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US 10,519,143 B2Granted
Substituted-indole-compounds as estrogen receptor down-regulators
AssigneeLuoxin Pharmaceutical (Shanghai) Co., Ltd.
InventorsJianyu Lu, Charles Z. Ding, Lihong Hu, Huijun He, Shuhui Chen, Jiaqiang Dong, Tie-Lin Wang
Life of this patent
Estimating the term…
Abstract
Disclosed is a new indole compound, in particular, the compound as shown in formula (I), and a preparation method, pharmaceutical composition and use thereof as an estrogen receptor down-regulator in preparing drugs for treating estrogen receptor-positive breast cancer.
Claims25
A compound represented by formula (I), a pharmaceutically acceptable salt or a hydrate thereof,
- wherein,
- R1 is selected from
- X is selected from single bond, O and S;
- Y and Z are CH;
- ring A is selected from 5-10 membered aryl and 5-10 membered heteroaryl;
- R2 is selected from H, halogen, CN, NO2, OH, COOH, NH2, or the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R3 is selected from H, halogen, CN, NO2, OH, COOH, NH2, or the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R4 and R5 are each independently selected from H, halogen, CN, NO2, OH, COOH, NH2, or the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R6 is selected from the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R is selected from H, F, Cl, Br, I, OH, CN, NH2, COOH, C(═O)NH2, or the group consisting of C1-8 alkyl, C1-8 heteroalkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl and C3-6 cycloalkyl-C1-3 alkyl-, each of which is optionally substituted with 1, 2, or 3 R′;
- n is selected from 0, 1, 2, 3 and 4;
- m is selected from 0, 1, 2, 3 and 4;
- P is selected from 0, 1, 2 and 3;
- or, when m is 2, R3 and R3 are connected together to form a 5-6 membered ring;
- R′ is selected from the group consisting of F, Cl, Br, I, OH, CN, NH2, COOH, Me, Et, CF3, CHF2, CH2F, NHCH3 and N(CH3)2;
- “hetero” represents a heteroatom or a heteroatom group, which is selected from the group consisting of —C(═O)N(R)—, —N(R)—, —S(═O)2N(R)—, —S(═O) N(R)—, —O—, —S—, ═O, ═S, —O—N═, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2— and —N(R)C(═O)N(R)—;
- in any of the above cases, the number of the heteroatom or the heteroatom group is independently selected from 1, 2 and 3.
14 more elements
A compound represented by formula (I), a pharmaceutically acceptable salt or a hydrate thereof,
- wherein,
- R1 is selected from
- Y and Z are CH;
- ring A is selected from 5-10 membered aryl and 5-10 membered heteroaryl;
- R2 is selected from H, halogen, CN, NO2, OH, COOH, NH2, or the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R3 is selected from H, halogen, CN, NO2, OH, COOH, NH2, or the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R4 and R5 are each independently selected from H, halogen, CN, NO2, OH, COOH, NH2, or the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R6 is selected from the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 R;
- R is selected from H, F, Cl, Br, I, OH, CN, NH2, COOH, C(═O)NH2, or the group consisting of C1-8 alkyl, C1-8 heteroalkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl and C3-6 cycloalkyl-C1-3 alkyl-, each of which is optionally substituted with 1, 2, or 3 R′;
- n is selected from 0, 1, 2, 3 and 4;
- m is selected from 0, 1, 2, 3 and 4;
- or, when m is 2, R3 and R3 are connected together to form a 5-6 membered ring;
- R′ is selected from the group consisting of F, Cl, Br, I, OH, CN, NH2, COOH, Me, Et, CF3, CHF2, CH2F, NHCH3 and N(CH3)2;
- “hetero” represents a heteroatom or a heteroatom group, which is selected from the group consisting of —C(═O)N(R)—, —N(R)—, —S(═O)2N(R)—, —S(═O)N(R)—, —O—, —S—, ═O, ═S, —O—N═, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2— and —N(R)C(═O)N(R)—;
- in any of the above cases, the number of the heteroatom or the heteroatom group is independently selected from 1, 2 and 3.
12 more elements
Dependencies are inferred from the claim text.