US 2020/0148705 A1Published application

Spiro-Sulfonamide Derivatives As Inhibitors Of Myeloid Cell Leukemia-1 (MCL-1) Protein

AssigneePrelude Therapeutics Incorporated

InventorsJincong Zhuo, Raul Leal, Rupa Shetty, Juan Luengo, Andrew Paul Combs

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Abstract

The disclosure is directed to compounds of Formula I Pharmaceutical compositions comprising compounds of Formula I as well as methods of their use and preparation, are also described.

Claims28

Dependent claims

A compound of Formula IA-5:

or a pharmaceutically acceptable salt or solvate thereof, wherein
W1 is —CH2— and W3 is —O—, or W1 is —O— and W3 is —CH2—, or W1 is —CH2— and W3 is —S—, or W1 is —S— and W3 is —CH2—, or W1 is —CH2— and W3 is —NR2B—, or W1 is —NR2B— and W3 is —CH2—, or W1 is —CH2— and W3 is —CH2—;
X is —O—, —NR9—, —CR7R8—, —S—, —S(O)—, —S02-;
R is halo or C1-C6alkyl;
each R2B is independently H, D, optionally substituted C1-C6alkyl;
represents a carbon-carbon single bond in which each carbon atom in the bond is substituted with R4 and R5, an (E)-carbon-carbon double bond substituted with R4A and R4B, or a (Z)-carbon-carbon double bond substituted with R4A and R4B;
Ra* is Ra wherein Ra is H, —C(O)Rb, —C(O)ORc, —C(O)NRcRd, P(ORc)2, P(O)RcRb, P(O)ORcORb, S(O)Rb, S(O)NRcRd, S(O)2Rb, S(O)2NRcRd, B(ORc)(ORb), SiRb3, C1-C10alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, wherein said C1-C10 alkyl, C2-C10alkenyl, C2-C10 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted;
each R4 or R7 is independently H, D, halo, —OH, —CN, —NO2, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, —ORa, —SRa, —NRcRd, —NRaRc, —C(O)Rb, —OC(O)Ra, —C(O)ORa, —C(O)NRcRd, —S(O)Rb, or —S(O)2Rb, wherein said C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkenyl, or heterocycloalkyl is optionally substituted;
each R4A or R4B is independently H, D, -Me, —CF3 or —F;
each R5 or R8 is independently H, D, fluoro, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —C(O)Rb, —C(O)ORa, —C(O)NRcRd, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, wherein said C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted;
or R4 and R5 together with the C atom to which they are attached form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted;
or an R4 and an R5 attached to adjacent carbon atoms, together with the C atoms to which they are attached, form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted;
or R7 and R8 together with the C atom to which they are both attached form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted, each optionally substituted;
or an R7 and an R8 attached to adjacent carbon atoms, together with the C atoms to which they are attached, form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted;
each R9 is independently H, D, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —OC1-C6alkyl, —C(O)Rb, —C(O)ORa, —C(O)NRcRd, —S(O)Rb or —S(O)2Rb, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group, wherein said C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —OC1-C6alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, is optionally substituted;
or R9 together with an R7 or R8 forms an optionally substituted heterocyclic alkylene;
each Ra is independently H, D, —C(O)Rb, —C(O)ORc, —C(O)NRcRd, —P(ORC)2, —P(O)RcRb, —P(O)ORcORb, —S(O)Rb, —S(O)NRcRd, —S(O)2Rb, —S(O)2NRcRd, —B(ORc)(ORb), SiRb3, —C1-C10alkyl, —C2-C10 alkenyl, —C2-C10 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl wherein said C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted;
each Rb, is independently H, D, —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl wherein said —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, aryl, cycloalkyl, cycloalkeneyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted;
each Rc or Rd is independently H, D, —C1-C10 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, wherein said C1-C10 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl are each optionally substituted;
or Rc and Rd, together with the N atom to which they are both attached, form an optionally substituted monocyclic or multicyclic heterocycloalkyl, or optionally substituted monocyclic or multicyclic heterocycloalkenyl group.

17 more elements

A compound, or a pharmaceutically acceptable salt or solvate thereof, wherein said compound is:

(3R,6R,7R,8E,22S)-6′-chloro-7-methoxy-12,12-ethylene-15,15-dioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
(3R,6R,7R,8E,12 S,22S)-6′-chloro-7-methoxy-12-methyl-15,15-dioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
(3R,6R,7R,8E,12R,22S)-6′-chloro-7-methoxy-11,12-dimethyl-15,15-dioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16(25),17,19(24)-tetraene-22,1′-tetralin]-13-one;
(3R,6R,7R,8E,22S)-6′-chloro-7-methoxy-12,12-dimethyl-15,15-dioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
(3R,6R,7R,8E,22S)-6′-chloro-7-hydroxy-12,12-dimethyl-15,15-dioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
(3R,6R,7R,8E,22S)-6′-chloro-7-methoxy-11,12,12-trimethyl-15,15-dioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-Chloro-12,12-ethylene-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-11,12,12-trimethyl-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-11-methyl-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-11,12,12-trimethyl-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-11-(trideuteriomethyl)spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] 3-(dimethylamino)azetidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] (3R)-3-(dimethylamino)pyrrolidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] 4-methyl-1,4-diazepane-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-11-ethyl-12,12-dimethyl-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-11-propyl-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] 4-methoxypiperidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-[2-(dimethylamino)ethyl]-N-methyl-carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] 3-methoxyazetidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-1-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] 3-ethoxyazetidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] (3R)-3-methoxypyrrolidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] (3R)-3-ethoxypyrrolidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-11,12,12-trimethyl-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl]morpholine-4-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] 4-(2-methoxyethyl)-1,4-diazepane-1-carboxylate;
[(3R,6R,7S,8E,22S)-7′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,4′-chromane]-7-yl] N,N-dimethylcarbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-[(3R)-tetrahydrofuran-3-yl]carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-[(3S)-tetrahydrofuran-3-yl]carbamate;
(3R,6R,7S,8E,22S)-6′-chloro-7-[2-(dimethylamino)ethoxy]-12,12-dimethyl-15,15-dioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-15,15-dioxo-7-(2-pyrrolidin-1-ylethoxy)spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-13-one;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] (3R)-3-methoxypyrrolidine-1-carboxylate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methoxy-N-methyl-carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-1,3-propylene-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16(25),17,19(24)-tetraene-22,1′-tetralin]-7-yl] N-methyl-N[2-(dimethylamino)ethyl] carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-[(3R)-tetrahydrofuran-3-yl]carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-[(3R)-tetrahydrofuran-3-yl]carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-11,12,12-trimethyl-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-[(3R)-tetrahydrofuran-3-yl]carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-bis(trideuteriomethyl)carbamate;
2-[(3R,6R,7S,8E,22S)-6′-chloro-12,12-dimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl]oxy-N-tetrahydropyran-4-yl-acetamide;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-(oxetan-3-yl)carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-tetrahydropyran-4-yl-carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-11-methyl-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-tetrahydropyran-4-yl-carbamate;
[(3R,6R,7S,8E,22S)-6′-chloro-10,12,12-trimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate
[(3R,6R,7S,8E,22S)-6′-chloro-7,12,12-trimethyl-13,15,15-trioxo-spiro[11,20-dioxa-15-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N,N-dimethylcarbamate
[(3R,6R,7S,8E,22S)-6′-chloro-11-methyl-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-(oxetan-3-yl)carbamate;
or
[(3R,6R,7S,8E,22S)-6′-chloro-11-methyl-12,12-(1,3-propylene)-13,15,15-trioxo-spiro[20-oxa-15-thia-1,11,14-triazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16,18,24-tetraene-22,1′-tetralin]-7-yl] N-methyl-N-[(3R)-tetrahydrofuran-3-yl]carbamate.

43 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/679,105Filed 8 Nov 2019
Priority: 9 Nov 2018
Published: 14 May 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 513/06
In which the condensed system contains two hetero rings: peri-condensed systems
C07D 515/10
In which the condensed system contains two hetero rings: spiro-condensed systems
C07D 267/16
Condensed with carbocyclic rings or ring systems: condensed with two six-membered rings
C07D 413/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms

Family

Application62/758,202Us provisional application · filed 9 Nov 2018
Application62/907,451Us provisional application · filed 27 Sep 2019
Application62/909,635Us provisional application · filed 2 Oct 2019
US 11,130,769 B2Related patent
US 2020/0148705 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

The disclosure is directed to compounds of Formula I Pharmaceutical compositions comprising compounds of Formula I as well as methods of their use and preparation, are also described.

A compound of Formula IA-5:

or a pharmaceutically acceptable salt or solvate thereof, wherein
W1 is —CH2— and W3 is —O—, or W1 is —O— and W3 is —CH2—, or W1 is —CH2— and W3 is —S—, or W1 is —S— and W3 is —CH2—, or W1 is —CH2— and W3 is —NR2B—, or W1 is —NR2B— and W3 is —CH2—, or W1 is —CH2— and W3 is —CH2—;
X is —O—, —NR9—, —CR7R8—, —S—, —S(O)—, —S02-;
R is halo or C1-C6alkyl;
each R2B is independently H, D, optionally substituted C1-C6alkyl;
represents a carbon-carbon single bond in which each carbon atom in the bond is substituted with R4 and R5, an (E)-carbon-carbon double bond substituted with R4A and R4B, or a (Z)-carbon-carbon double bond substituted with R4A and R4B;
Ra* is Ra wherein Ra is H, —C(O)Rb, —C(O)ORc, —C(O)NRcRd, P(ORc)2, P(O)RcRb, P(O)ORcORb, S(O)Rb, S(O)NRcRd, S(O)2Rb, S(O)2NRcRd, B(ORc)(ORb), SiRb3, C1-C10alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, wherein said C1-C10 alkyl, C2-C10alkenyl, C2-C10 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted;
each R4 or R7 is independently H, D, halo, —OH, —CN, —NO2, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, —ORa, —SRa, —NRcRd, —NRaRc, —C(O)Rb, —OC(O)Ra, —C(O)ORa, —C(O)NRcRd, —S(O)Rb, or —S(O)2Rb, wherein said C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkenyl, or heterocycloalkyl is optionally substituted;
each R4A or R4B is independently H, D, -Me, —CF3 or —F;
each R5 or R8 is independently H, D, fluoro, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —C(O)Rb, —C(O)ORa, —C(O)NRcRd, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, wherein said C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted;
or R4 and R5 together with the C atom to which they are attached form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted;
or an R4 and an R5 attached to adjacent carbon atoms, together with the C atoms to which they are attached, form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted;
or R7 and R8 together with the C atom to which they are both attached form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted, each optionally substituted;
or an R7 and an R8 attached to adjacent carbon atoms, together with the C atoms to which they are attached, form a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, each optionally substituted;
each R9 is independently H, D, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —OC1-C6alkyl, —C(O)Rb, —C(O)ORa, —C(O)NRcRd, —S(O)Rb or —S(O)2Rb, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group, wherein said C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, —OC1-C6alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl ring, is optionally substituted;
or R9 together with an R7 or R8 forms an optionally substituted heterocyclic alkylene;
each Ra is independently H, D, —C(O)Rb, —C(O)ORc, —C(O)NRcRd, —P(ORC)2, —P(O)RcRb, —P(O)ORcORb, —S(O)Rb, —S(O)NRcRd, —S(O)2Rb, —S(O)2NRcRd, —B(ORc)(ORb), SiRb3, —C1-C10alkyl, —C2-C10 alkenyl, —C2-C10 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl wherein said C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted;
each Rb, is independently H, D, —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl wherein said —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, aryl, cycloalkyl, cycloalkeneyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted;
each Rc or Rd is independently H, D, —C1-C10 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, wherein said C1-C10 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl are each optionally substituted;
or Rc and Rd, together with the N atom to which they are both attached, form an optionally substituted monocyclic or multicyclic heterocycloalkyl, or optionally substituted monocyclic or multicyclic heterocycloalkenyl group.

17 more elements

Facts

Application

16/679,105Filed 8 Nov 2019

Priority

9 Nov 2018

Published

14 May 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 513/06
In which the condensed system contains two hetero rings: peri-condensed systems
C07D 515/10
In which the condensed system contains two hetero rings: spiro-condensed systems
C07D 267/16
Condensed with carbocyclic rings or ring systems: condensed with two six-membered rings
C07D 413/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms

Family

Application62/758,202Us provisional application · filed 9 Nov 2018

Application62/907,451Us provisional application · filed 27 Sep 2019

Application62/909,635Us provisional application · filed 2 Oct 2019

US 11,130,769 B2Related patent

US 2020/0148705 A1This patent

From the US filing history. Foreign family members aren’t listed.