AR040734A1 - CICLOBUTEN 1,2- DIONAS 3, 4- DI-REPLACED AS LIGANDS OF THE CXC CHEMIOKIN RECEIVER - Google Patents

CICLOBUTEN 1,2- DIONAS 3, 4- DI-REPLACED AS LIGANDS OF THE CXC CHEMIOKIN RECEIVER

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Publication number
AR040734A1
AR040734A1 AR20030102737A ARP030102737A AR040734A1 AR 040734 A1 AR040734 A1 AR 040734A1 AR 20030102737 A AR20030102737 A AR 20030102737A AR P030102737 A ARP030102737 A AR P030102737A AR 040734 A1 AR040734 A1 AR 040734A1
Authority
AR
Argentina
Prior art keywords
substituted
group
unsubstituted
independently selected
alkyl
Prior art date
Application number
AR20030102737A
Other languages
Spanish (es)
Original Assignee
Pharmacopeia Drug Discovery
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US10/208,412 external-priority patent/US20040097547A1/en
Priority claimed from US10/241,326 external-priority patent/US20040106794A1/en
Application filed by Pharmacopeia Drug Discovery, Schering Corp filed Critical Pharmacopeia Drug Discovery
Publication of AR040734A1 publication Critical patent/AR040734A1/en

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Classifications

    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Se revelan nuevos compuestos de la fórmula general (1) y composiciones farmacéuticas que los contengan. Uso en el tratamiento de las enfermedades mediadas por quimiocina utilizando los compuestos de la fórmula. Reivindicación 1: Un compuesto de la fórmula general (1) y las sales y solvatos farmacéuticamente aceptables de los mismos, en donde A es seleccionado del grupo que consiste de los grupos de fórmula (2)y (3) en donde dichos anillos de dichos grupos A están sustituidos con 1 a 6 sustituyentes cada uno independientemente seleccionado del grupo que consiste de : grupos R9; y B está seleccionado del grupo que consiste de resto de fórmula (4) siempre que R3 para este grupo esté seleccionado del grupo que consiste de -C(O)NR13R14, restos de fórmulas (5) al 22; R2 está seleccionado del grupo que consiste de: H, -OH, -C(O)OH, -SH, -SO2NR13R14, -NHC(O)R13, -NHSO2NR13R14, -NHSO2R13, -NR13R14, -C(O)NR13R14, -C(O)NHOR13, -C(O)NR13OH, -S(O2)OH, -OC(O)R13, un grupo funcional ácido heterocíclico no sustituido, y un grupo funcional ácido heterocíclico sustituido, en donde hay 1 a 6 sustituyentes sobre dicho grupo funcional ácido heterocíclico sustituido, cada sustituyente está independientemente seleccionado del grupo que consiste de; grupos R9; cada R3 y R4 es independientemente seleccionado del grupo que consiste de: H, ciano, halógeno, alquilo, alcoxi, -OH, -CF3, -OCF3, -NO2, -C(O)R13, -C(O)OR13, -C(O)NHR17, -C(O)NR13R14, -SO(t)NR13R14, -SO(t)R13, -C(O)NR13OR14, arilo no sustituido o sustituido, heteroarilo no sustituido o sustituido, restos de fórmula (5) donde hay 1 a 6 sustituyentes en dicho grupo arilo sustituido y cada sustituyente es independientemente seleccionado del grupo que consiste de: grupos R9; y en donde hay 1 a 6 sustituyentes en dicho grupo heteroarilo sustituido y cada sustituyente es independientemente seleccionado del grupo que consiste en grupos R9; cada R5 y R6 son iguales o diferentes y son independientemente seleccionados del grupo que consiste de H, halógeno, alquilo, alcoxi, -CF3, -OCF3, -NO2, -C(O)R13, -C(O)OR13, -C(O)NR13R14, -SO(t)NR13R14, -C(O)NR13OR14, ciano, arilo sustituido o no sustituido, y grupo heteroarilo no sustituido o sustituido; donde hay 1 a 6 sustituyentes en dicho grupo arilo sustituido y cada sustituyente es independientemente seleccionado del grupo que consiste de: grupos R9; y donde hay 1 a 6 sustituyentes en dicho grupo heteroarilo sustituido y cada sustituyente es independientemente seleccionado del grupo que consiste de grupos: R9; cada R7 y R8 es independientemente seleccionado del grupo que consiste de H, alquilo no sustituido o sustituido, arilo no sustituido o sustituido, heteroarilo no sustituido o sustituido, arilalquilo no sustituido o sustituido, heteroarilalquilo no sustituido o sustituido, cicloalquilo no sustituido o sustituido, cicloalquilalquilo no sustituido o sustituido, -CO2R13, -CONR13R14, alquinilo, alquenilo y cicloalquenilo; y donde hay uno o más sustituyentes en dichos grupos R7 y R8, donde cada sustituyente es independientemente seleccionado del grupo que consiste de: a) halógeno, b) -CF3, c)-COR13, d)-OR13, e) -NR13R14, f)NO2, g)-CN, h)-SO2OR13, i) -Si(alquilo)3, donde cada alquilo es independientemente seleccionado, j) -Si(arilo)3, donde cada alquilo es independientemente seleccionado, k)-(R13)2R14Si, donde cada R13 es independientemente seleccionado, l)-CO2R13, m)-C(O)NR13R14, n)-SO2NR13R14, o)-SO2R13, p)-OC(O)R13, q)-OC(O)NR13R14, r)-NR13C(O)R14, y s)-NR13CO2R14; cada R9 es independientemente seleccionado del grupo que consiste de: a)-R13, b) halógeno, c)-CF3, d)-COR13, e)-OR13, f)-NR13R14, g)-NO2, h)-CN, i)-SO2R13, j)-SO2NR13R14, k)-NR13COR14, l)-CONR13R14, m)-NR13CO2R14, n)-CO2R13, o) como se muestra en el resto de fórmula (23), p) alquilo sustituido con uno o más grupos -OH, q) alquilo sustituido con uno o más grupos -NR13R14, y r) -N(R13)SO2R14; cada R10 y R11 es independientemente seleccionado a partir del grupo que consiste de R13, H, alquilo, -CF3, -OCF3, -NR13R14, -NR13C(O)NR13R14,-OH, -C(O)OR13, -SH, -SO(t)NR13R14, -SO2R13, -NHC(O)R13, -NHSO2NR13R14, -NHSO2R13, -C(O)NR13R14, -C(O)NR13OR14, -OC(O)R13 y ciano; R12 es seleccionado del grupo que consiste de H, -C(O)OR13, grupo arilo no sustituido o sustituido, heteroarilo no sustituido o sustituido, arilalquilo no sustituido o sustituido, cicloalquilo no sustituido o sustituido, alquilo no sustituido o sustituido, cicloalquilalquilo no sustituido o sustituido, y heteroarilalquilo no sustituido o sustituido; donde hay 1 a 6 grupos sustituyentes en los grupos R12 sustituido y cada sustituyente es independientemente seleccionado del grupo que consiste de grupos R9; cada R13 y R14 es independientemente seleccionado del grupo que consiste de H, alquilo no sustituido o sustituido, arilo no sustituido o sustituido, heteroarilo no sustituido o sustituido, arilalquilo no sustituido o sustituido, heteroarilalquilo no sustituido o sustituido, cicloalquilo no sustituido o sustituido, cicloalquilalquilo no sustituido o sustituido, heterocíclico no sustituido o sustituido, fluoralquilo no sustituido o sustituido, heterocicloalquilalquilo no sustituido o sustituido, donde hay 1 a 6 sustituyentes en dichos grupos R123 y R14 sustituidos y cada sustituyente es independientemente seleccionado del grupo que consiste de: alquilo, -CF3, -OH, alcoxi, arilo, arilalquilo, fluoralquilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, -N(R40)2, -C(O)OR15, -C(O)NR15R16, -S(O)tNR15R16, -C(O)R15,-SO2R15 siempre que R15 no sea H, halógeno y -NHC(O)NR15R16; o R13 y R14 tomados juntos con el N al cual están unidos en los grupos -C(O)NR13R14 y -SO2NR13R14 forman un anillo heterocíclico saturado no sustituido o sustituido, dicho anillo opcionalmente contiene un heteroátomo adicional seleccionado del grupo que consiste de O, S y NR18; en donde hay 1 a 3 sustituyentes en los grupos R13 y R14 ciclados sustituidos y cada sustituyente es independientemente seleccionado del grupo que consiste de: alquilo, arilo, hidroxi, hidroxialquilo, alcoxi, alcoxialquilo, arilalquilo, fluoralquilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heteroarilalquilo, amino, -C(O)OR15, -C(O)NR15R16, -SOtNR15R16, -C(O)R15, -SO2R15 siempre que R15 no sea H, -NHC(O)NR15R16, NHC(O)OR15, halógeno, y un grupo heterocicloalquenilo; cada R15 y R16 es independientemente seleccionado a partir del grupo que consiste de: H, alquilo, arilo, arilalquilo, cicloalquilo y heteroarilo; R17 es seleccionado a partir del grupo que consiste de: -SO2alquilo, -SO2arilo, -SO2cicloalquilo, y -SO2heteroarilo; R18 es seleccionado del grupo que consiste de H, alquilo, arilo, heteroarilo, -C(O)R19, -SO2R19 y -C(O)NR19R20; cada R19 y R20 es independientemente seleccionado del grupo que consiste de: alquilo, arilo y heteroarilo; R30 es seleccionado del grupo que consiste de: alquilo, cicloalquilo, -CN,-NO2, o -SO2R15 siempre que R15 no sea H; cada R31 es independientemente seleccionado del grupo que consiste de: alquilo no sustituido o sustituido, arilo no sustituido o sustituido, heteroarilo no sustituido o sustituido y cicloalquilo no sustituido o sustituido, en donde hay 1 a 6 sustituyentes en dichos grupos R31 sustituidos y cada sustituyente es independientemente seleccionado del grupo que consiste de; alquilo, halógeno y -CF3; cada R40 es independientemente seleccionado del grupo que consiste de: H, alquilo y cicloalquilo; y t es 0,1 o 2.New compounds of the general formula (1) and pharmaceutical compositions containing them are disclosed. Use in the treatment of chemokine mediated diseases using the compounds of the formula. Claim 1: A compound of the general formula (1) and pharmaceutically acceptable salts and solvates thereof, wherein A is selected from the group consisting of the groups of formula (2) and (3) wherein said rings of said Groups A are substituted with 1 to 6 substituents each independently selected from the group consisting of: R9 groups; and B is selected from the group consisting of the remainder of formula (4) provided that R3 for this group is selected from the group consisting of -C (O) NR13R14, residues of formulas (5) through 22; R2 is selected from the group consisting of: H, -OH, -C (O) OH, -SH, -SO2NR13R14, -NHC (O) R13, -NHSO2NR13R14, -NHSO2R13, -NR13R14, -C (O) NR13R14, -C (O) NHOR13, -C (O) NR13OH, -S (O2) OH, -OC (O) R13, an unsubstituted heterocyclic acid functional group, and a substituted heterocyclic acid functional group, wherein there are 1 to 6 substituents on said substituted heterocyclic acid functional group, each substituent is independently selected from the group consisting of; R9 groups; each R3 and R4 is independently selected from the group consisting of: H, cyano, halogen, alkyl, alkoxy, -OH, -CF3, -OCF3, -NO2, -C (O) R13, -C (O) OR13, - C (O) NHR17, -C (O) NR13R14, -SO (t) NR13R14, -SO (t) R13, -C (O) NR13OR14, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, residues of formula ( 5) where there are 1 to 6 substituents in said substituted aryl group and each substituent is independently selected from the group consisting of: R9 groups; and wherein there are 1 to 6 substituents in said substituted heteroaryl group and each substituent is independently selected from the group consisting of R9 groups; each R5 and R6 are the same or different and are independently selected from the group consisting of H, halogen, alkyl, alkoxy, -CF3, -OCF3, -NO2, -C (O) R13, -C (O) OR13, -C (O) NR13R14, -SO (t) NR13R14, -C (O) NR13OR14, cyano, substituted or unsubstituted aryl, and unsubstituted or substituted heteroaryl group; wherein there are 1 to 6 substituents in said substituted aryl group and each substituent is independently selected from the group consisting of: R9 groups; and where there are 1 to 6 substituents in said substituted heteroaryl group and each substituent is independently selected from the group consisting of groups: R9; each R7 and R8 is independently selected from the group consisting of H, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkylalkyl, -CO2R13, -CONR13R14, alkynyl, alkenyl and cycloalkenyl; and where there is one or more substituents in said R7 and R8 groups, where each substituent is independently selected from the group consisting of: a) halogen, b) -CF3, c) -COR13, d) -OR13, e) -NR13R14, f) NO2, g) -CN, h) -SO2OR13, i) -Si (alkyl) 3, where each alkyl is independently selected, j) -Si (aryl) 3, where each alkyl is independently selected, k) - ( R13) 2R14Si, where each R13 is independently selected, l) -CO2R13, m) -C (O) NR13R14, n) -SO2NR13R14, or) -SO2R13, p) -OC (O) R13, q) -OC (O ) NR13R14, r) -NR13C (O) R14, and s) -NR13CO2R14; each R9 is independently selected from the group consisting of: a) -R13, b) halogen, c) -CF3, d) -COR13, e) -OR13, f) -NR13R14, g) -NO2, h) -CN, i) -SO2R13, j) -SO2NR13R14, k) -NR13COR14, l) -CONR13R14, m) -NR13CO2R14, n) -CO2R13, or) as shown in the rest of formula (23), p) alkyl substituted with one or more groups -OH, q) alkyl substituted with one or more groups -NR13R14, and r) -N (R13) SO2R14; each R10 and R11 is independently selected from the group consisting of R13, H, alkyl, -CF3, -OCF3, -NR13R14, -NR13C (O) NR13R14, -OH, -C (O) OR13, -SH, - SO (t) NR13R14, -SO2R13, -NHC (O) R13, -NHSO2NR13R14, -NHSO2R13, -C (O) NR13R14, -C (O) NR13OR14, -OC (O) R13 and cyano; R12 is selected from the group consisting of H, -C (O) OR13, unsubstituted or substituted aryl group, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkyl, non-substituted cycloalkylalkyl substituted or substituted, and unsubstituted or substituted heteroarylalkyl; where there are 1 to 6 substituent groups in the substituted R12 groups and each substituent is independently selected from the group consisting of R9 groups; each R13 and R14 is independently selected from the group consisting of H, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heterocyclic, unsubstituted or substituted fluoralkyl, unsubstituted or substituted heterocycloalkylalkyl, where there are 1 to 6 substituents in said substituted R123 and R14 groups and each substituent is independently selected from the group consisting of: alkyl , -CF3, -OH, alkoxy, aryl, arylalkyl, fluoralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, -N (R40) 2, -C (O) OR15, -C (O) NR15R16, -S (O) tNR15R16 , -C (O) R15, -SO2R15 provided that R15 is not H, halogen and -NHC (O) NR15R16; or R13 and R14 taken together with the N to which they are attached in the -C (O) NR13R14 and -SO2NR13R14 groups form a saturated unsubstituted or substituted heterocyclic ring, said ring optionally containing an additional heteroatom selected from the group consisting of O, S and NR18; wherein there are 1 to 3 substituents in the substituted cycled R13 and R14 groups and each substituent is independently selected from the group consisting of: alkyl, aryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, arylalkyl, fluoralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl , amino, -C (O) OR15, -C (O) NR15R16, -SOtNR15R16, -C (O) R15, -SO2R15 provided that R15 is not H, -NHC (O) NR15R16, NHC (O) OR15, halogen , and a heterocycloalkenyl group; each R15 and R16 is independently selected from the group consisting of: H, alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl; R17 is selected from the group consisting of: -SO2alkyl, -SO2aryl, -SO2cycloalkyl, and -SO2heteroaryl; R18 is selected from the group consisting of H, alkyl, aryl, heteroaryl, -C (O) R19, -SO2R19 and -C (O) NR19R20; each R19 and R20 is independently selected from the group consisting of: alkyl, aryl and heteroaryl; R30 is selected from the group consisting of: alkyl, cycloalkyl, -CN, -NO2, or -SO2R15 provided that R15 is not H; each R31 is independently selected from the group consisting of: unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl and unsubstituted or substituted cycloalkyl, wherein there are 1 to 6 substituents in said substituted R31 groups and each substituent It is independently selected from the group consisting of; alkyl, halogen and -CF3; each R40 is independently selected from the group consisting of: H, alkyl and cycloalkyl; and t is 0.1 or 2.

AR20030102737A 2002-07-30 2003-07-30 CICLOBUTEN 1,2- DIONAS 3, 4- DI-REPLACED AS LIGANDS OF THE CXC CHEMIOKIN RECEIVER AR040734A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/208,412 US20040097547A1 (en) 2001-04-16 2002-07-30 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
US10/241,326 US20040106794A1 (en) 2001-04-16 2002-09-11 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands

Publications (1)

Publication Number Publication Date
AR040734A1 true AR040734A1 (en) 2005-04-20

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Application Number Title Priority Date Filing Date
AR20030102737A AR040734A1 (en) 2002-07-30 2003-07-30 CICLOBUTEN 1,2- DIONAS 3, 4- DI-REPLACED AS LIGANDS OF THE CXC CHEMIOKIN RECEIVER

Country Status (8)

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JP (1) JP2011063591A (en)
CN (1) CN100338032C (en)
AR (1) AR040734A1 (en)
CO (1) CO5680474A2 (en)
EC (1) ECSP055581A (en)
PE (1) PE20040746A1 (en)
TW (1) TWI330174B (en)
ZA (1) ZA200500837B (en)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1334797A (en) * 1998-12-14 2002-02-06 美国家用产品公司 3,4-diamino-3-cyclobutene-1,2-dione derivs. which inhibit leukocyte adhesion mediated by VLA-4
HUP0302382A3 (en) * 2000-05-30 2004-09-28 Smithkline Beecham Corp Il-8 receptor antagonists and pharmaceutical compositions containing them

Also Published As

Publication number Publication date
PE20040746A1 (en) 2004-10-23
JP2011063591A (en) 2011-03-31
ECSP055581A (en) 2005-04-18
CN1723194A (en) 2006-01-18
CN100338032C (en) 2007-09-19
TW200410920A (en) 2004-07-01
TWI330174B (en) 2010-09-11
CO5680474A2 (en) 2006-09-29
ZA200500837B (en) 2006-11-29

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