SCRIBNER, ANDREW,SJOGREN, ERIC BRIAN,DE LOMBAERT, STEPHANE,GOLDBERG, Daniel R.,BRAMELD, KENNETH
申请号：
PE0003402016
公开号：
PE06482016A1
申请日:
2014.09.05
申请国别(地区):
PE
年份:
2016
代理人:
摘要：
The present Invention relates to compounds of formula (i) espirociclicos where the cycloalkyl ring is C3 - C10, among others l or NR4 W is n or CR5 X is n or N or Cr6 and CR7 r1 is H,C1 - C10 alkyl R2 and R3 are h, c1-c4 alkyl and haloalquilo c1-c4 ra is H, Halo, among others RB is H, Halo, among others RC and Rd are h, Halo, among others n is 1 or 2.Preferred compounds are: acid (S) - 2 - (2 - amino - 4 - ((R) - 2,2,2-trifluoro-1 - (3 - (3 - metii - 1H pyrazol-1-yl) - 4 - (methylthio) - [1,1 - biphenyl] - 4-yl) ethoxy) pyrimidin-4-yl) - 2.8 - diazaspiro [4.5] Dean - 3 - carboxylic acid (S) - 2 - (2 - amino - 4 - ((R) - 1 - (3 - Carboxy - 3 - (3 - methyl - 1 - pyrazol-1-yl) - [1,1 - biphenyl) - 4-yl) - Chemical - trifluoroetoxi) pyrimidin-4-yl) - 2.8 - diazaspiro [4.5] Dean - 3 - carboxylic acid, among others.These compounds are inhibitors of tryptophan hydroxylase (TPH), particularly the isoform 1, being useful in the treatment of diseases related to Peripheral serotonin, for example,Gastrointestinal Diseases, cardiovascular, pulmonary, inflammatory and cancer, among othersLa presente invencion se refiere a compuestos espirociclicos de formula (I) en donde el anillo A es cicloalquilo C3-C10, entre otros L es O o NR4 W es N o CR5 X es N o CR6 Y es N o CR7 R1 es H, alquilo C1-C10, entre otros R2 y R3 son H, alquilo C1-C4 y haloalquilo C1-C4 RA es H, halo, entre otros RB es H, halo, entre otros RC y RD son H, halo, entre otros n es 1 o 2. Son compuestos preferidos: acido (S)-8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3-(3-metiI-1H-pirazol-1-il)-4-(metiltio)-[1,1-bifenil]-4-il)etoxi)pirimidin-4-il)-2,8-diazaspiro[4.5]decano-3-carboxilico, acido (S)-8-(2-amino-6-((R)-1-(3-carboxi-3-(3-metil-1H-pirazol-1-il)-[1,1-bifenil]-4-il)-2,2,2-trifluoroetoxi)pirimidin-4-il)-2,8-diazaspiro[4.5]decano-3-carboxilico, entre otros. Dichos compuestos son inhibidores de triptofano hidroxilasa (TPH), particularmente la isoforma 1, siendo utiles en el tratamiento de enfermedades relacionadas con
