The present invention relates a compound of formula (I) in Z-isomer form (Z-(l)) or a compound of formula (I) in E-isomer form (E-(l)) wherein: R2 is a radical of formula (II) and of formula (III); X1, X2, X3, X4 and X5 are CR3 and N; Y1 is NH, O and S; each R1, each R3 and R7 are H, halogen, -OH, -O-(C1-C8)alkyl, -N((C1-C8)alkyl)3, -NH((C1-C8)alkyl)2, and -NH2(C1-C8)alkyl; R4, R5 and R6 are H and (C1-C8)alkyl; - - - line indicates the position of R2 radical by which R2 is attached to the adjacent N; and the asterisk indicates a stereogenic carbon atom being in R-isomer, S-isomer and a mixture of R-isomer and S-isomer. It also relates to the compound Z-(l) for use as a medicament; and the compound E-(l) for use in the treatment of a disease or condition mediated by the dihydrofolate reductase, wherein the treatment comprises exposing a compound E-(I) to light irradiation to obtain the compound Z-(l).

PHOTOISOMERIZABLE DERIVATIVES OF DIHYDROFOLATE REDUCTASE INHIBITORS / P.I. GOROSTIZA LANGA, C. SOLER PRAT, C. Matera, N. CAMARERO PALAO, M. Libergoli, A. GOMILA JUANEDA.

PHOTOISOMERIZABLE DERIVATIVES OF DIHYDROFOLATE REDUCTASE INHIBITORS

C. Matera;
2019

Abstract

The present invention relates a compound of formula (I) in Z-isomer form (Z-(l)) or a compound of formula (I) in E-isomer form (E-(l)) wherein: R2 is a radical of formula (II) and of formula (III); X1, X2, X3, X4 and X5 are CR3 and N; Y1 is NH, O and S; each R1, each R3 and R7 are H, halogen, -OH, -O-(C1-C8)alkyl, -N((C1-C8)alkyl)3, -NH((C1-C8)alkyl)2, and -NH2(C1-C8)alkyl; R4, R5 and R6 are H and (C1-C8)alkyl; - - - line indicates the position of R2 radical by which R2 is attached to the adjacent N; and the asterisk indicates a stereogenic carbon atom being in R-isomer, S-isomer and a mixture of R-isomer and S-isomer. It also relates to the compound Z-(l) for use as a medicament; and the compound E-(l) for use in the treatment of a disease or condition mediated by the dihydrofolate reductase, wherein the treatment comprises exposing a compound E-(I) to light irradiation to obtain the compound Z-(l).
FUNDACIÓ INSTITUT DE BIOENGINYERIA DE CATALUNYA
UNIVERSITAT DE BARCELONA
CONSORCIO CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED, M.P.
INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS
WO2019/122151
PCT/EP2018/086233
17382894.8
27-giu-2019
dihydrofolate reductase; DHFR inhibitor; photoisomerizable; folate; antimetabolite; antifolate; methotrexate; pemetrexed; phototrexate
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019122151
PHOTOISOMERIZABLE DERIVATIVES OF DIHYDROFOLATE REDUCTASE INHIBITORS / P.I. GOROSTIZA LANGA, C. SOLER PRAT, C. Matera, N. CAMARERO PALAO, M. Libergoli, A. GOMILA JUANEDA.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/770279
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