INHIBIDORES MACROCICLICOS DE LAS INTERACCIONES PROTEINA/PROTEINA DE PROTEINA DE MUERTE PROGRAMADA 1 (PD-1)/LIGANDO DE MUERTE PROGRAMADA 1 (PD-L1) Y CUMULO DE DIFERENCIACION 80 (B7-1) CD80 (B7-1)/LIGANDO DE MUERTE PROGRAMADA 1 (PD-L1)
MILLER, MICHAEL MATTHEW,MAPELLI, CLAUDIO,ALLEN, MARTIN PATRICK,BOWSHER, MICHAEL S.,BOY, KENNETH M.,GILLIS, ERIC P.,LANGLEY, DAVID R.,MULL, ERIC,LANGLEY, DAVID R.,SANGHVI, NISHITH,SUN, LI-QIANG,TENNEY,
申请号：
PE0019572015
公开号：
PE16712015A1
申请日:
2014.03.13
申请国别(地区):
PE
年份:
2015
代理人:
摘要：
Macrocyclic peptides refers to formula (i), or pharmaceutically acceptable salts thereof, which is characterized because it is CH [C (o) NH2 (CH2)] - N - CH2 - S - CH2 -, * ch [C (o) NH2 (CH2)] - N - CH2 - S (*) - CH2 -, - C (o) CH [NH2] - N - (CH2) - S (CH2) 2 - CH2 -, * ch [C (o) NH2 (CH2)] - N - [- * CH CH2 or NH2] - C (o) n - (CH2) CH = CH - *, Others, where * indicates the Junction Point to carbonyl n is 0 OR 1 R1, R2, R3, R4, R5, R6, R7, R8, R9,R10, R11, R12 and R13 are independently an Unnatural amino acid side chain, among others ra, re, RJ and RK are independently H or Methyl RC, RF, RH, ir, RM and RN are h RB is Rd is H or Methyl Methyl R is H or Methyl or RB and Rd and R2, R4, R7 and RG, among others, along with the Atoms Which are form azetidine, morpholine, pyrrolidine, piperidine or piperazineAmong others. Macrocyclic peptides of the formula (i) inhibit Protein Protein Interaction \/ PPD - 1 \/ pd-l1 and pd-l1 \/ CD80, which are useful in the therapy of various diseases, including Cancer and Infectious DiseasesSE REFIERE A PEPTIDOS MACROCICLICOS DE FORMULA (I) O SALES DEL MISMO FARMACEUTICAMENTE ACEPTABLES, QUE SE CARACTERIZAN PORQUE A ES -CH[C(O)NH2]-(CH2)n-CH2-S-CH2-*, -CH[C(O)NH2]-(CH2)n-CH2-S(O)-CH2-*, -CH[C(O)NH2]-(CH2)n-CH2-S(O)2-CH2-*, -CH[C(O)NH2]-(CH2)n-CH2-* O -CH[C(O)NH2]-(CH2)n-CH=CH-*, ENTRE OTROS, DONDE * INDICA EL PUNTO DE UNION A CARBONILO n ES 0 o 1 R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 Y R13 SON INDEPENDIENTEMENTE UNA CADENA LATERAL DE AMINOACIDO NO NATURAL, ENTRE OTROS Ra, Re, Rj Y Rk SON INDEPENDIENTEMENTE H O METILO Rc, Rf, Rh, Ri, Rm Y Rn SON H Rb ES METILO Rd ES H O METILO Rg ES H O METILO O Rb Y R2, Rd Y R4, O Rg Y R7, ENTRE OTROS, JUNTO CON LOS ATOMOS A LOS CUALES ESTAN UNIDOS FORMAN AZETIDINA, PIRROLIDINA, MORFOLINA, PIPERIDINA O PIPERAZINA, ENTRE OTROS. LOS PEPTIDOS MACROCICLICOS DE FORMULA (I) INHIBEN LA INTERACCION PROTEINA/PROTEINA PPD-1/PD-L1 Y PD-L1/CD80, POR LO CUAL SON UTILES EN LA TERAPIA DE VARIAS ENFERME
