US 10,851,064 B2Granted

ACSS2 inhibitors and methods of use thereof

AssigneeMetabomed Ltd.

InventorsPhilippe Nakache, Omri Erez, Simone Botti, Andreas Goutopoulos

Life of this patent

Estimating the term…

Abstract

The present invention relates to novel ACSS2 inhibitors having activity as anti-cancer therapy, treatment of alcoholism, and viral infection (e.g., CMV), composition and methods of preparation thereof, and uses thereof for treating viral infection, alcoholism, alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH), obesity/weight gain, anxiety, depression, post-traumatic stress disorder, inflammatory/autoimmune conditions and cancer, including metastatic cancer, advanced cancer, and drug resistant cancer of various types.

Claims8

Dependent claims

An Acyl-CoA Synthetase Short-Chain Family Member 2 (ACSS2) inhibitor compound represented by the structure of formula (I):

wherein A and B rings are each independently a single or fused aromatic or heteroaromatic ring system, or a single or fused C3-C10 cycloalkyl or a single or fused C3-C10 heterocyclic ring;
R1 and R2 are each independently H, F, Cl, Br, I, OH, SH, R8—OH, CH2—OH, R8—SH, —R8—O—R10, —CH2—O—CH3, CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, R8—N(R10)(R11), CH2—NH2, CH2—N(CH3)2, R9—R8—N(R10)(R11), C≡C—CH2—NH2, B(OH)2, —OC(O)CF3, —OCH2Ph, NHC(O)—R10, NHC(O)CH3, NHCO—N(R10)(R11), NHC(O)N(CH3)2, COOH, —C(O)Ph, C(O)O—R10, C(O)O—CH3, C(O)O—CH(CH3)2, C(O)O—CH2CH3, R8—C(O)—R10, CH2C(O)CH3, C(O)H, C(O)—R10, C(O)—CH3, C(O)—CH2CH3, C(O)—CH2CH2CH3, C1-C5 linear or branched C(O)-haloalkyl, C(O)—CF3, —C(O)NH2, C(O)NHR, C(O)N(R10)(R11), C(O)N(CH3)2, SO2R, SO2N(R10)(R11), SO2N(CH3)2, SO2NHC(O)CH3), C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, 2, 3, or 4-CH2—C6H4—Cl, ethyl, propyl, iso-propyl, t-Bu, iso-butyl, pentyl, benzyl, C(CH3)(OH)Ph, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, C1-C5 linear, branched or cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, methoxy, ethoxy, propoxy, isopropoxy, O—CH2-cyclopropyl, O-cyclobutyl, O-cyclopentyl, O-cyclohexyl, 1-butoxy, 2-butoxy, O-tBu, O-1-oxacyclobutyl, O-2-oxacyclobutyl, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, OCF3, OCHF2, C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3—C8cycloalkyl, cyclopropyl, cyclopentyl, substituted or unsubstituted C3-C8 heterocyclic ring, 3-methyl-4H-1,2,4-triazole, 5-methyl-1,2,4-oxadiazole, thiophene, oxazole, oxadiazole, imidazole, furane, triazole, tetrazole, pyridine (2, 3, or 4-pyridine), pyrimidine, pyrazine, oxacyclobutane (1 or 2-oxacyclobutane), indole, protonated or deprotonated pyridine oxide, substituted or unsubstituted aryl, phenyl, or CH(CF3)(NH—R10);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, methyl, ethyl, OH, alkoxy, N(R)2, CF3, aryl, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
or R2 and R1 are joint together to form a 5 or 6 membered substituted or unsubstituted, aliphatic or aromatic, carbocyclic or heterocyclic ring;
R3 and R4 are each independently H, F, Cl, Br, I, OH, SH, R8—OH, CH2—OH, R8—SH, —R8—O—R10, CH2—O—CH3, CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, R8—N(R10)(R11), CH2—NH2, CH2—N(CH3)2, R9—R8—N(R10)(R11), B(OH)2, —OC(O)CF3, —OCH2Ph, —NHCO—R10, NHC(O)CH3, NHCO—N(R10)(R11), NHC(O)N(CH3)2, COOH, —C(O)Ph, C(O)O—R10, C(O)O—CH3, C(O)O—CH2CH3, R8—C(O)—R10, CH2C(O)CH3, C(O)H, C(O)—R10, C(O)—CH3, C(O)—CH2CH3, C(O)—CH2CH2CH3, C1-C5 linear or branched C(O)-haloalkyl, C(O)—CF3, —C(O)NH2, C(O)NHR, C(O)N(R10)(R11), C(O)N(CH3)2, SO2R, SO2N(R10)(R11), SO2N(CH3)2, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, C(OH)(CH3)(Ph), ethyl, propyl, iso-propyl, t-Bu, iso-butyl, pentyl, C(CH3)(OH)Ph, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, C1-C5 linear, branched or cyclic alkoxy, methoxy, ethoxy, propoxy, isopropoxy, O—CH2-cyclopropyl, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl, cyclopropyl, cyclopentyl, substituted or unsubstituted C3-C8 heterocyclic ring, 3-methyl-4H-1,2,4-triazole, 5-methyl-1,2,4-oxadiazole, thiophene, oxazole, isoxazole, imidazole, furane, triazole, pyridine (2, 3, or 4-pyridine), pyrimidine, pyrazine, oxacyclobutane (1 or 2-oxacyclobutane), indole), substituted or unsubstituted aryl, phenyl, or CH(CF3)(NH—R10);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, aryl, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
or R3 and R4 are joint together to form a 5 or 6 membered substituted or unsubstituted, aliphatic or aromatic, carbocyclic or heterocyclic ring;
R5 is H, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, CH2SH, ethyl, iso-propyl, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, R8-aryl, CH2—Ph, substituted or unsubstituted aryl, phenyl, substituted or unsubstituted heteroaryl, pyridine (2, 3, and 4-pyridine);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
R6 is H, C1-C5 linear or branched alkyl, methyl, C(O)R, or S(O)2R;
R8 is [CH2],
wherein p is between 1 and 10;
R9 is [CH]q, [C]q
wherein q is between 2 and 10;
R10 and R11 are each independently H, C1-C5 linear or branched alkyl, methyl, ethyl, C(O)R, or S(O)2R;
R is H, C1-C5 linear or branched alkyl, methyl, ethyl, C1-C5 linear or branched alkoxy, phenyl, aryl or heteroaryl, or two gem R substituents are joint together to form a 5 or 6 membered heterocyclic ring;
m, n, l and k are each independently an integer between 0 and 4;
Q1 and Q2 are each independently S, O, N—OH, CH2, C(R)2 or N—OMe;
or its pharmaceutically acceptable salt, optical isomer, tautomer, hydrate, N-oxide, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

19 more elements

An Acyl-CoA Synthetase Short-Chain Family Member 2 (ACSS2) inhibitor compound represented by the structure of formula (I):

wherein
A and B rings are each independently a single or fused aromatic or heteroaromatic ring system, or a single or fused C3-C10 cycloalkyl or a single or fused C3-C10 heterocyclic ring;
R1 and R2 are each independently H, F, Cl, Br, I, OH, SH, R8—OH, R8—SH, —R8—O—R10, CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, R8—N(R10)(R11), CH2—NH2, R9—R8—N(R10)(R11)C≡C—CH2—NH2, B(OH)2, —OC(O)CF3, —OCH2Ph, NHC(O)—R10, NHCO—N(R10)(R11), COOH, —C(O)Ph, C(O)O—R10, R8—C(O)—R10, C(O)H, C(O)—R10, C(O)—CH3, C(O)—CH2CH3, C(O)—CH2CH2CH3), C1-C5 linear or branched C(O)-haloalkyl, —C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), C1-C5 linear or branched, substituted or unsubstituted alkyl, 4-CH2—C6H4—Cl, benzyl, C(CH3)(OH)Ph, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, C1-C5 linear, branched or cyclic alkoxy, optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, O-1-oxacyclobutyl, O-2-oxacyclobutyl, O-cyclobutyl, O-cyclopentyl, O-cyclohexyl, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, OCHF2, CH(CF3)(NH—R10), C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3-C5 cycloalkyl, substituted or unsubstituted C3-C8 heterocyclic ring, substituted or unsubstituted aryl, phenyl, wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, aryl, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
or R2 and R1 are joint together to form a 5 or 6 membered substituted or unsubstituted, aliphatic or aromatic, carbocyclic or heterocyclic ring;
R3 is C2—C linear or branched haloalkyl, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, or CF(CH3)—CH(CH3)2);
R4 is H, F, Cl, Br, I, OH, SH, R8—OH, CH2—OH, R8—SH, —R8—O—R10, CH2—O—CH3, CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, R8—N(R10)(R11), CH2—NH2, CH2—N(CH3)2, R9—R8—N(R10)(R11), B(OH)2, —OC(O)CF3, —OCH2Ph, —NHCO—R10, NHC(O)CH3, NHCO—N(R10)(R11), NHC(O)N(CH3)2, COOH, —C(O)Ph, C(O)O—R10, C(O)O—CH3, C(O)O—CH2CH3, R8—C(O)—R10, CH2C(O)CH3, C(O)H, C(O)—R10, C(O)—CH3, C(O)—CH2CH3, C(O)—CH2CH2CH3, C1-C5 linear or branched C(O)-haloalkyl, C(O)—CF3, —C(O)NH2, C(O)NHR, C( )N(R10)(R11), C(O)N(CH3)2, SO2R, SO2N(R10)(R11), SO2N(CH3)2, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, C(OH)(CH3)(Ph), ethyl, propyl, iso-propyl, t-Bu, iso-butyl, pentyl, C(CH3)(OH)Ph, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, C1-C5 linear, branched or cyclic alkoxy, methoxy, ethoxy, propoxy, isopropoxy, O—CH2-cyclopropyl, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl, cyclopropyl, cyclopentyl, substituted or unsubstituted C3-C8 heterocyclic ring, 3-methyl-4H-1,2,4-triazole, 5-methyl-1,2,4-oxadiazole, thiophene, oxazole, isoxazole, imidazole, furane, triazole, pyridine (2, 3, or 4-pyridine), pyrimidine, pyrazine, oxacyclobutane (1 or 2-oxacyclobutane), indole), substituted or unsubstituted aryl, phenyl, or CH(CF3)(NH—R10);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, aryl, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
or R3 and R4 are joint together to form a 5 or 6 membered substituted or unsubstituted, aliphatic or aromatic, carbocyclic or heterocyclic ring;
R5 is H, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, CH2SH, ethyl, iso-propyl, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, R8-aryl, CH2—Ph, substituted or unsubstituted aryl, phenyl, substituted or unsubstituted heteroaryl, pyridine (2, 3, and 4-pyridine);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
R6 is H, C1-C5 linear or branched alkyl, methyl, C(O)R, or S(O)2R;
R8 is [CH2]p
wherein p is between 1 and 10;
R9 is [CH]q, [C]q
wherein q is between 2 and 10;
R10 and R11 are each independently H, C1-C5 linear or branched alkyl, methyl, ethyl, C(O)R, or S(O)2R;
R is H, C1-C5 linear or branched alkyl, methyl, ethyl, C1-C5 linear or branched alkoxy, phenyl, aryl or heteroaryl, or two gem R substituents are joint together to form a 5 or 6 membered heterocyclic ring;
m, n, l and k are each independently an integer between 0 and 4;
Q1 and Q2 are each independently S, 0, N—OH, CH2, C(R)2 or N—OMe;
or its pharmaceutically acceptable salt, optical isomer, tautomer, hydrate, N-oxide, prodrug, isotopic variant, PROTAC, pharmaceutical product or any combination thereof.

20 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/411,168Filed 14 May 2019 · continuation in part
Priority: 15 Nov 2017
Published: US 2019/0263758 A129 Aug 2019
Granted: 1 Dec 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification45 codes

C07D 231/22
One oxygen atom attached in position 3 or 5: with aryl radicals attached to ring nitrogen atoms
A61K 31/4152
1,2-Diazoles: having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
A61K 31/4155
1,2-Diazoles: non condensed and containing further heterocyclic rings
A61K 31/4178
1,3-Diazoles: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin

Family

Application62/586,195Us provisional application · filed 15 Nov 2017
PCT/IL2018/051232Parent of this continuation-in-part · filed 15 Nov 2018
US 2019/0263758 A1Pre-grant publication · published 29 Aug 2019
US 10,851,064 B2This patent

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

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Abstract

An Acyl-CoA Synthetase Short-Chain Family Member 2 (ACSS2) inhibitor compound represented by the structure of formula (I):

wherein A and B rings are each independently a single or fused aromatic or heteroaromatic ring system, or a single or fused C3-C10 cycloalkyl or a single or fused C3-C10 heterocyclic ring;
R1 and R2 are each independently H, F, Cl, Br, I, OH, SH, R8—OH, CH2—OH, R8—SH, —R8—O—R10, —CH2—O—CH3, CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, R8—N(R10)(R11), CH2—NH2, CH2—N(CH3)2, R9—R8—N(R10)(R11), C≡C—CH2—NH2, B(OH)2, —OC(O)CF3, —OCH2Ph, NHC(O)—R10, NHC(O)CH3, NHCO—N(R10)(R11), NHC(O)N(CH3)2, COOH, —C(O)Ph, C(O)O—R10, C(O)O—CH3, C(O)O—CH(CH3)2, C(O)O—CH2CH3, R8—C(O)—R10, CH2C(O)CH3, C(O)H, C(O)—R10, C(O)—CH3, C(O)—CH2CH3, C(O)—CH2CH2CH3, C1-C5 linear or branched C(O)-haloalkyl, C(O)—CF3, —C(O)NH2, C(O)NHR, C(O)N(R10)(R11), C(O)N(CH3)2, SO2R, SO2N(R10)(R11), SO2N(CH3)2, SO2NHC(O)CH3), C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, 2, 3, or 4-CH2—C6H4—Cl, ethyl, propyl, iso-propyl, t-Bu, iso-butyl, pentyl, benzyl, C(CH3)(OH)Ph, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, C1-C5 linear, branched or cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, methoxy, ethoxy, propoxy, isopropoxy, O—CH2-cyclopropyl, O-cyclobutyl, O-cyclopentyl, O-cyclohexyl, 1-butoxy, 2-butoxy, O-tBu, O-1-oxacyclobutyl, O-2-oxacyclobutyl, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, OCF3, OCHF2, C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3—C8cycloalkyl, cyclopropyl, cyclopentyl, substituted or unsubstituted C3-C8 heterocyclic ring, 3-methyl-4H-1,2,4-triazole, 5-methyl-1,2,4-oxadiazole, thiophene, oxazole, oxadiazole, imidazole, furane, triazole, tetrazole, pyridine (2, 3, or 4-pyridine), pyrimidine, pyrazine, oxacyclobutane (1 or 2-oxacyclobutane), indole, protonated or deprotonated pyridine oxide, substituted or unsubstituted aryl, phenyl, or CH(CF3)(NH—R10);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, methyl, ethyl, OH, alkoxy, N(R)2, CF3, aryl, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
or R2 and R1 are joint together to form a 5 or 6 membered substituted or unsubstituted, aliphatic or aromatic, carbocyclic or heterocyclic ring;
R3 and R4 are each independently H, F, Cl, Br, I, OH, SH, R8—OH, CH2—OH, R8—SH, —R8—O—R10, CH2—O—CH3, CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, R8—N(R10)(R11), CH2—NH2, CH2—N(CH3)2, R9—R8—N(R10)(R11), B(OH)2, —OC(O)CF3, —OCH2Ph, —NHCO—R10, NHC(O)CH3, NHCO—N(R10)(R11), NHC(O)N(CH3)2, COOH, —C(O)Ph, C(O)O—R10, C(O)O—CH3, C(O)O—CH2CH3, R8—C(O)—R10, CH2C(O)CH3, C(O)H, C(O)—R10, C(O)—CH3, C(O)—CH2CH3, C(O)—CH2CH2CH3, C1-C5 linear or branched C(O)-haloalkyl, C(O)—CF3, —C(O)NH2, C(O)NHR, C(O)N(R10)(R11), C(O)N(CH3)2, SO2R, SO2N(R10)(R11), SO2N(CH3)2, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, C(OH)(CH3)(Ph), ethyl, propyl, iso-propyl, t-Bu, iso-butyl, pentyl, C(CH3)(OH)Ph, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, C1-C5 linear, branched or cyclic alkoxy, methoxy, ethoxy, propoxy, isopropoxy, O—CH2-cyclopropyl, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl, cyclopropyl, cyclopentyl, substituted or unsubstituted C3-C8 heterocyclic ring, 3-methyl-4H-1,2,4-triazole, 5-methyl-1,2,4-oxadiazole, thiophene, oxazole, isoxazole, imidazole, furane, triazole, pyridine (2, 3, or 4-pyridine), pyrimidine, pyrazine, oxacyclobutane (1 or 2-oxacyclobutane), indole), substituted or unsubstituted aryl, phenyl, or CH(CF3)(NH—R10);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, aryl, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
or R3 and R4 are joint together to form a 5 or 6 membered substituted or unsubstituted, aliphatic or aromatic, carbocyclic or heterocyclic ring;
R5 is H, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, CH2SH, ethyl, iso-propyl, C1-C5 linear or branched haloalkyl, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, R8-aryl, CH2—Ph, substituted or unsubstituted aryl, phenyl, substituted or unsubstituted heteroaryl, pyridine (2, 3, and 4-pyridine);
wherein substitutions include:
F, Cl, Br, I, C1-C5 linear or branched alkyl, OH, alkoxy, N(R)2, CF3, phenyl, halophenyl, (benzyloxy)phenyl, CN, NO2 or any combination thereof;
R6 is H, C1-C5 linear or branched alkyl, methyl, C(O)R, or S(O)2R;
R8 is [CH2],
wherein p is between 1 and 10;
R9 is [CH]q, [C]q
wherein q is between 2 and 10;
R10 and R11 are each independently H, C1-C5 linear or branched alkyl, methyl, ethyl, C(O)R, or S(O)2R;
R is H, C1-C5 linear or branched alkyl, methyl, ethyl, C1-C5 linear or branched alkoxy, phenyl, aryl or heteroaryl, or two gem R substituents are joint together to form a 5 or 6 membered heterocyclic ring;
m, n, l and k are each independently an integer between 0 and 4;
Q1 and Q2 are each independently S, O, N—OH, CH2, C(R)2 or N—OMe;
or its pharmaceutically acceptable salt, optical isomer, tautomer, hydrate, N-oxide, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

19 more elements

Facts

Application

16/411,168Filed 14 May 2019 · continuation in part

Priority

15 Nov 2017

Published

US 2019/0263758 A129 Aug 2019

Granted

1 Dec 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification45 codes

C07D 231/22
One oxygen atom attached in position 3 or 5: with aryl radicals attached to ring nitrogen atoms
A61K 31/4152
1,2-Diazoles: having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
A61K 31/4155
1,2-Diazoles: non condensed and containing further heterocyclic rings
A61K 31/4178
1,3-Diazoles: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin