CN105008343B - 作为选择性雌激素受体降解剂的苯并噻吩衍生物及其组合物 - Google Patents

作为选择性雌激素受体降解剂的苯并噻吩衍生物及其组合物 Download PDF

Info

Publication number
CN105008343B
CN105008343B CN201480009342.8A CN201480009342A CN105008343B CN 105008343 B CN105008343 B CN 105008343B CN 201480009342 A CN201480009342 A CN 201480009342A CN 105008343 B CN105008343 B CN 105008343B
Authority
CN
China
Prior art keywords
alkyl
mmol
compound
phenyl
oxy
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.)
Active
Application number
CN201480009342.8A
Other languages
English (en)
Chinese (zh)
Other versions
CN105008343A (zh
Inventor
H·E·伯克斯
M·A·德长斯雷特尔
G·何
J·努涅斯
S·波伊克特
C·斯普林格
Y·孙
N·M-F·汤姆森
G·S·特里亚
B·于
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Novartis AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Novartis AG filed Critical Novartis AG
Publication of CN105008343A publication Critical patent/CN105008343A/zh
Application granted granted Critical
Publication of CN105008343B publication Critical patent/CN105008343B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/64—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/66—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
CN201480009342.8A 2013-02-19 2014-02-12 作为选择性雌激素受体降解剂的苯并噻吩衍生物及其组合物 Active CN105008343B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361766439P 2013-02-19 2013-02-19
US61/766,439 2013-02-19
PCT/US2014/015938 WO2014130310A1 (en) 2013-02-19 2014-02-12 Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders

Publications (2)

Publication Number Publication Date
CN105008343A CN105008343A (zh) 2015-10-28
CN105008343B true CN105008343B (zh) 2017-12-08

Family

ID=50239942

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201480009342.8A Active CN105008343B (zh) 2013-02-19 2014-02-12 作为选择性雌激素受体降解剂的苯并噻吩衍生物及其组合物

Country Status (46)

Country Link
US (5) US8877801B2 (https=)
EP (2) EP3360870A1 (https=)
JP (1) JP6364028B2 (https=)
KR (1) KR102279999B1 (https=)
CN (1) CN105008343B (https=)
AP (1) AP2015008618A0 (https=)
AR (1) AR094704A1 (https=)
AU (1) AU2014219283C1 (https=)
BR (1) BR112015018882B1 (https=)
CA (1) CA2899030C (https=)
CL (1) CL2015002098A1 (https=)
CR (1) CR20150424A (https=)
CU (1) CU24337B1 (https=)
CY (1) CY1120155T1 (https=)
DK (1) DK2958907T3 (https=)
DO (1) DOP2015000202A (https=)
EA (1) EA028032B1 (https=)
ES (1) ES2671516T3 (https=)
GE (1) GEP201706638B (https=)
GT (1) GT201500233A (https=)
HK (1) HK1251227A1 (https=)
HR (1) HRP20180816T1 (https=)
HU (1) HUE039052T2 (https=)
IL (1) IL240131B (https=)
JO (1) JO3494B1 (https=)
LT (1) LT2958907T (https=)
MA (1) MA38325B1 (https=)
ME (1) ME03061B (https=)
MX (1) MX359471B (https=)
MY (1) MY174888A (https=)
NI (1) NI201500106A (https=)
NO (1) NO3077717T3 (https=)
NZ (1) NZ710385A (https=)
PE (1) PE20151428A1 (https=)
PH (1) PH12015501832B1 (https=)
PL (1) PL2958907T3 (https=)
PT (1) PT2958907T (https=)
RS (1) RS57106B1 (https=)
SG (1) SG11201505697VA (https=)
SI (1) SI2958907T1 (https=)
TN (1) TN2015000323A1 (https=)
TR (1) TR201806882T4 (https=)
TW (1) TWI612040B (https=)
UY (1) UY35334A (https=)
WO (1) WO2014130310A1 (https=)
ZA (1) ZA201505305B (https=)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112015018882B1 (pt) 2013-02-19 2021-09-14 Novartis Ag Derivados de benzotiofeno e composições dos mesmos como degradadores de receptor de estrogênio seletivo
US10308871B2 (en) 2015-02-19 2019-06-04 Jnc Corporation Liquid crystal compound having benzothiophene, liquid crystal composition and liquid crystal display device
TWI708770B (zh) * 2015-06-08 2020-11-01 日商捷恩智股份有限公司 具有苯并噻吩的液晶性化合物、液晶組成物及液晶顯示元件
SMT202300018T1 (it) * 2015-12-09 2023-03-17 Univ Illinois Downregolatori del recettore degli estrogeni a base di benzotiofene
CN112745316A (zh) 2016-04-01 2021-05-04 里科瑞尔姆Ip控股有限责任公司 雌激素受体调节剂
WO2018081168A2 (en) * 2016-10-24 2018-05-03 The Board Of Trustees Of The University Of Illinois Benzothiophene-based selective mixed estrogen receptor downregulators
EP3565558B1 (en) 2017-01-06 2023-12-06 G1 Therapeutics, Inc. Combination therapy with a serd compound and a cdk4/6 inhibitor for the treatment of cancer
KR20190117582A (ko) 2017-02-10 2019-10-16 쥐원 쎄라퓨틱스, 인크. 벤조티오펜 에스트로겐 수용체 조정제
CN111315378A (zh) 2017-11-16 2020-06-19 诺华股份有限公司 包含lsz102和瑞博西尼的药物组合
TW201922291A (zh) 2017-11-16 2019-06-16 瑞士商諾華公司 組合療法
WO2019106604A1 (en) 2017-12-01 2019-06-06 Novartis Ag Pharmaceutical combination comprising lsz102 and alpelisib
IL276152B2 (en) 2018-01-22 2023-12-01 Radius Pharmaceuticals Inc Estrogen receptor-modulating compounds
EP3749654B1 (en) * 2018-02-06 2025-04-23 The Board of Trustees of the University of Illinois Substituted benzothiophene analogs as selective estrogen receptor degraders
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
CN112839646A (zh) * 2018-08-16 2021-05-25 G1治疗公司 用于治疗医学疾病的苯并噻吩雌激素受体调节剂
KR20210106437A (ko) 2018-12-20 2021-08-30 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물
EP3924055B1 (en) 2019-02-15 2024-04-03 Novartis AG Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
CN113490528B (zh) 2019-02-15 2024-12-03 诺华股份有限公司 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途
KR20220024106A (ko) 2019-05-20 2022-03-03 노파르티스 아게 Mcl-1 억제제 항체-약물 접합체 및 사용 방법
CA3148221A1 (en) 2019-08-06 2021-02-11 Recurium Ip Holdings, Llc Estrogen receptor modulators for treating mutants
MX2022007759A (es) 2019-12-20 2022-07-19 Novartis Ag Combinacion del anticuerpo anti tim-3 mbg453 y anticuerpo anti tgf-beta nis793, con o sin decitabina o el anticuerpo anti pd-1 spartalizumab, para el tratamiento de mielofibrosis y sindrome mielodisplasico.
CN111057065B (zh) * 2019-12-24 2021-04-23 沈阳药科大学 噻吩并嘧啶类化合物的制备方法和用途
CN111646972B (zh) * 2020-06-12 2021-06-29 上海皓元医药股份有限公司 一种选择性雌激素受体降解剂及其中间体的制备方法
CN115916199A (zh) 2020-06-23 2023-04-04 诺华股份有限公司 包含3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物的给药方案
CA3182412A1 (en) * 2020-07-06 2022-01-13 Mathew BAGGOTT Advantageous benzothiophene compositions for mental disorders or enhancement
US20230271940A1 (en) 2020-08-03 2023-08-31 Novartis Ag Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
US20240042051A1 (en) 2020-11-24 2024-02-08 Francesca Rocchetti Mcl-1 inhibitor antibody-drug conjugates and methods of use
CA3200858A1 (en) 2020-11-24 2022-06-02 Novartis Ag Anti-cd48 antibodies, antibody drug conjugates, and uses thereof
EP4267578A4 (en) 2020-12-23 2024-11-20 Recurium IP Holdings, LLC ESTROGEN RECEPTOR MODULATORS
CN117794929A (zh) 2021-02-02 2024-03-29 法国施维雅药厂 选择性bcl-xl protac化合物及使用方法
TW202304979A (zh) 2021-04-07 2023-02-01 瑞士商諾華公司 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途
AR125874A1 (es) 2021-05-18 2023-08-23 Novartis Ag Terapias de combinación
CN116265458A (zh) * 2021-12-17 2023-06-20 中国科学院上海药物研究所 苯并噻吩类衍生物、及其制备方法和用途
GB2617173B (en) 2022-03-31 2024-11-20 Iceye Oy Detecting and suppressing ambiguities in synthetic aperture radar data and images
US20250339547A1 (en) 2022-05-20 2025-11-06 Novartis Ag Met bcl-xl inhibitor antibody-drug conjugates and methods of use thereof
IL317102A (en) 2022-05-20 2025-01-01 Novartis Ag EPHA2 BCL-XL inhibitor antibody-drug conjugates and methods of using them
CN115710248B (zh) * 2022-11-18 2024-06-21 南京中医药大学 新型选择性雌激素受体下调剂化合物、制备方法及用途
AU2024234194A1 (en) 2023-03-10 2025-08-07 Novartis Ag Panras inhibitor antibody-drug conjugates and methods of use thereof
PY24103486A (es) 2023-11-22 2025-06-06 Servier Lab Conjugados de anticuerpo anti-cd74-fármaco y métodos de uso de los mismos
WO2025215536A1 (en) 2024-04-10 2025-10-16 Novartis Ag Macrocyclic panras inhibitors for the treatment of cancer

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1133040A (zh) * 1993-10-12 1996-10-09 辉瑞大药厂 作为雌激素激动剂的苯并噻吩及其有关化合物
US6562862B1 (en) * 1994-10-20 2003-05-13 Eli Lilly And Company Methods of inhibiting physiological conditions associated with an excess of neuropeptide Y
CN102477033A (zh) * 2010-11-23 2012-05-30 苏州波锐生物医药科技有限公司 苯并噻酚类化合物及其在制备预防和/或治疗乳腺癌骨质疏松症药物中的用途

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH445129A (fr) 1964-04-29 1967-10-15 Nestle Sa Procédé pour la préparation de composés d'inclusion à poids moléculaire élevé
US3459731A (en) 1966-12-16 1969-08-05 Corn Products Co Cyclodextrin polyethers and their production
US3426011A (en) 1967-02-13 1969-02-04 Corn Products Co Cyclodextrins with anionic properties
US3453257A (en) 1967-02-13 1969-07-01 Corn Products Co Cyclodextrin with cationic properties
US3453259A (en) 1967-03-22 1969-07-01 Corn Products Co Cyclodextrin polyol ethers and their oxidation products
JPS6041077B2 (ja) 1976-09-06 1985-09-13 喜徳 喜谷 １，２‐ジアミノシクロヘキサン異性体のシス白金（２）錯体
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4261989A (en) 1979-02-19 1981-04-14 Kaken Chemical Co. Ltd. Geldanamycin derivatives and antitumor drug
ZA822247B (en) * 1981-04-03 1983-11-30 Lilly Co Eli Benzothiophene compounds and process for preparing them
US4418068A (en) 1981-04-03 1983-11-29 Eli Lilly And Company Antiestrogenic and antiandrugenic benzothiophenes
US4737323A (en) 1986-02-13 1988-04-12 Liposome Technology, Inc. Liposome extrusion method
US5266573A (en) 1989-08-07 1993-11-30 Elf Sanofi Trifluoromethylphenyltetrahydropyridines for the treatment and/or prophylaxis of intestinal motility disorders
KR0166088B1 (ko) 1990-01-23 1999-01-15 . 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도
EP0647450A1 (en) 1993-09-09 1995-04-12 BEHRINGWERKE Aktiengesellschaft Improved prodrugs for enzyme mediated activation
IL115849A0 (en) 1994-11-03 1996-01-31 Merz & Co Gmbh & Co Tangential filtration preparation of liposomal drugs and liposome product thereof
US5589482A (en) 1994-12-14 1996-12-31 Pfizer Inc. Benzo-thiophene estrogen agonists to treat prostatic hyperplasia
US5510357A (en) 1995-02-28 1996-04-23 Eli Lilly And Company Benzothiophene compounds as anti-estrogenic agents
UA44710C2 (uk) * 1995-02-28 2002-03-15 Елі Ліллі Енд Компані Похідні бензотіофену, спосіб їх одержання (варіанти), проміжні сполуки, фармацевтична композиція
US5998441A (en) * 1995-02-28 1999-12-07 Eli Lilly And Company Benzothiophene compounds, intermediates, compositions, and methods
US6417199B1 (en) 1995-03-10 2002-07-09 Eli Lilly And Company 3-benzyl-benzothiophenes
JPH11508269A (ja) * 1995-06-26 1999-07-21 イーライ・リリー・アンド・カンパニー ベンゾチオフェン化合物
US5731342A (en) 1996-02-22 1998-03-24 Eli Lilly And Company Benzothiophenes, formulations containing same, and methods
US5827876A (en) * 1996-04-09 1998-10-27 American Home Products Corporation Inhibition of bone loss by 3-(4-acrylamidobenzoyl) benzo b!-thiophenes
US5886025A (en) 1997-03-06 1999-03-23 Baylor University Anti-mitotic agents which inhibit tubulin polymerization
ZA982877B (en) 1997-04-09 1999-10-04 Lilly Co Eli Treatment of central nervous system disorders with selective estrogen receptor modulators.
ZA982819B (en) 1997-04-09 1999-10-04 Lilly Co Eli Treatment or prophylaxis of prostatic cancer and benign prostatic hyperplasia with selective estrogn receptor modulators.
ZA982818B (en) 1997-04-09 1999-10-04 Lilly Co Eli Prevention of breast cancer using selective estrogen receptor modulators.
AU3791799A (en) 1998-05-12 1999-11-29 American Home Products Corporation Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US6166069A (en) 1998-05-12 2000-12-26 American Home Products Corporation Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
PE20010306A1 (es) 1999-07-02 2001-03-29 Agouron Pharma Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa
GB0018891D0 (en) 2000-08-01 2000-09-20 Novartis Ag Organic compounds
KR20020081424A (ko) 2000-03-09 2002-10-26 아벤티스 파마 도이칠란트 게엠베하 Ｐｐａｒ 매개인자의 치료학적 용도
US7091240B2 (en) 2000-03-10 2006-08-15 Oxigene, Inc. Tubulin binding ligands and corresponding prodrug constructs
US6995162B2 (en) 2001-01-12 2006-02-07 Amgen Inc. Substituted alkylamine derivatives and methods of use
US7425565B2 (en) 2002-05-09 2008-09-16 Cedars-Sinai Medical Center Use of benzothiopenes to treat and prevent prostate cancer
JP4547911B2 (ja) 2002-02-01 2010-09-22 アリアド・ファーマシューティカルズ・インコーポレイテッド リン含有化合物およびその用途
US7375134B2 (en) 2002-03-05 2008-05-20 Axys Pharmaceuticals, Inc. Cathepsin cysteine protease inhibitors
TWI275390B (en) 2002-04-30 2007-03-11 Wyeth Corp Process for the preparation of 7-substituted-3- quinolinecarbonitriles
ATE433322T1 (de) 2002-07-22 2009-06-15 Lilly Co Eli Selektive östrogenrezeptor modulatoren, die eine phenylsulfonyl-gruppe enthalten
US7462647B2 (en) 2003-06-10 2008-12-09 Eli Lilly And Company Pentalfluoroalkanesulfinyl naphthalenes and related estrogen receptor modulators
US7399865B2 (en) 2003-09-15 2008-07-15 Wyeth Protein tyrosine kinase enzyme inhibitors
ATE448215T1 (de) * 2004-01-22 2009-11-15 Lilly Co Eli Selektive östrogen-rezeptor-modulatoren
WO2005073205A1 (en) 2004-01-22 2005-08-11 Eli Lilly And Company Selective estrogen receptor modulators
EP1713770A1 (en) 2004-01-29 2006-10-25 Eli Lilly And Company Selective estrogen receptor modulators
DK1789390T3 (da) 2004-09-02 2012-02-27 Genentech Inc Pyridyl-inhibitorer af hedgehog-signalering
AU2006218403A1 (en) 2005-03-03 2006-09-08 Sirtris Pharmaceuticals, Inc. Fused heterocyclic compounds and their use as sirtuin modulators
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
EA200970863A1 (ru) 2007-03-16 2010-02-26 Эли Лилли Энд Компани Способ и промежуточные соединения для получения арзоксифена
AU2008298948B2 (en) 2007-09-12 2014-09-04 F. Hoffmann-La Roche Ag Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use
US20090069380A1 (en) 2007-09-12 2009-03-12 Protia, Llc Deuterium-enriched aroxifene
US8354528B2 (en) 2007-10-25 2013-01-15 Genentech, Inc. Process for making thienopyrimidine compounds
US8168784B2 (en) 2008-06-20 2012-05-01 Abbott Laboratories Processes to make apoptosis promoters
CA2819299A1 (en) 2010-12-24 2012-06-28 Merck Sharp & Dohme B.V. N-substituted azetidine derivatives
BR112015018882B1 (pt) 2013-02-19 2021-09-14 Novartis Ag Derivados de benzotiofeno e composições dos mesmos como degradadores de receptor de estrogênio seletivo

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1133040A (zh) * 1993-10-12 1996-10-09 辉瑞大药厂 作为雌激素激动剂的苯并噻吩及其有关化合物
US6562862B1 (en) * 1994-10-20 2003-05-13 Eli Lilly And Company Methods of inhibiting physiological conditions associated with an excess of neuropeptide Y
CN102477033A (zh) * 2010-11-23 2012-05-30 苏州波锐生物医药科技有限公司 苯并噻酚类化合物及其在制备预防和/或治疗乳腺癌骨质疏松症药物中的用途

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Characterization of the Pharmacophore Properties of Novel Selective Estrogen Receptor Downregulators (SERDs);Karen J. Kieser et.al.;《J. Med. Chem.》;20100324;第53卷(第8期);3320-3329 *
Structure–Activity Relationships for a Family of Benzothiophene Selective Estrogen Receptor Modulators Including Raloxifene and Arzoxifene;Cassia R. Overk et.al.;《CHEMMEDCHEM》;20070726;第2卷;1520-1526 *

Also Published As

Publication number Publication date
TW201443034A (zh) 2014-11-16
DOP2015000202A (es) 2015-11-30
SI2958907T1 (en) 2018-05-31
CR20150424A (es) 2015-10-19
DK2958907T3 (en) 2018-06-06
SG11201505697VA (en) 2015-09-29
PE20151428A1 (es) 2015-09-24
US9561211B2 (en) 2017-02-07
IL240131B (en) 2018-11-29
AP2015008618A0 (en) 2015-07-31
JP6364028B2 (ja) 2018-07-25
HRP20180816T1 (hr) 2018-06-29
US8877801B2 (en) 2014-11-04
NO3077717T3 (https=) 2018-07-21
US20170112805A1 (en) 2017-04-27
MA38325B1 (fr) 2019-03-29
LT2958907T (lt) 2018-04-25
KR102279999B1 (ko) 2021-07-22
CU20150090A7 (es) 2016-04-25
EP2958907A1 (en) 2015-12-30
NI201500106A (es) 2015-10-20
WO2014130310A1 (en) 2014-08-28
US20140235660A1 (en) 2014-08-21
BR112015018882B1 (pt) 2021-09-14
ME03061B (me) 2019-01-20
AU2014219283C1 (en) 2016-10-27
RS57106B1 (sr) 2018-06-29
TR201806882T4 (tr) 2018-06-21
PT2958907T (pt) 2018-03-23
US20160184265A1 (en) 2016-06-30
US10058534B2 (en) 2018-08-28
US9931317B2 (en) 2018-04-03
EP2958907B1 (en) 2018-02-28
TWI612040B (zh) 2018-01-21
MA38325A3 (fr) 2018-05-31
AU2014219283A1 (en) 2015-08-13
CA2899030C (en) 2021-03-09
PL2958907T3 (pl) 2018-07-31
CU24337B1 (es) 2018-04-03
MA38325A2 (fr) 2016-12-30
JO3494B1 (ar) 2020-07-05
ZA201505305B (en) 2016-09-28
CN105008343A (zh) 2015-10-28
EA028032B1 (ru) 2017-09-29
US9321746B2 (en) 2016-04-26
AU2014219283B2 (en) 2015-10-29
NZ710385A (en) 2016-10-28
CA2899030A1 (en) 2014-08-28
IL240131A0 (en) 2015-09-24
TN2015000323A1 (en) 2017-01-03
MX2015010752A (es) 2015-11-30
UY35334A (es) 2014-09-30
CL2015002098A1 (es) 2015-11-13
US20180169063A1 (en) 2018-06-21
EA201591537A1 (ru) 2015-12-30
HUE039052T2 (hu) 2018-12-28
MX359471B (es) 2018-09-28
GEP201706638B (en) 2017-03-10
JP2016509022A (ja) 2016-03-24
MY174888A (en) 2020-05-20
HK1251227A1 (en) 2019-01-25
GT201500233A (es) 2016-01-21
EP3360870A1 (en) 2018-08-15
BR112015018882A2 (pt) 2017-07-18
PH12015501832A1 (en) 2015-11-09
AR094704A1 (es) 2015-08-19
US20150361065A1 (en) 2015-12-17
CY1120155T1 (el) 2018-12-12
PH12015501832B1 (en) 2015-11-09
HK1211941A1 (en) 2016-06-03
KR20150119385A (ko) 2015-10-23
ES2671516T3 (es) 2018-06-06

Similar Documents

Publication Publication Date Title
CN105008343B (zh) 作为选择性雌激素受体降解剂的苯并噻吩衍生物及其组合物
TWI851542B (zh) Ｓｈｐ２之八氫環戊烷并[c]吡咯別構抑制劑
ES2548131T3 (es) Sales farmacéuticamente aceptables de 2-{4-[(3S)-piperidin-3-il]fenil}-2H-indazol-7-carboxamida
CN101528716B (zh) 抑制bcl蛋白与结合伴侣的相互作用的化合物和方法
WO2015092634A1 (en) 1,2,3,4-tetrahydroisoquinoline compounds and compositions as selective estrogen receptor antagonists and degraders
JP2022530097A (ja) がんを処置するためのアシルスルホンアミド類
KR20100137551A (ko) 벤조피란 및 벤족세핀 ｐｉ３ｋ 저해제 화합물 및 이의 사용 방법
CN110678459A (zh) 用于治疗癌症的2-杂芳基-3-氧代-2,3-二氢哒嗪-4-甲酰胺
CN101801965A (zh) 作为细胞坏死抑制剂的吲哚化合物
JP2016519674A (ja) 過剰増殖障害を治療または予防するための３−アセチルアミノ−１−（フェニル−ヘテロアリール−アミノカルボニルまたはフェニル−ヘテロアリール−カルボニルアミノ）ベンゼン誘導体
CA2970987A1 (en) Substituted pyridyl-cycloalkyl-carboxylic acids, compositions containing them and medical uses thereof
CN113727973A (zh) 可用作类法尼醇x受体调节剂的取代酰胺化合物
WO2006080323A1 (ja) ヘテロ６員環化合物及びその用途
WO2011124087A1 (zh) 噁二唑基哌嗪衍生物及其用途
HK1211941B (en) Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant