RU2012138709A - Производные арилметокси изоиндолина и композиции, включающие их, и способы их применения - Google Patents

Производные арилметокси изоиндолина и композиции, включающие их, и способы их применения Download PDF

Info

Publication number
RU2012138709A
RU2012138709A RU2012138709/04A RU2012138709A RU2012138709A RU 2012138709 A RU2012138709 A RU 2012138709A RU 2012138709/04 A RU2012138709/04 A RU 2012138709/04A RU 2012138709 A RU2012138709 A RU 2012138709A RU 2012138709 A RU2012138709 A RU 2012138709A
Authority
RU
Russia
Prior art keywords
alkyl
substituted
halogens
aryl
heteroaryl
Prior art date
Application number
RU2012138709/04A
Other languages
English (en)
Other versions
RU2567753C2 (ru
Inventor
Хон-Вах МАН
Джордж В. Мюллер
Александер РАЧЕЛМЕН
Эхаб М. ХАЛИЛ
Роджер Шэнь-Чу Чэнь
Вэйхун ЧЖАН
Original Assignee
Селджин Корпорейшн
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 Селджин Корпорейшн filed Critical Селджин Корпорейшн
Publication of RU2012138709A publication Critical patent/RU2012138709A/ru
Application granted granted Critical
Publication of RU2567753C2 publication Critical patent/RU2567753C2/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero 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
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Molecular Biology (AREA)
  • Anesthesiology (AREA)
  • AIDS & HIV (AREA)
  • Ophthalmology & Optometry (AREA)
  • Dermatology (AREA)
  • Pulmonology (AREA)

Abstract

1. Соединение формулы (I):или его фармацевтически приемлемая соль, сольват или стереоизомер, в которой:X обозначает C=O илиCH;Rобозначает -Y-R;Rобозначает H или(C-C)алкил;Y обозначает 6-10-членный арил, гетероарил или гетероцикл, каждый из которых может быть замещен одним или более галогенами; или связь;Rобозначает -(CH)-арил, -O-(CH)-арил или -(CH)-O-арил, в которых арил может быть замещен одним или более из следующих заместителей:(C-C)алкил, который сам может быть замещен одним или более галогенами; (C-C)алкокси, который сам замещен одним или более галогенами; оксо; амино; карбоксил; циано; гидроксил; галоген; дейтерий; 6-10-членный арил или гетероарил, в случае необходимости замещенный одним или более (C-C)алкилами, (C-C)алкокси или галогенами; -CONH; или -COO-(C-C)алкил, причем алкил может быть замещен одним или более галогенами;-(CH)-гетероцикл, -O-(CH)-гетероцикл или -(CH)-O-гетероцикл, причем гетероцикл может быть замещен одним или более из следующих заместителей: (C-C)алкил, сам в случае необходимости замещенный одним или более галогенами; (C-C)алкокси, сам замещенный одним или более галогенами; оксо; амино; карбоксил; циано; гидроксил; галоген; дейтерий; 6-10-членный арил или гетероарил, в случае необходимости замещенный одним или более (C-C)алкилами, (C-C)алкокси или галогенами; -CONH; или -COO-(C-C)алкил, причем алкил может быть замещен одним или более галогенами; или-(CH)-гетероарил, -O-(CH)-гетероарил или -(CH)-O-гетероарил, причем гетероарил может быть замещен одним или более из следующих заместителей: (C-C)алкил, сам в случае необходимости замещенный одним или более галогенами;(C-C)алкокси, сам замещенный одним или более галогенами; оксо; амино; карбоксил; циано; гидроксил; галоген; д

Claims (20)

1. Соединение формулы (I):
Figure 00000001
или его фармацевтически приемлемая соль, сольват или стереоизомер, в которой:
X обозначает C=O или CH2;
R1 обозначает -Y-R3;
R2 обозначает H или (C1-C6)алкил;
Y обозначает 6-10-членный арил, гетероарил или гетероцикл, каждый из которых может быть замещен одним или более галогенами; или связь;
R3 обозначает -(CH2)n-арил, -O-(CH2)n-арил или -(CH2)n-O-арил, в которых арил может быть замещен одним или более из следующих заместителей: (C1-C6)алкил, который сам может быть замещен одним или более галогенами; (C1-C6)алкокси, который сам замещен одним или более галогенами; оксо; амино; карбоксил; циано; гидроксил; галоген; дейтерий; 6-10-членный арил или гетероарил, в случае необходимости замещенный одним или более (C1-C6)алкилами, (C1-C6)алкокси или галогенами; -CONH2; или -COO-(C1-C6)алкил, причем алкил может быть замещен одним или более галогенами;
-(CH2)n-гетероцикл, -O-(CH2)n-гетероцикл или -(CH2)n-O-гетероцикл, причем гетероцикл может быть замещен одним или более из следующих заместителей: (C1-C6)алкил, сам в случае необходимости замещенный одним или более галогенами; (C1-C6)алкокси, сам замещенный одним или более галогенами; оксо; амино; карбоксил; циано; гидроксил; галоген; дейтерий; 6-10-членный арил или гетероарил, в случае необходимости замещенный одним или более (C1-C6)алкилами, (C1-C6)алкокси или галогенами; -CONH2; или -COO-(C1-C6)алкил, причем алкил может быть замещен одним или более галогенами; или
-(CH2)n-гетероарил, -O-(CH2)n-гетероарил или -(CH2)n-O-гетероарил, причем гетероарил может быть замещен одним или более из следующих заместителей: (C1-C6)алкил, сам в случае необходимости замещенный одним или более галогенами; (C1-C6)алкокси, сам замещенный одним или более галогенами; оксо; амино; карбоксил; циано; гидроксил; галоген; дейтерий; 6-10-членный арил или гетероарил, в случае необходимости замещенный одним или более (C1-C6)алкилами, (C1-C6)алкокси или галогенами; -CONH2; или -COO-(C1-C6)алкил, причем алкил может быть замещен одним или более галогенами; и
n=0, 1, 2 или 3.
2. Соединение по п.1, в котором X обозначает CH2.
3. Соединение по п.1, в котором Y обозначает фенил и R3 обозначает (CH2)n-гетероцикл.
4. Соединение по п.1, в котором Y обозначает гетероарил и R3 обозначает (CH2)n-гетероцикл.
5. Соединение по п.1, в котором Y обозначает связь.
6. Соединение по п.1, в котором Y обозначает связь и R3 обозначает (CH2)n-гетероцикл или -(CH2)n-гетероарил.
7. Соединение по п.1, которое представляет собой:
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
,
или его фармацевтически приемлемая соль, сольват или стереоизомер.
8. Соединение формулы (II):
Figure 00000015
или его фармацевтически приемлемая соль, сольват или стереоизомер, в которой:
R4 обозначает незамещенное 9-10-членное бициклическое кольцо, представляющее собой бензотиазол, хинолин, изохинолин, нафталин, 2,3-дигидро-1H-инден, бензо[d][1,2,3]триазол, имидазо[1,2-а]пиридин, бензофуран, 2,3-дигидробензофуран, бензотиофен, бензо[d]оксазол изоиндолин или хроман;
при условии, что, если бициклическое кольцо представляет собой бензофуран или бензотиофен, то кольцо не связано с изоиндольным кольцом через положение 2.
9. Соединение по п.8, которое представляет собой:
Figure 00000016
Figure 00000017
,
или его фармацевтически приемлемая соль, сольват или стереоизомер.
10. Соединение формулы (III):
Figure 00000018
или его фармацевтически приемлемая соль, сольват или стереоизомер, в которой:
X обозначает CH2 или C=O;
R5, R6 и R7 обозначают каждый независимо водород, галоген, нитро, карбамоил, амино, -SO2R8, -CONR9R10, -(C1-C6)алкил или -(C1-C6)алкокси, причем указанный алкил или алкокси может быть замещен одним или более галогенами, амино, гидроксилами или NR9R10;
R8 обозначает (C1-C6)алкил, в случае необходимости замещенный (C1-C6)алкилом или (C6-C10)арилом; амино, в случае необходимости замещенный (C1-C6)алкилом или (C6-C10)арилом; или 6-10-членный гетероцикл, в случае необходимости замещенный (C1-C6)алкилом или (C6-C10)арилом;
R9 и R10 обозначают каждый независимо водород, 6-10-членный арил, -COO-(C1-C6)алкил, -(C0-C6)алкил-CHO, -(C0-C6)алкил-COOH, -(C0-C6)алкил-NR9'R10', -(C0-C6)алкил-(5-10-членный гетероцикл), -(C1-C6)алкил-ОН, -(C1-C6)алкил-О-(C1-C6)алкил, (C1-C6)алкил или (C3-C6)циклоалкил; или
R9 и R10 вместе могут образовывать в случае необходимости замещенное 5-6-членное кольцо, содержащее один или более гетероатомов; и
R9' и R10' обозначают каждым независимо водород или (C1-C6)алкил;
при условии, что все R5-R7 не могут быть водородом; и
при условии, что, если один из R5-R7 обозначает водород и остальные два из R5-R7 оба являются хлором, тогда два атома хлора не могут быть в положениях 3 и 4 фенильного кольца.
11. Соединение по п.10, в котором один из R5-R7 обозначает водород и остальные два из R5-R7 обозначают каждый независимо галоген, (C1-C6)алкокси или (C1-C6)алкил.
12. Соединение по п.10, в котором два из R5-R7 обозначают водород и оставшийся из R5-R7 обозначает галоген, (C1-C6)алкокси или (C1-C6)алкил.
13. Соединение по п.10, которое представляет собой:
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
,
или его фармацевтически приемлемая соль, сольват или стереоизомер.
14. Соединение формулы (IV):
Figure 00000024
или его фармацевтически приемлемая соль, сольват или стереоизомер, в которой:
X обозначает N или C;
Y обозначает CH2 или C=O;
R11 и R12 обозначают каждый независимо водород, -(C1-C6)алкил, -(C1-C6)алкил-(C3-C6)циклоалкил, -(C1-C6)алкокси, -(C6-C10)арил, -CO(C1-C6)алкил, -CO(C3-C6)циклоалкил, -CO(C6-C10)арил, -COO(C1-C6)алкил, галоген, гидроксил, оксо, 3-10-членный гетероцикл, 6-10-членный гетероарил, -NHCO(C1-C6)алкил, -(CH2)n-фенил, -SO2(C1-C6)алкил, -SO2(C3-C6)циклоалкил, -SO2(C6-C10)арил или -NR14R15, причем алкильная, арильная или гетероарильная часть каждой из групп может быть замещенной одним или более галогенами, гидроксилами или -(C1-C6)алкокси;
R13 обозначает водород или -(C1-C6)алкил;
R14 и R15 обозначают каждый независимо водород или -(C1-C6)алкил; и
n=0, 1, 2 или 3.
15. Соединение по п.14, в котором X обозначает N.
16. Соединение по п.14, в котором Y обозначает CH2.
17. Соединение по п.14, которое представляет собой:
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
,
или его фармацевтически приемлемая соль, сольват или стереоизомер.
18. Соединение, которое представляет собой:
Figure 00000036
Figure 00000037
,
или его фармацевтически приемлемая соль, сольват или стереоизомер.
19. Фармацевтическая композиция, включающая соединение по любому из пп.1-18 или его фармацевтически приемлемую соль, сольват или стереоизомер.
20. Способ лечения, контроля или профилактики заболевания или нарушения, включающий введение пациенту соединения по любому из пп.1-18 или его фармацевтически приемлемой соли, сольвата или стереоизомера, причем заболевание или нарушение представляет собой рак, нарушения, связанные с ангиогенезом, боль, дегенерацию желтого пятна или связанный синдром, кожное заболевание, легочное нарушение, связанное с асбестом нарушение, паразитарное заболевание, иммунодефицит, нарушение ЦНС, повреждение ЦНС, атеросклероз или связанное нарушение, дисфункциональный сон или связанное нарушение, инфекционное заболевание, гемоглобинопатию или связанное нарушение или связанное с TNFα нарушение.
RU2012138709/04A 2010-02-11 2011-02-10 Производные арилметокси изоиндолина и композиции, включающие их, и способы их применения RU2567753C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US30361810P 2010-02-11 2010-02-11
US61/303,618 2010-02-11
PCT/US2011/024269 WO2011100380A1 (en) 2010-02-11 2011-02-10 Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same

Publications (2)

Publication Number Publication Date
RU2012138709A true RU2012138709A (ru) 2014-03-20
RU2567753C2 RU2567753C2 (ru) 2015-11-10

Family

ID=43708752

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2012138709/04A RU2567753C2 (ru) 2010-02-11 2011-02-10 Производные арилметокси изоиндолина и композиции, включающие их, и способы их применения

Country Status (33)

Country Link
US (8) US8518972B2 (ru)
EP (6) EP3202461B1 (ru)
JP (5) JP2013519675A (ru)
KR (2) KR101931468B1 (ru)
CN (2) CN104693193B (ru)
AR (1) AR081058A1 (ru)
AU (1) AU2011215877C1 (ru)
CA (1) CA2787823C (ru)
CO (1) CO6571916A2 (ru)
CR (1) CR20120414A (ru)
CY (3) CY1119177T1 (ru)
DK (3) DK3202461T3 (ru)
EC (1) ECSP12012098A (ru)
ES (5) ES2956743T3 (ru)
HR (3) HRP20171078T1 (ru)
HU (3) HUE042011T2 (ru)
IL (2) IL220992A (ru)
LT (3) LT2536706T (ru)
ME (2) ME03441B (ru)
MX (3) MX2012009237A (ru)
NI (1) NI201200132A (ru)
NZ (3) NZ601289A (ru)
PH (2) PH12012501607A1 (ru)
PL (3) PL3202460T3 (ru)
PT (3) PT3202461T (ru)
RS (3) RS59275B1 (ru)
RU (1) RU2567753C2 (ru)
SG (3) SG10201501062SA (ru)
SI (3) SI3202460T1 (ru)
SM (3) SMT201700360T1 (ru)
TR (1) TR201903027T4 (ru)
UA (2) UA115220C2 (ru)
WO (1) WO2011100380A1 (ru)

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2695521C2 (ru) * 2014-10-30 2019-07-23 Канпу Биофармасьютикалс, Лтд. Производное изоиндолина, промежуточный продукт, способ получения, фармацевтическая композиция и ее применение
US10584101B2 (en) 2016-10-11 2020-03-10 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
US10604506B2 (en) 2017-01-26 2020-03-31 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
US10647698B2 (en) 2016-12-01 2020-05-12 Arvinas Operations, Inc. Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
US10723717B2 (en) 2016-12-23 2020-07-28 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
RU2738833C2 (ru) * 2014-04-14 2020-12-17 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
US10946017B2 (en) 2015-06-05 2021-03-16 Arvinas Operations, Inc. Tank-binding kinase-1 PROTACs and associated methods of use
US10994015B2 (en) 2016-12-23 2021-05-04 Arvinas Operations, Inc. EGFR proteolysis targeting chimeric molecules and associated methods of use
US11065231B2 (en) 2017-11-17 2021-07-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides
US11161841B2 (en) 2018-04-04 2021-11-02 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
US11352351B2 (en) 2015-01-20 2022-06-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11427548B2 (en) 2015-01-20 2022-08-30 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11458123B2 (en) 2016-11-01 2022-10-04 Arvinas Operations, Inc. Tau-protein targeting PROTACs and associated methods of use
RU2781643C2 (ru) * 2018-01-25 2022-10-17 Фудзимото Ко., Лтд. Производное тиофена и его применение
US11707452B2 (en) 2018-08-20 2023-07-25 Arvinas Operations, Inc. Modulators of alpha-synuclein proteolysis and associated methods of use
US11883393B2 (en) 2019-12-19 2024-01-30 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11912699B2 (en) 2019-07-17 2024-02-27 Arvinas Operations, Inc. Tau-protein targeting compounds and associated
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
US11986532B2 (en) 2021-04-16 2024-05-21 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
US12043612B2 (en) 2020-05-09 2024-07-23 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same
US12162859B2 (en) 2020-09-14 2024-12-10 Arvinas Operations, Inc. Crystalline and amorphous forms of a compound for the targeted degradation of estrogen receptor
US12180193B2 (en) 2020-08-28 2024-12-31 Arvinas Operations, Inc. Accelerating fibrosarcoma protein degrading compounds and associated methods of use
US12208095B2 (en) 2019-08-26 2025-01-28 Arvinas Operations, Inc. Methods of treating breast cancer with tetrahydronaphthalene derivatives as estrogen receptor degraders
US12239711B2 (en) 2014-04-14 2025-03-04 Arvinas Operations, Inc. Cereblon ligands and bifunctional compounds comprising the same
US12310975B2 (en) 2019-10-17 2025-05-27 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
US12441708B2 (en) 2017-01-31 2025-10-14 Arvinas Operations, Inc. Cereblon ligands and bifunctional compounds comprising the same
US12448399B2 (en) 2023-01-26 2025-10-21 Arvinas Operations, Inc. Cereblon-based KRAS degrading PROTACs and uses related thereto
US12496301B2 (en) 2023-12-08 2025-12-16 Arvinas Operations, Inc. Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy
US12569464B2 (en) 2016-04-05 2026-03-10 Arvinas Operations, Inc. Protein-protein interaction inducing technology

Families Citing this family (136)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2436387B1 (en) 2009-05-25 2018-07-25 Celgene Corporation Pharmaceutical composition comprising crbn for use in treating a disease of the cerebral cortex
SG10201501062SA (en) 2010-02-11 2015-04-29 Celgene Corp Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
AU2012236655B2 (en) * 2011-03-28 2016-09-22 Deuterx, Llc, 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds
EP3096142A3 (en) 2011-04-29 2017-03-08 Celgene Corporation Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor
CA2877736C (en) 2012-06-29 2021-12-07 Celgene Corporation Methods for determining drug efficacy using cereblon-associated proteins
CA3108974C (en) * 2012-08-09 2023-04-04 Celgene Corporation Processes for the preparation of (s)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable forms thereof
CN114366746A (zh) * 2012-08-09 2022-04-19 细胞基因公司 使用氧代异吲哚化合物治疗癌症
US20140343058A1 (en) * 2012-08-09 2014-11-20 Celgene Corporation Treatment of systemic lupus erythematosus
US20150038511A1 (en) 2012-08-09 2015-02-05 Celgene Corporation Treatment of immune-related and inflammatory diseases
CN114939119A (zh) * 2012-08-09 2022-08-26 细胞基因公司 免疫相关和炎性疾病的治疗
TR201904785T4 (tr) 2012-08-09 2019-05-21 Celgene Corp (S)-3-(4-((4-MORFOLINOMETİL)BENZİL)OKSİ)-1-OKSOİZOİNDOLİN-2-il)PİPERİDİN-2,6-DİON HİDROKLORİDİN BİR KATI FORMU.
US9587281B2 (en) 2012-08-14 2017-03-07 Celgene Corporation Cereblon isoforms and their use as biomarkers for therapeutic treatment
US9694015B2 (en) * 2012-09-10 2017-07-04 Celgene Corporation Methods for the treatment of locally advanced breast cancer
AU2013204922B2 (en) 2012-12-20 2015-05-14 Celgene Corporation Chimeric antigen receptors
CA2935495C (en) 2013-01-14 2021-04-20 Deuterx, Llc 3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives
US9695145B2 (en) 2013-01-22 2017-07-04 Celgene Corporation Processes for the preparation of isotopologues of 3-(4-((4- morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable salts thereof
US9290475B2 (en) 2013-03-14 2016-03-22 Deuterx, Llc 3-(substituted-4-oxoquinazolin-3(4H)-yl)-3-deutero-piperidine-2,6-dione derivatives and compositions comprising and methods of using the same
CA2907397C (en) 2013-03-15 2022-11-22 Anthrogenesis Corporation Modified t lymphocytes
EP2986318A1 (en) 2013-04-17 2016-02-24 Signal Pharmaceuticals, LLC Combination therapy comprising a tor kinase inhibitor and an imid compound for treating cancer
UA117141C2 (uk) * 2013-10-08 2018-06-25 Селджин Корпорейшн Склади (s)-3-(4-((4-(морфолінометил)бензил)оксі)-1-оксоізоіндолін-2-іл)піперидин-2,6-діону
CA2932120C (en) * 2013-12-06 2023-09-19 Celgene Corporation Methods for determining drug efficacy for the treatment of diffuse large b-cell lymphoma, multiple myeloma, and myeloid cancers
TWI745271B (zh) 2014-05-19 2021-11-11 美商西建公司 全身紅斑性狼瘡之治療
EP3160486B1 (en) 2014-06-27 2020-11-18 Celgene Corporation Compositions and methods for inducing conformational changes in cereblon other e3 ubiquitin ligases
EA037738B1 (ru) 2014-08-07 2021-05-17 Калитера Байосайенсиз, Инк. Кристаллические формы ингибиторов глутаминазы
US10034872B2 (en) 2014-08-22 2018-07-31 Celgene Corporation Methods of treating multiple myeloma with immunomodulatory compounds in combination with antibodies
SMT202000004T1 (it) * 2015-07-21 2020-03-13 Immunogen Inc Metodi di preparazione dei derivati citotossici di benzodiazepina
US9809603B1 (en) 2015-08-18 2017-11-07 Deuterx, Llc Deuterium-enriched isoindolinonyl-piperidinonyl conjugates and oxoquinazolin-3(4H)-yl-piperidinonyl conjugates and methods of treating medical disorders using same
US20180271849A1 (en) * 2015-09-29 2018-09-27 Kangpu Biopharmaceuticals, Ltd. Pharmaceutical composition and application thereof
US10830762B2 (en) 2015-12-28 2020-11-10 Celgene Corporation Compositions and methods for inducing conformational changes in cereblon and other E3 ubiquitin ligases
AU2017246453A1 (en) * 2016-04-06 2018-11-08 The Regents Of The University Of Michigan Monofunctional intermediates for ligand-dependent target protein degradation
AU2017250076B2 (en) * 2016-04-12 2021-07-22 The Regents Of The University Of Michigan Bet protein degraders
TWI794171B (zh) 2016-05-11 2023-03-01 美商滬亞生物國際有限公司 Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
AU2017348322B8 (en) * 2016-10-28 2021-12-23 Icahn School Of Medicine At Mount Sinai Compositions and methods for treating EZH2-mediated cancer
EP3535295A1 (en) 2016-11-02 2019-09-11 EngMab Sàrl Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma
AU2017370694A1 (en) 2016-12-08 2019-07-25 Icahn School Of Medicine At Mount Sinai Compositions and methods for treating CDK4/6-mediated cancer
US10933059B2 (en) * 2016-12-16 2021-03-02 Kangpu Biopharmaceuticals. Ltd. Combination, application thereof and treatment method
EP3573979A1 (en) * 2017-01-27 2019-12-04 Celgene Corporation 3-(1-oxo-4-((4-((3-oxomorpholino) methyl)benzyl)oxy)isoindolin-2-yl)piperidine-2,6-dione and isotopologues thereof
EP3577459A4 (en) 2017-02-03 2020-12-16 Celgene Corporation METHOD OF MEASURING THE AFFINITY OF SMALL MOLECULES FOR CEREBLON
KR102125661B1 (ko) 2017-02-13 2020-06-22 강푸 바이오파마슈티칼즈 리미티드 전립선암 치료용 조합, 약학 조성물 및 치료 방법
CN108929307A (zh) * 2017-05-22 2018-12-04 苏州偶领生物医药有限公司 一类异吲哚酮-酰亚胺环-1,3-二酮-2-烯化合物、其组合物和用途
JP7258009B2 (ja) * 2017-07-10 2023-04-14 セルジーン コーポレイション 抗増殖化合物及びその使用方法
WO2019040109A1 (en) 2017-08-21 2019-02-28 Celgene Corporation PROCESSES FOR THE PREPARATION OF (S) -TERT-BUTYL 4,5-DIAMINO-5-OXOPENTANOATE
US10513515B2 (en) * 2017-08-25 2019-12-24 Biotheryx, Inc. Ether compounds and uses thereof
SG11202002032SA (en) 2017-09-22 2020-04-29 Jubilant Epipad LLC Heterocyclic compounds as pad inhibitors
CA3076476A1 (en) 2017-10-18 2019-04-25 Jubilant Epipad LLC Imidazo-pyridine compounds as pad inhibitors
BR112020008851A2 (pt) 2017-11-06 2020-10-20 Jubilant Prodel LLC composto da fórmula i, processo de preparação de compostos da fórmula i, composição farmacêutica, método para o tratamento e/ou prevenção de várias doenças, uso, método para o tratamento de câncer, método de tratamento de câncer e método para o tratamento e/ou prevenção de câncer e doenças infecciosas
PL3704120T3 (pl) 2017-11-24 2024-09-16 Jubilant Episcribe Llc Związki heterocykliczne jako inhibitory prmt5
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
EP3737666A4 (en) 2018-01-12 2022-01-05 Kymera Therapeutics, Inc. PROTEIN DEGRADATION AGENTS AND ASSOCIATED USES
CA3089553A1 (en) * 2018-01-25 2019-08-01 Fujimoto Co., Ltd. Thiophene derivative and use thereof
JP2021512153A (ja) 2018-01-26 2021-05-13 イエール ユニバーシティ タンパク質分解のイミド系モジュレーターおよび使用方法
WO2019164891A1 (en) 2018-02-21 2019-08-29 Celgene Corporation Bcma-binding antibodies and uses thereof
WO2019173516A1 (en) 2018-03-06 2019-09-12 Icahn School Of Medicine At Mount Sinai Serine threonine kinase (akt) degradation / disruption compounds and methods of use
SG11202008950PA (en) 2018-03-13 2020-10-29 Jubilant Prodel LLC Bicyclic compounds as inhibitors of pd1/pd-l1 interaction/activation
FI3784663T3 (fi) 2018-04-23 2023-10-06 Celgene Corp Substituoituja 4-aminoisoindoliini-1,3-dioniyhdisteitä ja niiden käyttö lymfooman hoitamiseksi
CA3104298A1 (en) 2018-06-21 2019-12-26 Icahn School Of Medicine At Mount Sinai Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use
CA3103166A1 (en) 2018-06-29 2020-01-02 F. Hoffmann-La Roche Ag Compounds
EP3817822A4 (en) 2018-07-06 2022-07-27 Kymera Therapeutics, Inc. PROTEIN DEGRADANTS AND USES THEREOF
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
CU20210002A7 (es) * 2018-07-10 2021-08-06 Novartis Ag Derivados de 3-(5-hidroxi-1-oxoisoindolin-2-il)piperidina-2,6-diona y su uso en el tratamiento de trastornos dependientes de la proteína con dedos de zinc 2 de la familia ikaros (ikzf2)
CA3106239A1 (en) 2018-07-27 2020-01-30 Biotheryx, Inc. Bifunctional compounds as cdk modulators
US20210317109A1 (en) * 2018-09-07 2021-10-14 Medshine Discovery Inc. Tricyclic substituted piperidine dione compound
US12459921B2 (en) 2018-09-30 2025-11-04 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences Isoindoline compound, preparation method, pharmaceutical composition and use thereof
AU2019351811B2 (en) 2018-10-01 2025-01-02 Celgene Corporation Combination therapy for the treatment of cancer
CA3117978A1 (en) 2018-11-08 2020-05-14 Juno Therapeutics, Inc. Methods and combinations for treatment and t cell modulation
JP7623943B2 (ja) 2018-11-30 2025-01-29 カイメラ セラピューティクス， インコーポレイテッド Ｉｒａｋ分解剤およびそれらの使用
US20230045737A1 (en) * 2018-12-05 2023-02-09 Vividion Therapeutics, Inc. Substituted isoindolinones as modulators of cereblon-mediated neo-substrate recruitment
EP3896062A4 (en) 2018-12-06 2022-06-15 Shanghai Institute of Materia Medica, Chinese Academy of Sciences ISOINDOLINE COMPOUND, METHOD FOR PREPARATION, PHARMACEUTICAL COMPOSITION AND USE OF ISOINDOLINE COMPOUND
ES3059967T3 (en) 2019-01-09 2026-03-24 Celgene Corp Solid forms comprising (s)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl) benzyl)piperazin-1-yl)-3-fluorobenzonitrile and salts thereof, and compositions comprising and methods of using the same
SG11202107438WA (en) 2019-01-09 2021-08-30 Celgene Corp Pharmaceutical compositions comprising (s)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl) benzyl)piperazin-1-yl)-3-fluorobenzonitrile and methods of using the same
CA3125753A1 (en) 2019-01-09 2020-07-16 Celgene Corporation Antiproliferative compounds and second active agents for use in treating multiple myeloma
US12582641B2 (en) 2019-02-25 2026-03-24 Shanghaitech University Sulfur-containing compound based on glutarimide skeleton and application thereof
AR119715A1 (es) * 2019-04-12 2022-01-05 Celgene Corp Métodos para tratar linfoma no hodgkin con el uso de 2-(2,6-dioxopiperidin-3-il)-4-((2-fluoro-4-((3-morfolinoazetidin-1-il)metil)bencil)amino)isoindolin-1,3-diona
US12465648B2 (en) 2019-05-06 2025-11-11 Icahn School Of Medicine At Mount Sinai Heterobifunctional compounds as degraders of HPK1
BR112021026517A2 (pt) 2019-06-28 2022-05-10 Kymera Therapeutics Inc Degradadores de irak e usos dos mesmos
WO2021011868A1 (en) 2019-07-17 2021-01-21 Kymera Therapeutics, Inc. Irak degraders and uses thereof
CN112321566B (zh) 2019-08-05 2022-06-10 上海科技大学 Egfr蛋白降解剂及其抗肿瘤应用
BR112022007580A2 (pt) * 2019-10-21 2022-07-05 Celgene Corp Formas sólidas que compreendem (s)-2-(2,6-dioxopiperidin-3-il)-4-((2-fluoro-4-((3-morfolinoazetidin-1-il)metil)benzil)amino)isoindolino-1,3-diona e seus sais e composições que compreendem as mesmas e seus usos
CA3160178A1 (en) 2019-11-05 2021-05-14 Celgene Corporation Uses of anti-bcma chimeric antigen receptors
IL292667B1 (en) 2019-11-07 2026-02-01 Juno Therapeutics Inc Combination of T-cell therapy and (s)-3-[4-(4-morpholin-4-ylmethyl-benzyloxy)-l-oxo-3,l-dihydro-isoindol-2-yl]-piperidine-6,2-dione
EP4065576A1 (en) 2019-11-27 2022-10-05 Captor Therapeutics S.A. Piperidine-2, 6-dione derivatives which bind to cereblon, and methods of use thereof
AU2020392427B2 (en) 2019-11-27 2024-03-07 Captor Therapeutics S.A. Piperidine-2, 6-dione derivatives which bind to cereblon, and methods of use thereof
CN115315260A (zh) 2019-12-02 2022-11-08 新基公司 治疗癌症的疗法
EP4072591A4 (en) 2019-12-10 2024-06-05 Kymera Therapeutics, Inc. IRAQ DEGRADER AND USES THEREOF
EP4420728A3 (en) * 2019-12-12 2024-10-30 Accutar Biotechnology Inc. Novel chroman derivatives having estrogen receptor degradation activity and uses thereof
JP2023509366A (ja) * 2019-12-17 2023-03-08 カイメラ セラピューティクス， インコーポレイテッド Ｉｒａｋ分解剤およびそれらの使用
ES2980575T3 (es) * 2019-12-18 2024-10-02 Novartis Ag Derivados de 3-(5-metoxi-1-oxoisoindolin-2-il)piperidin-2,6-diona y usos de los mismos
WO2021133886A1 (en) 2019-12-23 2021-07-01 Accutar Biotechnology Combinations of estrogen receptor degraders and cyclin-dependent kinase inhibitors for treating cancer
KR20220124228A (ko) * 2020-01-20 2022-09-13 강푸 바이오파마슈티칼즈 리미티드 이소인돌린 유도체, 및 이의 제약 조성물 및 용도
CN113372327B (zh) * 2020-02-25 2023-07-18 上海科技大学 基于戊二酰亚胺骨架的化合物及其应用
WO2021222150A2 (en) 2020-04-28 2021-11-04 Anwita Biosciences, Inc. Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications
EP4142722A1 (en) 2020-04-30 2023-03-08 Bristol-Myers Squibb Company Methods of treating cytokine-related adverse events
US12103924B2 (en) 2020-06-01 2024-10-01 Icahn School Of Medicine At Mount Sinai Mitogen-activated protein kinase kinase (MEK) degradation compounds and methods of use
EP4171550A1 (en) 2020-06-25 2023-05-03 Celgene Corporation Methods for treating cancer with combination therapies
CN113896711A (zh) * 2020-07-06 2022-01-07 北京诺诚健华医药科技有限公司 杂环类免疫调节剂
KR20230042057A (ko) * 2020-07-20 2023-03-27 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 황-함유 이소인돌린 유도체, 및 이의 제조 방법 및 이의 의학적 용도
CN116457344B (zh) 2020-08-03 2026-05-12 凯普托尔治疗学股份有限公司 低分子量蛋白质降解剂及其应用
US20230310478A1 (en) * 2020-09-02 2023-10-05 Ann And Robert H. Lurie Children's Hospital Of Chicago Methods and compositions for the treatment of pulmonary hypertension and cancer
CA3191282A1 (en) 2020-09-11 2022-03-17 William Pierceall Combination therapy for cancer
WO2022066580A1 (en) * 2020-09-23 2022-03-31 Kinnate Biopharma Inc. Raf degrading compounds
JP2023544351A (ja) 2020-10-02 2023-10-23 セルジーン コーポレーション 全身性エリテマトーデスを治療する方法及び治療に対する臨床的感受性の予測因子としてのバイオマーカの使用
JP2023550309A (ja) 2020-11-04 2023-12-01 セルジーン コーポレーション 以前に抗がんアルキル化剤療法を受けた患者におけるｃａｒ ｔ細胞療法
CN112174976A (zh) * 2020-11-19 2021-01-05 江西中医药大学 从水芹菜中分离的二苯并呋喃型木脂素及其方法和在抗痛风性关节炎上的用途
WO2022146151A1 (en) 2020-12-30 2022-07-07 Captor Therapeutics S.A. Novel compounds which bind to cereblon, and methods of use thereof
WO2022147465A1 (en) 2020-12-30 2022-07-07 Kymera Therapeutics, Inc. Irak degraders and uses thereof
WO2022148358A1 (zh) * 2021-01-05 2022-07-14 江苏恒瑞医药股份有限公司 稠杂环基取代的环己二酰亚胺衍生物、其制备方法及其在医药上的应用
JP2024504932A (ja) 2021-01-13 2024-02-02 モンテ ローザ セラピューティクス， インコーポレイテッド イソインドリノン化合物
TW202245788A (zh) 2021-02-15 2022-12-01 美商凱麥拉醫療公司 Irak4降解劑及其用途
CN116867494A (zh) 2021-02-15 2023-10-10 凯麦拉医疗公司 Irak4降解剂和其用途
UY39671A (es) * 2021-03-15 2022-10-31 Novartis Ag Derivados de pirazolopiridina y sus usos.
US20240217968A1 (en) * 2021-03-31 2024-07-04 Duke Street Bio Limited Pharmaceutical compound
WO2022255890A1 (en) 2021-06-01 2022-12-08 Captor Therapeutics S.A. Compounds which bind to cereblon, and use thereof
WO2022255889A1 (en) 2021-06-01 2022-12-08 Captor Therapeutics S.A. Compounds which bind to cereblon, and use thereof
CR20230614A (es) 2021-06-03 2024-02-01 Novartis Ag Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos médicos
CN115504963A (zh) * 2021-06-22 2022-12-23 苏州开拓药业股份有限公司 一种c-Myc蛋白降解剂
WO2023025136A1 (zh) * 2021-08-27 2023-03-02 杭州格博生物医药有限公司 异吲哚啉酮化合物及其用途
WO2023034411A1 (en) * 2021-09-01 2023-03-09 Oerth Bio Llc Compositions and methods for targeted degradation of proteins in a plant cell
EP4422635A4 (en) 2021-10-29 2025-11-26 Kymera Therapeutics Inc IRAQ4 DEGRADATION AGENTS AND THEIR SYNTHESIS
CN116462660A (zh) * 2022-01-19 2023-07-21 江苏恒瑞医药股份有限公司 一种异喹啉酮类化合物的盐及其晶型
WO2023138647A1 (zh) * 2022-01-19 2023-07-27 江苏恒瑞医药股份有限公司 一种含硫异吲哚啉类衍生物的晶型
IL314437A (en) 2022-01-31 2024-09-01 Kymera Therapeutics Inc IRAK joints and their uses
US20250295771A1 (en) 2022-05-11 2025-09-25 Celgene Corporation Methods and uses related to t cell therapy and production of same
US20250302954A1 (en) 2022-05-11 2025-10-02 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
CN115160211B (zh) * 2022-06-23 2023-11-03 温州大学 一种异吲哚啉酮类化合物的绿色合成方法
CN117285524A (zh) * 2022-06-24 2023-12-26 中国科学院上海药物研究所 一类取代的4-氨基异吲哚啉类化合物、其制备方法、药物组合物及应用
US20260098035A1 (en) 2022-09-20 2026-04-09 Celgene Corporation Salts and solid forms of (s)- or racemic 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and methods of using the same
WO2024097905A1 (en) 2022-11-02 2024-05-10 Celgene Corporation Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy
EP4619399A1 (en) 2022-11-16 2025-09-24 Basf Se New substituted tetrahydrobenzoxazepine
WO2024167423A1 (en) 2023-02-07 2024-08-15 Captor Therapeutics S.A. Gspt1 degrader compounds
WO2025042742A1 (en) 2023-08-18 2025-02-27 Bristol-Myers Squibb Company Compositions comprising antibodies that bind bcma and cd3 and methods of treatment
WO2025076472A1 (en) 2023-10-06 2025-04-10 Juno Therapeutics, Inc. Combination therapies with a cell therapy expressing a gprc5d-targeting car and related methods and uses
TW202532072A (zh) 2023-12-08 2025-08-16 美商西建公司 治療多發性骨髓瘤之療法
WO2025195464A1 (zh) * 2024-03-21 2025-09-25 上海惠康济民生物医药技术有限公司 取代的异吲哚啉类化合物、制备方法、药物组合物及应用
WO2026022712A1 (en) 2024-07-23 2026-01-29 Sanofi Cereblon ligase modulator and bcma nk cell engager combination therapy
WO2026035999A1 (en) 2024-08-09 2026-02-12 Triana Biomedicines, Inc. Anaplastic lymphoma kinase (alk) degraders and uses thereof

Family Cites Families (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3536809A (en) 1969-02-17 1970-10-27 Alza Corp Medication method
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4008719A (en) 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
US4421865A (en) * 1981-06-08 1983-12-20 Standard Oil Company (Sohio) Selective hydrogen-deuterium interchange using ion exchange resins
US4994443A (en) 1982-12-20 1991-02-19 The Children's Medical Center Corporation Inhibition of angiogenesis
US5001116A (en) 1982-12-20 1991-03-19 The Children's Medical Center Corporation Inhibition of angiogenesis
KR890002631B1 (ko) 1984-10-04 1989-07-21 몬산토 캄파니 생물학적으로 활성인 소마토트로핀을 지속적으로 유리하는 조성물
IE58110B1 (en) 1984-10-30 1993-07-14 Elan Corp Plc Controlled release powder and process for its preparation
US5149820A (en) * 1987-03-11 1992-09-22 Norsk Hydro A.S. Deuterated compounds
US5073543A (en) 1988-07-21 1991-12-17 G. D. Searle & Co. Controlled release formulations of trophic factors in ganglioside-lipsome vehicle
IT1229203B (it) 1989-03-22 1991-07-25 Bioresearch Spa Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative.
PH30995A (en) 1989-07-07 1997-12-23 Novartis Inc Sustained release formulations of water soluble peptides.
US5120548A (en) 1989-11-07 1992-06-09 Merck & Co., Inc. Swelling modulated polymeric drug delivery device
KR0166088B1 (ko) 1990-01-23 1999-01-15 . 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도
US5733566A (en) 1990-05-15 1998-03-31 Alkermes Controlled Therapeutics Inc. Ii Controlled release of antiparasitic agents in animals
AU1531492A (en) * 1991-02-14 1992-09-15 Rockefeller University, The Method for controlling abnormal concentration tnf alpha in human tissues
US5580578A (en) 1992-01-27 1996-12-03 Euro-Celtique, S.A. Controlled release formulations coated with aqueous dispersions of acrylic polymers
WO1994007498A1 (fr) * 1992-10-07 1994-04-14 Sumitomo Pharmaceuticals Company, Limited Composition pharmaceutique utilisee pour inhiber la production des facteurs de necrose tumorale
TW333456B (en) 1992-12-07 1998-06-11 Takeda Pharm Ind Co Ltd A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide.
US5591767A (en) 1993-01-25 1997-01-07 Pharmetrix Corporation Liquid reservoir transdermal patch for the administration of ketorolac
US6087324A (en) 1993-06-24 2000-07-11 Takeda Chemical Industries, Ltd. Sustained-release preparation
WO1995003009A1 (en) 1993-07-22 1995-02-02 Oculex Pharmaceuticals, Inc. Method of treatment of macular degeneration
US5770589A (en) 1993-07-27 1998-06-23 The University Of Sydney Treatment of macular degeneration
IT1270594B (it) 1994-07-07 1997-05-07 Recordati Chem Pharm Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida
IT1274549B (it) 1995-05-23 1997-07-17 Indena Spa Uso di flavanolignani per la preparazione di medicamenti ad attivita' antiproliferativa nei tumori dell'utero,dell'ovaio e del seno
WO1997001331A2 (en) 1995-06-27 1997-01-16 Takeda Chemical Industries, Ltd. Method of producing sustained-release preparation
TW448055B (en) 1995-09-04 2001-08-01 Takeda Chemical Industries Ltd Method of production of sustained-release preparation
JP2909418B2 (ja) 1995-09-18 1999-06-23 株式会社資生堂 薬物の遅延放出型マイクロスフイア
US5980945A (en) 1996-01-16 1999-11-09 Societe De Conseils De Recherches Et D'applications Scientifique S.A. Sustained release drug formulations
US5800819A (en) 1996-01-25 1998-09-01 National Institute For Pharmaceutical Research And Development Federal Ministry Of Science And Technology Piper guineense, pterocarpus osun, eugenia caryophyllata, and sorghum bicolor extracts for treating sickle cell disease
US6264970B1 (en) 1996-06-26 2001-07-24 Takeda Chemical Industries, Ltd. Sustained-release preparation
US5635517B1 (en) 1996-07-24 1999-06-29 Celgene Corp Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines
HU228769B1 (en) 1996-07-24 2013-05-28 Celgene Corp Substituted 2(2,6-dioxopiperidin-3-yl)phthalimides and -1-oxoisoindolines and their use for production of pharmaceutical compositions for mammals to reduce the level of tnf-alpha
PT2177517E (pt) 1996-07-24 2011-11-10 Celgene Corp 2-(2,6-dioxopiperidin-3-il)-ftalimida amino-substituída para redução dos níveis de tnf-alfa
US6281230B1 (en) 1996-07-24 2001-08-28 Celgene Corporation Isoindolines, method of use, and pharmaceutical compositions
US6419961B1 (en) 1996-08-29 2002-07-16 Takeda Chemical Industries, Ltd. Sustained release microcapsules of a bioactive substance and a biodegradable polymer
CA2217134A1 (en) 1996-10-09 1998-04-09 Sumitomo Pharmaceuticals Co., Ltd. Sustained release formulation
ES2221019T3 (es) 1996-10-31 2004-12-16 Takeda Chemical Industries, Ltd. Preparacion de liberacion mantenida.
ZA9711385B (en) 1996-12-20 1999-06-18 Takeda Chemical Industries Ltd Method of producing a sustained-release preparation
US5891474A (en) 1997-01-29 1999-04-06 Poli Industria Chimica, S.P.A. Time-specific controlled release dosage formulations and method of preparing same
US20010006973A1 (en) 1998-03-16 2001-07-05 Hon-Wah Man 1-oxo- and 1,3-dioxoisoindolines and method of reducing inflammatory cytokine levels
US6613358B2 (en) 1998-03-18 2003-09-02 Theodore W. Randolph Sustained-release composition including amorphous polymer
US6015803A (en) 1998-05-04 2000-01-18 Wirostko; Emil Antibiotic treatment of age-related macular degeneration
KR19990085365A (ko) 1998-05-16 1999-12-06 허영섭 지속적으로 약물 조절방출이 가능한 생분해성 고분자 미립구 및그 제조방법
US6225348B1 (en) 1998-08-20 2001-05-01 Alfred W. Paulsen Method of treating macular degeneration with a prostaglandin derivative
US6001368A (en) 1998-09-03 1999-12-14 Protein Technologies International, Inc. Method for inhibiting or reducing the risk of macular degeneration
US6248363B1 (en) 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US7182953B2 (en) 1999-12-15 2007-02-27 Celgene Corporation Methods and compositions for the prevention and treatment of atherosclerosis restenosis and related disorders
EP1182681B1 (en) 2000-08-23 2006-03-01 General Electric Company Injection molded ceramic metal halide arc tube having non-tapered end
US6458810B1 (en) * 2000-11-14 2002-10-01 George Muller Pharmaceutically active isoindoline derivatives
US20030045552A1 (en) * 2000-12-27 2003-03-06 Robarge Michael J. Isoindole-imide compounds, compositions, and uses thereof
AU2002343220A1 (en) 2001-11-09 2003-05-19 Matsushita Electric Industrial Co., Ltd. Moving picture coding method and apparatus
US7393862B2 (en) 2002-05-17 2008-07-01 Celgene Corporation Method using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for treatment of certain leukemias
EP2272513A1 (en) 2002-05-17 2011-01-12 Celgene Corporation Pharmaceutical compositions for treating cancer
US7968569B2 (en) 2002-05-17 2011-06-28 Celgene Corporation Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione
US7323479B2 (en) 2002-05-17 2008-01-29 Celgene Corporation Methods for treatment and management of brain cancer using 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-methylisoindoline
US7189740B2 (en) 2002-10-15 2007-03-13 Celgene Corporation Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes
US20050203142A1 (en) 2002-10-24 2005-09-15 Zeldis Jerome B. Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain
US20040091455A1 (en) 2002-10-31 2004-05-13 Zeldis Jerome B. Methods of using and compositions comprising immunomodulatory compounds for treatment and management of macular degeneration
US7563810B2 (en) 2002-11-06 2009-07-21 Celgene Corporation Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases
UA83504C2 (en) 2003-09-04 2008-07-25 Селджин Корпорейшн Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
WO2005028436A2 (en) 2003-09-17 2005-03-31 The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services Thalidomide analogs as tnf-alpha modulators
US20050100529A1 (en) 2003-11-06 2005-05-12 Zeldis Jerome B. Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of asbestos-related diseases and disorders
NZ548049A (en) 2003-12-02 2009-01-31 Celgene Corp Methods and compositions for the treatment and management of hemoglobinopathy and anemia
US20050143344A1 (en) 2003-12-30 2005-06-30 Zeldis Jerome B. Methods and compositions using immunomodulatory compounds for the treatment and management of central nervous system disorders or diseases
MXPA06010699A (es) 2004-03-22 2006-12-15 Celgene Corp Metodos de usos y composiciones que contienen compuestos inmunomoduladores para el tratamiento y manejo de enfermedades o alteraciones de la piel.
US20050222209A1 (en) 2004-04-01 2005-10-06 Zeldis Jerome B Methods and compositions for the treatment, prevention or management of dysfunctional sleep and dysfunctional sleep associated with disease
JP2007533761A (ja) 2004-04-23 2007-11-22 セルジーン・コーポレーション 肺高血圧症を治療し管理するための、免疫調節性化合物の使用方法及び免疫調節性化合物を含む組成物
WO2005112928A1 (en) 2004-05-05 2005-12-01 Celgene Corporation Method of using and compositions comprising immunomodulatory compounds for the treatment and management of myeloproliferative diseases
WO2006019768A1 (en) 2004-07-16 2006-02-23 Schering Corporation Hydantoin derivatives for the treatment of inflammatory disorders
US7244759B2 (en) 2004-07-28 2007-07-17 Celgene Corporation Isoindoline compounds and methods of making and using the same
US7405237B2 (en) 2004-07-28 2008-07-29 Celgene Corporation Isoindoline compounds and methods of their use
ES2437592T3 (es) * 2004-09-03 2014-01-13 Celgene Corporation Procedimientos para la preparación de 2-(2,6-dioxopiperidin-3-il)-1-oxoisoindolinas sustituidas
ZA200704784B (en) 2004-11-12 2008-10-29 Celgene Corp Methods and compositions using immunomodulatory compounds for treatment and management of parasitic diseases
CA2588597A1 (en) 2004-11-23 2006-06-01 Celgene Corporation Methods and compositions using immunomodulatory compounds for treatment and management of central nervous system injury
CN101111234A (zh) 2004-12-01 2008-01-23 细胞基因公司 包含免疫调节化合物的组合物及其治疗免疫缺陷疾病的用途
JP5366544B2 (ja) 2005-06-30 2013-12-11 セルジーン コーポレイション ４−アミノ−２−（２，６−ジオキソピペリジン−３−イル）イソインドリン−１，３−ジオン化合物を調製するための方法
ES2434946T3 (es) 2005-08-31 2013-12-18 Celgene Corporation Compuestos de isoindol imida y composiciones que los comprenden y métodos para usarlo
JO3235B1 (ar) 2006-05-26 2018-03-08 Astex Therapeutics Ltd مركبات بيررولوبيريميدين و استعمالاتها
WO2008033567A1 (en) 2006-09-15 2008-03-20 Celgene Corporation N-methylaminomethyl isoindole compounds and compositions comprising and methods of using the same
EP2081561A2 (en) 2006-10-19 2009-07-29 Celgene Corporation Methods and compositions using immunomodulatory compounds for the treatment and management of spirochete and other obligate intracellular bacterial diseases
AU2008229383B2 (en) * 2007-03-20 2013-09-05 Celgene Corporation 4'-O-substituted isoindoline derivatives and compositions comprising and methods of using the same
SG10201501062SA (en) 2010-02-11 2015-04-29 Celgene Corp Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
WO2012027065A2 (en) 2010-08-27 2012-03-01 Celgene Corporation Combination therapy for treatment of disease
AU2011329619A1 (en) 2010-11-18 2013-05-02 Deuteria Pharmaceuticals, Inc. 3-deutero-pomalidomide
WO2012079022A1 (en) 2010-12-10 2012-06-14 Concert Pharmaceuticals, Inc. Substituted dioxopiperidinyl phthalimide derivatives
AU2012236655B2 (en) 2011-03-28 2016-09-22 Deuterx, Llc, 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds
CA2877736C (en) 2012-06-29 2021-12-07 Celgene Corporation Methods for determining drug efficacy using cereblon-associated proteins
US20140343058A1 (en) 2012-08-09 2014-11-20 Celgene Corporation Treatment of systemic lupus erythematosus
CN114939119A (zh) 2012-08-09 2022-08-26 细胞基因公司 免疫相关和炎性疾病的治疗
TR201904785T4 (tr) 2012-08-09 2019-05-21 Celgene Corp (S)-3-(4-((4-MORFOLINOMETİL)BENZİL)OKSİ)-1-OKSOİZOİNDOLİN-2-il)PİPERİDİN-2,6-DİON HİDROKLORİDİN BİR KATI FORMU.
US20150038511A1 (en) 2012-08-09 2015-02-05 Celgene Corporation Treatment of immune-related and inflammatory diseases
CN114366746A (zh) 2012-08-09 2022-04-19 细胞基因公司 使用氧代异吲哚化合物治疗癌症
CA3108974C (en) 2012-08-09 2023-04-04 Celgene Corporation Processes for the preparation of (s)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable forms thereof
US9587281B2 (en) 2012-08-14 2017-03-07 Celgene Corporation Cereblon isoforms and their use as biomarkers for therapeutic treatment
US9694015B2 (en) 2012-09-10 2017-07-04 Celgene Corporation Methods for the treatment of locally advanced breast cancer
US9695145B2 (en) 2013-01-22 2017-07-04 Celgene Corporation Processes for the preparation of isotopologues of 3-(4-((4- morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable salts thereof
NZ628320A (en) 2013-03-14 2017-04-28 Celgene Corp Treatment of psoriatic arthritis using apremilast
EP2986318A1 (en) 2013-04-17 2016-02-24 Signal Pharmaceuticals, LLC Combination therapy comprising a tor kinase inhibitor and an imid compound for treating cancer
UA117141C2 (uk) 2013-10-08 2018-06-25 Селджин Корпорейшн Склади (s)-3-(4-((4-(морфолінометил)бензил)оксі)-1-оксоізоіндолін-2-іл)піперидин-2,6-діону
CA2932120C (en) 2013-12-06 2023-09-19 Celgene Corporation Methods for determining drug efficacy for the treatment of diffuse large b-cell lymphoma, multiple myeloma, and myeloid cancers
US9415049B2 (en) 2013-12-20 2016-08-16 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof
TWI745271B (zh) 2014-05-19 2021-11-11 美商西建公司 全身紅斑性狼瘡之治療
EP3160486B1 (en) 2014-06-27 2020-11-18 Celgene Corporation Compositions and methods for inducing conformational changes in cereblon other e3 ubiquitin ligases
US10092541B2 (en) 2014-08-15 2018-10-09 Celgene Corporation Methods for the treatment of diseases ameliorated by PDE4 inhibition using dosage titration of apremilast
WO2016060702A1 (en) 2014-10-13 2016-04-21 Celgene Corporaton Methods for treating solid tumors and the use of biomarkers as a predictor of clinical sensitivity to immunomodulatory therapies
ES2901509T3 (es) 2014-10-30 2022-03-22 Kangpu Biopharmaceuticals Ltd Derivado de isoindolina, compuesto intermedio, métodos de preparación, composición farmacéutica y uso del mismo
US9717745B2 (en) 2015-03-19 2017-08-01 Zhejiang DTRM Biopharma Co. Ltd. Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases

Cited By (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2738833C2 (ru) * 2014-04-14 2020-12-17 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
US12239711B2 (en) 2014-04-14 2025-03-04 Arvinas Operations, Inc. Cereblon ligands and bifunctional compounds comprising the same
RU2738833C9 (ru) * 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
RU2695521C9 (ru) * 2014-10-30 2019-08-19 Канпу Биофармасьютикалс, Лтд. Производное изоиндолина, промежуточный продукт, способ получения, фармацевтическая композиция и ее применение
RU2695521C2 (ru) * 2014-10-30 2019-07-23 Канпу Биофармасьютикалс, Лтд. Производное изоиндолина, промежуточный продукт, способ получения, фармацевтическая композиция и ее применение
US12312316B2 (en) 2015-01-20 2025-05-27 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11427548B2 (en) 2015-01-20 2022-08-30 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11352351B2 (en) 2015-01-20 2022-06-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US10946017B2 (en) 2015-06-05 2021-03-16 Arvinas Operations, Inc. Tank-binding kinase-1 PROTACs and associated methods of use
US12171831B2 (en) 2015-08-19 2024-12-24 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain- containing proteins
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US11554171B2 (en) 2015-08-19 2023-01-17 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
US12569464B2 (en) 2016-04-05 2026-03-10 Arvinas Operations, Inc. Protein-protein interaction inducing technology
US12077509B2 (en) 2016-10-11 2024-09-03 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11952347B2 (en) 2016-10-11 2024-04-09 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US10584101B2 (en) 2016-10-11 2020-03-10 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
US10844021B2 (en) 2016-10-11 2020-11-24 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11236051B2 (en) 2016-10-11 2022-02-01 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11964945B2 (en) 2016-10-11 2024-04-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11458123B2 (en) 2016-11-01 2022-10-04 Arvinas Operations, Inc. Tau-protein targeting PROTACs and associated methods of use
US10899742B1 (en) 2016-12-01 2021-01-26 Arvinas Operations, Inc. Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
US12172981B2 (en) 2016-12-01 2024-12-24 Arvinas Operations, Inc. Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
US11597720B2 (en) 2016-12-01 2023-03-07 Arvinas Operations, Inc. Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
US11104666B2 (en) 2016-12-01 2021-08-31 Arvinas Operations, Inc. Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
US10647698B2 (en) 2016-12-01 2020-05-12 Arvinas Operations, Inc. Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
US11986531B2 (en) 2016-12-23 2024-05-21 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
US10994015B2 (en) 2016-12-23 2021-05-04 Arvinas Operations, Inc. EGFR proteolysis targeting chimeric molecules and associated methods of use
US10806737B2 (en) 2016-12-23 2020-10-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
US10723717B2 (en) 2016-12-23 2020-07-28 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
US11191741B2 (en) 2016-12-24 2021-12-07 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
US11857519B2 (en) 2016-12-24 2024-01-02 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide
US12275716B2 (en) 2017-01-26 2025-04-15 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
US11384063B2 (en) 2017-01-26 2022-07-12 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
US10604506B2 (en) 2017-01-26 2020-03-31 Arvinas Operations, Inc. Modulators of estrogen receptor proteolysis and associated methods of use
US12441708B2 (en) 2017-01-31 2025-10-14 Arvinas Operations, Inc. Cereblon ligands and bifunctional compounds comprising the same
US11065231B2 (en) 2017-11-17 2021-07-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides
US12036209B2 (en) 2017-11-17 2024-07-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of Interleukin-1 receptor-associated kinase 4 polypeptides
RU2781643C2 (ru) * 2018-01-25 2022-10-17 Фудзимото Ко., Лтд. Производное тиофена и его применение
US11161841B2 (en) 2018-04-04 2021-11-02 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
US12552783B2 (en) 2018-04-04 2026-02-17 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
US11707452B2 (en) 2018-08-20 2023-07-25 Arvinas Operations, Inc. Modulators of alpha-synuclein proteolysis and associated methods of use
US12594264B2 (en) 2018-08-20 2026-04-07 Arvinas Operations, Inc. Modulators of alpha-synuclein proteolysis and associated methods of use
US12559486B2 (en) 2019-07-17 2026-02-24 Arvinas Operations, Inc. Tau-protein targeting compounds and associated methods of use
US11912699B2 (en) 2019-07-17 2024-02-27 Arvinas Operations, Inc. Tau-protein targeting compounds and associated
US12208095B2 (en) 2019-08-26 2025-01-28 Arvinas Operations, Inc. Methods of treating breast cancer with tetrahydronaphthalene derivatives as estrogen receptor degraders
US12310975B2 (en) 2019-10-17 2025-05-27 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
US12427144B2 (en) 2019-12-19 2025-09-30 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11883393B2 (en) 2019-12-19 2024-01-30 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US12043612B2 (en) 2020-05-09 2024-07-23 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same
US12180193B2 (en) 2020-08-28 2024-12-31 Arvinas Operations, Inc. Accelerating fibrosarcoma protein degrading compounds and associated methods of use
US12162859B2 (en) 2020-09-14 2024-12-10 Arvinas Operations, Inc. Crystalline and amorphous forms of a compound for the targeted degradation of estrogen receptor
US11986532B2 (en) 2021-04-16 2024-05-21 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
US12156916B2 (en) 2022-09-07 2024-12-03 Arvinas Operations, Inc. Rapid accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use
US12448399B2 (en) 2023-01-26 2025-10-21 Arvinas Operations, Inc. Cereblon-based KRAS degrading PROTACs and uses related thereto
US12496301B2 (en) 2023-12-08 2025-12-16 Arvinas Operations, Inc. Use of androgen receptor degrader for the treatment of spinal and bulbar muscular atrophy

Also Published As

Publication number Publication date
JP2016106106A (ja) 2016-06-16
EP3599236A1 (en) 2020-01-29
PL3202461T3 (pl) 2019-07-31
PL3202460T3 (pl) 2019-12-31
CN102822165B (zh) 2015-02-25
ES2730763T3 (es) 2019-11-12
EP2536706B1 (en) 2017-06-14
US20200231567A1 (en) 2020-07-23
SMT201900420T1 (it) 2019-11-13
EP4289838A3 (en) 2024-03-13
US9828361B2 (en) 2017-11-28
MX337169B (es) 2016-02-16
NI201200132A (es) 2013-04-22
US8518972B2 (en) 2013-08-27
EP3202461B1 (en) 2018-12-26
ES2713482T3 (es) 2019-05-22
US20190135780A1 (en) 2019-05-09
JP6270944B2 (ja) 2018-01-31
RS56232B1 (sr) 2017-11-30
ME02766B (me) 2018-01-20
AU2011215877B2 (en) 2013-11-07
JP2017031165A (ja) 2017-02-09
IL248843B (en) 2019-12-31
EP3202460A1 (en) 2017-08-09
JP6215976B2 (ja) 2017-10-18
MX2012009237A (es) 2012-08-23
PT3202460T (pt) 2019-08-05
US9822094B2 (en) 2017-11-21
IL248843A0 (en) 2017-01-31
PT2536706T (pt) 2017-07-20
DK3202460T3 (da) 2019-07-29
LT3202460T (lt) 2019-10-10
HRP20171078T1 (hr) 2017-10-06
LT3202461T (lt) 2019-04-25
PL2536706T3 (pl) 2017-10-31
SMT201700360T1 (it) 2017-09-07
ES2738776T3 (es) 2020-01-27
SMT201900155T1 (it) 2019-05-10
HRP20190368T1 (hr) 2019-04-19
SI3202460T1 (sl) 2019-10-30
EP3106460A1 (en) 2016-12-21
NZ601289A (en) 2014-10-31
ES2956743T3 (es) 2023-12-27
EP3599236B1 (en) 2023-08-23
SG183257A1 (en) 2012-09-27
AU2011215877A1 (en) 2012-08-16
WO2011100380A1 (en) 2011-08-18
PH12014501082A1 (en) 2015-09-28
RS58523B1 (sr) 2019-04-30
ME03441B (me) 2020-01-20
UA114856C2 (uk) 2017-08-10
CN102822165A (zh) 2012-12-12
MX367522B (es) 2019-08-26
US20110196150A1 (en) 2011-08-11
NZ717149A (en) 2017-06-30
EP3202461A1 (en) 2017-08-09
US20160159772A1 (en) 2016-06-09
AU2011215877C1 (en) 2017-01-19
SG10201501062SA (en) 2015-04-29
CA2787823C (en) 2018-04-10
US10189814B2 (en) 2019-01-29
CY1121858T1 (el) 2020-10-14
RU2567753C2 (ru) 2015-11-10
CN104693193A (zh) 2015-06-10
ECSP12012098A (es) 2012-10-30
PH12014501082B1 (en) 2015-09-28
JP2013519675A (ja) 2013-05-30
DK2536706T3 (en) 2017-08-14
ES2638517T3 (es) 2017-10-23
CY1119177T1 (el) 2018-02-14
EP3202460B1 (en) 2019-06-12
HUE033009T2 (en) 2017-11-28
SG10202012179RA (en) 2021-01-28
DK3202461T3 (en) 2019-03-18
EP3106460B1 (en) 2019-04-10
US20220411402A1 (en) 2022-12-29
LT2536706T (lt) 2017-10-25
CR20120414A (es) 2012-10-31
KR101931468B1 (ko) 2018-12-20
PT3202461T (pt) 2019-03-19
KR101812356B1 (ko) 2017-12-26
AR081058A1 (es) 2012-06-06
HUE044652T2 (hu) 2019-11-28
CO6571916A2 (es) 2012-11-30
JP2017200944A (ja) 2017-11-09
SI3202461T1 (sl) 2019-05-31
EP2536706A1 (en) 2012-12-26
US20180037567A1 (en) 2018-02-08
UA115220C2 (uk) 2017-10-10
SI2536706T1 (sl) 2017-10-30
NZ700054A (en) 2016-03-31
US11414399B2 (en) 2022-08-16
CA2787823A1 (en) 2011-08-18
PH12012501607A1 (en) 2012-10-22
EP4289838A2 (en) 2023-12-13
CN104693193B (zh) 2018-09-18
US9309219B2 (en) 2016-04-12
KR20180000338A (ko) 2018-01-02
TR201903027T4 (tr) 2019-03-21
JP2016172746A (ja) 2016-09-29
IL220992A (en) 2016-11-30
RS59275B1 (sr) 2019-10-31
US20160159768A1 (en) 2016-06-09
CY1121729T1 (el) 2020-07-31
US10669257B2 (en) 2020-06-02
KR20130010888A (ko) 2013-01-29
HUE042011T2 (hu) 2019-06-28
US20130324518A1 (en) 2013-12-05
HRP20191312T1 (hr) 2019-10-18

Similar Documents

Publication Publication Date Title
JP2022538228A5 (ru)
JP2013520443A5 (ru)
CN103328447B (zh) 作为c-Met激酶抑制剂的化合物
RU2010119645A (ru) Замещенные гетероциклом пиперазинодигидротиенопиримидины
RU2015120478A (ru) Пери-карбинолы
RU2016130932A (ru) Производные хинолона как ингибиторы рецептора фактора роста фибробластов
RU2016137181A (ru) Противофиброзные пиридиноны
JP2014511893A5 (ru)
RU2012110246A (ru) Замещенные бензоазепины в качестве модуляторов toll-подобного рецептора
RU2013142012A (ru) 1,4 тиазепины/сульфоны в качестве ингибиторов васе1 и(или) васе2
JP2013510124A5 (ru)
RU2019138177A (ru) Производные 2-аминохинолина
RU2012121630A (ru) АЛЛОСТЕРИЧЕСКИЕ СРЕДСТВА ПОТЕНЦИРОВАНИЯ mGluR4 КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ НЕВРОЛОГИЧЕСКИХ ДИСФУНКЦИЙ
JP2013510178A5 (ru)
JP2017501205A5 (ru)
RU2016102036A (ru) Производное хинолина
JP2018501315A5 (ru)
AR093532A1 (es) Compuestos y composiciones para el tratamiento de enfermedades parasitarias
JPWO2016104617A1 (ja) キノリン誘導体
KR20030046509A (ko) 인지 장애의 치료를 위한 아세틸콜린에스테라제 저해제 및지에이비에이에이 역 작용물질의 조합 용도
RU2018114518A (ru) Новые бициклические соединения в качестве двойных ингибиторов аутотаксина (atx)/карбоангидразы (ca)
RU2016150326A (ru) Производные изоиндолина для применения в лечении вирусной инфекции
RU2017115809A (ru) Комбинированная терапия ингибиторами с-с хемокинового рецептора 9 (ccr9) и антителами, блокирующими альфа4бета7-интегрин
RU2014120477A (ru) Производные пиримидин-4-она и их применение в лечении, облегчении или профилактике вирусного заболевания
JP2012522766A5 (ru)