WATHIER, Michel,DOLLE, Roland,MARCUCCIO, Sebastian, Mario,JOYCE, Rohan, David,TUCKER, Simon
申请号：
USUS2019/022555
公开号：
WO2019/221813A1
申请日:
2019.03.15
申请国别(地区):
US
年份:
2019
代理人:
摘要：
The present invention relates to inorganic salts of nicotinic acid mononucleotides and compositions of Formula I, useful in the treatment of disorders and diseases associated with deficiencies in NAD+:wherein A is O"； M1 and M2 are independently an inorganic cation； R1 and R2 are independently H, C1-C6 alkyl, C1-C6 haloalkyl, (C0-C3 aikylene)C(0)C1-C6 alkyl, -C(0)0Ra, -C(O) NR a R b, or -[CH2- CH2-0]n-Ra, or R1 and R2, taken together with the atom to which each is attached, form a 5-membered heterocyclic ring optionally substituted with one or more substituents selected from C1-C6 alkyl, C2-C6alkenyl, C2-C6 alkynyl, (C0-C3 alkylene) C3-C8 cycloakyl, (C0-C3 alkylene)heterocycloakyl, (C0-C3 alkylene)C6-C14 aryl, and (C0-C3 alkylene)heteroaryl； R3 is a negative charge, H, or C1-C6 alkyl； Ra and Rb are independently, at each occurrence, H, or C1-C6 alkyl, wherein the alkyl is optionally substituted with one or more substituents selected from (C0-C3 alkylene)C3-C8 cycloakyl, (C0-C3 alkylene) heterocycloakyl, (C0-C3 alkylene)C6-C14 aryl, and (C0-C3 alkylene) heteroaryl； k is 1 or 2； and n is an integer from 1 to 8, provided that when R3 is H or C1-C6 alkyl, then M1 is absent. The compounds are used for treating or preventing (age-related) infertility or for improving oocyte or blastocyst quality and maturation.La présente invention concerne des sels inorganiques de mononucléotides d'acide nicotinique et des compositions de formule I, utiles dans le traitement de troubles et de maladies associés à des déficiences en NAD+ : dans la formule A est O" ； M1 et M2 représentent indépendamment un cation inorganique ； R1 et R2 représentent indépendamment H, alkyle en C1-C6, haloalkyle en C1-C6, (aikylène en C0-C3) alkyle en C(0)C1-C6, -C(0)0Ra, -C(O) NR a R b, ou -[CH2- CH2-0]n-Ra, ou R1 et R2, pris ensemble avec l'atome auquel ils sont attachés chacun, forment un cycle hétérocyclique à 5 chaînons éventuellement substitué par un ou plusieurs substituants choisis parmi un alkyle en
