PE20221278A1 - Inhibidores de ras - Google Patents

Inhibidores de ras

Info

Publication number
PE20221278A1
PE20221278A1 PE2022000712A PE2022000712A PE20221278A1 PE 20221278 A1 PE20221278 A1 PE 20221278A1 PE 2022000712 A PE2022000712 A PE 2022000712A PE 2022000712 A PE2022000712 A PE 2022000712A PE 20221278 A1 PE20221278 A1 PE 20221278A1
Authority
PE
Peru
Prior art keywords
optionally substituted
hydrogen
alkyl
membered
cyano
Prior art date
Application number
PE2022000712A
Other languages
English (en)
Inventor
Elena S Koltun
James Cregg
Adrian L Gill
James Aggen
G Leslie Burnett
Jennifer Pitzen
Andreas Buckl
John E Knox
Yang Liu
Original Assignee
Revolution Medicines Inc
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 Revolution Medicines Inc filed Critical Revolution Medicines Inc
Publication of PE20221278A1 publication Critical patent/PE20221278A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
    • C07D245/04—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring 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
    • C07D498/12—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 three hetero rings
    • C07D498/18—Bridged systems
    • 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/504—Pyridazines; Hydrogenated pyridazines forming part of bridged ring systems
    • 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
    • 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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • 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
    • C07D498/22—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 four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Referida a un compuesto de formula (I), donde: A es -N(H o CH3)C(O)-(CH2)- donde el nitrogeno amino esta unido al atomo de carbono de - CH(R10)-, cicloalquileno de 3 a 6 miembros opcionalmente sustituido, heterocicloalquileno de 3 a 6 miembros opcionalmente sustituido, arileno de 6 miembros opcionalmente sustituido o heteroarileno de 5 a 10 miembros opcionalmente sustituido; B esta ausente, -CH(R9 ) -, >C=CR9R9' o >CR9R9' donde el carbono esta unido al carbono carbonilo de -N(R11)C(O)-, cicloalquileno de 3 a 6 miembros opcionalmente sustituido, heterocicloalquileno de 3 a 6 miembros opcionalmente sustituido, arileno de 6 miembros opcionalmente sustituido, o heteroarileno de 5 a 6 miembros; G es alquileno C1-C4 opcionalmente sustituido, alquenileno C1-C4 opcionalmente sustituido, heteroalquileno C1-C4 opcionalmente sustituido, -C(O)O-CH(R6 )- donde C esta unido a -C(R7R8 )-, - C(O)NH-CH(R6 )- donde C esta unido a -C(R7R8 )-, heteroalquileno C1-C4 opcionalmente sustituido o heteroarileno de 3 a 8 miembros; L esta ausente o es un enlazador; W es un grupo de reticulacion que comprende una vinilcetona, una vinil sulfona, una inona, un haloacetal o una alquinilsulfona; X 1 es alquileno C1-C2 opcionalmente sustituido, NR, O o S(O)n; X 2 es O o NH; X 3 es N o CH; n es 0, 1 o 2; R es hidrogeno, ciano, alquilo C1-C4 opcionalmente sustituido, entre otros; Y 1 es C, CH o N; Y 2 , Y 3 , Y 4 e Y 7 son, independientemente, C o N; Y 5 es CH, CH2 o N; Y 6 es C(O), CH, CH2 o N; R1 es ciano, alquilo C1-C6 opcionalmente sustituido, heteroalquilo C1-C6 opcionalmente sustituido, entre otros; R2 esta ausente, hidrogeno, alquilo C1-C6 opcionalmente sustituido, alquenilo C2-C6 opcionalmente sustituido, entre otros; R3 esta ausente, o R2 y R3 se combinan con el atomo al que estan unidos para formar un cicloalquilo de 3 a 8 miembros opcionalmente sustituido o un heterocicloalquilo de 3 a 14 miembros opcionalmente sustituido; R4 esta ausente, hidrogeno, halogeno, ciano o metilo opcionalmente sustituido con 1 a 3 halogenos; R5 es hidrogeno, alquilo C1-C4 opcionalmente sustituido con halogeno, ciano, hidroxi o alcoxi C1-C4, ciclopropilo o ciclobutilo; R6 es hidrogeno o metilo; R7 es hidrogeno, halogeno o alquilo C1-C3 opcionalmente sustituido, entre otros; R8 es hidrogeno, halogeno, hidroxi, ciano, alcoxi C1-C3 opcionalmente sustituido, alquilo C1-C3 opcionalmente sustituido, entre otros; R7a y R8a son, independientemente, hidrogeno, halo, alquilo C1-C3 opcionalmente sustituido, o se combinan con el carbono al que estan unidos para formar un carbonilo; R9 es H, F, alquilo C1-C6 opcionalmente sustituido, heteroalquilo C1-C6 opcionalmente sustituido, entre otros; R9' es hidrogeno o alquilo C1-C6 opcionalmente sustituido; R10 es hidrogeno, halo, hidroxi, alcoxi C1-C3 o alquilo C1-C3; R10a es hidrogeno o halo; R11 es hidrogeno o alquilo C1-C3; y R21 es hidrogeno o alquilo C1-C3. Dichos compuestos inhiben las proteinas Ras y son utiles en el tratamiento de canceres.
PE2022000712A 2019-11-04 2020-11-04 Inhibidores de ras PE20221278A1 (es)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201962930355P 2019-11-04 2019-11-04
US201962951652P 2019-12-20 2019-12-20
US202063000357P 2020-03-26 2020-03-26
US202063011636P 2020-04-17 2020-04-17
US202063043588P 2020-06-24 2020-06-24
PCT/US2020/058841 WO2021091982A1 (en) 2019-11-04 2020-11-04 Ras inhibitors

Publications (1)

Publication Number Publication Date
PE20221278A1 true PE20221278A1 (es) 2022-09-05

Family

ID=73598995

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2022000712A PE20221278A1 (es) 2019-11-04 2020-11-04 Inhibidores de ras

Country Status (15)

Country Link
US (2) US11566007B2 (es)
EP (1) EP4054719A1 (es)
JP (1) JP2022553858A (es)
KR (1) KR20220109408A (es)
CN (2) CN115894606A (es)
AU (1) AU2020379734A1 (es)
CA (1) CA3159561A1 (es)
CL (1) CL2023000974A1 (es)
CO (1) CO2022006033A2 (es)
CR (1) CR20220241A (es)
IL (1) IL292644A (es)
MX (1) MX2022005359A (es)
PE (1) PE20221278A1 (es)
TW (1) TW202132316A (es)
WO (1) WO2021091982A1 (es)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3790551A4 (en) 2018-05-07 2022-03-09 Mirati Therapeutics, Inc. KRAS G12C INHIBITORS
EP3908283A4 (en) 2019-01-10 2022-10-12 Mirati Therapeutics, Inc. KRAS G12C INHIBITORS
JP2022546043A (ja) 2019-08-29 2022-11-02 ミラティ セラピューティクス， インコーポレイテッド Ｋｒａｓ ｇ１２ｄ阻害剤
WO2021061749A1 (en) 2019-09-24 2021-04-01 Mirati Therapeutics, Inc. Combination therapies
JP2022553859A (ja) 2019-11-04 2022-12-26 レボリューション メディシンズ インコーポレイテッド Ｒａｓ阻害剤
CA3159561A1 (en) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Ras inhibitors
WO2021091967A1 (en) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Ras inhibitors
CN115135315A (zh) 2019-12-20 2022-09-30 米拉蒂治疗股份有限公司 Sos1抑制剂
CA3194067A1 (en) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Ras inhibitors
US20230107642A1 (en) 2020-12-18 2023-04-06 Erasca, Inc. Tricyclic pyridones and pyrimidones
PE20240088A1 (es) 2021-05-05 2024-01-16 Revolution Medicines Inc Inhibidores de ras
WO2022235866A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Covalent ras inhibitors and uses thereof
AR125787A1 (es) 2021-05-05 2023-08-16 Revolution Medicines Inc Inhibidores de ras
IL308771A (en) 2021-05-25 2024-01-01 Revolution Medicines Inc Methods of inhibiting RAS
WO2023015559A1 (en) * 2021-08-13 2023-02-16 Nutshell Biotech (Shanghai) Co., Ltd. Macrocycle compounds as inhibitors of ras
AR126854A1 (es) 2021-08-27 2023-11-22 Hoffmann La Roche Compuestos macrocíclicos para el tratamiento de cáncer
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
WO2023086341A1 (en) 2021-11-09 2023-05-19 Biomea Fusion, Inc. Inhibitors of kras
CN118525020A (zh) * 2021-12-07 2024-08-20 赛诺哈勃药业（成都）有限公司 具有clk和dyrk抑制活性的化合物、其制备方法及用途
TW202340214A (zh) 2021-12-17 2023-10-16 美商健臻公司 做為shp2抑制劑之吡唑并吡𠯤化合物
WO2023133543A1 (en) 2022-01-10 2023-07-13 Revolution Medicines, Inc. Ras inhibitors
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
WO2023172940A1 (en) * 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
WO2023205701A1 (en) 2022-04-20 2023-10-26 Kumquat Biosciences Inc. Macrocyclic heterocycles and uses thereof
WO2023208005A1 (en) * 2022-04-25 2023-11-02 Hansoh Bio Llc Cyclic compounds, preparation methods and medicinal uses thereof
WO2023232776A1 (en) * 2022-06-01 2023-12-07 F. Hoffmann-La Roche Ag Haloindole macrocyclic compounds for the treatment of cancer
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
TW202408507A (zh) * 2022-07-04 2024-03-01 瑞士商赫孚孟拉羅股份公司 用於治療癌症之鹵炔基化合物
WO2024008834A1 (en) * 2022-07-08 2024-01-11 F. Hoffmann-La Roche Ag Macrocycle compounds useful as kras inhibitors
WO2024040131A1 (en) 2022-08-17 2024-02-22 Treeline Biosciences, Inc. Pyridopyrimidine kras inhibitors
WO2024060966A1 (zh) * 2022-09-19 2024-03-28 杭州阿诺生物医药科技有限公司 一种pan-KRAS抑制剂化合物
WO2024067857A1 (zh) * 2022-09-29 2024-04-04 南京明德新药研发有限公司 大环衍生物及其应用
WO2024081363A1 (en) 2022-10-12 2024-04-18 Revolution Medicines, Inc. Composition comprising a first ras inhibitor, second ras inhibitor and a shp2 inhibitor for use in the treatment of cancer
WO2024149819A1 (en) * 2023-01-13 2024-07-18 F. Hoffmann-La Roche Ag Sulfonylvinyl compounds for the treatment of cancer
WO2024169914A1 (en) * 2023-02-14 2024-08-22 F. Hoffmann-La Roche Ag Tricyclic compounds for the treatment of cancer
WO2024173761A1 (en) * 2023-02-17 2024-08-22 Ikena Oncology, Inc. Combinations comprising mek inhibitors for use in the treatment of cancer
WO2024206858A1 (en) * 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
WO2024211663A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors

Family Cites Families (321)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0314861A1 (en) 1984-10-04 1989-05-10 Sandoz Ag Labeled derivatives of cyclosporins
EP0194972B1 (en) 1985-03-11 1992-07-29 Sandoz Ag Novel cyclosporins
GB8827305D0 (en) 1988-11-23 1988-12-29 British Bio Technology Compounds
US6905680B2 (en) 1988-11-23 2005-06-14 Genetics Institute, Inc. Methods of treating HIV infected subjects
US6534055B1 (en) 1988-11-23 2003-03-18 Genetics Institute, Inc. Methods for selectively stimulating proliferation of T cells
US5858358A (en) 1992-04-07 1999-01-12 The United States Of America As Represented By The Secretary Of The Navy Methods for selectively stimulating proliferation of T cells
US6352694B1 (en) 1994-06-03 2002-03-05 Genetics Institute, Inc. Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells
ATE113606T1 (de) 1989-04-15 1994-11-15 Nippon Chemiphar Co Peptide und diese peptide enthaltende wirkstoffe gegen dementia.
PT98990A (pt) 1990-09-19 1992-08-31 American Home Prod Processo para a preparacao de esteres de acidos carboxilicos de rapamicina
US5120842A (en) 1991-04-01 1992-06-09 American Home Products Corporation Silyl ethers of rapamycin
US5100883A (en) 1991-04-08 1992-03-31 American Home Products Corporation Fluorinated esters of rapamycin
US5118678A (en) 1991-04-17 1992-06-02 American Home Products Corporation Carbamates of rapamycin
WO1992020642A1 (en) 1991-05-10 1992-11-26 Rhone-Poulenc Rorer International (Holdings) Inc. Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase
US5118677A (en) 1991-05-20 1992-06-02 American Home Products Corporation Amide esters of rapamycin
NZ243082A (en) 1991-06-28 1995-02-24 Ici Plc 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof
US5151413A (en) 1991-11-06 1992-09-29 American Home Products Corporation Rapamycin acetals as immunosuppressant and antifungal agents
GB9125660D0 (en) 1991-12-03 1992-01-29 Smithkline Beecham Plc Novel compound
AU661533B2 (en) 1992-01-20 1995-07-27 Astrazeneca Ab Quinazoline derivatives
EP0562853B1 (en) 1992-03-27 1996-06-05 American Home Products Corporation 29-Demethoxyrapamycin for inducing immunosuppression
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
ZA935112B (en) 1992-07-17 1994-02-08 Smithkline Beecham Corp Rapamycin derivatives
ZA935111B (en) 1992-07-17 1994-02-04 Smithkline Beecham Corp Rapamycin derivatives
US5256790A (en) 1992-08-13 1993-10-26 American Home Products Corporation 27-hydroxyrapamycin and derivatives thereof
GB9221220D0 (en) 1992-10-09 1992-11-25 Sandoz Ag Organic componds
US5258389A (en) 1992-11-09 1993-11-02 Merck & Co., Inc. O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives
DK0669929T3 (da) 1992-11-13 2007-01-29 Immunex Corp Elk-ligand, et cytokin
US5455258A (en) 1993-01-06 1995-10-03 Ciba-Geigy Corporation Arylsulfonamido-substituted hydroxamic acids
GB9303681D0 (en) 1993-02-24 1993-04-14 Pitman Moore Inc Vaccines
US5516658A (en) 1993-08-20 1996-05-14 Immunex Corporation DNA encoding cytokines that bind the cell surface receptor hek
ES2240259T3 (es) 1993-09-20 2005-10-16 The Leland Stanford Junior University Produccion recombinante de poliquetidos aromaticos.
US5612340A (en) 1993-10-01 1997-03-18 Ciba-Geigy Corporation Pyrimidineamine derivatives and processes for the preparation thereof
US5656643A (en) 1993-11-08 1997-08-12 Rhone-Poulenc Rorer Pharmaceuticals Inc. Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase
WO1995014023A1 (en) 1993-11-19 1995-05-26 Abbott Laboratories Semisynthetic analogs of rapamycin (macrolides) being immunomodulators
JP3745772B2 (ja) 1993-12-17 2006-02-15 ノバルティス アクチエンゲゼルシャフト 免疫抑制剤として有用なラパマイシン誘導体
US5700823A (en) 1994-01-07 1997-12-23 Sugen, Inc. Treatment of platelet derived growth factor related disorders such as cancers
IL112248A0 (en) 1994-01-25 1995-03-30 Warner Lambert Co Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them
IL112249A (en) 1994-01-25 2001-11-25 Warner Lambert Co Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds
AU2096895A (en) 1994-03-07 1995-09-25 Sugen, Incorporated Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof
IL112873A (en) 1994-03-08 2005-03-20 Wyeth Corp Rapamycin-fkbp12 binding proteins, their isolation and their use
EP1464706A3 (en) 1994-04-15 2004-11-03 Amgen Inc., HEK5, HEK7, HEK8, HEK11, EPH-like receptor protein tyrosine kinases
DE59500788D1 (de) 1994-05-03 1997-11-20 Ciba Geigy Ag Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
GB9410142D0 (en) 1994-05-20 1994-07-06 Univ Warwick Carbapenems
US7175843B2 (en) 1994-06-03 2007-02-13 Genetics Institute, Llc Methods for selectively stimulating proliferation of T cells
US6303769B1 (en) 1994-07-08 2001-10-16 Immunex Corporation Lerk-5 dna
US5919905A (en) 1994-10-05 1999-07-06 Immunex Corporation Cytokine designated LERK-6
GB9524630D0 (en) 1994-12-24 1996-01-31 Zeneca Ltd Chemical compounds
US6057124A (en) 1995-01-27 2000-05-02 Amgen Inc. Nucleic acids encoding ligands for HEK4 receptors
US5863949A (en) 1995-03-08 1999-01-26 Pfizer Inc Arylsulfonylamino hydroxamic acid derivatives
EP3103799B1 (en) 1995-03-30 2018-06-06 OSI Pharmaceuticals, LLC Quinazoline derivatives
WO1996031510A1 (en) 1995-04-03 1996-10-10 Novartis Ag Pyrazole derivatives and processes for the preparation thereof
EP0821671B1 (en) 1995-04-20 2000-12-27 Pfizer Inc. Arylsulfonyl hydroxamic acid derivatives as mmp and tnf inhibitors
GB9508538D0 (en) 1995-04-27 1995-06-14 Zeneca Ltd Quinazoline derivatives
US7067318B2 (en) 1995-06-07 2006-06-27 The Regents Of The University Of Michigan Methods for transfecting T cells
US6692964B1 (en) 1995-05-04 2004-02-17 The United States Of America As Represented By The Secretary Of The Navy Methods for transfecting T cells
US5747498A (en) 1996-05-28 1998-05-05 Pfizer Inc. Alkynyl and azido-substituted 4-anilinoquinazolines
US5650415A (en) 1995-06-07 1997-07-22 Sugen, Inc. Quinoline compounds
DK0833828T3 (da) 1995-06-09 2003-03-17 Novartis Ag Rapamycinderivater
US5624677A (en) 1995-06-13 1997-04-29 Pentech Pharmaceuticals, Inc. Controlled release of drugs delivered by sublingual or buccal administration
US6124453A (en) 1995-07-04 2000-09-26 Novartis Ag Macrolides
CA2224435C (en) 1995-07-06 2008-08-05 Novartis Ag Pyrrolopyrimidines and processes for the preparation thereof
AR004010A1 (es) 1995-10-11 1998-09-30 Glaxo Group Ltd Compuestos heterociclicos
GB9523675D0 (en) 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
DK0780386T3 (da) 1995-12-20 2003-02-03 Hoffmann La Roche Matrixmetalloproteaseinhibitorer
WO1997027199A1 (en) 1996-01-23 1997-07-31 Novartis Ag Pyrrolopyrimidines and processes for their preparation
JP3406763B2 (ja) 1996-01-30 2003-05-12 東レ・ダウコーニング・シリコーン株式会社 シリコーンゴム組成物
GB9603095D0 (en) 1996-02-14 1996-04-10 Zeneca Ltd Quinazoline derivatives
GB9603097D0 (en) 1996-02-14 1996-04-10 Zeneca Ltd Quinazoline compounds
DE19629652A1 (de) 1996-03-06 1998-01-29 Thomae Gmbh Dr K 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE19608588A1 (de) 1996-03-06 1997-09-11 Thomae Gmbh Dr K Pyrimido [5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
BR9709443B1 (pt) 1996-03-15 2009-05-05 n-7-heterociclil-pirrol[2,3-d]pirimidinas, bem como composições farmacêuticas compreendendo as mesmas.
IL126351A0 (en) 1996-04-12 1999-05-09 Warner Lambert Co Irreversible inhibitors of tyrosine kinases
GB9607729D0 (en) 1996-04-13 1996-06-19 Zeneca Ltd Quinazoline derivatives
JP2000512990A (ja) 1996-06-24 2000-10-03 ファイザー・インク 過増殖性疾患を処置するためのフェニルアミノ置換三環式誘導体
CA2259463A1 (en) 1996-07-05 1998-01-15 Biotica Technology Limited Polyketides and their synthesis
EP0818442A3 (en) 1996-07-12 1998-12-30 Pfizer Inc. Cyclic sulphone derivatives as inhibitors of metalloproteinases and of the production of tumour necrosis factor
EP0937082A2 (en) 1996-07-12 1999-08-25 Ariad Pharmaceuticals, Inc. Materials and method for treating or preventing pathogenic fungal infection
HRP970371A2 (en) 1996-07-13 1998-08-31 Kathryn Jane Smith Heterocyclic compounds
US6207669B1 (en) 1996-07-13 2001-03-27 Glaxo Wellcome Inc. Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors
DK0912559T3 (da) 1996-07-13 2003-03-10 Glaxo Group Ltd Kondenserede heterocykliske forbindelser som proteintyrosinkinaseinhibitorer
TR199900066T2 (xx) 1996-07-18 1999-04-21 Pfizer Inc. Matriks metalloproteazlar�n fosfinat bazl� inhibit�rleri
US6111090A (en) 1996-08-16 2000-08-29 Schering Corporation Mammalian cell surface antigens; related reagents
EP1947183B1 (en) 1996-08-16 2013-07-17 Merck Sharp & Dohme Corp. Mammalian cell surface antigens; related reagents
PL331895A1 (en) 1996-08-23 1999-08-16 Pfizer Arylosulphonylamino derivatives of hydroxamic acid
EP0938486B1 (en) 1996-08-23 2008-01-16 Novartis AG Substituted pyrrolopyrimidines and processes for their preparation
SE9603465D0 (sv) 1996-09-23 1996-09-23 Astra Ab New compounds
WO1998014450A1 (en) 1996-10-02 1998-04-09 Novartis Ag Pyrimidine derivatives and processes for the preparation thereof
AU4779897A (en) 1996-10-02 1998-04-24 Novartis Ag Fused pyrazole derivatives and processes for their preparation
ID18494A (id) 1996-10-02 1998-04-16 Novartis Ag Turunan pirazola leburan dan proses pembuatannya
EP0837063A1 (en) 1996-10-17 1998-04-22 Pfizer Inc. 4-Aminoquinazoline derivatives
GB9621757D0 (en) 1996-10-18 1996-12-11 Ciba Geigy Ag Phenyl-substituted bicyclic heterocyclyl derivatives and their use
US6077864A (en) 1997-01-06 2000-06-20 Pfizer Inc. Cyclic sulfone derivatives
BR9807815A (pt) 1997-02-03 2000-03-08 Pfizer Prod Inc Derivados de ácido arilsulfonilamino-hidroxâmico
WO1998033798A2 (en) 1997-02-05 1998-08-06 Warner Lambert Company Pyrido[2,3-d]pyrimidines and 4-amino-pyrimidines as inhibitors of cell proliferation
WO1998034915A1 (en) 1997-02-07 1998-08-13 Pfizer Inc. N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases
HUP0000657A3 (en) 1997-02-11 2000-10-30 Pfizer N-arylsulfonyl-piperidine, -morpholine hydroxamic acid derivatives and pharmaceutical compositions containing them
CO4950519A1 (es) 1997-02-13 2000-09-01 Novartis Ag Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion
US6902913B2 (en) 1997-04-30 2005-06-07 Kosan Biosciences, Inc. Recombinant narbonolide polyketide synthase
US6150395A (en) 1997-05-30 2000-11-21 The Regents Of The University Of California Indole-3-carbinol (I3C) derivatives and methods
AU8689298A (en) 1997-08-05 1999-03-01 Sugen, Inc. Tricyclic quinoxaline derivatives as protein tyrosine kinase inhibitors
EA002490B1 (ru) 1997-08-08 2002-06-27 Пфайзер Продактс Инк. Производные арилоксиарилсульфониламиногидроксамовой кислоты
EP1025228A4 (en) 1997-10-21 2002-09-18 Human Genome Sciences Inc HUMAN PROTEIN TR11, TR11SV1 AND TR11SV2 SIMILAR TO THE TUMOR NECROSIS FACTOR RECEPTOR
GB9725782D0 (en) 1997-12-05 1998-02-04 Pfizer Ltd Therapeutic agents
US6153383A (en) 1997-12-09 2000-11-28 Verdine; Gregory L. Synthetic transcriptional modulators and uses thereof
RS49779B (sr) 1998-01-12 2008-06-05 Glaxo Group Limited, Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze
GB9800575D0 (en) 1998-01-12 1998-03-11 Glaxo Group Ltd Heterocyclic compounds
JP2002502607A (ja) 1998-02-09 2002-01-29 ジェネンテク・インコーポレイテッド 新規な腫瘍壊死因子レセプター相同体及びそれをコードする核酸
DE69940808D1 (de) 1998-03-04 2009-06-10 Bristol Myers Squibb Co Heterocyclen substituierte imidazopyrazine als protein- tyrosin-kinase-inhibitoren
PA8469501A1 (es) 1998-04-10 2000-09-29 Pfizer Prod Inc Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico
PA8469401A1 (es) 1998-04-10 2000-05-24 Pfizer Prod Inc Derivados biciclicos del acido hidroxamico
ATE473759T1 (de) 1998-05-22 2010-07-15 Univ Leland Stanford Junior Bifunktionelle moleküle sowie darauf basierende therapien.
AU759226B2 (en) 1998-05-29 2003-04-10 Sugen, Inc. Pyrrole substituted 2-indolinone protein kinase inhibitors
UA60365C2 (uk) 1998-06-04 2003-10-15 Пфайзер Продактс Інк. Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця
CA2336848A1 (en) 1998-07-10 2000-01-20 Merck & Co., Inc. Novel angiogenesis inhibitors
AU760020B2 (en) 1998-08-31 2003-05-08 Merck & Co., Inc. Novel angiogenesis inhibitors
AU773517B2 (en) 1998-10-02 2004-05-27 Kosan Biosciences, Inc. Polyketide synthase enzymes and recombinant DNA constructs therefor
US6686454B1 (en) 1998-10-09 2004-02-03 Isotechnika, Inc. Antibodies to specific regions of cyclosporine related compounds
US6114361A (en) 1998-11-05 2000-09-05 Pfizer Inc. 5-oxo-pyrrolidine-2-carboxylic acid hydroxamide derivatives
JP2002536014A (ja) 1999-02-09 2002-10-29 ザ、ボード、オブ、トラスティーズ、オブ、ザ、リーランド、スタンフォード、ジュニア、ユニバーシティ ポリケチドシンターゼモジュールの有効性を媒介する方法
PT1165085E (pt) 1999-03-30 2006-10-31 Novartis Ag Derivados de ftalazina para tratar doencas inflamatorias
GB9912961D0 (en) 1999-06-03 1999-08-04 Pfizer Ltd Metalloprotease inhibitors
NZ516258A (en) 1999-06-07 2004-02-27 Immunex Corp Tek antagonists
US6521424B2 (en) 1999-06-07 2003-02-18 Immunex Corporation Recombinant expression of Tek antagonists
EP1196186B1 (en) 1999-07-12 2007-10-31 Genentech, Inc. Promotion or inhibition of angiogenesis and cardiovascularization by tumor necrosis factor ligand/receptor homologs
ES2219388T3 (es) 1999-08-24 2004-12-01 Ariad Gene Therapeutics, Inc. 28-epi-rapalogos.
PT1244647E (pt) 1999-11-05 2006-10-31 Astrazeneca Ab Derivados de quinazolina como inibidores de vegf
GB9927191D0 (en) 1999-11-17 2000-01-12 Angeletti P Ist Richerche Bio Methods and means for regulation of gene expression
US7220552B1 (en) 1999-11-19 2007-05-22 The Board Of Trustees Of The Leland Stanford Junior University Bifunctional molecules and their use in the disruption of protein-protein interactions
EP1230353A4 (en) 1999-11-19 2002-11-06 Univ Leland Stanford Junior BIFUNCTIONAL MOLECULES AND THEIR USE FOR INHIBITING PROTEIN-PROTEIN INTERACTIONS
AU1928501A (en) 1999-11-24 2001-06-04 Sugen, Inc. Formulations for pharmaceutical agents ionizable as free acids or free bases
US6515004B1 (en) 1999-12-15 2003-02-04 Bristol-Myers Squibb Company N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases
US6727225B2 (en) 1999-12-20 2004-04-27 Immunex Corporation TWEAK receptor
EP1255840A2 (en) 2000-02-08 2002-11-13 Norges Teknisk Naturvitenskapelige Universitet Gene cluster encoding a nystatin polyketide synthase and its manipulation and utility
IL151287A0 (en) 2000-02-24 2003-04-10 Xcyte Therapies Inc A method for stimulation and concentrating cells
US7572631B2 (en) 2000-02-24 2009-08-11 Invitrogen Corporation Activation and expansion of T cells
US6797514B2 (en) 2000-02-24 2004-09-28 Xcyte Therapies, Inc. Simultaneous stimulation and concentration of cells
US6867041B2 (en) 2000-02-24 2005-03-15 Xcyte Therapies, Inc. Simultaneous stimulation and concentration of cells
DE60127656T2 (de) 2000-02-25 2007-12-20 Immunex Corp., Seattle Integrin antagonisten
MXPA02000823A (es) 2000-05-23 2002-07-30 Vertex Pharma Inhibidores de caspasa y uso de los mismos.
US7176037B2 (en) 2000-07-13 2007-02-13 The Scripps Research Institute Labeled peptides, proteins and antibodies and processes and intermediates useful for their preparation
US6630500B2 (en) 2000-08-25 2003-10-07 Cephalon, Inc. Selected fused pyrrolocarbazoles
MXPA03005696A (es) 2000-12-21 2003-10-06 Glaxo Group Ltd Pirimidinaminas como moduladores de angiogenesis.
US20020147198A1 (en) 2001-01-12 2002-10-10 Guoqing Chen Substituted arylamine derivatives and methods of use
US7105682B2 (en) 2001-01-12 2006-09-12 Amgen Inc. Substituted amine derivatives and methods of use
US6878714B2 (en) 2001-01-12 2005-04-12 Amgen Inc. Substituted alkylamine derivatives and methods of use
US6995162B2 (en) 2001-01-12 2006-02-07 Amgen Inc. Substituted alkylamine derivatives and methods of use
US7102009B2 (en) 2001-01-12 2006-09-05 Amgen Inc. Substituted amine derivatives and methods of use
US20030153053A1 (en) 2001-08-06 2003-08-14 Ralph Reid Methods for altering polyketide synthase genes
US6809077B2 (en) 2001-10-12 2004-10-26 Enanta Pharmaceuticals, Inc. Cyclosporin analogs for the treatment of autoimmune diseases
US6987090B2 (en) 2002-05-09 2006-01-17 Lg Household & Health Care Ltd. Use of 3-position cyclosporin derivatives for hair growth
US7307088B2 (en) 2002-07-09 2007-12-11 Amgen Inc. Substituted anthranilic amide derivatives and methods of use
TWI329112B (en) 2002-07-19 2010-08-21 Bristol Myers Squibb Co Novel inhibitors of kinases
US7012065B2 (en) 2003-02-07 2006-03-14 Enanta Pharmaceuticals, Inc. Cyclosporins for the treatment of immune disorders
EP1477563A3 (en) 2003-05-16 2004-11-24 Wyeth Cloning genes from streptomyces cyaneogriseus subsp.noncyanogenus for biosynthesis of antibiotics and methods of use
BRPI0410785A (pt) 2003-05-23 2006-06-20 Wyeth Corp molécula de ácido nucleico isolada, célula hospedeira, animal transgênico não humano, proteìna isolada, oligonucleotìdeo anti-sentido, molécula de sirna, anticorpo isolado, métodos de triagem quanto aos compostos de teste capazes de inibir, de intensificar ou imitar a interação do gitrl com o gitr, para diagnosticar doenças, para tratar um paciente em risco ou diagnosticado com uma doença, para induzir e para inibir a proliferação de uma população celular contendo células t efetoras, de bloquear a supressão e de supressão de uma população celular que inclua células t efetoras na presença de células t reguladoras cd4+cd25+, e para tratar uma doença, composição farmacêutica, e, adjuvante de vacina
ES2316995T3 (es) 2003-07-08 2009-04-16 Novartis Ag Uso de rapamicina y derivados de rapamicida para el tratamiento de la perdida osea.
WO2005016252A2 (en) 2003-07-11 2005-02-24 Ariad Gene Therapeutics, Inc. Phosphorus-containing macrocycles
US20050048054A1 (en) 2003-07-11 2005-03-03 Shino Hanabuchi Lymphocytes; methods
AR045134A1 (es) 2003-07-29 2005-10-19 Smithkline Beecham Plc Compuesto de 1h - imidazo [4,5-c] piridin-ilo, composicion farmaceutica que lo comprende, proceso para prepararla, su uso para preparar dicha composicion farmaceutica, combinacion farmaceutica, uso de la combinacion farmaceutica para la preparacion de un medicamento, procedimientos para preparar dic
CA2533320A1 (en) 2003-08-15 2006-02-24 Novartis Ag 2, 4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders
JP2007518399A (ja) 2003-12-02 2007-07-12 ジェンザイム コーポレイション 肺癌を診断および治療する組成物並びに方法
WO2005094314A2 (en) 2004-03-26 2005-10-13 The Burnham Institute Modulators of shp2 tyrosine phosphatase and their use in the treatment of body weight disorders
GB0409799D0 (en) 2004-04-30 2004-06-09 Isis Innovation Method of generating improved immune response
WO2006083289A2 (en) 2004-06-04 2006-08-10 Duke University Methods and compositions for enhancement of immunity by in vivo depletion of immunosuppressive cell activity
PL1786785T3 (pl) 2004-08-26 2010-08-31 Pfizer Enancjomerycznie czyste związki aminoheteroarylowe jako kinazy białkowe
TW200626610A (en) 2004-10-13 2006-08-01 Wyeth Corp Analogs of 17-hydroxywortmannin as PI3K inhibitors
DK1866339T3 (da) 2005-03-25 2013-09-02 Gitr Inc GTR-bindende molekyler og anvendelser heraf
NZ563193A (en) 2005-05-09 2010-05-28 Ono Pharmaceutical Co Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
CN101267824A (zh) 2005-09-20 2008-09-17 辉瑞产品公司 使用酪氨酸激酶抑制剂的治疗剂型和方法
WO2007133822A1 (en) 2006-01-19 2007-11-22 Genzyme Corporation Gitr antibodies for the treatment of cancer
BRPI0708299A2 (pt) 2006-02-27 2011-05-24 Univ Leland Stanford Junior composições e métodos para o transporte de moléculas com propriedades melhoradas de liberação através de barreiras biológicas
US20070203168A1 (en) 2006-02-28 2007-08-30 Zhao Jonathon Z Isomers of rapamycin and 42-Epi-rapamycin, methods of making and using the same
WO2007117699A2 (en) 2006-04-07 2007-10-18 University Of South Florida Inhibition of shp2/ptpn11 protein tyrosine phosphatase by nsc-87877, nsc-117199 and their analogs
US7601852B2 (en) 2006-05-11 2009-10-13 Kosan Biosciences Incorporated Macrocyclic kinase inhibitors
MY180595A (en) 2006-12-07 2020-12-03 Genentech Inc Phosphoinositide 3-kinase inhibitor compounds and methods of use
WO2008124815A1 (en) 2007-04-10 2008-10-16 University Of South Florida Method of activating nk cells
CN101801413A (zh) 2007-07-12 2010-08-11 托勒克斯股份有限公司 采用gitr结合分子的联合疗法
ES2537352T3 (es) 2007-09-12 2015-06-05 Genentech, Inc. Combinaciones de compuestos inhibidores de fosfoinositida 3-cinasa y agentes quimioterapéuticos, y metodos para su uso
WO2009049098A2 (en) 2007-10-09 2009-04-16 Indiana University Research & Technology Corporation Materials and methods for regulating the activity of phosphatases
KR100945483B1 (ko) 2007-10-25 2010-03-05 이화여자대학교 산학협력단 ｐｉｋＤ 조절유전자의 발현벡터를 이용한 스트렙토미세스베네주엘라에（Ｓｔｒｅｐｔｏｍｙｃｅｓｖｅｎｅｚｕｅｌａｅ）에서폴리케타이드（ｐｏｌｙｋｅｔｉｄｅ）의 생산성 증가방법
WO2009055730A1 (en) 2007-10-25 2009-04-30 Genentech, Inc. Process for making thienopyrimidine compounds
GB0805363D0 (en) 2008-03-20 2008-04-30 Sinvent As Novel NRPS-PKS gene cluster and its manipulation and utility
WO2009135000A2 (en) 2008-04-30 2009-11-05 H. Lee Moffitt Cancer Center And Research Institute, Inc. Inhibition of shp2/ptpn11 protein tyrosine phosphatase by nsc-117199 and analogs
CN102203258A (zh) 2008-07-02 2011-09-28 新兴产品开发西雅图有限公司 TGF-β拮抗剂多靶点结合蛋白
US9174969B2 (en) 2008-07-21 2015-11-03 University Of South Florida Indoline scaffold SHP-2 inhibitors and cancer treatment method
WO2010030002A1 (ja) 2008-09-12 2010-03-18 国立大学法人三重大学 外来性ｇｉｔｒリガンド発現細胞
EP2352526A1 (en) 2008-09-19 2011-08-10 Protox Therapeutics Inc. Treating cancer stem cells using targeted cargo proteins
US8962329B2 (en) 2008-09-24 2015-02-24 Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences Gene cluster
WO2010088573A1 (en) 2009-01-30 2010-08-05 Enanta Pharmaceuticals, Inc. Cyclosporin analogues for preventing or treating hepatitis c infection
HUE061640T2 (hu) 2009-04-06 2023-07-28 Wyeth Llc Gyógykezelési rendszer mellrákhoz neratinib alkalmazásával
WO2010121212A2 (en) 2009-04-17 2010-10-21 H. Lee Moffit Cancer Center And Research Institute, Inc. Indoline scaffold shp-2 inhibitors and method of treating cancer
US9163330B2 (en) 2009-07-13 2015-10-20 President And Fellows Of Harvard College Bifunctional stapled polypeptides and uses thereof
US8664186B2 (en) 2009-07-24 2014-03-04 Universite De Lorraine Stambomycin and derivatives, their production and their uses as drugs
US9567318B2 (en) 2009-08-17 2017-02-14 Memorial Sloan-Kettering Cancer Center Substituted pyrimidine compounds and uses thereof
US8709424B2 (en) 2009-09-03 2014-04-29 Merck Sharp & Dohme Corp. Anti-GITR antibodies
EP2480565A4 (en) 2009-09-22 2014-01-01 Aileron Therapeutics Inc PEPTIDOMIMETIC MACROCYCLES
WO2011049157A1 (ja) 2009-10-22 2011-04-28 ペプチドリーム株式会社 ペプチド翻訳合成におけるrapidディスプレイ法
GB0919054D0 (en) 2009-10-30 2009-12-16 Isis Innovation Treatment of obesity
ME02505B (me) 2009-12-29 2017-02-20 Aptevo Res & Development Llc Heterodimerni vezujući proteini i njihove upotrebe
ES2541853T3 (es) 2010-02-09 2015-07-27 Neurovive Pharmaceutical Ab Compuestos basados en sangliferina
US8637684B2 (en) 2010-05-12 2014-01-28 Wisconsin Alumni Research Foundation Tautomycetin and tautomycetin analog biosynthesis
WO2012041524A1 (en) 2010-10-01 2012-04-05 Max-Delbrück-Centrum Für Molekulare Medizin (Mdc) Hydrazonopyrazolones as protein tyrosine phosphatase inhibitors
CA2819501C (en) 2010-11-30 2020-03-31 The Johns Hopkins University Hybrid cyclic libraries and screens thereof
UY33775A (es) 2010-12-10 2012-07-31 Gilead Sciences Inc Inhibidores macrocíclicos de virus flaviviridae, composiciones farmacéuticas que los comprenden y sus usos
US9428845B1 (en) 2010-12-28 2016-08-30 Warp Drive Bio, Inc. Identifying new therapeutic agents
CA2830516C (en) 2011-03-23 2017-01-24 Amgen Inc. Fused tricyclic dual inhibitors of cdk 4/6 and flt3
KR101953210B1 (ko) 2011-05-19 2019-02-28 푼다시온 센트로 나시오날 드 인베스티가시오네스 온콜로기카스 카를로스Ⅲ 단백질 키나아제 억제제로서의 대환식 화합물
US9260484B2 (en) 2011-06-15 2016-02-16 Ohio State Innovation Foundation Small molecule composite surfaces as inhibitors of protein-protein interactions
WO2013001310A1 (en) 2011-06-30 2013-01-03 Centro Nacional De Investigaciones Oncológicas (Cnio) Macrocyclic compounds and their use as cdk8 inhibitors
TW201311689A (zh) 2011-08-05 2013-03-16 必治妥美雅史谷比公司 作為因子ｘｉａ抑制劑之新穎巨環化合物
DE102011111991A1 (de) 2011-08-30 2013-02-28 Lead Discovery Center Gmbh Neue Cyclosporin-Derivate
US20130108641A1 (en) 2011-09-14 2013-05-02 Sanofi Anti-gitr antibodies
JP6399660B2 (ja) 2012-04-10 2018-10-03 ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア 癌治療用組成物および方法
MX2014014766A (es) 2012-06-08 2015-05-11 Gilead Sciences Inc Inhibidores macrociclicos de virus flaviviridae.
AR091279A1 (es) 2012-06-08 2015-01-21 Gilead Sciences Inc Inhibidores macrociclicos de virus flaviviridae
PL2859009T3 (pl) * 2012-06-08 2018-03-30 Gilead Sciences, Inc. Makrocykliczne inhibitory wirusów flaviviridae
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
WO2014080251A1 (en) 2012-11-24 2014-05-30 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
WO2014113584A1 (en) 2013-01-16 2014-07-24 Rhode Island Hospital Compositions and methods for the prevention and treatment of osteolysis and osteoporosis
NZ710929A (en) 2013-03-15 2018-02-23 Novartis Ag Antibody drug conjugates
EP3401314B1 (en) 2013-03-15 2023-11-08 Araxes Pharma LLC Covalent inhibitors of kras g12c
WO2014143659A1 (en) 2013-03-15 2014-09-18 Araxes Pharma Llc Irreversible covalent inhibitors of the gtpase k-ras g12c
EP2988741B1 (en) 2013-04-26 2019-11-27 Indiana University Research&Technology Corporation Hydroxyindole carboxylic acid based inhibitors for oncogenic src homology-2 domain containing protein tyrosine phosphatase-2 (shp2)
WO2014180271A1 (zh) 2013-05-10 2014-11-13 苏州明锐医药科技有限公司 阿法替尼及其中间体的制备方法
EP2806274A1 (en) 2013-05-24 2014-11-26 AIT Austrian Institute of Technology GmbH Lung cancer diagnostic method and means
WO2015003094A2 (en) 2013-07-03 2015-01-08 Indiana University Research & Technology Corporation Shp2 inhibitors and methods of treating autoimmune and/or glomerulonephritis-associated diseases using shp2 inhibitors
EP2826586A1 (en) 2013-07-18 2015-01-21 Siemens Aktiengesellschaft A method and a system for machining an object
EP3055290B1 (en) 2013-10-10 2019-10-02 Araxes Pharma LLC Inhibitors of kras g12c
US9815813B2 (en) 2014-01-17 2017-11-14 Novartis Ag 1-(triazin-3-yl/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions therefor for inhibiting the activity of SHP2
WO2015107493A1 (en) 2014-01-17 2015-07-23 Novartis Ag 1 -pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and and compositions thereof for inhibiting the activity of shp2
US10233431B2 (en) 2014-02-26 2019-03-19 The Regents Of The University Of California Producing 3-hydroxycarboxylic acid and ketone using polyketide synthases
EP3114483A1 (en) 2014-03-03 2017-01-11 Yissum Research and Development Company of the Hebrew University of Jerusalem Ltd. Method and device for detection of pseudomonas aeruginosa
US10011600B2 (en) 2014-09-25 2018-07-03 Araxes Pharma Llc Methods and compositions for inhibition of Ras
EP3197870B1 (en) 2014-09-25 2020-08-19 Araxes Pharma LLC Inhibitors of kras g12c mutant proteins
EP4289950A3 (en) 2015-01-09 2024-01-24 Revolution Medicines, Inc. Macrocyclic compounds that participate in cooperative binding and medical uses thereof
TW201629069A (zh) 2015-01-09 2016-08-16 霍普驅動生物科技股份有限公司 參與協同結合之化合物及其用途
WO2016160362A1 (en) 2015-03-31 2016-10-06 Allergan, Inc. Cyclosporins modified on the mebmt sidechain by heterocyclic rings
WO2016164675A1 (en) 2015-04-10 2016-10-13 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
US10428064B2 (en) 2015-04-15 2019-10-01 Araxes Pharma Llc Fused-tricyclic inhibitors of KRAS and methods of use thereof
CA2986732A1 (en) 2015-05-22 2016-12-01 Allosta Pharmaceuticals Methods to prepare and employ binding site models for modulation of phosphatase activity and selectivity determination
US10494332B2 (en) 2015-06-01 2019-12-03 Indiana University Research And Technology Corporation Protein tyrosine phosphatases or SHP2 inhibitors and uses thereof
WO2016203406A1 (en) 2015-06-19 2016-12-22 Novartis Ag Compounds and compositions for inhibiting the activity of shp2
EP3310779B1 (en) 2015-06-19 2019-05-08 Novartis AG Compounds and compositions for inhibiting the activity of shp2
WO2016203405A1 (en) 2015-06-19 2016-12-22 Novartis Ag Compounds and compositions for inhibiting the activity of shp2
MX2018000777A (es) 2015-07-22 2018-03-23 Araxes Pharma Llc Compuestos de quinazolina sustituido y su uso como inhibidores de proteinas kras, hras y/o nras mutantes g12c.
WO2017058805A1 (en) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
WO2017058728A1 (en) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
EP3356359B1 (en) 2015-09-28 2021-10-20 Araxes Pharma LLC Inhibitors of kras g12c mutant proteins
US10875842B2 (en) 2015-09-28 2020-12-29 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
WO2017058902A1 (en) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
US10647703B2 (en) 2015-09-28 2020-05-12 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
US10975071B2 (en) 2015-09-28 2021-04-13 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
AU2016329064B2 (en) 2015-10-01 2023-10-19 Warp Drive Bio, Inc. Methods and reagents for analyzing protein-protein interfaces
WO2017078499A2 (ko) 2015-11-06 2017-05-11 경북대학교 산학협력단 단백질 타이로신 탈인산화효소 억제제를 포함하는 신경염증성 질환의 예방 또는 치료용 조성물
US11008372B2 (en) 2015-11-07 2021-05-18 Board Of Regents, The University Of Texas System Targeting proteins for degradation
JP7015059B2 (ja) 2015-11-16 2022-02-15 アラクセス ファーマ エルエルシー 置換複素環式基を含む２－置換キナゾリン化合物およびその使用方法
WO2017100279A1 (en) 2015-12-09 2017-06-15 West Virginia University Chemical compound for inhibition of shp2 function and for use as an anti-cancer agent
US9988357B2 (en) 2015-12-09 2018-06-05 Araxes Pharma Llc Methods for preparation of quinazoline derivatives
WO2017156397A1 (en) 2016-03-11 2017-09-14 Board Of Regents, The University Of Texas Sysytem Heterocyclic inhibitors of ptpn11
US10822312B2 (en) 2016-03-30 2020-11-03 Araxes Pharma Llc Substituted quinazoline compounds and methods of use
JP7039489B2 (ja) 2016-05-18 2022-03-22 ミラティ セラピューティクス， インコーポレイテッド Ｋｒａｓ ｇ１２ｃ阻害剤
CN109475531B (zh) 2016-05-31 2021-08-17 得克萨斯州立大学董事会 Ptpn11的杂环抑制剂
KR20210141778A (ko) 2016-06-07 2021-11-23 자코바이오 파마슈티칼스 컴퍼니 리미티드 Shp2 억제제로서 유용한 신규한 헤테로환형 유도체
SG11201900157RA (en) 2016-07-12 2019-02-27 Revolution Medicines Inc 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric shp2 inhibitors
WO2018064510A1 (en) 2016-09-29 2018-04-05 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
CN110312711A (zh) 2016-10-07 2019-10-08 亚瑞克西斯制药公司 作为ras抑制剂的杂环化合物及其使用方法
US11479797B2 (en) 2016-10-28 2022-10-25 Ginkgo Bioworks, Inc. Compositions and methods for the production of compounds
CA3043131A1 (en) * 2016-11-18 2018-05-24 Neurovive Pharmaceutical Ab Use of sanglifehrin macrocyclic analogues as anticancer compounds
AU2017378487B2 (en) 2016-12-15 2022-03-31 The Regents Of The University Of California Compositions and methods for treating cancer
HUE056777T2 (hu) 2016-12-22 2022-03-28 Amgen Inc Benzizotiazol-, izotiazolo[3,4-b]piridin-, kinazolin-, ftálazin-, pirido[2,3-d]piridazin- és pirido[2,3-d]pirimidin-származékok mint KRAS G12C inhibitorok tüdõ-, hasnyálmirigy- vagy vastagbélrák kezelésére
WO2018129402A1 (en) 2017-01-06 2018-07-12 Oregon Health & Science University Compositions and methods used in diagnosing and treating colorectal cancer
CN110730678B (zh) 2017-01-10 2022-07-15 诺华股份有限公司 包含alk抑制剂和shp2抑制剂的药物组合
CN117327075A (zh) 2017-01-23 2024-01-02 锐新医药公司 作为变构shp2抑制剂的二环化合物
MX2019008696A (es) 2017-01-23 2019-09-13 Revolution Medicines Inc Compuestos de piridina como inhibidores de shp2 alostericos.
EP3573971A1 (en) 2017-01-26 2019-12-04 Araxes Pharma LLC 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer
US11358959B2 (en) 2017-01-26 2022-06-14 Araxes Pharma Llc Benzothiophene and benzothiazole compounds and methods of use thereof
EP3573970A1 (en) 2017-01-26 2019-12-04 Araxes Pharma LLC 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds as kras g12c inhibitors for the treatment of cancer
EP3573967A1 (en) 2017-01-26 2019-12-04 Araxes Pharma LLC Fused hetero-hetero bicyclic compounds and methods of use thereof
WO2018140598A1 (en) 2017-01-26 2018-08-02 Araxes Pharma Llc Fused n-heterocyclic compounds and methods of use thereof
US11274093B2 (en) 2017-01-26 2022-03-15 Araxes Pharma Llc Fused bicyclic benzoheteroaromatic compounds and methods of use thereof
JOP20190186A1 (ar) 2017-02-02 2019-08-01 Astellas Pharma Inc مركب كينازولين
EP3589647A1 (en) 2017-02-28 2020-01-08 Novartis AG Shp inhibitor compositions and uses for chimeric antigen receptor therapy
KR20220113545A (ko) 2017-03-23 2022-08-12 자코바이오 파마슈티칼스 컴퍼니 리미티드 Shp2 억제제로서 유용한 신규한 헤테로환형 유도체
WO2018187423A1 (en) 2017-04-05 2018-10-11 Warp Drive Bio, Inc. Methods and reagents for analyzing protein-protein interfaces
CA3058953A1 (en) 2017-04-05 2018-10-11 Revolution Medicines, Inc. Compounds that participate in cooperative binding and uses thereof
WO2018191815A1 (en) 2017-04-20 2018-10-25 Apotex Inc. Processes for the preparation of acalabrutinib and intermediates thereof
JP7348071B2 (ja) 2017-05-02 2023-09-20 レヴォリューション・メディスンズ，インコーポレイテッド ｍＴＯＲ阻害剤としてのラパマイシン類似体
TW201906848A (zh) 2017-05-11 2019-02-16 瑞典商阿斯特捷利康公司 化學化合物
JOP20190272A1 (ar) 2017-05-22 2019-11-21 Amgen Inc مثبطات kras g12c وطرق لاستخدامها
JP2020521742A (ja) 2017-05-25 2020-07-27 アラクセス ファーマ エルエルシー Ｋｒａｓの共有結合性阻害剤
WO2018218069A1 (en) 2017-05-25 2018-11-29 Araxes Pharma Llc Quinazoline derivatives as modulators of mutant kras, hras or nras
EP3630746A1 (en) 2017-05-25 2020-04-08 Araxes Pharma LLC Compounds and methods of use thereof for treatment of cancer
BR112020004246A2 (pt) 2017-09-07 2020-09-01 Revolution Medicines, Inc. composições inibidoras de shp2 e métodos para o tratamento de câncer
MA50077A (fr) 2017-09-08 2020-07-15 Amgen Inc Inhibiteurs de kras g12c et leurs procédés d'utilisation
MA50245A (fr) 2017-09-11 2020-07-22 Krouzon Pharmaceuticals Inc Inhibiteurs allostériques octahydrocyclopenta[c]pyrrole de shp2
AU2018369759B2 (en) 2017-11-15 2022-11-24 Array Biopharma Inc. KRas G12C inhibitors
TW201938561A (zh) 2017-12-08 2019-10-01 瑞典商阿斯特捷利康公司 化學化合物
TW201942115A (zh) 2018-02-01 2019-11-01 美商輝瑞股份有限公司 作為抗癌藥之經取代的喹唑啉和吡啶並嘧啶衍生物
TW201942116A (zh) 2018-02-09 2019-11-01 美商輝瑞股份有限公司 作為抗癌劑之四氫喹唑啉衍生物
EP3788050B1 (en) 2018-05-01 2024-08-28 Revolution Medicines, Inc. C26-linked rapamycin analogs as mtor inhibitors
IL300091A (en) 2018-05-01 2023-03-01 Revolution Medicines Inc C40-, C28-, and C-32-linked rapamycin analogs as MTOR inhibitors
CA3098574A1 (en) 2018-05-04 2019-11-07 Amgen Inc. Kras g12c inhibitors and methods of using the same
MX2020011582A (es) 2018-05-04 2020-11-24 Amgen Inc Inhibidores de kras g12c y metodos para su uso.
EP3790551A4 (en) 2018-05-07 2022-03-09 Mirati Therapeutics, Inc. KRAS G12C INHIBITORS
TW202012415A (zh) 2018-05-08 2020-04-01 瑞典商阿斯特捷利康公司 化學化合物
MA52564A (fr) 2018-05-10 2021-03-17 Amgen Inc Inhibiteurs de kras g12c pour le traitement du cancer
MA52765A (fr) 2018-06-01 2021-04-14 Amgen Inc Inhibiteurs de kras g12c et leurs procédés d'utilisation
AU2019284472B2 (en) 2018-06-11 2024-05-30 Amgen Inc. KRAS G12C inhibitors for treating cancer
CA3100390A1 (en) 2018-06-12 2020-03-12 Amgen Inc. Kras g12c inhibitors encompassing piperazine ring and use thereof in the treatment of cancer
AU2019312670A1 (en) 2018-08-01 2021-02-04 Araxes Pharma Llc Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer
US11760744B2 (en) 2018-08-16 2023-09-19 Genentech, Inc. Fused ring compounds
WO2020047192A1 (en) 2018-08-31 2020-03-05 Mirati Therapeutics, Inc. Kras g12c inhibitors
MX2021005700A (es) 2018-11-19 2021-07-07 Amgen Inc Inhibidores de kras g12c y metodos de uso de los mismos.
EP3897644A4 (en) * 2018-12-21 2022-09-07 Revolution Medicines, Inc. CONNECTIONS INVOLVING IN A COOPERATIVE BINDING AND USES THEREOF
CA3159561A1 (en) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Ras inhibitors
JP2022553859A (ja) 2019-11-04 2022-12-26 レボリューション メディシンズ インコーポレイテッド Ｒａｓ阻害剤
WO2021091967A1 (en) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Ras inhibitors
CN114980976A (zh) 2019-11-27 2022-08-30 锐新医药公司 共价ras抑制剂及其用途
MX2023002248A (es) 2020-09-03 2023-05-16 Revolution Medicines Inc Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2.
CA3194067A1 (en) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Ras inhibitors
PE20240088A1 (es) 2021-05-05 2024-01-16 Revolution Medicines Inc Inhibidores de ras

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