JPWO2021129653A5 - - Google Patents
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- JPWO2021129653A5 JPWO2021129653A5 JP2022539058A JP2022539058A JPWO2021129653A5 JP WO2021129653 A5 JPWO2021129653 A5 JP WO2021129653A5 JP 2022539058 A JP2022539058 A JP 2022539058A JP 2022539058 A JP2022539058 A JP 2022539058A JP WO2021129653 A5 JPWO2021129653 A5 JP WO2021129653A5
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- JP
- Japan
- Prior art keywords
- alkyl
- pharmaceutically acceptable
- acceptable salt
- compound according
- optical isomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 claims 34
- 125000000217 alkyl group Chemical group 0.000 claims 32
- 150000003839 salts Chemical class 0.000 claims 28
- 230000003287 optical effect Effects 0.000 claims 23
- 125000003545 alkoxy group Chemical group 0.000 claims 10
- 229910052736 halogen Inorganic materials 0.000 claims 9
- 150000002367 halogens Chemical class 0.000 claims 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 7
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
- 125000003342 alkenyl group Chemical group 0.000 claims 6
- 125000000304 alkynyl group Chemical group 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 4
- 125000002393 azetidinyl group Chemical group 0.000 claims 4
- 229910052794 bromium Inorganic materials 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 229910052801 chlorine Inorganic materials 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 229910052731 fluorine Inorganic materials 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 229910052740 iodine Inorganic materials 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000004193 piperazinyl group Chemical group 0.000 claims 4
- 125000003386 piperidinyl group Chemical group 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 2
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 2
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 2
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 2
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 claims 1
- 208000027747 Kennedy disease Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
Claims (30)
T1、T2、T3、T4は、それぞれ独立して、C(R)又はNであり;
T5は、-(C=O)-又は-CH2-であり;
R1、R2、R3、R4は、それぞれ独立して、CN、ハロゲン、C1-6アルキル、及びC1-6アルコキシからなる群から選択され、ここで前記C1-6アルキル又はC1-6アルコキシは任意選択で、1、2又は3つのRで置換され;
L1、L2、L3は、それぞれ独立して、単結合、O、S、NH、C(=O)、S(=O)、S(=O)2、C1-6アルキル、-C1-6アルキル-O-、-C1-6アルキル-NH-、-O-C1-6アルキル-O-、-O-C1-6アルキル-O-C1-6アルキル-、-O-C2-3アルケニル、C2-3アルキニル、C3-10シクロアルキル、3~10員ヘテロシクロアルキル、フェニル及び5~9員ヘテロアリールからなる群から選択され、ここで前記C1-6アルキル、-C1-6アルキル-O-、-C1-3アルキル-NH-、-O-C1-6アルキル-O-、-O-C1-6アルキル-O-C1-6アルキル-、C2-3アルケニル、C2-3アルキニル、C3-10シクロアルキル、3~10員ヘテロシクロアルキル、フェニル又は5~9員ヘテロアリールは、任意選択で、1、2又は3つのRLで置換され;
RLは、それぞれ独立して、H、ハロゲン、OH、NH2、CN、
R’は、F、Cl、Br、I、OH、NH2、
Rは、H、F、Cl、Br、I、OH、又はC1-6アルキルであり;
R5は、H、ハロゲン、又はC1-6アルキルであり;
上記3~10員ヘテロシクロアルキル又は5~9員ヘテロアリールは、1、2又は3つの独立して、-O-、-NH-、-S-、-C(=O)-、-C(=O)O-、-S(=O)-、-S(=O)2-及びNからなる群から選択されるヘテロ原子又はヘテロ原子団を含む。) A compound represented by formula (I), an optical isomer thereof , or a pharmaceutically acceptable salt thereof.
T 1 , T 2 , T 3 , and T 4 are each independently C(R) or N;
T 5 is -(C=O)- or -CH 2 -;
R 1 , R 2 , R 3 , R 4 are each independently selected from the group consisting of CN, halogen, C 1-6 alkyl, and C 1-6 alkoxy, where said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with 1, 2 or 3 R;
L 1 , L 2 , and L 3 are each independently a single bond, O, S, NH, C(=O), S(=O), S(=O) 2 , C 1-6 alkyl, - C 1-6 alkyl-O-, -C 1-6 alkyl-NH-, -O-C 1-6 alkyl-O-, -O-C 1-6 alkyl-O-C 1-6 alkyl-, - selected from the group consisting of O-C 2-3 alkenyl, C 2-3 alkynyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, phenyl and 5-9 membered heteroaryl, where said C 1- 6 alkyl, -C 1-6 alkyl-O-, -C 1-3 alkyl-NH-, -O-C 1-6 alkyl-O-, -O-C 1-6 alkyl-O-C 1-6 Alkyl-, C 2-3 alkenyl, C 2-3 alkynyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, phenyl or 5-9 membered heteroaryl, optionally has 1, 2 or 3 members substituted with R L ;
R L each independently represents H, halogen, OH, NH 2 , CN,
R' is F, Cl, Br, I, OH, NH2 ,
R is H, F, Cl, Br, I, OH , or C 1-6 alkyl;
R 5 is H, halogen , or C 1-6 alkyl;
The above 3- to 10-membered heterocycloalkyl or 5- to 9-membered heteroaryl is 1, 2 or 3 independently -O-, -NH-, -S-, -C(=O)-, -C( includes a heteroatom or heteroatom group selected from the group consisting of =O)O-, -S(=O)-, -S(=O) 2 -, and N. )
R1、R2、R3、R4は、それぞれ独立して、CN、ハロゲン、C1-6アルキル、C1-6アルコキシからなる群から選択され、ここで前記C1-6アルキル又はC1-6アルコキシは、任意選択で、1、2又は3つのRで置換され;
Xは、C(R)又はNであり;
T1、T2、T3、T4は、それぞれ独立して、C(R)又はNであり;
T5は、-(C=O)-又は-CH2-であり;
L2は、単結合、O、S、NH、C(=O)、S(=O)、S(=O)2、C1-6アルキル、-C1-6アルキル-O-、-C1-3アルキル-NH-、-O-C1-6アルキル-O-、-O-C1-6アルキル-O-C1-6アルキル-、-O-C2-3アルケニル、C2-3アルキニル、C3-10シクロアルキル、3~10員ヘテロシクロアルキル、フェニル、又は5~9員ヘテロアリールから選択され;ここで前記C1-6アルキル、-C1-6アルキル-O-、-C1-3アルキル-NH-、-O-C1-6アルキル-O-、-O-C1-6アルキル-O-C1-6アルキル-、C2-3アルケニル、C2-3アルキニル、C3-10シクロアルキル、3~10員ヘテロシクロアルキル、フェニル又は5~9員ヘテロアリールは、任意選択で、1、2又は3つのRLで置換され;
RLは、それぞれ独立して、H、ハロゲン、OH、NH2、CN、
R’は、F、Cl、Br、I、OH、NH2、
Rは、H、F、Cl、Br、I、OH又はC1-6アルキルであり;
R5は、H、ハロゲン、又はC1-6アルキルであり;
上記3~8員ヘテロシクロアルキル、3~10員ヘテロシクロアルキル、5~6員ヘテロアリール又は5~9員ヘテロアリールは、1、2又は3つの独立して、-O-、-NH-、-S-、-C(=O)-、-C(=O)O-、-S(=O)-、-S(=O)2-及びNから選択されるヘテロ原子又はヘテロ原子団を含む。)
で表される、請求項1に記載の化合物、その光学異性体、又はその薬学的に許容される塩。 Formula (II):
R 1 , R 2 , R 3 , R 4 are each independently selected from the group consisting of CN, halogen, C 1-6 alkyl, C 1-6 alkoxy, where said C 1-6 alkyl or C 1-6 alkyl 1-6 alkoxy optionally substituted with 1, 2 or 3 R;
X is C(R) or N;
T 1 , T 2 , T 3 , and T 4 are each independently C(R) or N;
T 5 is -(C=O)- or -CH 2 -;
L 2 is a single bond, O, S, NH, C(=O), S(=O), S(=O) 2 , C 1-6 alkyl, -C 1-6 alkyl-O-, -C 1-3 alkyl-NH-, -O-C 1-6 alkyl-O-, -O-C 1-6 alkyl-O-C 1-6 alkyl-, -O-C 2-3 alkenyl, C 2- 3 alkynyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, phenyl , or 5-9 membered heteroaryl; where said C 1-6 alkyl, -C 1-6 alkyl-O-, -C 1-3 alkyl-NH-, -O-C 1-6 alkyl-O-, -O-C 1-6 alkyl-O-C 1-6 alkyl-, C 2-3 alkenyl, C 2-3 alkynyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, phenyl or 5-9 membered heteroaryl optionally substituted with 1, 2 or 3 R L ;
R L each independently represents H, halogen, OH, NH 2 , CN,
R' is F, Cl, Br, I, OH, NH2 ,
R is H, F, Cl, Br, I, OH or C 1-6 alkyl;
R 5 is H, halogen , or C 1-6 alkyl;
The above-mentioned 3- to 8-membered heterocycloalkyl, 3- to 10-membered heterocycloalkyl, 5- to 6-membered heteroaryl, or 5- to 9-membered heteroaryl is 1, 2 or 3 independently -O-, -NH-, A heteroatom or heteroatom group selected from -S-, -C(=O)-, -C(=O)O-, -S(=O)-, -S(=O) 2 - and N include. )
The compound according to claim 1 , an optical isomer thereof, or a pharmaceutically acceptable salt thereof, represented by:
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911342649.0 | 2019-12-23 | ||
CN201911342649 | 2019-12-23 | ||
CN202010200682 | 2020-03-20 | ||
CN202010200682.6 | 2020-03-20 | ||
CN202010496353 | 2020-06-03 | ||
CN202010496353.0 | 2020-06-03 | ||
CN202011486334 | 2020-12-16 | ||
CN202011486334.6 | 2020-12-16 | ||
PCT/CN2020/138572 WO2021129653A1 (en) | 2019-12-23 | 2020-12-23 | Protein degradation agent compound preparation method and application |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2023508097A JP2023508097A (en) | 2023-02-28 |
JPWO2021129653A5 true JPWO2021129653A5 (en) | 2024-01-09 |
Family
ID=76573691
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022539058A Pending JP2023508097A (en) | 2019-12-23 | 2020-12-23 | Methods of making and using proteolytic compounds |
Country Status (18)
Country | Link |
---|---|
US (1) | US20230111119A1 (en) |
EP (1) | EP4083020A4 (en) |
JP (1) | JP2023508097A (en) |
KR (1) | KR20220120629A (en) |
CN (2) | CN114829342A (en) |
AU (1) | AU2020414151A1 (en) |
BR (1) | BR112022012385A2 (en) |
CA (1) | CA3162523A1 (en) |
CL (1) | CL2022001724A1 (en) |
CO (1) | CO2022010305A2 (en) |
EC (1) | ECSP22056811A (en) |
IL (1) | IL294225A (en) |
JO (1) | JOP20220159A1 (en) |
MX (1) | MX2022007885A (en) |
PE (1) | PE20230114A1 (en) |
TW (1) | TWI755992B (en) |
WO (1) | WO2021129653A1 (en) |
ZA (1) | ZA202208051B (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW202136240A (en) | 2019-12-19 | 2021-10-01 | 美商亞文納營運公司 | Compounds and methods for the targeted degradation of androgen receptor |
CR20230007A (en) | 2020-06-12 | 2023-06-01 | Shanghai Jemincare Pharmaceuticals Co Ltd | Phthalazinone compound, and preparation method therefor and medical use thereof |
CA3226162A1 (en) | 2021-07-09 | 2023-01-12 | Plexium, Inc. | Aryl compounds and pharmaceutical compositions that modulate ikzf2 |
WO2024002205A1 (en) * | 2022-06-30 | 2024-01-04 | Anhorn Medicines Co., Ltd. | Bifunctional compound and pharmaceutical composition comprising the bifunctional compound, and method for treating androgen receptor related disease by using the same |
WO2024012570A1 (en) * | 2022-07-15 | 2024-01-18 | 西藏海思科制药有限公司 | Nitrogen-containing heterocyclic derivative, and composition and pharmaceutical use thereof |
WO2024054591A1 (en) | 2022-09-07 | 2024-03-14 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180228907A1 (en) * | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
WO2016118666A1 (en) * | 2015-01-20 | 2016-07-28 | Arvinas, Inc. | Compounds and methods for the targeted degradation of the androgen receptor |
KR102173463B1 (en) * | 2016-10-11 | 2020-11-04 | 아비나스 오퍼레이션스, 인코포레이티드 | Compounds and methods for the targeted degradation of androgen receptor |
US10842878B2 (en) * | 2016-11-22 | 2020-11-24 | Dana-Farber Cancer Institute, Inc. | Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use |
EP3544957A4 (en) * | 2016-11-22 | 2020-09-02 | Dana-Farber Cancer Institute, Inc. | Degradation of protein kinases by conjugation of protein kinase inhibitors with e3 ligase ligand and methods of use |
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2020
- 2020-12-23 BR BR112022012385A patent/BR112022012385A2/en unknown
- 2020-12-23 CA CA3162523A patent/CA3162523A1/en active Pending
- 2020-12-23 KR KR1020227025429A patent/KR20220120629A/en active Search and Examination
- 2020-12-23 CN CN202080087926.2A patent/CN114829342A/en active Pending
- 2020-12-23 MX MX2022007885A patent/MX2022007885A/en unknown
- 2020-12-23 TW TW109145818A patent/TWI755992B/en active
- 2020-12-23 PE PE2022001313A patent/PE20230114A1/en unknown
- 2020-12-23 AU AU2020414151A patent/AU2020414151A1/en active Pending
- 2020-12-23 JP JP2022539058A patent/JP2023508097A/en active Pending
- 2020-12-23 IL IL294225A patent/IL294225A/en unknown
- 2020-12-23 CN CN202011545626.2A patent/CN113087704B/en active Active
- 2020-12-23 EP EP20908128.0A patent/EP4083020A4/en active Pending
- 2020-12-23 JO JOP/2022/0159A patent/JOP20220159A1/en unknown
- 2020-12-23 WO PCT/CN2020/138572 patent/WO2021129653A1/en unknown
- 2020-12-23 US US17/788,154 patent/US20230111119A1/en active Pending
-
2022
- 2022-06-22 CL CL2022001724A patent/CL2022001724A1/en unknown
- 2022-07-19 ZA ZA2022/08051A patent/ZA202208051B/en unknown
- 2022-07-20 EC ECSENADI202256811A patent/ECSP22056811A/en unknown
- 2022-07-21 CO CONC2022/0010305A patent/CO2022010305A2/en unknown
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