AR105557A2 - SULFONAMID PYRIMIDIN DERIVATIVES - Google Patents

SULFONAMID PYRIMIDIN DERIVATIVES

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Publication number
AR105557A2
AR105557A2 ARP160102336A ARP160102336A AR105557A2 AR 105557 A2 AR105557 A2 AR 105557A2 AR P160102336 A ARP160102336 A AR P160102336A AR P160102336 A ARP160102336 A AR P160102336A AR 105557 A2 AR105557 A2 AR 105557A2
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Argentina
Prior art keywords
phenyl
group
6alkyl
substituents independently
independently selected
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ARP160102336A
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Spanish (es)
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Paul Stonehouse Jeffrey
Michael Smith Neal
Francis Preston Cherylin
Meghani Premji
Jane Cox Rhona
Ranuff Cheshire David
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Astrazeneca Ab
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Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR105557A2 publication Critical patent/AR105557A2/en

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  • Plural Heterocyclic Compounds (AREA)

Abstract

Reivindicación 1: Un compuesto caracterizado porque responde a la fórmula (1) en donde R¹ es un grupo seleccionado entre C₃₋₇carbociclilo, C₁₋₈alquilo, C₂₋₆alquenilo y C₂₋₆alquinilo; en el grupo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre fluoro, nitrilo, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, fenilo o heteroarilo; en donde fenilo y heteroarilo están opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, C₁₋₆alquilo y trifluorometilo; X es -CH₂-, un enlace, oxígeno, azufre, sulfóxido, o sulfona; R² es C₃₋₇carbociclilo, opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre: fluoro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹; o R² es un anillo de 3 a 8 miembros que contiene opcionalmente 1, 2 ó 3 átomos seleccionados entre O, S, -NR⁸ y con lo cual el anillo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre C₁₋₃alquilo, fluoro, -OR⁴, -NR⁵R⁶ -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹; o R² es fenilo o heteroarilo, cada uno de los cuales está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -NR⁸COR⁹, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, C₁₋₆alquilo y trifluorometilo; o R² es un grupo seleccionado entre C₁₋₈alquilo, C₂₋₆alquenilo o C₂₋₆alquinilo en donde el grupo está sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre hidroxi, amino, C₁₋₆alcoxi, C₁₋₆alquilamino, di(C₁₋₆alquil)amino, N-(C₁₋₆alquil)-N-(fenil)amino, N-C₁₋₆alquilcarbamoilo, N,N-di(C₁₋₆alquil)carbamoilo, N-(C₁₋₆alquil)-N-(fenil)carbamoilo, carboxi, fenoxicarbonilo, -NR⁸COR⁹, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹ y -CONR⁵R⁶; R³ es trifluorometilo o un grupo -NR⁵R⁶, o R³ es fenilo, naptilo, heteroarilo monocíclico o bicíclico en donde un heteroátomo puede ser parcial o totalmente saturado y uno o más átomos de carbono del anillo pueden formar un grupo carbonilo, y en donde cada grupo fenilo o heteroarilo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, fenilo, heteroarilo, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COR²⁰, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, trifluorometilo o C₁₋₆alquilo [opcionalmente sustituido adicionalmente por 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, -OR²⁰, -COOR²⁰, -COR²⁰, -NR¹⁸R¹⁹, -CONR¹⁸R¹⁹, -NR¹⁸COR¹⁹, -SO₂R²⁰, -SO₂NR¹⁸R¹⁹, NR¹⁸SO₂R¹⁹, fenilo o heteroarilo monocíclico o bicíclico, en donde un anillo heterocíclico puede estar parcial o totalmente saturado; y en donde cada grupo fenilo o heteroarilo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, -OR²⁰, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, heteroarilo, C₁₋₆alquilo (opcionalmente sustituido adicionalmente por 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, -OR²⁰, -COOR²⁰, -COR²⁰, -NR¹⁸R¹⁹, -CONR¹⁸R¹⁹, -NR¹⁸COR¹⁹, -SO₂R²⁰, -SO₂NR¹⁸R¹⁹, NR¹⁸SO₂R¹⁹), o R³ es un grupo seleccionado entre C₃₋₇ carbociclilo, C₁₋₈alquilo, C₂₋₆alquenilo y C₂₋₆alquinilo con lo cual el grupo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, fenilo o heteroarilo monocíclico o bicíclico, en donde un anillo heterocíclico puede estar parcial o totalmente saturado; y en donde cada grupo fenilo o heteroarilo monocíclico o bicíclico está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, ciano, nitro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, C₁₋₆alquilo, o trifluorometilo; R⁴ es hidrógeno o un grupo seleccionado entre C₁₋₆alquilo y fenilo, en el grupo está opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados en forma independiente entre halo, fenilo, -OR¹¹ y -NR¹²R¹³; R⁵ y R⁶ son en forma independiente hidrógeno o un grupo seleccionado entre C₁₋₆alquilo y fenilo y heteroarilo monocíclico o bicíclico, en donde un anillo heterocíclico puede estar parcial o totalmente saturado; en el grupo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, fenilo, -OR¹⁴, -NR¹⁵R¹⁶, -COOR¹⁴, -CONR¹⁵R¹⁶, -NR¹⁵COR¹⁶, -SO₂R¹⁰, -SO₂NR¹⁵R¹⁶ y NR¹⁵SO₂R¹⁶; o R⁵ y R⁶ junto con el átomo de nitrógeno al cual están unidos forman un sistema de anillo heterocíclico de 4 a 7 miembros que contiene opcionalmente un heteroátomo adicional seleccionado entre oxígeno, -SO₍ₙ₎- (donde n = 0, 1 ó 2) y átomos de nitrógeno, en el cual el anillo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre fenilo, heteroarilo, -OR¹⁴, -COR²⁰, -COOR¹⁴, -NR¹⁵R¹⁶, -CONR¹⁵R¹⁶, -NR¹⁵COR¹⁶, -SO₂R¹⁰, -SO₂NR¹⁵R¹⁶, NR¹⁵SO₂R¹⁶ o C₁₋₆alquilo (opcionalmente sustituido adicionalmente por 1 ó 2 ó 3 sustituyentes seleccionados en forma independiente entre grupos halo, -NR¹⁵R¹⁶ y -OR¹⁷ o ciano, nitro, -OR²⁰, -COOR²⁰, -COR²⁰, -NR¹⁸R¹⁹, -CONR¹⁸R¹⁹, -NR¹⁸COR¹⁹, -SO₂R²⁰, -SO₂NR¹⁸R¹⁹, NR¹⁸SO₂R¹⁹); R¹⁰ es hidrógeno o un grupo seleccionado entre C₁₋₆alquilo o fenilo, en el grupo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, fenilo, -OR¹⁷ y -NR¹⁵R¹⁶; y cada uno de R⁷, R⁸, R⁹, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷ es en forma independiente hidrógeno, C₁₋₆alquilo o fenilo; R¹⁸, R¹⁹, y R²⁰ son hidrógeno o un grupo seleccionado entre C₁₋₆alquilo o heteroarilo (en donde un anillo heterocíclico puede estar parcial o totalmente saturado) o fenilo, en el grupo está opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados en forma independiente entre halo, nitro, -CN, -OR⁴, -NR⁸R⁹, -CONR⁸R⁹, -COR⁷ -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁸R⁹, -NR⁸SO₂R⁹, C₁₋₆alquilo o heteroarilo; o una sal aceptable para uso farmacéutico, solvato o un éster hidrolizable en vivo del mismo.Claim 1: A compound characterized in that it responds to formula (1) wherein R¹ is a group selected from C₃₋₇carbocyclyl, C₁₋₈alkyl, C₂₋₆alkenyl and C₂₋₆alquinyl; in the group it is optionally substituted with 1, 2 or 3 substituents independently selected from fluoro, nitrile, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, phenyl or heteroaryl; wherein phenyl and heteroaryl are optionally substituted with 1, 2 or 3 substituents independently selected from halo, cyano, nitro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, C₁₋₆alkyl and trifluoromethyl; X is -CH₂-, a bond, oxygen, sulfur, sulfoxide, or sulfone; R² is C₃₋₇carbocyclyl, optionally substituted with 1, 2 or 3 substituents independently selected from: fluoro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹; or R² is a 3 to 8 member ring that optionally contains 1, 2 or 3 atoms selected from O, S, -NR⁸ and whereby the ring is optionally substituted with 1, 2 or 3 substituents independently selected from C₁₋ ₃alkyl, fluoro, -OR⁴, -NR⁵R⁶ -CONR⁵R⁶, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹; or R² is phenyl or heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from halo, cyano, nitro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -NR⁸COR⁹, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹ , C₁₋₆alkyl and trifluoromethyl; or R² is a group selected from C₁₋₈alkyl, C₂₋₆alkenyl or C₂₋₆alkynyl wherein the group is substituted with 1, 2 or 3 substituents independently selected from hydroxy, amino, C₁₋₆alkoxy, C₁₋₆alkylamino, di ( C₁₋₆alkyl) amino, N- (C₁₋₆alkyl) -N- (phenyl) amino, N-C₁₋₆alkylcarbamoyl, N, N-di (C₁₋₆alkyl) carbamoyl, N- (C₁₋₆alkyl) -N- ( phenyl) carbamoyl, carboxy, phenoxycarbonyl, -NR⁸COR⁹, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹ and -CONR⁵R⁶; R³ is trifluoromethyl or a group -NR⁵R⁶, or R³ is phenyl, naptyl, monocyclic or bicyclic heteroaryl wherein a heteroatom can be partially or fully saturated and one or more carbon atoms of the ring can form a carbonyl group, and where each group phenyl or heteroaryl is optionally substituted with 1, 2 or 3 substituents independently selected from halo, cyano, nitro, phenyl, heteroaryl, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COR²⁰, -COOR⁷, -NR⁸COR⁹, - SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, trifluoromethyl or C₁₋₆alkyl [optionally further substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, -OR²⁰, -COOR²⁰, -COR²⁰, -NR¹⁸R¹⁹, -CONR¹⁸R¹⁹, -NR¹⁸COR¹⁹, -SO₂R²⁰, -SO₂NR¹⁸R¹⁹, NR¹⁸SO₂R¹⁹, monocyclic or bicyclic phenyl or heteroaryl, where a heterocyclic ring may be partially or totally sat urate; and wherein each phenyl or heteroaryl group is optionally substituted with 1, 2 or 3 substituents independently selected from halo, cyano, nitro, -OR²⁰, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, heteroaryl, C₁₋₆alkyl (optionally further substituted by 1, 2 or 3 substituents independently selected from halo, cyano, nitro, -OR²⁰, -COOR²⁰, -COR²⁰, -NR¹⁸R¹⁹, -CONR¹⁸R¹⁹ , -NR¹⁸COR¹⁹, -SO₂R²⁰, -SO₂NR¹⁸R¹⁹, NR¹⁸SO₂R¹⁹), or R³ is a group selected from C₃₋₇ carbocyclyl, C₁₋₈alkyl, C₂₋₆alkenyl and C₂₋₆alquinyl whereby the group is optionally substituted with 1, 2 or 3 substituents independently selected from halo, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, phenyl or mono heteroaryl colic or bicyclic, where a heterocyclic ring may be partially or fully saturated; and wherein each monocyclic or bicyclic phenyl or heteroaryl group is optionally substituted with 1, 2 or 3 substituents independently selected from halo, cyano, nitro, -OR⁴, -NR⁵R⁶, -CONR⁵R⁶, -COR⁷, -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁵R⁶, -NR⁸SO₂R⁹, C₁₋₆alkyl, or trifluoromethyl; R⁴ is hydrogen or a group selected from C₁₋₆alkyl and phenyl, in the group it is optionally substituted with 1 or 2 substituents independently selected from halo, phenyl, -OR¹¹ and -NR¹²R¹³; R⁵ and R⁶ are independently hydrogen or a group selected from C₁₋₆alkyl and phenyl and monocyclic or bicyclic heteroaryl, wherein a heterocyclic ring may be partially or fully saturated; in the group it is optionally substituted with 1, 2 or 3 substituents independently selected from halo, phenyl, -OR¹⁴, -NR¹⁵R¹⁶, -COOR¹⁴, -CONR¹⁵R¹⁶, -NR¹⁵COR¹⁶, -SO₂R¹⁰, -SO₂NR¹⁵R¹⁶ and NR¹⁵SO₂R¹⁶; or R⁵ and R⁶ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocyclic ring system that optionally contains an additional heteroatom selected from oxygen, -SO₍ₙ₎- (where n = 0, 1 or 2 ) and nitrogen atoms, in which the ring is optionally substituted with 1, 2 or 3 substituents independently selected from phenyl, heteroaryl, -OR¹⁴, -COR²⁰, -COOR¹⁴, -NR¹⁵R¹⁶, -CONR¹⁵R¹⁶, -NR¹⁵COR¹⁶, -SO₂R¹⁰ , -SO₂NR¹⁵R¹⁶, NR¹⁵SO₂R¹⁶ or C₁₋₆alkyl (optionally additionally substituted by 1 or 2 or 3 substituents independently selected from halo, -NR¹⁵R¹⁶ and -OR¹⁷ or cyano, nitro, -OR²⁰, -COOR²⁰, -COR²⁰, -NR¹⁸R¹⁹, -CONR¹⁸R¹⁹, -NR¹⁸COR¹⁹, -SO₂R²⁰, -SO₂NR¹⁸R¹⁹, NR¹⁸SO₂R¹⁹); R¹⁰ is hydrogen or a group selected from C₁₋₆alkyl or phenyl, in the group it is optionally substituted with 1, 2 or 3 substituents independently selected from halo, phenyl, -OR¹⁷ and -NR¹⁵R¹⁶; and each of R⁷, R⁸, R⁹, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷ is independently hydrogen, C₁₋₆alkyl or phenyl; R¹⁸, R¹⁹, and R²⁰ are hydrogen or a group selected from C₁₋₆alkyl or heteroaryl (where a heterocyclic ring may be partially or fully saturated) or phenyl, in the group it is optionally substituted with 1, 2 or 3 substituents selected in form independent between halo, nitro, -CN, -OR⁴, -NR⁸R⁹, -CONR⁸R⁹, -COR⁷ -COOR⁷, -NR⁸COR⁹, -SR¹⁰, -SO₂R¹⁰, -SO₂NR⁸R⁹, -NR⁸SO₂R⁹, C₁₋₆alkyl or heteroaryl; or a salt acceptable for pharmaceutical use, solvate or a live hydrolysable ester thereof.

ARP160102336A 2004-08-28 2016-08-01 SULFONAMID PYRIMIDIN DERIVATIVES AR105557A2 (en)

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CN101445813B (en) * 2007-12-21 2013-03-27 清华大学 Method for producing 3-hydracrylic acid
WO2010007427A1 (en) * 2008-07-16 2010-01-21 Astrazeneca Ab Pyrimidyl sulfonaminde derivative and its use for the treatment of chemokine mediated diseases
CN103781781B (en) * 2011-07-12 2015-08-26 阿斯利康(瑞典)有限公司 N-(6-((2R, 3S)-3,4-dihydroxyl fourth-2-base oxygen base)-2-(4-Fluorobenzylthio) pyrimidine-4-yl as chemokine receptor modulators)-3-methyl azetidine-1-sulphonamide
JP6096808B2 (en) * 2012-02-07 2017-03-15 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft Novel azetidine derivatives
CN112457259B (en) * 2020-12-08 2024-02-20 重庆康乐制药有限公司 Preparation method of sulfadoxine

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