = +6,8º (MeOH, c = 1,01, 23ºC)
\vskip1.000000\baselineskip
Nº2f-2
[\alpha]_{D} = -2,6º (MeOH, c = 1,00, 22ºC)
\vskip1.000000\baselineskip
Nº2f-3
[\alpha]_{D} = -3,5º (MeOH, c = 1,01, 22ºC)
\vskip1.000000\baselineskip
Nº2g-1
[\alpha]_{D} = +54,6º (MeOH, c = 1,01, 24ºC)
Se sometieron a ensayo los compuestos preparados en los ejemplos anteriores para determinar su actividad in vivo e in vitro con arreglo al método que se indica en los ejemplos experimentales a continuación.
Experimento 1
Unión a receptor PGD_{2} Material y método (1) Preparación de fracción de membrana de plaquetas humanas
Se obtuvo una muestra de sangre utilizando una jeringuilla de plástico que contenía 3,8% citrato sódico de las venas de voluntarios sanos (hombre y mujer adultos), se colocó en un tubo de ensayo de plástico y se mezcló suavemente por inversión. A continuación, se centrifugó la muestra a 1800 rpm, 10 minutos, a temperatura ambiente y se recogió el sobrenadante que contenía plasma rico en plaquetas, PRP. Se volvió a centrifugar el PRP a 2300 rpm, 22 minutos, a temperatura ambiente para obtener plaquetas. Se homogeneizaron las plaquetas utilizando un homogeneizador (Ultra-Turrax) seguido de centrifugado 3 veces a 20.000 rpm, 10 minutos, a 4ºC para obtener una fracción de membrana de plaquetas. Después de la determinación de las proteínas, se ajustó la fracción de membrana a 2 mg/ml y se preservó en un refrigerador a -80ºC hasta su uso.
(2) Unión a receptor PGD_{2}
Se añadieron a una solución de reacción de unión (Tris/HCl 50 mM, pH 7,4, MgCl_{2} 5 mM) (0,2 ml) fracción de membrana de plaquetas humanas (0,1 mg) y [^{3}H] PGD_{2} 5 nM (115 Ci/mmoles) y se hizo reaccionar a 4ºC durante 90 minutos. Una vez acabada la reacción, se filtró la mezcla de reacción a través de un papel de filtro de fibra de vidrio, se lavó varias veces con solución salina enfriada y se realizó la medida de la radioactividad retenida en el papel de filtro. Se calculó la unión específica sustrayendo la unión no específica (la unión en presencia de 10 \muM PGD_{2}) de la unión o total. Se expresó la actividad de inhibición de unión de cada compuesto como la concentración necesaria para un 50% de inhibición (IC_{50}), que se determinó describiendo una curva de sustitución por representación en gráfico de la relación de unión (%) en presencia de cada compuesto, siendo la relación de unión en ausencia de un compuesto de ensayo-100%. En la tabla a continuación, se muestran los resultados.
\newpage
Número de compuesto Actividad (\muM)
2a-4 0,54
2a-17 0,12
2a-21 5,2
2a-28 0,046
2a-95 1,6
2a-109 0,003
Experimento 2
Evaluación de la actividad antagonista contra receptor PGD_{2} utilizando plaquetas humanas
Se obtuvo sangre periférica de un voluntario sano utilizando una jeringuilla a la que se había añadido previamente un volumen de 1/9 de solución de ácido cítrico/dextrosa. Se sometió a centrifugado la jeringuilla a 180 g durante 10 minutos para obtener el sobrenandante (PRP: plasma rico en plaquetas). Se lavó el PRP resultante tres veces con un tampón de lavado y se hizo el recuento del número de plaquetas con un contador microcelular. Se templó una suspensión ajustada para contener plaquetas a una concentración final de 5 x 10^{8}/ml a 37ºC, y a continuación se sometió a un pretratamiento con 3-isobutil-1-metilxantina (0,5 mM) durante 5 minutos. Se añadió a la suspensión un compuesto de ensayo diluido a varias concentraciones. Diez minutos después, se indujo la reacción por adición de 0,1-2,0 \muM PGD_{2}, y 15 minutos después, se detuvo por adición de HCl. Se destruyeron las plaquetas con un homogeneizador ultrasónico. Tras el centrifugado, se determinó el cAMP en el sobrenadante por radioensayo. Se evaluó el antagonismo de receptor PGD_{2} de un fármaco del siguiente modo. Se determinó el índice de inhibición de cAMP aumentó por adición de PGD_{2} a una concentración individual y a continuación se calculó la concentración del fármaco requerida para un 50% de inhibición (IC_{50}). En la tabla a continuación, se muestran los resultados.
Número de compuesto Inhibición de aumento de cAMP de plaquetas humanas (IC_{50}) (\muM)
2a-2 0,77
2a-4 0,94
2a-35 1,52
2a-75 0,71
Experimento 3
Experimento utilizando un modelo de oclusión nasal
A continuación se explica el método utilizado para medir la resistencia de la cavidad nasal y para evaluar la anti-oclusión nasal utilizando coballas.
Se trató ovalbúmina al 1% (OVA) con un nebulizador ultrasónico para obtener un aerosol. Se sensibilizó una coballa Hartley macho inhalando dos veces el aeorosol durante 10 minutos a intervalos de una semana. Siete días después de la sensibilización, se expuso a la coballa a un antígeno para iniciar la reacción. A continuación, se realizó una incisión en la tráquea con anestesia con pentobarbital (30 mg/kg, i.p.) y se insertaron cánulas en la tráquea en los lados de la cavidad nasal y pulmonar. Se conectó el canal insertado en el lado pulmonar con un respirador artificial que proporcionaba 4 ml de aire 60 veces/minuto. Tras detener la respiración espontánea de una coballa con Garamina (2 mg/kg, i.v.), se suministró aire por el lateral del morro con un respirador artificial a la frecuencia de 70 veces/minuto, y se midió la velocidad de flujo de 4 ml de aire/cada vez, y la presión atmosférica requerida para la ventilación mediante el uso de un transductor ajustado en la ramificación. Se utilizó la medida como parámetro de la resistencia de la cavidad nasal. Se llevó a cabo la exposición de un antígeno por generación de un aerosol de una solución OVA al 3% durante 3 minutos entre el respirador y la cánula de la cavidad nasal. Se inyectó el fármaco de ensayo por vía intravenosa 10 minutos antes de la exposición del antígeno. Se midió la resistencia nasal entre 0 y 30 minutos continuamente y se expresó el efecto como el índice de inhibición con respecto al obtenido para el vehículo utilizando la AUC durante 30 minutos (en el eje vertical, la resistencia de la cavidad nasal (cm H_{2}O) y el eje horizontal, tiempo (0-30 minuto) como indicación. A continuación se muestran los resultados.
\newpage
Número de compuesto índice de inhibición 1 mg/kg (i.v.) Comentarios
2a-4 60
2a-21 52
2a-28 54
2a-95 77
2a-96 77 10 mg/kg (p.o.)
2a-109 73
2a-110 66 10 mg/kg (p.o.)
2a-194 79
Formulación 1
Preparación de tabletas
Se prepararon tabletas que contenían 40 mg de ingrediente activo cada una según el modo convencional.

Claims (10)

1. Un compuesto de fórmula (Ib):
54
en la que:
55
es
56 
\vskip1.000000\baselineskip
en la que A es alquileno que opcionalmente está sustituido por heteroátomo o fenileno, contiene grupos oxo, y/o tiene un enlace insaturado;
B es hidrógeno, alquilo, aralquilo o acilo;
R es COOR_{1}, CH_{2}OR_{2} ó CON(R_{3})R_{4};
R_{1} es hidrógeno o alquilo;
R_{2} es hidrógeno o alquilo;
R_{3} y R_{4} son cada uno de ellos independientemente hidrógeno, alquilo, hidroxi o alquilsulfonilo;
X_{1} es un enlace simple, fenileno, naftileno, tiofenediilo, indolediilo o oxazolediilo;
X_{2} es un enlace simple; -N=N-, -N=CH-, -CH=N-, -CH=N-N-, -CH=N-O; -C=NNHCSNH-, -C=NNHCONH-,
-CH=CH-, -CH(OH)-, -C(Cl)=C(Cl)-, -(CH_{2})n-, etinileno, -N(R_{5})-, -N(R_{51})CO- -N(R_{52})SO_{2}-, -N(R_{53})CON(R_{54})-,
-CON(R_{55})-, -SO_{2}N(R_{56})-, -O-, -S-, -SO-, -SO_{2}-, -CO-, oxadiazolediilo, tiadiazolediilo o tetrazolediilo;
X_{3} es alquilo, alquenilo, alquinilo, arilo, aralquilo, grupo heterocíclico, cicloalquilo, cicloalquenilo, tiazolilnilidenmetilo, tiazolidinilidenmetilo, -CH=NR_{6} ó -N=C(R_{7})R_{8};
R_{5}, R_{51}, R_{52}, R_{53}, R_{54}, R_{55} y R_{56} son cada uno de ellos hidrógeno o alquilo;
R_{6} es hidrógeno, alquilo, hidroxi, alcoxi, carbamoíloxi, tiocarbamoiloxi, ureido o tioureido;
R_{7} y R_{8} son cada uno de ellos independientemente alquilo, alcoxi o arilo; y
n es 1 ó 2;
pudiendo ser tener un sustituyente cíclico uno a tres sustituyentes seleccionados del grupo que consiste en nitro, alcoxi, sulfamoílo, amino sustituido o sin sustituir, acilo, aciloxi, hidoxi, halógeno, alquilo, alquinilo, carboxi, alcoxicarbonilo, aralcoxicarbonilo, ariloxicarbonilo, mesiloxi, ciano, alqueniloxi, hidroxialquilo, trifluorometilo, alquiltio, -N=PPh_{3}, oxo, tioxo, hidroxiimino, alcoxiimino, fenilo y alquilendioxi, o su sal o hidrato del mismo; siempre y cuando se excluyan los compuestos (a) en los que X_{1} y X_{2} son un enlace simple y X_{3} es fenilo; (b) en los que X_{1} es un enlace simple, X_{2} es -O-, y X_{3} es bencilo;
Se excluyen los compuestos representados por las fórmulas:
57 
\vskip1.000000\baselineskip
58 
\vskip1.000000\baselineskip
59 
\vskip1.000000\baselineskip
60
2. El compuesto de la reivindicación 1, una sal o hidrato del mismo, en el que
61
es
62
3. El compuesto de la reivindicación 2, una sal o hidrato del mismo, en el que R es COOR_{1}.
4. El compuesto de la reivindicación 2, sal o hidrato del mismo, en el que X_{1} es fenileno o tiofenediilo, X_{2} es un enlace simple, -N=N-, -CH=CH-, etinileno, -O-, -S-, -CO-, -CON(R_{55})-, -N(R_{51})CO- y X3 es fenilo o tienilo.
5. El compuesto de la reivindicación 1, una sal o hidrato del mismo en el que
63
es
64
6. El compuesto de la reivindicación 5, una sal o hidrato del mismo, en el que B es hidrógeno, tanto X_{1} como X_{2} son un enlace simple, X_{3} es tienilo, tiazolilo, tiadiazolilo, isotiazolilo, pirrolilo, piridilo, benzofurilo, bencimidazolilo, benzotienilo, dibenzofurilo, dibenzotienilo, quinolilo o indolilo.
7. El compuesto de la reivindicación 5, una sal o hidrato del mismo, en el que X_{1} es fenileno, tiofenediilo, indolediilo o oxazolediilo, X_{2} es un enlace simple, -N=N-, -CH=CH-, etilnileno, -S- o -O-, y X_{3} es arilo o un grupo heterocíclico.
8. Un compuesto de fórmula (Ib) a continuación, para su uso en un método de tratamiento de enfermedades en las que participa una disfunción en las células cebadoras, contracción traqueal, asma, rinitis alérgica, conjuntivitis alérgica, urticaria, lesión debida a reperfusión isquémica, oclusión nasal e inflamación:
65
en la que:
66
es
67 
\vskip1.000000\baselineskip
en la que A es alquileno que opcionalmente está sustituido por heteroátomo o fenileno, contiene grupo oxo, y/o tiene un enlace insaturado;
B es hidrógeno, alquilo, aralquilo o acilo;
R es COOR_{1}, CH_{2}OR_{2} ó CON(R_{3})R_{4};
R_{1} es hidrógeno o alquilo;
R_{2} es hidrógeno o alquilo;
R_{3} y R_{4} son cada uno de ellos independientemente hidrógeno, alquilo, hidroxi o alquilsulfonilo;
X_{1} es un enlace simple, fenileno, naftileno, tiofenediilo, indolediilo o oxazolediilo;
X_{2} es un enlace simple; -N=N-, -N=CH-, -CH=N-, -CH=N-N-, -CH=N-O; -C=NNHCSNH-, -C=NNHCONH-,
-CH=CH-, -CH(OH)-, -C(Cl)=C(Cl)-, -(CH_{2})n-, etinileno, -N(R_{5})-, -N(R_{51})CO- -N(R_{52})SO_{2}-, -N(R_{53})CON(R_{54})-,
-CON(R_{55})-, -SO_{2}N(R_{56})-, -O-, -S-, -SO-, -SO_{2}-, -CO-, oxadiazolediilo, tiadiazolediilo o tetrazolediilo;
X_{3} es alquilo, alquenilo, alquinilo, arilo, aralquilo, grupo heterocíclico, cicloalquilo, cicloalquenilo, tiazolilnilidenmetilo, tiazolidinilidenmetilo, -CH=NR_{6} ó -N=C(R_{7})R_{8};
R_{5}, R_{51}, R_{52}, R_{53}, R_{54}, R_{55} y R_{56} son cada uno de ellos hidrógeno o alquilo;
R_{6} es hidrógeno, alquilo, hidroxi, alcoxi, carbamoíloxi, tiocarbamoiloxi, ureido o tioureido;
R_{7} y R_{8} son cada uno de ellos independientemente alquilo, alcoxi o arilo; y
n es 1 ó 2;
pudiendo tener un sustituyente cíclico uno a tres sustituyentes seleccionados del grupo que consiste en nitro, alcoxi, sulfamoílo, amino sustituido o sin sustituir, acilo, aciloxi, hidroxi, halógeno, alquilo, alquinilo, carboxi, alcoxicarbonilo, aralcoxicarbonilo, ariloxicarbonilo, mesiloxi, ciano, alqueniloxi, hidroxialquilo, trifluorometilo, alquiltio, -N=PPh_{3}, oxo, tioxo, hidroxiimino, alcoxiimino, fenilo y alquilendioxi, o su sal o hidrato del mismo; siempre y cuando se excluyan los compuestos (a) en los que X_{1} y X_{2} son un enlace simple y X_{3} es fenilo; (b) en los que X_{1} es un enlace simple, X_{2} es -O-, y X_{3} es bencilo.
9. Uso de un antagonista de PGD_{2} que comprende un compuesto de fórmula (Ib) tal como se ha definido en la reivindicación 8, o una sal o hidrato del mismo, como ingrediente activo en la fabricación de una composición farmacéutica para el tratamiento de una enfermedad en la que participa una disfunción en las células cebadoras, contracción traqueal, asma, rinitis alérgica, conjuntivitis alérgica, urticaria, lesión debida a reperfusión isquémica, oclusión nasal e inflamación.
10. Uso de un antagonista de PGD_{2} que comprende un compuesto de fórmula (Ib) tal como se define en la reivindicación 9, o una sal o hidrato del mismo, como ingrediente activo en la fabricación de una composición farmacéutica para el tratamiento de enfermedades en las que participa una disfunción en las células cebadoras, contracción traqueal, asma, rinitis alérgica, conjuntivitis alérgica, urticaria, lesión debida a reperfusión isquémica, oclusión nasal e inflamación.
ES96918841T 1995-06-21 1996-06-19 Derivados amino biciclicos y agonista de pgd2 que contienen los mismos. Expired - Lifetime ES2270438T3 (es)

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Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4120993B2 (ja) * 1996-12-12 2008-07-16 塩野義製薬株式会社 ヘテロ環縮合ベンゼンカルボン酸アミド誘導体およびそれを含有するｐｇｄ２拮抗剤
CN1105112C (zh) * 1996-12-13 2003-04-09 盐野义制药株式会社 苯并噻吩酰胺类衍生物以及含有它们的pgd2拮抗剂
KR100517006B1 (ko) * 1997-04-28 2005-09-27 닛토덴코 가부시키가이샤 광학 활성 단량체를 포함하는 측쇄형 액정 중합체, 및 이를 포함하는 광학 소자
EP1016660B1 (en) 1997-09-19 2003-10-29 Shionogi & Co., Ltd. Compounds having 2.2.1]bicyclo skeleton
JP3455181B2 (ja) * 1998-03-31 2003-10-14 塩野義製薬株式会社 ５−ヒドロキシベンゾ［ｂ］チオフェン−３−カルボン酸誘導体の製造法
US6506789B2 (en) 1998-06-03 2003-01-14 Shionogi & Co., Ltd. Methods for the treatment of itching comprising administering PGD2 receptor antagonist
DE69925270T2 (de) * 1998-06-03 2006-02-23 Shionogi & Co., Ltd. Mittel zur linderung von juckreiz, enthaltend pgd2- antagonisten
WO2000030683A1 (fr) * 1998-11-19 2000-06-02 Shionogi & C0., Ltd. Composes prophylactiques et/ou therapeutiques destines a des maladies du systeme nerveux central et possedant des composes antagonistes du recepteur de txa2 et/ou inhibiteurs de la txa2 synthase
US7105564B1 (en) * 1999-03-10 2006-09-12 Shionogi & Co., Ltd. Pharmaceutical composition comprising a dual antagonist against PGD2/TXA2 receptors having a [2.2.1] or [3.1.1] bicyclic skeleton
KR20020069183A (ko) * 1999-07-26 2002-08-29 시오노기세이야쿠가부시키가이샤 트롬보포이에틴 작동성을 나타내는 의약 조성물
EP1201238A4 (en) * 1999-07-29 2003-01-15 Ono Pharmaceutical Co SULPHONAMIDE DERIVATIVES AND HEALING AGENTS FOR ALLODYNIA
EP2014285B1 (en) 1999-11-26 2010-05-05 Shionogi&Co., Ltd. NPYY5 antagonists
JP4292742B2 (ja) 2000-03-09 2009-07-08 小野薬品工業株式会社 インドール誘導体、その製造方法および用途
WO2001070677A1 (en) * 2000-03-20 2001-09-27 Merck Sharp & Dohme Limited Sulphonamido-substituted bridged bicycloalkyl derivatives
JP2003530426A (ja) * 2000-04-12 2003-10-14 メルク フロスト カナダ アンド カンパニー Ｐｇｄ２受容体拮抗薬を用いるアレルギー状態の治療のための方法および組成物
EP1295872A4 (en) 2000-06-02 2007-05-16 Shionogi & Co ANTAGONIST MEDICINAL PRODUCT FOR PGD2 / TXA2 RECEPTORS
US6410583B1 (en) * 2000-07-25 2002-06-25 Merck Frosst Canada & Co. Cyclopentanoindoles, compositions containing such compounds and methods of treatment
EP1312601A4 (en) * 2000-08-22 2005-09-21 Ono Pharmaceutical Co CARBOXYLENE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, AND MEDICAMENTS CONTAINING THEM AS AN ACTIVE SUBSTANCE
EP1314719A4 (en) * 2000-09-01 2005-09-21 Ono Pharmaceutical Co BENZOIC ACID DERIVATIVES AND MEDICAMENTS HAVING THE SAME AS ACTIVE INGREDIENT
US7273883B2 (en) 2000-09-14 2007-09-25 Allergan, Inc. Prostaglandin EP4 antagonist
US6693203B2 (en) * 2000-10-17 2004-02-17 Shionogi & Co., Ltd Process for the preparation of PGD2 antagonist
US6933317B2 (en) * 2000-11-01 2005-08-23 Shionogi & Co. Ltd. PGD2 receptor antagonistic pharmaceutical compositions
US7867516B2 (en) 2001-01-29 2011-01-11 Shionogi & Co., Ltd. Medicinal preparation containing 5-methyl-1-phenyl-2-(1h)-pyridone as active ingredient
JP2005508172A (ja) * 2001-11-07 2005-03-31 ミレニアム・ファーマシューティカルズ・インコーポレイテッド フラクタルカインレセプターのモジュレーターを同定する方法、およびフラクタルカインレセプターのモジュレーターを使用する方法
AR038136A1 (es) 2002-01-24 2004-12-29 Merck Frosst Canada Inc Cicloalcanindoles con sustitucion con fluor composiciones que contienen estos compuestos y metodos de tratamiento
CA2503767C (en) 2002-10-30 2009-09-22 Merck Frosst Canada & Co./Merck Frosst Canada & Cie Pyridopyrrolizine and pyridoindolizine derivatives
CA2558848C (en) 2004-03-05 2013-11-19 Nissan Chemical Industries, Ltd. Isoxazoline-substituted benzamide compound and pesticide
PL1725553T3 (pl) 2004-03-11 2008-10-31 Idorsia Pharmaceuticals Ltd Pochodne tetrahydropirydoindolu
JPWO2006068162A1 (ja) * 2004-12-24 2008-06-12 塩野義製薬株式会社 慢性閉塞性肺疾患の治療剤
RU2453540C2 (ru) * 2005-04-21 2012-06-20 Лаборатуар Сероно С.А. 2,3-замещенные пиразинсульфонамиды в качестве ингибиторов crth2
EP2155675B1 (en) * 2007-06-12 2014-02-19 Provid Pharmaceuticals, Inc. Kinase inhibitors, compositions thereof, and methods of use therewith
US8324385B2 (en) * 2008-10-30 2012-12-04 Madrigal Pharmaceuticals, Inc. Diacylglycerol acyltransferase inhibitors
MY159870A (en) * 2009-03-09 2017-02-15 Taiho Pharmaceutical Co Ltd Piperazine compound capable of inhibiting prostaglandin d synthase
WO2011079007A1 (en) 2009-12-23 2011-06-30 Ironwood Pharmaceuticals, Inc. Crth2 modulators
US20130178475A1 (en) 2010-03-17 2013-07-11 Ironwood Pharmaceuticals, Inc. sGC STIMULATORS
MX2012015252A (es) 2010-06-30 2013-05-30 Ironwood Pharmaceuticals Inc Estimuladores de sgc.
US20130259830A1 (en) 2010-07-12 2013-10-03 Ironwood Pharmaceuticals, Inc. Crth2 modulators
US20130216552A1 (en) 2010-07-12 2013-08-22 Ironwood Pharmaceuticals, Inc. Crth2 modulators
CN107266433A (zh) 2010-11-09 2017-10-20 铁木医药有限公司 sGC刺激剂
JP6130827B2 (ja) 2011-05-17 2017-05-17 塩野義製薬株式会社 ヘテロ環化合物
CN104066731B (zh) 2011-12-27 2016-06-15 铁木医药有限公司 可用作sgc刺激剂的2-苄基、3-(嘧啶-2-基)取代的吡唑类
US9309235B2 (en) 2012-09-18 2016-04-12 Ironwood Pharmaceuticals, Inc. SGC stimulators
EP2897953B8 (en) 2012-09-19 2019-06-26 Cyclerion Therapeutics, Inc. Sgc stimulators
ES2911276T3 (es) 2013-03-15 2022-05-18 Cyclerion Therapeutics Inc Estimuladores de sGC
CN106304835A (zh) 2013-12-11 2017-01-04 铁木医药有限公司 sGC刺激剂
WO2015106268A1 (en) 2014-01-13 2015-07-16 Ironwood Pharmaceuticals, Inc. USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS
WO2016044445A2 (en) 2014-09-17 2016-03-24 Ironwood Pharmaceuticals, Inc. sGC STIMULATORS
WO2016044447A1 (en) 2014-09-17 2016-03-24 Ironwood Pharmaceuticals, Inc. Pyrazole derivatives as sgc stimulators
MX2017003518A (es) 2014-09-17 2017-07-28 Ironwood Pharmaceuticals Inc Estimuladores de guanilato ciclasa soluble (sgc).
CA2937365C (en) 2016-03-29 2018-09-18 F. Hoffmann-La Roche Ag Granulate formulation of 5-methyl-1-phenyl-2-(1h)-pyridone and method of making the same
CN109563087A (zh) 2016-07-07 2019-04-02 铁木医药有限公司 sGC刺激剂的固体形式
CN109476686B (zh) 2016-07-07 2022-01-18 赛克里翁治疗有限公司 sGC刺激剂的磷前药

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0082646B1 (en) 1981-12-23 1989-11-15 National Research Development Corporation Prostaglandins
US4837234A (en) 1981-12-23 1989-06-06 National Research Development Corporation Prostaglandins
US4526901A (en) * 1984-01-26 1985-07-02 E. R. Squibb & Sons, Inc. 7-Oxabicycloheptane substituted oxamide prostaglandin analogs and their use in treating thrombolytic disease
JPS6149A (ja) 1984-06-12 1986-01-06 Ono Pharmaceut Co Ltd 新規な１３―アザ―１４―オキソ―ＴｘＡ２類似化合物およびそれらを有効成分として含有するトロンボキサン起因疾患治療剤
CA1278577C (en) 1985-11-18 1991-01-02 Tatsuo Tsuri Bicyclic sulfonamide derivatives
CA1294974C (en) 1987-05-08 1992-01-28 Sanji Hagishita Bicyclic sulfonamide derivatives and process therefor
JP2565746B2 (ja) * 1987-10-23 1996-12-18 小野薬品工業株式会社 新規な炭素環系スルホンアミド誘導体
EP0312906A3 (en) * 1987-10-23 1990-09-05 Ono Pharmaceutical Co., Ltd. Novel sulfonamide derivatives
JPH0262546A (ja) 1988-08-30 1990-03-02 Asahi Chem Ind Co Ltd 改良された光学用感光性樹脂組成物
CA2113787A1 (en) * 1993-01-29 1994-07-30 Nobuyuki Hamanaka Carbocyclic sulfonamides

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