US 12,479,841 B2
Anthelmintic compounds comprising azaindoles structure
Michael Berger, Wiesbaden (DE); Michael R. Linder, Ingelheim (DE); Carolin Schneider, Hofheim (DE); Janina Tanzler, Nierder-Olm (DE); and Ulrich Sondern, Dortmund (DE)
Assigned to Intervet, Inc., Rahway, NJ (US)
Appl. No. 17/785,646
Filed by Intervet Inc., Madison, NJ (US)
PCT Filed Dec. 17, 2020, PCT No. PCT/EP2020/086660
§ 371(c)(1), (2) Date Jun. 15, 2022,
PCT Pub. No. WO2021/122906, PCT Pub. Date Jun. 24, 2021.
Claims priority of application No. 19217671 (EP), filed on Dec. 18, 2019; and application No. 20213299 (EP), filed on Dec. 11, 2020.
Prior Publication US 2023/0110397 A1, Apr. 13, 2023
Int. Cl. A01N 43/90 (2006.01); A01P 5/00 (2006.01); A61P 33/10 (2006.01); C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) [A01N 43/90 (2013.01); A01P 5/00 (2021.08); A61P 33/10 (2018.01)] 20 Claims
 
1. Compound of Formula (I)

OG Complex Work Unit Chemistry
wherein
R1 is independently selected from the group consisting of
hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10 aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, C1-6-alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR2R3, COOH, C(═O)OR4, SR4, SOR4, SO2R4, SO2NR5R6 and C(═O)NR5R6,
wherein each C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10 aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy or C1-6-alkylmercapto, is optionally substituted with one or more substituent(s) independently selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, C1-6-alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR2′R3′, C(═O)OR4′, SR4′, SOR4′, SO2R4′, SO2NR5′R6′ and C(═O)NR5′R6′,
R2 and R3 are independently selected from the group consisting of
hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy-C1-6-alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C1-6-alkyl substituted with 5- to 10-membered heterocyclyl, C1-6-alkyl substituted with C6-10-aryl and C1-6-alkyl substituted with 5- to 10-membered heteroaryl, or
R2 and R3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 0, 1, 2, or 3 further ring atoms are selected from N, S and O,
wherein each C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy-C1-6-alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C1-6-alkyl substituted with 5- to 10-membered heterocyclyl, C1-6-alkyl substituted with C6-10-aryl or C1-6-alkyl substituted with 5- to 10-membered heteroaryl or the heterocyclic ring formed by R2 and R3 together with the N atom to which they are attached is optionally substituted with one or more substituent(s) independently selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR2″R3″, C(═O)OR4″, SR4″, SOR4, SO2R4″, SO2NR5″R6″ and C(═O)NR5″R6″,
R4, R5 and R6 are independently selected from hydrogen and C1-6-alkyl,
R2′, R3′, R4′, R5′ and R6′ are independently selected from hydrogen and C1-6-alkyl,
R2″, R3″, R4″, R5″ and R6″ are independently selected from hydrogen and C1-6-alkyl,
R7 is independently selected from the group consisting of
hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 4- to 10-membered heterocyclyl, C6-10 aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, C1-6-alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR8R9, COOH, C(═O)OR10, SR10, SOR10 SO2R10, SO2NR11R12 and C(═O)NR11R12,
wherein each C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 4- to 10-membered heterocyclyl, C6-10 aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy or C1-6-alkylmercapto is optionally substituted with one or more substituent(s) independently selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, C1-6-alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR8′R9′, C(═O)OR10′, SR10′, SOR10′, SO2R10′, SO2NR11′R12′ and C(═O)NR11′R12′,
R8 and R9 are independently selected from the group consisting of
hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy-C1-6-alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C1-6-alkyl substituted with 5- to 10-membered heterocyclyl, C1-6-alkyl substituted with C6-10-aryl, and C1-6-alkyl substituted with 5- to 10-membered heteroaryl, or
R8 and R9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 0, 1, 2, or 3 further ring atoms are selected from N, S and O,
wherein each C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy-C1-6-alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C1-6-alkyl substituted with 5- to 10-membered heterocyclyl, C1-6-alkyl substituted with C6-10-aryl or C1-6-alkyl substituted with 5- to 10-membered heteroaryl or the heterocyclic ring formed by R8 and R9 together with the N atom to which they are attached is optionally substituted with one or more substituent(s) independently selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR8″R9″, C(═O)OR10″, SR10″, SOR10″, SO2R10″, SO2NR11″R12″ and C(═O)NR11″R12″,
R10, R11 and R12 are independently selected from hydrogen and C1-6-alkyl,
R8′, R9′, R10′, R11′ and R12′ are independently selected from hydrogen and C1-6-alkyl,
R8″, R9″, R10″, R11″ and R12″ are independently selected from hydrogen and C1-6-alkyl,
R13 is hydrogen or C1-3 alkyl,
R14 is hydrogen, C1-3 alkyl, C1-3 alkoxy, NR14′R14″, wherein R14′ and R14″ are independently C1-3-alkyl or
R13 and R14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing non-aromatic ring, wherein the 5 or 6-carbon atoms containing ring is optionally substituted with one or more C1-3-alkyl or ═O, and/or wherein one or more of the ring forming carbon atoms are optionally replaced by —NH—, —N═, ═N—, —O—, —S(O)—, —S(O)2— or —S—, or R13 and R14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing aromatic ring, wherein the 5 or 6-carbon atoms containing ring is optionally substituted with one or more C1-3-alkyl, and/or wherein one or more of the ring forming carbon atoms are optionally replaced by —NH—, —N═, ═N—, —O— or —S—,
R15 is independently hydrogen, halogen, C1-3 alkyl, C1-3 alkoxy, or NR15′R15″, wherein R15′ and R15″ are independently C1-3-alkyl,
R16 is independently hydrogen, halogen, C1-3 alkyl, C1-3 alkoxy, or NR16′R16″, wherein R16′ and R16′″ are independently C1-3-alkyl,
R17 is independently hydrogen, C1-3 alkyl, C1-3 alkoxy, or NR17′R17″, wherein R17′ and R17″ are independently C1-3-alkyl,
R18 is independently hydrogen, C1-3 alkyl, C1-3 alkoxy, or NR18′R18″, wherein R18′ and R18″ are independently C1-3-alkyl,
R19 is independently selected from the group consisting of C6-10-aryl and 5- to 10-membered heteroaryl,
wherein each C6-10-aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, C1-6-alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR20R21, C(═O)OR22, SR22, SOR22, SO2R22, SO2NR23R24 and C(═O)NR23R24,
R20 and R21 are independently selected from the group consisting of
hydrogen, C1-6-alkyl, C3-10-cycloalkyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy-C1-6-alkyl, C1-C6-alkyl substituted with C6-10-aryl, and C1-6-alkyl substituted with 5- to 10-membered heteroaryl, or
R20 and R21 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 0, 1, 2, or 3 further ring atoms are selected from N, S and O,
wherein each C1-6-alkyl, C3-10-cycloalkyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy-C1-6-alkyl, C1-C6-alkyl substituted with C6-10-aryl, and C1-6-alkyl substituted with 5- to 10-membered heteroaryl or the heterocyclic ring formed by R20 and R21 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the group consisting of
C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl, 5- to 10-membered heterocyclyl, C6-10-aryl, 5- to 10-membered heteroaryl, C1-6-alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR20′R21′, C(═O)OR22′, SR22′, SOR22′, SO2R22′, SO2NR23′R24′, and C(═O)NR23′R24′,
R22, R23 and R24 are independently selected from hydrogen and C1-6-alkyl,
R20′, R21′, R22′, R23′ and R24′ are independently selected from hydrogen and C1-6-alkyl,
R25 is independently selected from hydrogen and C1-6-alkyl,
or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph or prodrug or a mixture thereof.