초록 ▼

The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TPO activity, particularly diseases or disorders that involve thrombocytopeni

The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TPO activity, particularly diseases or disorders that involve thrombocytopenia.

대표청구항 ▼

We claim: 1. A compound of Formula (Ia): in which: n is selected from 0, 1, 2 and 3; m is selected from 0, 1, 2, 3, 4 and 5; Z is CR8; wherein R8 is selected from hydrogen, halo, C1-6alkyl, halo-substituted-C1-6alkyl; wherein any alkyl of R8 can optionally have a methylene replaced by an atom or

We claim: 1. A compound of Formula (Ia): in which: n is selected from 0, 1, 2 and 3; m is selected from 0, 1, 2, 3, 4 and 5; Z is CR8; wherein R8 is selected from hydrogen, halo, C1-6alkyl, halo-substituted-C1-6alkyl; wherein any alkyl of R8 can optionally have a methylene replaced by an atom or group selected from —S(O)0-2—, —C(O)—, —NR9— and —O—; wherein R9 is selected from hydrogen and C1-6alkyl; R1, R2, R4 and R5 are independently selected from hydrogen, halo, hydroxy, nitro, —XNR9R10, C1-6alkyl, and halo-substituted-C1-6alkyl; wherein X is selected from a bond and C1-6alkylene; and R9 and R10 are independently is selected from hydrogen and C1-6alkyl; R3 is selected from —C(O)OR11, —C(O)NR11R12, —NR11S(O)2R12, —S(O)2NR11R12, —NR11C(O)R12, —NR11C(O)NR11 R12, —NR11R12, —NR 11C(O)C(O)OR12 and —NR11C(O)OR12; wherein R11 and R12 are independently selected from hydrogen, C1-6alkyl, halo-substituted-C1-6alkyl, C1-6alkoxy, cyano-C1-6alkyl, hydroxy-C1-6alkyl and C1-6alkyl substituted with —NR9R10; and wherein when R3 is —C(O)OR11, or C(O)NR11R12 , then R11 and R12 are independently selected from hydrogen and C1-6alkyl; R6 is selected from halo and C1-6alkyl; and R20 is selected from halo and C1-6alkyl, and the pharmaceutically acceptable salts thereof. 2. The compound of claim 1 in which R6 is fluoro and R20 is selected from fluoro, methyl and butyl. 3. The compound of claim 2 in which R3 is selected from carboxyl, amino-carbonyl, amino-sulfonyl, methyl-sulfonyl-amino and amino; and R4 is selected from hydrogen, hydroxyl, nitro and amino. 4. The compound of claim 3 selected from 4-[6-(4-butyl-phenyl)-7-fluoro-1H-indol-2-yl]-benzoic acid; 4-[6-(4-butyl-phenyl)-7-fluoro-1H-indol-2-yl]-benzamide; 4-[7-fluoro-6-(4-fluoro-3-methyl-phenyl)-1H-indol-2-yl]-benzoic acid; 4-[7-fluoro-6-(4-fluoro -3-methyl-phenyl)-1H-indol-2-yl]-benzenesulfonamide; 4-[6-(4-butyl-phenyl)-3-ethyl-7-fluoro -1H-indol-2-yl]-2-hydroxy-benzoic acid; 4-[6-(4-butyl-phenyl)-7-fluoro-3-isopropyl-1H-indol-2-yl]-2-hydroxy-benzoic acid; 4-[6-(4-butyl-phenyl)-7-fluoro-1H-indol-2-yl]-2-hydroxy-benzoic acid; 4-[6-(4-butyl-phenyl)-7-fluoro-3-methyl-1H-indol-2-yl]-2-hydroxy-benzoic acid; N-{4-[6-(4-Butyl-phenyl)-7-fluoro-1H-indol-2-yl]-phenyl }-methanesulfonamide; N-{4-[6-(4-Butyl -phenyl)-7-fluoro-1H-indol-2-yl]-phenyl}-acetamide; N-{4-[6-(4-Butyl-phenyl)-7-fluoro-1H -indol-2-yl]-2-chloro-phenyl}-acetamide; 4-[6-(4-Butyl-phenyl)-7-fluoro-1H-indol-2-yl]-2-chloro-phenylamine; and 2-Amino-4-[6-(4-butyl-phenyl)-7-fluoro-1H-indol-2-yl]-benzoic acid. 5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable excipient. 6. A method for treating thrombocytopenia in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula (Ia) of claim 1.