Heterocyclic Compound
AssigneeTakeda Pharmaceutical Company Limited
InventorsKentaro HASHIMOTO, Tomoyasu ISHIKAWA, Yuya OGURO
Life of this patent
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Abstract
The present invention provides a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof. The compound of the present invention shows a strong IAP antagonistic activity.
Claims29
A compound represented by the formula (I):
- wherein
- ring A is a nitrogen-containing heterocycle optionally having substituent(s);
- R1 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s), —OR11, —(═O)—R11, —C(═O)—O—R11, —N(R12)—R11 or —C(═O)—N(R12)—R11;
- R11 is a chain aliphatic hydrocarbon group optionally having substituent(s);
- R12 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R2 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s), —C(═O)—R21, —C(═O)—O—R21 or —C(═O)—N(R22)—R21;
- R21 is a chain aliphatic hydrocarbon group optionally having substituent(s);
- R22 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R3 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- or
- R1 and R2 in combination or R1 and R3 in combination form a 4- to 7-membered nitrogen-containing non-aromatic heterocycle optionally having substituent(s);
- R4 is a cyclic group optionally having substituent(s) or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R5 is a cyclic group optionally having substituent(s), —C(═O)NR51—X1—R52, C(═S)NR51—X1—R52, —X2—R52, —X2—NR51R53, —X2—NR51—C(═O)—R53 or —C(═NR54)—NR51—X1—R52;
- X1 is a bond or C1-6 alkylene optionally having substituent(s);
- X2 is C1-6 alkylene optionally having substituent(s);
- R51 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s) or a cyclic group optionally having substituent(s);
- R52 is a cyclic group optionally having substituent(s);
- R53 is a chain aliphatic hydrocarbon group optionally having substituent(s) or a cyclic group optionally having substituent(s);
- and
- R54 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s),
- or a salt thereof.
A compound represented by the formula (II):
- wherein
- ring A100 is a nitrogen-containing heterocycle optionally having substituent(s);
- R101 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s), —OR111, —C(═O)—O—R111, —N(R112)—R111 or —C(═O)—N(R112)—R111;
- R111 is a chain aliphatic hydrocarbon group optionally having substituent(s);
- R112 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R102 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s), —C(═O)—R121, —C(═O)—O—R121 or —C(═O)—N(R122)—R121;
- R121 is a chain aliphatic hydrocarbon group optionally having substituent(s);
- R122 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R103 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- or
- R101 and R102 in combination or R101 and R103 in combination form a 4- to 7-membered nitrogen-containing non-aromatic heterocycle optionally having substituent(s);
- R105 is a cyclic group optionally having substituent(s), —C(═O)—NR151—X101—R152, —C(═S)—NR151—X101—R152, —X102—R152, X102—NR151R153, —X102—NR151—C(═O)—R153 or —C(═NR154)—NR151—X101—R152;
- X101 is a bond or C1-6 alkylene optionally having substituent(s);
- X102 is C1-6 alkylene optionally having substituent(s);
- R151 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s) or a cyclic group optionally having substituent(s);
- R152 is a cyclic group optionally having substituent(s);
- R153 is a chain aliphatic hydrocarbon group optionally having substituent(s) or a cyclic group optionally having substituent(s);
- R154 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- —Y101— is a divalent chain aliphatic hydrocarbon group optionally having substituent(s) or a divalent cyclic group optionally having substituent(s);
- —Y102— is a bond, —C(═O)—, —C(═O)—O—, —C(═O)—NR106—, —O—, —O—C(═O)—, —O—C(═O)—NR106—, —NR106—, —NR106—C(═O)—, —NR106—S(═O)2—, —S—, —S(═O)—, —S(═O)2— or —S(═O)2—NR106—;
- R106 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- —Y103— is a bond or a spacer having 1 to 20 atoms in the main chain;
- ring A200 is a nitrogen-containing heterocycle optionally having substituent(s);
- R201 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s), —OR211, —C(═O)—R211, —C(═O)—O—R211, —N(R212)—R211 or —C(═O)—N(R212)—R211;
- R211 is a chain aliphatic hydrocarbon group optionally having substituent(s);
- R212 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R202 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s), —C(═O)—R221, —C(═O)—O—R221 or —C(═O)—N(R222)—R221;
- R221 is a chain aliphatic hydrocarbon group optionally having substituent(s);
- R222 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- R203 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- or
- R201 and R202 in combination or R201 and R203 in combination form a 4- to 7-membered nitrogen-containing non-aromatic heterocycle optionally having substituent(s);
- R205 is a cyclic group optionally having substituent(s), —C(═O)—NR251—X201—R252, —C(═S)—NR251—X201—R252, —X202—R252, —X202—NR251R253, —X202—NR251—C(═O)—R253 or —C(═NR254)—NR251—X201—R252;
- X201 is a bond or C1-6 alkylene optionally having substituent(s);
- X202 is C1-6 alkylene optionally having substituent(s);
- R251 is a hydrogen atom, a chain aliphatic hydrocarbon group optionally having substituent(s) or a cyclic group optionally having substituent(s);
- R252 is a cyclic group optionally having substituent(s);
- R253 is a chain aliphatic hydrocarbon group optionally having substituent(s) or a cyclic group optionally having substituent(s);
- R254 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s);
- —Y201— is a divalent chain aliphatic hydrocarbon group optionally having substituent(s) or a divalent cyclic group optionally having substituent(s);
- —Y202— is a bond, —C(═O)—, —C(═O)—O—, —C(═O)—NR206—, —O—, —O—C(═O)—, —O—C(═O)—NR206—, —NR206—, —NR206—C(═O)—O—, —NR206—S(═O)2—, —S—, —S(═O)—, —S(═O)2— or —S(═O)2—NR206—;
- R206 is a hydrogen atom or a chain aliphatic hydrocarbon group optionally having substituent(s),
- or a salt thereof.
A compound which is (3S,7R,8aR)-2-{(2S)-2-cyclohexyl-2-[(N-methyl-L-alanyl)amino]acetyl}-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-7-ethoxyoctahydropyrrolo[1,2-a]pyrazine-3-carboxamide, or a salt thereof.
A compound which is (3S,8aR)—N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-2-{(2S)-2-[(N-methyl-L-alanyl)amino]-2-phenylacetyl}octahydropyrrolo[1,2-a]pyrazine-3-carboxamide, or a salt thereof.
A compound which is (3S,7R,8aR)—N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-7-ethoxy-2-{(2S)-2-[(N-methyl-L-alanyl)amino]-2-phenylacetyl}octahydropyrrolo[1,2-a]pyrazine-3-carboxamide, or a salt thereof.
A compound which is (3S,7R,8aR)-2-{(2S)-2-(4,4-difluorocyclohexyl)-2-[(N-methyl-L-alanyl)amino]acetyl}-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-7-ethoxyoctahydropyrrolo[1,2-a]pyrazine-3-carboxamide, or a salt thereof.
A compound which is (3S,8aR)-2-{(2S)-2-cyclohexyl-2-[(N-methyl-L-alanyl)amino]acetyl}-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]octahydropyrrolo[1,2-a]pyrazine-3-carboxamide, or a salt thereof.
A compound which is (3S,8aR)-2-{(2S)-2-(4,4-difluorocyclohexyl)-2-[(N-methyl-L-alanyl)amino]acetyl}-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]octahydropyrrolo[1,2-a]pyrazine-3-carboxamide, or a salt thereof.
Dependencies are inferred from the claim text.