阅读说明：本技术 作为pcsk9抑制剂的哌啶类化合物 (Piperidines as PCSK9 inhibitors ) 是由 吴成德 颜杰 许文杰 于涛 李宁 陈曙辉 于 2018-04-17 设计创作，主要内容包括：本发明公开了新的一类具有哌啶环结构的PCSK9抑制剂的化合物,具体公开了式(I)所示化合物及其药学上可接受的盐。<Image he="755" wi="387" file="DDA0002207125050000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention discloses a novel PCSK9 inhibitor compound with a piperidine ring structure, and particularly discloses a compound shown as a formula (I) and a pharmaceutically acceptable salt thereof.)

A compound of formula (I) or a pharmaceutically acceptable salt thereof,

wherein the content of the first and second substances,

T₁is selected from N orCH；

T₂Selected from CH or N;

T₃selected from CH or N;

d is selected from

n is selected from 0, 1,2 or 3;

R₁each independently selected from halogen, OH, NH₂Or each is independently selected from optionally substituted with 1,2 or 3R: c_1-3Alkyl radical, C_1-3Heteroalkyl group, C_3-6Cycloalkyl, phenyl, 5-to 6-membered heteroaryl;

or two adjacent R₁Joined together to form a 5-6 membered ring optionally substituted with 1,2 or 3R;

R₃selected from H, halogen, OH, NH₂Or selected from optionally substituted with 1,2 or 3R: c_1-3An alkyl group;

R₄each independently selected from H, OH, or each independently selected from optionally substituted with 1,2 or 3R: c_1-3Alkyl or C_1-3An alkoxy group;

r is selected from F, Cl, Br, I, OH and NH₂、NH(CH₃)、N(CH₃)₂Me or

Said C is_1-3The "hetero" of heteroalkyl, 5-to 6-membered heterocycloalkyl, 5-to 6-membered heterocyclyl is independently selected from: -NH-, N, -O-, -S-;

in any of the above cases, the number of atoms or groups of atoms of the "hetero" is independently selected from 1,2 or 3, respectively.

A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R₁Each independently selected from F, Cl, Br, I, OH, NH₂Or each is independently selected from optionally 1,2 or 3R is substituted: c_1-3Alkyl radical, C_1-3An alkoxy group.

A compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein R₁Each independently selected from F, Cl, Br, I, OH, NH₂Or each is independently selected from optionally substituted with 1,2 or 3R: me, Et,

A compound according to claim 3, or a pharmaceutically acceptable salt thereof, wherein R₁Each independently selected from F, Cl, Br, I, OH, NH₂、Me、Et、

A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein the structural unitSelected from:

a compound according to claim 5, or a pharmaceutically acceptable salt thereof, wherein the building blockSelected from:

a compound according to claim 1 or 6, or a pharmaceutically acceptable salt thereof, wherein the building block

a compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein two adjacent R1 are joined together to form a single moiety which is optionally substituted with 1,2 or 3R: a nitrogen-containing 5-membered ring, an oxygen-containing 5-membered ring or a benzene ring.

A compound according to claim 8, or a pharmaceutically acceptable salt thereof, wherein the building block

A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from H, F, Cl, Br, I, OH, NH2, or is selected from the group optionally substituted by 1,2 or 3R: me and Et.

A compound or pharmaceutically acceptable salt thereof according to claim 10, wherein R3 is selected from H, F, Cl, Br, I, OH, NH₂、Me、Et。

A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein the structural unit

a compound according to claim 12, or a pharmaceutically acceptable salt thereof, wherein the building block

a compound according to claim 1 or 13, or a pharmaceutically acceptable salt thereof, wherein the building blockSelected from:

a compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R₄Each independently selected from H, OH, or each independently selected from optionally substituted with 1,2 or 3R: me, Et,

A compound according to any one of claims 15, or a pharmaceutically acceptable salt thereof, wherein R₄Each independently selected from: H. OH, Me,

A compound according to claim 16, or a pharmaceutically acceptable salt thereof, wherein the building block

A compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, selected from:

wherein R is₁、R₃And n is as defined in claims 1 to 17.

A compound according to any one of claims 1 to 18, or a pharmaceutically acceptable salt thereof, formula (I) is selected from the following formulae (IA) and (IB):

A compound of the formula or a pharmaceutically acceptable salt thereof selected from:

the compound according to claim 20, or a pharmaceutically acceptable salt thereof, selected from:

use of a compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of PCSK9 receptor-related diseases.