US 12,421,206 B2
Aryl-n-aryl derivatives for treating a RNA virus infection
Didier Scherrer, Castelnau-le-Lez (FR); Jamal Tazi, Clapiers (FR); Florence Mahuteau-Betzer, Saint Remy-les-Chevreuse (FR); Romain Najman, L'Hay-les-Roses (FR); Julien Santo, Grabels (FR); and Cécile Apolit, Grabels (FR)
Assigned to ABIVAX, Paris (FR); CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); UNIVERSITE DE MONTPELLIER, Montpellier (FR); and INSTITUT CURIE, Paris (FR)
Appl. No. 17/259,451
Filed by ABIVAX, Paris (FR); CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); UNIVERSITE DE MONTPELLIER, Montpellier (FR); and INSTITUT CURIE, Paris (FR)
PCT Filed Jul. 9, 2019, PCT No. PCT/EP2019/068465
§ 371(c)(1), (2) Date Jan. 11, 2021,
PCT Pub. No. WO2020/011816, PCT Pub. Date Jan. 16, 2020.
Claims priority of application No. 18305911 (EP), filed on Jul. 9, 2018.
Prior Publication US 2021/0122732 A1, Apr. 29, 2021
Int. Cl. C07D 401/12 (2006.01); A61P 31/12 (2006.01); C07C 233/65 (2006.01); C07C 237/40 (2006.01); C07C 255/50 (2006.01); C07C 311/16 (2006.01); C07D 205/04 (2006.01); C07D 213/38 (2006.01); C07D 213/74 (2006.01); C07D 213/75 (2006.01); C07D 213/81 (2006.01); C07D 239/16 (2006.01); C07D 239/22 (2006.01); C07D 239/42 (2006.01); C07D 241/12 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 413/12 (2006.01); C07F 7/18 (2006.01)
CPC C07D 401/12 (2013.01) [A61P 31/12 (2018.01); C07C 233/65 (2013.01); C07C 237/40 (2013.01); C07C 255/50 (2013.01); C07C 311/16 (2013.01); C07D 205/04 (2013.01); C07D 213/38 (2013.01); C07D 213/74 (2013.01); C07D 213/75 (2013.01); C07D 213/81 (2013.01); C07D 239/16 (2013.01); C07D 239/22 (2013.01); C07D 239/42 (2013.01); C07D 241/12 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 413/12 (2013.01); C07F 7/1804 (2013.01)] 17 Claims
 
1. A compound of formula (Ie):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:

OG Complex Work Unit Chemistry
ring and

OG Complex Work Unit Chemistry
 ring both represent a phenylene group,
Y1 represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, the aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C1-C4)alkyl group, a cyano group, a (C1-C5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO2—NRaRb group, a —SO3H group, a —OH group, a —O—SO2—ORc group or
 a —O—P(═O)—(ORc)(ORd) group,
Ra, Rb, Rc and Rd independently represent a hydrogen atom or a (C1-C4)alkyl group,
X2 represents
a —O— group,
a —NH— group,
a —S— group,
a —CO—NH— group,
a —NH—CO— group,
a —CH(OH)— group,
a —CH(COOH)NH— group,
a —CH(COOCH3)NH— group,
a —C(OH)(CH2OH)—,
a

OG Complex Work Unit Chemistry
 group,
a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or heteroatoms,
a —SO2— group, or
a —SO2—NH— group,
n is 0, 1, 2 or 3,
m and m′ are independently 0, 1 or 2,
Y2 represents
a hydroxyl group,
a —CHC(OH)2,
a morpholinyl group,
a dihydropyranyl group, a

OG Complex Work Unit Chemistry
 group,
a

OG Complex Work Unit Chemistry
 group,
a —PO(ORf)(OR′f) group, wherein Rf and R′f independently represents a hydrogen atom or a (C1-C4)alkyl group,
an oxetanyl group,
a —Si(CH3)3 group,
a —NHCOO—(C1-C4)alkyl group, or
a —CR1R2R3 group, wherein R1, R2 and R3 independently represent a hydrogen atom or a (C1-C4)alkyl group, so long as no more than one of R1, R2 and R3 is a hydrogen atom, or R1 and R2 form together with the carbon atom bearing them a (C4-C8)cycloalkyl group, the (C4-C8)cycloalkyl group being optionally substituted by one or two (C1-C4)alkyl group, halogen atom or (C1-C4)alkoxy group, and the (C4-C8)cycloalkyl group optionally being a (C4 or C6-C8)cycloalkyl group that is interrupted on the R1 and/or R2 by an oxygen atom,
or alternatively, X2—(CH2)n—Y2 represents a —O—(CH2)n—COORf group, wherein Rf represents a hydrogen atom or a (C1-C4)alkyl group,
or alternatively, X2—(CH2)n—Y2 represents a CO—NH—(CH2)n—Y2 group, wherein Y2 represents a cyclopropyl group,
or alternatively, X2—(CH2)n—Y2 represents a —SO2—NH—(CH2)n—Y2 group, wherein Y2 represents a cyclopropyl group,
or alternatively, X2—(CH2)n—Y2 is defined by X2 being a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms, and Y2 being a cyclopropyl group, a hydrogen atom, or a (C1-C4)alkoxy group,
or alternatively, X2—(CH2)n—Y2 represents a —O—(CH2)n—Y2 group, wherein Y2 represents a (C1-C4)alkoxy group,
or alternatively, X2—(CH2)n—Y2 represents a CO—NH—(CH2)n—Y2 group, wherein Y2 represents a —CF3,
or alternatively, X2—(CH2)n—Y2 represents a —NH—CO—NH—(CH2)n—Y2 group, wherein n is 1, 2, or 3, and Y2 represents a —CR1R2R3 group,
or alternatively X2-Y2 represents a group —CONRcRd, wherein RC and Rd form, together with the nitrogen atom a heterocyclic group, optionally substituted by a hydroxy group or a (C1-C4)alkyl group,
R and R′ independently represent
a (C1-C4)alkyl group,
a —S—(C1-C4)alkyl group,
a (C3-C6)cycloalkyl group,
a halogen atom,
a trifluoromethyl group,
a —SO2(C1-C4)alkyl group,
a (C3-C6)cycloalkenyl group,
a (C1-C5)alkoxy group,
a —SO2—NRaRb group,
a —SO3H or SO2—CH3 group,
a —OH group,
a —CONHRg, wherein Rg represents a hydrogen atom or a (C1-C4)alkyl group,
a —O—SO2—ORc group,
a azetidinyl group,
a morpholinyl group, or
a cyano group, and
R″ represents a hydrogen atom, a (C1-C4)alkyl group optionally substituted by a —COOH group.