Substituted heteroaryl compounds and methods of use thereof
Provided herein are novel heteroaryl compounds, pharmaceutically acceptable salts and pharmaceutical formulations thereof for selectively inhibiting serotonin reuptake and/or acting as 5-HT 1A receptor agonists. Also provided herein are pharmaceutical compositions comprising the heteroaryl compounds and methods of using the pharmaceutical compositions in treating central nervous system (CNS) dysfunction in a mammal, especially a human being.
1. A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof,
wherein
X is O, S or NH;
Y 1 is CH or N;
Y 2 is CR 2 or N;
Y 3 is CR 3 or N;
Y 4 is CR 4 or N;
E is N or CH;
is either a single bond or a double bond, provided that: (1) when is a single bond, G is CH or N; or (2) when is a double bond, G is C;
Ar is
wherein each W is independently O or NH;
each R x is independently D, F, Cl, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —NR 11 R 11a , —OR 10 , —(C 1 -C 6 alkylene)-NR 11 R 11a , —(C 1 -C 6 alkylene)-OR 10 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a or —(C 1 -C 6 alkylene)-aryl, or two R x on two adjacent ring carbon atoms, together with the ring carbon atoms to which they are attached, form a C 3 -C 6 carbocyclic or 3-6 membered heterocyclic ring;
k is 0, 1, 2, 3 or 4;
each of R 1 , R 2 , R 3 and R 4 is independently H, D, F, Cl, Br, I, NO 2 , CN, —SCN, —OR 10 , —SR 10 , —NR 11 R 11a , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —OC(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )C(═O)R 10 , —N(R 11 )S(═O) 2 R 10 , alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl or heteroarylalkylene, wherein each of alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl and heteroarylalkylene is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , alkyl, alkoxy, alkylthio and alkylamino;
each R 5 , R 6 and R 7 is independently H, D, F, Cl, Br, I, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , -alkylene-C(═O)NR 11 R 11a , —OC(═O)R 10 , —N(R 11 )C(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )S(═O) 2 R 10 , alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, alkylamino, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl or heteroarylalkylene, with the proviso that at least one of R 5 , R 6 and R 7 is not H, wherein each of alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, alkylamino, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl and heteroarylalkylene is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , alkyl, alkoxy, alkylthio and alkylamino;
each R 8 is independently H, D, alkyl, alkenyl, alkynyl, alkoxy or cycloalkyl, wherein each of alkenyl, alkynyl, alkoxy and cycloalkyl is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , alkyl, alkoxy, alkylthio, alkylamino, cycloalkyl, heterocyclyl, aryl and heteroaryl;
each R 9 is independently F, Cl, Br, I, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —OC(═O)R 10 , —N(R 11 )C(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )S(═O) 2 R 10 , alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, alkylamino, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl or heteroarylalkylene, wherein each of alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, alkylamino, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl and heteroarylalkylene is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , alkyl, alkoxy, alkylthio and alkylamino;
each R 10 is independently H, D, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl or heteroarylalkylene, wherein each of alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl and heteroarylalkylene is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , alkyl, alkoxy, alkylthio and alkylamino;
each R 11 and R 11a is independently H, D, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl or heteroarylalkylene, or R 11 and R 11a , together with the nitrogen atom to which they are attached, form a heterocyclic ring, wherein each of alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkylene, heterocyclyl, heterocyclylalkylene, aryl, arylalkylene, heteroaryl, heteroarylalkylene and heterocyclic ring is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , alkyl, alkoxy, alkylthio and alkylamino; and
m is 3, 4, 5 or 6.
2. The compound according to claim 1 having Formula (II) or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof,
3. The compound according to claim 1 , wherein each of R 1 , R 2 , R 3 and R 4 is independently H, D, F, Cl, NO 2 , CN, —OR 10 , —SR 10 , —NR 11 R 11a , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —OC(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 1 )C(═O)R 10 , —N(R 11 )S(═O) 2 R 10 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl or (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)-, wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl and (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)- is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino; or
wherein each of R 1 , R 2 , R 3 and R 4 is independently H, D, F, Cl, NO 2 , CN, —OR 10 , —SR 10 , —NR 11 R 11a , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 cycloalkyl)-(C 1 -C 4 alkylene)-, C 2 -C 7 heterocyclyl, (C 2 -C 7 heterocyclyl)-(C 1 -C 4 alkylene)-, phenyl, (phenyl)-(C 1 -C 4 alkylene)-, C 1 -C 5 heteroaryl or (C 1 -C 5 heteroaryl)-(C 1 -C 4 alkylene)-, wherein each of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 cycloalkyl)-(C 1 -C 4 alkylene)-, C 2 -C 7 heterocyclyl, (C 2 -C 7 heterocyclyl)-(C 1 -C 4 alkylene)-, phenyl, (phenyl)-(C 1 -C 4 alkylene)-, C 1 -C 5 heteroaryl and (C 1 -C 5 heteroaryl)-(C 1 -C 4 alkylene)- is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino.
4. The compound according to claim 1 , wherein each R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —(C 1 -C 6 alkylene)-C(═O)NR 11 R 11a , —OC(═O)R 10 , —N(R 11 )C(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )S(═O) 2 R 10 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylamino, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl or (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)-, with the proviso that at least one of R 5 , R 6 and R 7 is not H, wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylamino, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl and (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)- is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino; or
wherein each R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —(C 1 -C 4 alkylene)-C(═O)NR 11 R 11a , —OC(═O)R 10 , —N(R 11 )C(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )S(═O) 2 R 10 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or C 1 -C 4 alkylamino, with the proviso that at least one of R 5 , R 6 and R 7 is not H, wherein each of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino.
5. The compound according to claim 1 , wherein each R 10 is independently H, D, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 3 -C 10 cycloalkyl, wherein each of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 10 cycloalkyl is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino; and
each R 11 and R 11a is independently H, D, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 3 -C 10 cycloalkyl, or R 11 and R 11a , together with the nitrogen atom to which they are attached, form a C 2 -C 10 heterocyclic ring, wherein each of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 10 cycloalkyl and C 2 -C 10 heterocyclic ring is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino.
6. The compound according to claim 1 having Formula (III):
wherein
each R x is independently D, Cl, Me, —CF 3 , —OMe, OH or NH 2 ;
k is 0, 1, 2, 3 or 4;
R 1 is H, D, F, Cl, CN, —OR 10 , —NR 11 R 11a , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 8 cycloalkyl, C 2 -C 7 heterocyclyl, phenyl or C 1 -C 5 heteroaryl, wherein each of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 8 cycloalkyl, C 2 -C 7 heterocyclyl, phenyl and C 1 -C 5 heteroaryl is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino;
each of R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —(C 1 -C 4 alkylene)-C(═O)NR 11 R 11a , —OC(═O)R 10 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or C 1 -C 4 alkylamino, with the proviso that at least one of R 5 , R 6 and R 7 is not H, wherein each of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino;
each R 10 is independently H, D, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 3 -C 8 cycloalkyl;
each R 11 and R 11a is independently H, D, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 3 -C 8 cycloalkyl, or R 11 and R 11a , together with the nitrogen atom to which they are attached, form a C 2 -C 7 heterocyclic ring; and
m is 3, 4, 5 or 6.
7. The compound according to claim 6 having Formula (IV):
8. The compound according to claim 6 , wherein R 1 is H, D, F, Cl, CN, OH, NH 2 , Me, Et, n-Pr, i-Pr, —CF 3 , —OMe, —OEt, —O(i-Pr), —O(t-Bu) or —NMe 2 .
9. The compound according to claim 6 , wherein each of R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)H, —C(═O)OH, —C(═O)OMe, —C(═O)NH 2 , —CH 2 —C(═O)NH 2 , —C(═O)NMe 2 , Me, Et, n-Pr, i-Pr, —CF 3 , —OMe, —OEt, —O(i-Pr), —O(t-Bu) or —NMe 2 , with the proviso that at least one of R 5 , R 6 and R 7 is not H.
10. A compound having one of the following structures:
or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising the compound according to claim 1 , and a pharmaceutically acceptable excipient, carrier, adjuvant or a combination thereof.
12. The pharmaceutical composition according to claim 11 , further comprising at least one therapeutic agent for central nervous system dysfunction, wherein the therapeutic agent for central nervous system dysfunction is an antidepressant, an antianxiety agent, a lithium agent of a mood stabilizer, an atypical antipsychotic agent, an antiepileptic agent, an anti-Parkinson agent, a selective serotonin reuptake inhibitor, a 5-HT 1A receptor agonist, a central nervous system stimulant, a nicotine antagonist or a combination thereof; or
wherein the therapeutic agent for central nervous system dysfunction is amitriptyline, desipramine, mirtazapine, bupropion, reboxetine, fluoxetine, trazodone, sertraline, duloxetine, fluvoxamine, milnacipran, levomilnacipran, desvenlafaxine, vilazodone, venlafaxine, dapoxetine, nefazodone, femoxetine, clomipramine, citalopram, escitalopram, paroxetine, lithium carbonate, buspirone, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, perospirone, clozapine, modafinil, mecamylamine, cabergoline, adamantane, imipramine, pramipexole, thyroxine, dextromethorphan, quinidine, naltrexone, samidorphan, buprenorphine, melatonin, alprazolam, pipamperone, vestipitant, chlordiazepoxide, perphenazine or a combination thereof.
13. A method of treating or lessening the severity of a central nervous system dysfunction in a human comprising administrating a therapeutically effective amount of the compound according to claim 1 to the human, wherein the central nervous system dysfunction is depression, anxiety, mania, schizophrenia, bipolar disorder, obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, Parkinson's disease, and Huntington's disease.
14. A method of treating or lessening the severity of a central nervous system dysfunction in a human comprising administrating a therapeutically effective amount of the pharmaceutical composition according to claim 11 to the human, wherein the central nervous system dysfunction is depression, anxiety, mania, schizophrenia, bipolar disorder, obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, Parkinson's disease, and Huntington's disease.
15. The compound according to claim 2 , wherein each of R 1 , R 2 , R 3 and R 4 is independently H, D, F, Cl, NO 2 , CN, —OR 10 , —SR 10 , —NR 11 R 11a , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —OC(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )C(═O)R 10 , —N(R 11 )S(═O) 2 R 10 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl or (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)-, wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl and (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)- is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino; or
wherein each of R 1 , R 2 , R 3 and R 4 is independently H, D, F, Cl, NO 2 , CN, —OR 10 , —SR 10 , —NR 11 R 11a , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 cycloalkyl)-(C 1 -C 4 alkylene)-, C 2 -C 7 heterocyclyl, (C 2 -C 7 heterocyclyl)-(C 1 -C 4 alkylene)-, phenyl, (phenyl)-(C 1 -C 4 alkylene)-, C 1 -C 5 heteroaryl or (C 1 -C 5 heteroaryl)-(C 1 -C 4 alkylene)-, wherein each of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 cycloalkyl)-(C 1 -C 4 alkylene)-, C 2 -C 7 heterocyclyl, (C 2 -C 7 heterocyclyl)-(C 1 -C 4 alkylene)-, phenyl, (phenyl)-(C 1 -C 4 alkylene)-, C 1 -C 5 heteroaryl and (C 1 -C 5 heteroaryl)-(C 1 -C 4 alkylene)- is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino.
16. The compound according to claim 2 , wherein each R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —(C 1 -C 6 alkylene)-C(═O)NR 11 R 11a , —OC(═O)R 10 , —N(R 11 )C(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )S(═O) 2 R 10 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylamino, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl or (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)-, with the proviso that at least one of R 5 , R 6 and R 7 is not H, wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylamino, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)-(C 1 -C 6 alkylene)-, C 2 -C 10 heterocyclyl, (C 2 -C 10 heterocyclyl)-(C 1 -C 6 alkylene)-, C 6 -C 10 aryl, (C 6 -C 10 aryl)-(C 1 -C 6 alkylene)-, C 1 -C 9 heteroaryl and (C 1 -C 9 heteroaryl)-(C 1 -C 6 alkylene)- is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino; or
wherein each R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 11 R 11a , —(C 1 -C 4 alkylene)-C(═O)NR 11 R 11a , —OC(═O)R 10 , —N(R 11 )C(═O)R 10 , —S(═O)R 10 , —S(═O) 2 R 10 , —S(═O) 2 OR 10 , —S(═O) 2 NR 11 R 11a , —N(R 11 )S(═O) 2 R 10 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or C 1 -C 4 alkylamino, with the proviso that at least one of R 5 , R 6 and R 7 is not H, wherein each of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio and C 1 -C 4 alkylamino.
17. The compound according to claim 2 , wherein each R 10 is independently H, D, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 3 -C 10 cycloalkyl, wherein each of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 10 cycloalkyl is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino; and
each R 11 and R 11a is independently H, D, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 3 -C 10 cycloalkyl, or R 11 and R 11a , together with the nitrogen atom to which they are attached, form a C 2 -C 10 heterocyclic ring, wherein each of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 10 cycloalkyl and C 2 -C 10 heterocyclic ring is optionally substituted with one or more substituents independently selected from D, F, Cl, N 3 , CN, OH, SH, NH 2 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio and C 1 -C 6 alkylamino.
18. The compound according to claim 7 , wherein R 1 is H, D, F, Cl, CN, OH, NH 2 , Me, Et, n-Pr, i-Pr, —CF 3 , —OMe, —OEt, —O(i-Pr), —O(t-Bu) or —NMe 2 .
19. The compound according to claim 7 , wherein each of R 5 , R 6 and R 7 is independently H, D, F, Cl, NO 2 , CN, NH 2 , —C(═O)H, —C(═O)OH, —C(═O)OMe, —C(═O)NH 2 , —CH 2 —C(═O)NH 2 , —C(═O)NMe 2 , Me, Et, n-Pr, i-Pr, —CF 3 , —OMe, —OEt, —O(i-Pr), —O(t-Bu) or —NMe 2 , with the proviso that at least one of R 5 , R 6 and R 7 is not H.