SV2016005245A - Compuestos derivados y composiciones de n-azaspirocicloalcano n-heteroaril sustituido para inhibir la actividad de shp2 - Google Patents

Compuestos derivados y composiciones de n-azaspirocicloalcano n-heteroaril sustituido para inhibir la actividad de shp2

Info

Publication number
SV2016005245A
SV2016005245A SV2016005245A SV2016005245A SV2016005245A SV 2016005245 A SV2016005245 A SV 2016005245A SV 2016005245 A SV2016005245 A SV 2016005245A SV 2016005245 A SV2016005245 A SV 2016005245A SV 2016005245 A SV2016005245 A SV 2016005245A
Authority
SV
El Salvador
Prior art keywords
activity
shp2
inhibit
compositions
azaspirocicloalcano
Prior art date
Application number
SV2016005245A
Other languages
English (en)
Inventor
Christine Hiung-Tung Chen
Zhuoliang Chen
Michael Dore
Fortanet Jorge Garcia
Rajesh Karki
Mitsunori Kato
Matthew J Lamarche
Lawrence Blas Perez
Troy Douglas Smith
Sarah Williams
John William Giraldes
Bakary-Barry Toure
Martin Sendzik
Original Assignee
Novartis Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of SV2016005245A publication Critical patent/SV2016005245A/es

Links

Classifications

    • 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
    • C07D498/10—Spiro-condensed 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/18—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20—Nitrogen atoms
    • 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
    • C07D401/02—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
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic 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
    • C07D471/10—Spiro-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
    • 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
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

LA PRESENTE INVENCIÓN SE REFIERE A LOS COMPUESTOS DE LA FÓRMULA I: (VER FORMULA); EN DONDE P, Q, Y1, Y2, R1, R2A, R2B, R3A, R3B, R4A, R4B, R5A, R5B, R7 Y R8 SE DEFINEN EN LA BREVE DESCRIPCIÓN DE LA INVENCIÓN; CAPACES DE INHIBIR LA ACTIVIDAD DE SHP2. LA INVENCIÓN PROPORCIONA ADEMÁS UN PROCESO PARA LA PREPARACIÓN DE LOS COMPUESTOS DE LA INVENCIÓN, LAS PREPARACIONES FARMACÉUTICAS QUE COMPRENDEN ESTOS COMPUESTOS, Y LOS MÉTODOS PARA UTILIZAR TALES COMPUESTOS Y COMPOSICIONES EN EL MANEJO DE LAS ENFERMEDADES O LOS TRASTORNOS ASOCIADOS CON LA ACTIVIDAD ABERRANTE DE SHP2
SV2016005245A 2014-01-17 2016-07-15 Compuestos derivados y composiciones de n-azaspirocicloalcano n-heteroaril sustituido para inhibir la actividad de shp2 SV2016005245A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201461928754P 2014-01-17 2014-01-17
US201461991129P 2014-05-09 2014-05-09

Publications (1)

Publication Number Publication Date
SV2016005245A true SV2016005245A (es) 2016-11-21

Family

ID=52462974

Family Applications (1)

Application Number Title Priority Date Filing Date
SV2016005245A SV2016005245A (es) 2014-01-17 2016-07-15 Compuestos derivados y composiciones de n-azaspirocicloalcano n-heteroaril sustituido para inhibir la actividad de shp2

Country Status (42)

Country Link
US (6) US10077276B2 (es)
EP (1) EP3094628B1 (es)
JP (1) JP6534389B2 (es)
KR (2) KR102501558B1 (es)
CN (1) CN105916845B (es)
AP (1) AP2016009299A0 (es)
AR (1) AR100033A1 (es)
AU (1) AU2015207757B8 (es)
BR (1) BR112016016432B1 (es)
CA (1) CA2935695C (es)
CL (1) CL2016001790A1 (es)
CR (2) CR20200617A (es)
CU (1) CU24424B1 (es)
CY (1) CY1121155T1 (es)
DK (1) DK3094628T3 (es)
DO (1) DOP2016000177A (es)
EA (1) EA031573B1 (es)
EC (1) ECSP16067692A (es)
ES (1) ES2695242T3 (es)
GT (1) GT201600147A (es)
HR (1) HRP20181832T1 (es)
HU (1) HUE039869T2 (es)
IL (1) IL246436B (es)
JO (1) JO3517B1 (es)
LT (1) LT3094628T (es)
MA (1) MA39282B1 (es)
MX (1) MX356895B (es)
MY (1) MY176357A (es)
NI (1) NI201600101A (es)
NZ (1) NZ721598A (es)
PE (1) PE20170011A1 (es)
PH (1) PH12016501336B1 (es)
PL (1) PL3094628T3 (es)
PT (1) PT3094628T (es)
RS (1) RS57757B1 (es)
SG (1) SG11201605272SA (es)
SI (1) SI3094628T1 (es)
SV (1) SV2016005245A (es)
TN (1) TN2016000268A1 (es)
TW (1) TWI657083B (es)
UY (1) UY35957A (es)
WO (1) WO2015107495A1 (es)

Families Citing this family (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10357184B2 (en) * 2012-06-21 2019-07-23 Globus Medical, Inc. Surgical tool systems and method
US11466017B2 (en) 2011-03-10 2022-10-11 Board Of Regents, The University Of Texas System Heterocyclic inhibitors of PTPN11
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
ES2699351T3 (es) 2014-01-17 2019-02-08 Novartis Ag Derivados de 1-piridazin/triazin-3-il-piper(-azina)/idina/pirolidina y composiciones de las mismas para inhibir la actividad de SHP2
JO3517B1 (ar) 2014-01-17 2020-07-05 Novartis Ag ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2
WO2016151501A1 (en) * 2015-03-25 2016-09-29 Novartis Ag Pharmaceutical combinations
EP3310771B1 (en) * 2015-06-19 2020-07-22 Novartis AG Compounds and compositions for inhibiting the activity of shp2
CN112625028A (zh) * 2015-06-19 2021-04-09 诺华股份有限公司 用于抑制shp2活性的化合物和组合物
CN105503725B (zh) * 2015-12-30 2018-03-27 天津药明康德新药开发有限公司 一种叔丁基1‑羟基‑8‑氮杂螺烷[4,5]葵烷‑8‑羧酸酯的制备方法
WO2017210134A1 (en) * 2016-05-31 2017-12-07 Board Of Regents, University Of Texas System Heterocyclic inhibitors of ptpn11
CA3026784A1 (en) * 2016-06-07 2017-12-14 Jacobio Pharmaceuticals Co., Ltd. Heterocyclic pyrazine derivatives useful as shp2 inhibitors
MX2018015625A (es) * 2016-06-14 2019-03-06 Novartis Ag Compuestos y composiciones para inhibir la actividad de shp2.
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
KR102503590B1 (ko) 2016-08-01 2023-02-24 앱티닉스 인크. 스피로-락탐 nmda 수용체 조정제 및 그의 용도
PE20190501A1 (es) 2016-08-01 2019-04-10 Aptinyx Inc Moduladores nmda espiro-lactam y metodos de uso de los mismos
EP3490992B1 (en) 2016-08-01 2023-03-22 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof
EP3515916B1 (en) 2016-09-22 2023-06-07 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
TW201819386A (zh) 2016-10-24 2018-06-01 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
WO2018130928A1 (en) * 2017-01-10 2018-07-19 Novartis Ag Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor
JP7240319B2 (ja) 2017-01-23 2023-03-15 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 アロステリックｓｈｐ２阻害剤としての二環式化合物
EP3571189B1 (en) * 2017-01-23 2023-03-29 Revolution Medicines, Inc. Pyridine compounds as allosteric shp2 inhibitors
EP3601239A4 (en) * 2017-03-23 2020-05-13 Jacobio Pharmaceuticals Co., Ltd. INNOVATIVE HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS
EP3630770A1 (en) 2017-05-26 2020-04-08 Relay Therapeutics, Inc. Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors
US10690253B2 (en) * 2017-06-20 2020-06-23 Control Components, Inc. Multi-stage, multi-path rotary disc
WO2019051084A1 (en) * 2017-09-07 2019-03-14 Revolution Medicines, Inc. SHP2 INHIBITOR COMPOSITIONS AND METHODS OF TREATING CANCER
US10435389B2 (en) 2017-09-11 2019-10-08 Krouzon Pharmaccuticals, Inc. Octahydrocyclopenta[c]pyrrole allosteric inhibitors of SHP2
US11701354B2 (en) 2017-09-29 2023-07-18 D. E. Shaw Research, Llc Pyrazolo[3,4-b]pyrazine derivatives as SHP2 phosphatase inhibitors
WO2019075265A1 (en) * 2017-10-12 2019-04-18 Revolution Medicines, Inc. PYRIDINE, PYRAZINE AND TRIAZINE COMPOUNDS AS ALLOSTERIC INHIBITORS OF SHP2
TWI697490B (zh) * 2017-12-06 2020-07-01 大陸商北京加科思新藥研發有限公司 用於作為shp2抑制劑之新穎雜環衍生物
MX2020006273A (es) * 2017-12-15 2020-09-14 Revolution Medicines Inc Compuestos policiclicos como inhibidores alostericos de shp2.
US11426422B2 (en) 2018-01-30 2022-08-30 Research Development Foundation SHP2 inhibitors and methods of use thereof
CA3089561A1 (en) 2018-01-31 2019-08-08 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof
CN115448923B (zh) * 2018-02-13 2024-03-22 上海青煜医药科技有限公司 嘧啶并环化合物及其制备方法和应用
AU2019222026B2 (en) * 2018-02-13 2022-05-12 Shanghai Blueray Biopharma Co., Ltd. Pyrimidine-fused cyclic compound, preparation method therefor and application thereof
WO2019165073A1 (en) 2018-02-21 2019-08-29 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
SG11202006778TA (en) 2018-03-02 2020-08-28 Otsuka Pharma Co Ltd Pharmaceutical compounds
TW202003471A (zh) * 2018-03-21 2020-01-16 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
US10561655B2 (en) 2018-03-21 2020-02-18 Synblia Therapeutics, Inc. SHP2 inhibitors and uses thereof
US20210069188A1 (en) 2018-03-21 2021-03-11 Relay Therapeutics, Inc. Pyrazolo[3,4-b]pyrazine shp2 phosphatase inhibitors and methods of use thereof
CN112203689A (zh) * 2018-04-10 2021-01-08 锐新医药公司 治疗癌症的shp2抑制剂组合物和方法
CA3098692A1 (en) 2018-05-01 2019-11-07 Revolution Medicines, Inc. C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors
MX2020011528A (es) * 2018-05-02 2021-02-09 Navire Pharma Inc Inhibidores heterociclicos sustituidos de ptpn11.
CN110143949A (zh) * 2018-05-09 2019-08-20 北京加科思新药研发有限公司 可用作shp2抑制剂的新型杂环衍生物
EP4356973A2 (en) 2018-08-10 2024-04-24 Navire Pharma, Inc. 6-(4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4(3h)-one derivatives and related compounds as ptpn11 (shp2) inhibitors for treating cancer
CA3113233A1 (en) 2018-09-18 2020-03-26 Nikang Therapeutics, Inc. Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors
CN112867718A (zh) 2018-09-29 2021-05-28 诺华股份有限公司 用于抑制shp2活性的化合物和组合物的制造
IL305106A (en) * 2018-09-29 2023-10-01 Novartis Ag A process for producing a compound to inhibit the activity of SHP2
WO2020072656A1 (en) 2018-10-03 2020-04-09 Gilead Sciences, Inc. Imidozopyrimidine derivatives
TW202028183A (zh) * 2018-10-10 2020-08-01 大陸商江蘇豪森藥業集團有限公司 含氮雜芳類衍生物調節劑、其製備方法和應用
BR112021005733A2 (pt) 2018-10-17 2021-07-27 Array Biopharma Inc. inibidores de proteína tirosina fosfatase
CN111138412B (zh) * 2018-11-06 2023-09-15 上海奕拓医药科技有限责任公司 一种螺芳环化合物及其应用
CN111153899B (zh) * 2018-11-08 2023-12-01 四川科伦博泰生物医药股份有限公司 一种取代吡啶化合物、其制备方法和用途
BR112021009880A2 (pt) 2018-11-30 2021-08-17 Tuojie Biotech (Shanghai) Co., Ltd. pirimidina e derivado de heterociclo de nitrogênio de cinco membros, método de preparação para os mesmos e usos médicos dos mesmos
CN113164418A (zh) 2018-12-05 2021-07-23 米拉蒂治疗股份有限公司 组合疗法
CN113316574B (zh) * 2019-01-31 2024-01-30 贝达药业股份有限公司 Shp2抑制剂及其应用
EP3924053A1 (en) 2019-02-12 2021-12-22 Novartis AG Pharmaceutical combination comprising tno155 and a krasg12c inhibitor
AU2020222295B2 (en) 2019-02-12 2023-04-06 Novartis Ag Pharmaceutical combination comprising TNO155 and a PD-1 inhibitor
US20220160707A1 (en) 2019-02-12 2022-05-26 Novartis Ag Pharmaceutical combination comprising tno155 and ribociclib
CN111647000B (zh) 2019-03-04 2021-10-12 勤浩医药（苏州）有限公司 吡嗪类衍生物及其在抑制shp2中的应用
JP2022524759A (ja) 2019-03-07 2022-05-10 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｓｈｐ２アンタゴニストとしてのカルボキサミド－ピリミジン誘導体
GEP20237561B (en) 2019-04-02 2023-10-25 Array Biopharma Inc Protein tyrosine phosphatase inhibitors
CN113646049A (zh) * 2019-04-08 2021-11-12 默克专利有限公司 作为shp2拮抗剂的嘧啶酮衍生物
EP4306529A3 (en) 2019-05-13 2024-04-10 Relay Therapeutics, Inc. Fgfr inhibitors and methods of use thereof
TWI817018B (zh) 2019-06-28 2023-10-01 美商艾瑞生藥股份有限公司 用於治療ｂｒａｆ相關的疾病和失調症之化合物
US20220380385A1 (en) 2019-06-28 2022-12-01 Tuojie Biotech(Shanghai) Co., Ltd. Pyrimidine five-membered nitrogen heterocyclic derivative, preparation method thereof and pharmaceutical use thereof
CN111704611B (zh) * 2019-07-25 2022-01-14 上海凌达生物医药有限公司 一类芳基螺环类shp2抑制剂化合物、制备方法和用途
CN112300160A (zh) * 2019-08-01 2021-02-02 上海奕拓医药科技有限责任公司 一种螺芳环化合物、其制备及应用
EP3772513A1 (en) 2019-08-09 2021-02-10 C.N.C.C.S. S.c.a.r.l. Collezione Nazionale Dei Composti Chimici e Centro Screening Shp2 inhibitors
EP4034539A1 (en) 2019-09-24 2022-08-03 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of making and using the same
CN114901662A (zh) 2019-11-08 2022-08-12 锐新医药公司 双环杂芳基化合物及其用途
WO2021143823A1 (zh) * 2020-01-16 2021-07-22 浙江海正药业股份有限公司 吡啶或嘧啶类衍生物及其制备方法和用途
CN113135910A (zh) 2020-01-19 2021-07-20 北京诺诚健华医药科技有限公司 嘧啶-4(3h)-酮类杂环化合物、其制备方法及其在医药学上的应用
WO2021171261A1 (en) 2020-02-28 2021-09-02 Novartis Ag A triple pharmaceutical combination comprising dabrafenib, an erk inhibitor and a shp2 inhibitor
CN113493440A (zh) * 2020-04-03 2021-10-12 上海翰森生物医药科技有限公司 含氮杂芳类衍生物的盐及其晶型
TW202144334A (zh) * 2020-04-03 2021-12-01 大陸商上海翰森生物醫藥科技有限公司 含氮雜芳類衍生物游離鹼的晶型
CN115279749B (zh) * 2020-04-30 2024-05-10 贝达药业股份有限公司 Shp2抑制剂及其组合物和应用
KR20230008719A (ko) 2020-05-08 2023-01-16 노파르티스 아게 Tno155 및 나자르티닙을 포함하는 약제학적 조합물
US20230218765A1 (en) * 2020-05-19 2023-07-13 The Regents Of The University Of Michigan Small molecule degraders of shp2 protein
WO2021247836A1 (en) 2020-06-03 2021-12-09 Board Of Regents, The University Of Texas System Methods for targeting shp-2 to overcome resistance
CN115734966A (zh) * 2020-06-12 2023-03-03 石药集团中奇制药技术（石家庄）有限公司 杂环化合物及其用途
IL299131A (en) 2020-06-18 2023-02-01 Revolution Medicines Inc Methods for delaying, preventing and treating acquired resistance to RAS inhibitors
JP2023530838A (ja) 2020-06-22 2023-07-20 スーチュアン・コールン－バイオテック・バイオファーマシューティカル・カンパニー・リミテッド 置換されたピラジン化合物、当該化合物を含む医薬組成物、及びその使用
WO2022006780A1 (en) * 2020-07-08 2022-01-13 Novartis Ag Manufacture of compounds and compositions for inhibiting activity of shp2
EP4178962A1 (en) 2020-07-08 2023-05-17 Novartis AG Manufacture of compounds and compositions for inhibiting the activity of shp2
CN115515947B (zh) * 2020-07-24 2024-02-06 贝达药业股份有限公司 Shp2抑制剂及其组合物和应用
EP4208261A1 (en) 2020-09-03 2023-07-12 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
EP4214209A1 (en) 2020-09-15 2023-07-26 Revolution Medicines, Inc. Indole derivatives as ras inhibitors in the treatment of cancer
WO2022063190A1 (zh) * 2020-09-23 2022-03-31 南京明德新药研发有限公司 吡嗪硫联苯基类化合物及其应用
EP4039685A1 (en) 2021-02-08 2022-08-10 Irbm S.P.A. Azabicyclic shp2 inhibitors
EP4317144A1 (en) * 2021-03-23 2024-02-07 Shanghai Haiyan Pharmaceutical Technology Co., Ltd. Heterocycle substituted ketone derivative, and composition and medicinal use thereof
WO2022206684A1 (zh) * 2021-03-31 2022-10-06 南京明德新药研发有限公司 一系列含Se的吡嗪类化合物及其应用
TWI825637B (zh) 2021-03-31 2023-12-11 美商輝瑞股份有限公司 啶－１，６（２ｈ，７ｈ）－二酮
EP4067358A1 (en) 2021-04-02 2022-10-05 C.N.C.C.S. S.c.a.r.l. Collezione Nazionale Dei Composti Chimici e Centro Screening (s)-1-(5-((pyridin-3-yl)thio)pyrazin-2-yl)-4'h,6'h-spiro[piperidine-4,5'-pyrrolo[1,2-b]pyrazol]-4'-amine derivatives and similar compounds as shp2 inhibitors for the treatment of e.g. cancer
EP4334321A1 (en) 2021-05-05 2024-03-13 Revolution Medicines, Inc. Ras inhibitors
CN117616031A (zh) 2021-05-05 2024-02-27 锐新医药公司 用于治疗癌症的ras抑制剂
WO2022235866A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Covalent ras inhibitors and uses thereof
CN117177752A (zh) 2021-05-05 2023-12-05 诺华股份有限公司 用于治疗mpnst的化合物和组合物
BR112023025738A2 (pt) 2021-06-09 2024-02-27 Hoffmann La Roche Combinação de um inibidor de braf e um antagonista de ligação ao eixo pd-1, uso de uma combinação de um inibidor de braf e um antagonista de ligação ao eixo pd-1, método para o tratamento ou profilaxia de câncer, composição farmacêutica e invenção
IL307964A (en) 2021-06-09 2023-12-01 Chugai Pharmaceutical Co Ltd Combined treatment for cancer
WO2022259157A1 (en) 2021-06-09 2022-12-15 Novartis Ag A triple pharmaceutical combination comprising dabrafenib, trametinib and a shp2 inhibitor
TW202317100A (zh) 2021-06-23 2023-05-01 瑞士商諾華公司 包含ｋｒａｓ ｇ１２ｃ抑制劑的藥物組合及其用於治療癌症之用途
EP4368614A1 (en) * 2021-07-07 2024-05-15 Hinova Pharmaceuticals Inc. Synthesis and application of phosphatase degrader
KR20240055778A (ko) 2021-09-01 2024-04-29 노파르티스 아게 Tead 억제제를 포함하는 제약 조합물 및 암의 치료를 위한 이의 용도
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
WO2023078881A1 (en) 2021-11-04 2023-05-11 F. Hoffmann-La Roche Ag Novel use of quinazolinone compound for the treatment of cancer
TW202342040A (zh) 2022-02-21 2023-11-01 瑞士商諾華公司 藥物配製物
CN114524772B (zh) * 2022-02-28 2023-07-11 中国药科大学 一种含杂环串联类化合物及其制备方法与应用
WO2023172940A1 (en) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
WO2024035830A1 (en) 2022-08-11 2024-02-15 Relay Therapeutics, Inc. Solid forms of a cdk inhibitor
EP4345101A1 (en) 2022-09-29 2024-04-03 Irbm S.P.A. Azole derivatives as shp2 inhibitors

Family Cites Families (134)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH445129A (fr) 1964-04-29 1967-10-15 Nestle Sa Procédé pour la préparation de composés d'inclusion à poids moléculaire élevé
US3459731A (en) 1966-12-16 1969-08-05 Corn Products Co Cyclodextrin polyethers and their production
US3453257A (en) 1967-02-13 1969-07-01 Corn Products Co Cyclodextrin with cationic properties
US3426011A (en) 1967-02-13 1969-02-04 Corn Products Co Cyclodextrins with anionic properties
US3453259A (en) 1967-03-22 1969-07-01 Corn Products Co Cyclodextrin polyol ethers and their oxidation products
JPS6041077B2 (ja) 1976-09-06 1985-09-13 喜徳 喜谷 １，２‐ジアミノシクロヘキサン異性体のシス白金（２）錯体
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4261989A (en) 1979-02-19 1981-04-14 Kaken Chemical Co. Ltd. Geldanamycin derivatives and antitumor drug
EP0090505B1 (en) 1982-03-03 1990-08-08 Genentech, Inc. Human antithrombin iii, dna sequences therefor, expression vehicles and cloning vectors containing such sequences and cell cultures transformed thereby, a process for expressing human antithrombin iii, and pharmaceutical compositions comprising it
US4512991A (en) * 1982-12-27 1985-04-23 Merck & Co., Inc. 3-Acyl-2-amino-5-halo-6-(substituted)pyrazine antimicrobial compounds
FR2567518B1 (fr) 1984-07-11 1987-11-13 Sanofi Sa Nouveaux composes a noyau heterocyclique azote, leur preparation et les medicaments qui en contiennent
US4737323A (en) 1986-02-13 1988-04-12 Liposome Technology, Inc. Liposome extrusion method
US4959368A (en) 1986-02-24 1990-09-25 Mitsui Petrochemical Industries Ltd. Therapeutic agent for neurological diseases
US5266573A (en) 1989-08-07 1993-11-30 Elf Sanofi Trifluoromethylphenyltetrahydropyridines for the treatment and/or prophylaxis of intestinal motility disorders
KR0166088B1 (ko) 1990-01-23 1999-01-15 . 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도
DK169008B1 (da) 1990-06-01 1994-07-25 Holec Lk A S Fremgangsmåde og skærm til afskærmning af en strømtransformer samt strømtransformer med en sådan afskærmning
GB9012316D0 (en) 1990-06-01 1990-07-18 Wellcome Found Pharmacologically active cns compounds
EP0647450A1 (en) 1993-09-09 1995-04-12 BEHRINGWERKE Aktiengesellschaft Improved prodrugs for enzyme mediated activation
IL115849A0 (en) 1994-11-03 1996-01-31 Merz & Co Gmbh & Co Tangential filtration preparation of liposomal drugs and liposome product thereof
US6111090A (en) 1996-08-16 2000-08-29 Schering Corporation Mammalian cell surface antigens; related reagents
JP4440344B2 (ja) 1996-08-16 2010-03-24 シェーリング コーポレイション 哺乳動物細胞表面抗原；関連試薬
MA26473A1 (fr) * 1997-03-01 2004-12-20 Glaxo Group Ltd Composes pharmacologiquement actifs.
AU1102399A (en) 1997-10-21 1999-05-10 Human Genome Sciences, Inc. Human tumor necrosis factor receptor-like proteins tr11, tr11sv1, and tr11sv2
WO1999040196A1 (en) 1998-02-09 1999-08-12 Genentech, Inc. Novel tumor necrosis factor receptor homolog and nucleic acids encoding the same
AU4198400A (en) 1999-04-06 2000-10-23 Krenitsky Pharmaceuticals Inc. Neurotrophic thio substituted pyrimidines
PE20010306A1 (es) 1999-07-02 2001-03-29 Agouron Pharma Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa
JP2003504343A (ja) 1999-07-12 2003-02-04 ジェネンテック・インコーポレーテッド 腫瘍壊死因子リガンド／レセプター相同体による血管形成及び心血管形成の促進と抑制
GB0018891D0 (en) 2000-08-01 2000-09-20 Novartis Ag Organic compounds
JP4272338B2 (ja) 2000-09-22 2009-06-03 バイエル アクチェンゲゼルシャフト ピリジン誘導体
US6995162B2 (en) 2001-01-12 2006-02-07 Amgen Inc. Substituted alkylamine derivatives and methods of use
ATE407678T1 (de) 2001-10-17 2008-09-15 Boehringer Ingelheim Pharma Pyrimidinderivate, arzneimittel enthaltend diese verbindungen, deren verwendung und verfahren zu ihrer herstellung
EA011488B1 (ru) 2002-02-01 2009-04-28 Ариад Джин Терапьютикс, Инк. Фосфорсодержащие соединения и их получение
EP2322521B1 (en) * 2002-02-06 2013-09-04 Vertex Pharmaceuticals, Inc. Heteroaryl compounds useful as inhibitors of GSK-3
WO2003075836A2 (en) 2002-03-05 2003-09-18 Merck Frosst Canada & Co. Cathepsin cysteine protease inhibitors
TWI275390B (en) 2002-04-30 2007-03-11 Wyeth Corp Process for the preparation of 7-substituted-3- quinolinecarbonitriles
CA2508660C (en) 2002-12-23 2013-08-20 Wyeth Antibodies against pd-1 and uses therefor
GB0300783D0 (en) 2003-01-14 2003-02-12 Btg Int Ltd Treatment of neurodegenerative conditions
JP2006519822A (ja) 2003-03-07 2006-08-31 メルク シャープ エンド ドーム リミテッド タキキニン拮抗薬としてのテトラヒドロピラン化合物
WO2004107618A2 (en) 2003-05-23 2004-12-09 Wyeth Gitr ligand and gitr ligand-related molecules and antibodies and uses thereof
EP1660126A1 (en) 2003-07-11 2006-05-31 Schering Corporation Agonists or antagonists of the clucocorticoid-induced tumour necrosis factor receptor (gitr) or its ligand for the treatment of immune disorders, infections and cancer
US7399865B2 (en) 2003-09-15 2008-07-15 Wyeth Protein tyrosine kinase enzyme inhibitors
WO2005055808A2 (en) 2003-12-02 2005-06-23 Genzyme Corporation Compositions and methods to diagnose and treat lung cancer
EP1737841A1 (en) 2004-04-01 2007-01-03 Astellas Pharma Inc. Pyrazine derivatives and pharmaceutical use thereof as adenosine antagonists
US8076338B2 (en) 2004-04-23 2011-12-13 Exelixis, Inc. Kinase modulators and methods of use
GB0409799D0 (en) 2004-04-30 2004-06-09 Isis Innovation Method of generating improved immune response
EP1765402A2 (en) 2004-06-04 2007-03-28 Duke University Methods and compositions for enhancement of immunity by in vivo depletion of immunosuppressive cell activity
CA2579002C (en) 2004-09-02 2012-11-27 Genentech, Inc. Pyridyl inhibitors of hedgehog signalling
WO2006065946A1 (en) 2004-12-16 2006-06-22 Vertex Pharmaceuticals Incorporated Pyrid-2-ones useful as inhibitors of tec family protein kinases for the treatment of inflammatory, proliferative and immunologically-mediated diseases
ES2657443T3 (es) 2005-03-25 2018-03-05 Gitr, Inc. Anticuerpos anti-GITR y usos de los mismos
SI2439273T1 (sl) 2005-05-09 2019-05-31 Ono Pharmaceutical Co., Ltd. Človeška monoklonska protitelesa za programirano smrt 1 (PD-1) in postopki za zdravljenje raka z uporabo protiteles proti PD-1 samostojno ali v kombinaciji z ostalimi imunoterapevtiki
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
CN101248089A (zh) 2005-07-01 2008-08-20 米德列斯公司 抗程序性死亡配体1（pd-l1）的人单克隆抗体
US20090306038A1 (en) 2005-09-13 2009-12-10 Carceller Gonzalez Elena 2-Aminopyrimidine derivatives as modulators of the histamine H4 receptor activity
AR057579A1 (es) * 2005-11-23 2007-12-05 Merck & Co Inc Compuestos espirociclicos como inhibidores de histona de acetilasa (hdac)
EP1981969A4 (en) 2006-01-19 2009-06-03 Genzyme Corp ANTI-GITRANT ANTIBODIES FOR THE TREATMENT OF CANCER
US20100029941A1 (en) 2006-03-28 2010-02-04 Takeda Pharmaceutical Company Limited Preparation of (r)-3-aminopiperidine dihydrochloride
US7515405B2 (en) 2006-07-25 2009-04-07 Hewlett-Packard Development Company, L.P. Anti-rotation mechanism for an electronic device
US20090137549A1 (en) 2006-11-09 2009-05-28 Paul John Edward Novel compounds useful for the treatment of degenerative & inflamatory diseases
AU2008216842A1 (en) 2007-02-12 2008-08-21 Merck Sharp & Dohme Corp. Piperidine derivatives
AU2008225766B2 (en) * 2007-03-15 2012-06-07 Novartis Ag Organic compounds and their uses
KR101586617B1 (ko) 2007-06-18 2016-01-20 머크 샤프 앤 도메 비.브이. 사람 프로그램된 사멸 수용체 ｐｄ-1에 대한 항체
EP3124046B1 (en) 2007-07-12 2019-12-25 GITR, Inc. Combination therapies employing gitr binding molecules
BRPI0816769A2 (pt) 2007-09-12 2016-11-29 Hoffmann La Roche combinações de compostos inibidores de fosfoinositida 3-cinase e agentes quimioterapêuticos, e métodos de uso
WO2009055730A1 (en) 2007-10-25 2009-04-30 Genentech, Inc. Process for making thienopyrimidine compounds
WO2009101611A1 (en) 2008-02-11 2009-08-20 Curetech Ltd. Monoclonal antibodies for tumor treatment
EP2262837A4 (en) 2008-03-12 2011-04-06 Merck Sharp & Dohme PD-1 BINDING PROTEINS
AU2009238590A1 (en) 2008-04-22 2009-10-29 Portola Pharmaceuticals, Inc. Inhibitors of protein kinases
KR20110031318A (ko) 2008-06-13 2011-03-25 노파르티스 아게 Ｉａ 심부전 및 암 치료에 유용한 단백질 키나제 ｄ 억제제로서의 2,4'-비피리디닐 화합물
JP2011524917A (ja) 2008-06-20 2011-09-08 メタボレックス， インコーポレイテッド アリールｇｐｒ１１９作動薬およびその使用
US8168784B2 (en) 2008-06-20 2012-05-01 Abbott Laboratories Processes to make apoptosis promoters
KR101892989B1 (ko) 2008-06-27 2018-08-30 셀젠 카르 엘엘씨 헤테로아릴 화합물 및 이의 용도
GB0812031D0 (en) 2008-07-01 2008-08-06 7Tm Pharma As Thiazole derivatives
AU2009266873A1 (en) 2008-07-02 2010-01-07 Emergent Product Development Seattle, Llc TGF-beta antagonist multi-target binding proteins
US9174969B2 (en) 2008-07-21 2015-11-03 University Of South Florida Indoline scaffold SHP-2 inhibitors and cancer treatment method
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
PE20110435A1 (es) 2008-08-25 2011-07-20 Amplimmune Inc Composiciones antagonistas del pd-1
JP2012510429A (ja) 2008-08-25 2012-05-10 アンプリミューン、インコーポレーテッド Ｐｄ−１アンタゴニストおよびその使用方法
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
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
RU2011123647A (ru) * 2008-11-10 2012-12-20 Вертекс Фармасьютикалз Инкорпорейтед Соединения, полезные в качестве ингибиторов atr киназы
UA109108C2 (uk) 2008-12-09 2015-07-27 Дженентек, Інк. Антитіло до pd-l1 та його застосування для посилення функції t-клітин
KR20100067046A (ko) 2008-12-10 2010-06-18 동화약품주식회사 신규한 ２，６―위치에 치환된 ３―니트로피리딘 유도체, 그의 제조방법 및 이를 포함하는 약학 조성물
FR2941696B1 (fr) 2009-02-05 2011-04-15 Sanofi Aventis Derives d'azaspiranyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique
ES2629337T3 (es) 2009-02-09 2017-08-08 Inserm - Institut National De La Santé Et De La Recherche Médicale Anticuerpos contra PD-1 y anticuerpos contra PD-L1 y usos de los mismos
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
AU2010284255B2 (en) 2009-08-17 2016-11-17 Memorial Sloan-Kettering Cancer Center Heat shock protein binding compounds, compositions, and methods for making and using same
EP2473531A4 (en) 2009-09-03 2013-05-01 Merck Sharp & Dohme ANTI-GITRANT ANTIBODIES
GB0919054D0 (en) 2009-10-30 2009-12-16 Isis Innovation Treatment of obesity
US8673913B2 (en) 2009-11-13 2014-03-18 Case Western Reserve University SHP-2 phosphatase inhibitor
US20130017199A1 (en) 2009-11-24 2013-01-17 AMPLIMMUNE ,Inc. a corporation Simultaneous inhibition of pd-l1/pd-l2
WO2011078143A1 (ja) 2009-12-22 2011-06-30 塩野義製薬株式会社 ピリミジン誘導体およびそれらを含有する医薬組成物
EP3112382A1 (en) 2009-12-29 2017-01-04 Emergent Product Development Seattle, LLC Heterodimer binding proteins and uses thereof
ES2689103T3 (es) 2010-06-30 2018-11-08 Fujifilm Corporation Nuevo derivado de nicotinamida o sal del mismo
AU2011279509A1 (en) 2010-07-13 2013-01-10 Merck Sharp & Dohme Corp. Spirocyclic compounds
MY165584A (en) 2010-07-29 2018-04-05 Rigel Pharmaceuticals Inc Ampk-activating heterocyclic compounds and methods for using the same
US8609672B2 (en) * 2010-08-27 2013-12-17 University Of The Pacific Piperazinylpyrimidine analogues as protein kinase inhibitors
CA2813162C (en) 2010-10-20 2015-06-16 Pfizer Inc. Pyridine-2- derivatives as smoothened receptor modulators
RU2591195C2 (ru) 2010-12-13 2016-07-10 Эррэй Биофарма Инк. Замещенные n-(1h-индазол-4-ил) имидазол [1,2-а]пиридин-3- карбоксамидные соединения в качестве ингибиторов рецепторной тирозинкиназы iii типа
JP5727276B2 (ja) 2011-03-04 2015-06-03 協同油脂株式会社 グリース組成物及びグリース封入転がり軸受
AU2012308681B2 (en) 2011-09-12 2017-07-13 Merck Patent Gmbh Aminopyrimidine derivatives for use as modulators of kinase activity
WO2013039954A1 (en) 2011-09-14 2013-03-21 Sanofi Anti-gitr antibodies
DK2785375T3 (da) 2011-11-28 2020-10-12 Merck Patent Gmbh Anti-pd-l1-antistoffer og anvendelser deraf
WO2013096093A1 (en) 2011-12-21 2013-06-27 Merck Sharp & Dohme Corp. Compounds as dgat-1 inhibitors
KR20150016406A (ko) 2012-06-07 2015-02-11 에프. 호프만-라 로슈 아게 탄키라제의 피라졸로피리미돈 및 피라졸로피리돈 억제제
CN104364239B (zh) 2012-06-13 2017-08-25 霍夫曼-拉罗奇有限公司 二氮杂螺环烷烃和氮杂螺环烷烃
AR091649A1 (es) 2012-07-02 2015-02-18 Bristol Myers Squibb Co Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos
WO2014054053A1 (en) 2012-10-03 2014-04-10 Advinus Therapeutics Limited Spirocyclic compounds, compositions and medicinal applications thereof
EP2970231A1 (en) * 2013-03-15 2016-01-20 Blueprint Medicines Corporation Piperazine derivatives and their use as kit modulators
US10189859B2 (en) 2013-12-21 2019-01-29 Nektar Therapeutics Derivatives of 6-(2,3-dichlorophenyl)-1,2,4-triazin-5-amine
ES2699351T3 (es) 2014-01-17 2019-02-08 Novartis Ag Derivados de 1-piridazin/triazin-3-il-piper(-azina)/idina/pirolidina y composiciones de las mismas para inhibir la actividad de SHP2
JO3517B1 (ar) 2014-01-17 2020-07-05 Novartis Ag ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2
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
SG11201609033TA (en) 2014-05-01 2016-11-29 Celgene Quanticel Res Inc Inhibitors of lysine specific demethylase-1
US10174032B2 (en) 2014-05-05 2019-01-08 Signalrx Pharmaceuticals, Inc. Heterocyclic compound classes for signaling modulation
EP3310771B1 (en) 2015-06-19 2020-07-22 Novartis AG Compounds and compositions for inhibiting the activity of shp2
ES2741746T3 (es) 2015-06-19 2020-02-12 Novartis Ag Compuestos y composiciones para inhibir la actividad de SHP2
CN112625028A (zh) 2015-06-19 2021-04-09 诺华股份有限公司 用于抑制shp2活性的化合物和组合物
WO2017156397A1 (en) 2016-03-11 2017-09-14 Board Of Regents, The University Of Texas Sysytem Heterocyclic inhibitors of ptpn11
WO2017210134A1 (en) 2016-05-31 2017-12-07 Board Of Regents, University Of Texas System Heterocyclic inhibitors of ptpn11
CA3026784A1 (en) 2016-06-07 2017-12-14 Jacobio Pharmaceuticals Co., Ltd. Heterocyclic pyrazine derivatives useful as shp2 inhibitors
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
EP3515916B1 (en) 2016-09-22 2023-06-07 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
TW201819386A (zh) 2016-10-24 2018-06-01 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
WO2018130928A1 (en) 2017-01-10 2018-07-19 Novartis Ag Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor
JP7240319B2 (ja) 2017-01-23 2023-03-15 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 アロステリックｓｈｐ２阻害剤としての二環式化合物
EP3571189B1 (en) 2017-01-23 2023-03-29 Revolution Medicines, Inc. Pyridine compounds as allosteric shp2 inhibitors
EP3601239A4 (en) 2017-03-23 2020-05-13 Jacobio Pharmaceuticals Co., Ltd. INNOVATIVE HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS
WO2019051084A1 (en) 2017-09-07 2019-03-14 Revolution Medicines, Inc. SHP2 INHIBITOR COMPOSITIONS AND METHODS OF TREATING CANCER
US11701354B2 (en) 2017-09-29 2023-07-18 D. E. Shaw Research, Llc Pyrazolo[3,4-b]pyrazine derivatives as SHP2 phosphatase inhibitors
WO2019075265A1 (en) 2017-10-12 2019-04-18 Revolution Medicines, Inc. PYRIDINE, PYRAZINE AND TRIAZINE COMPOUNDS AS ALLOSTERIC INHIBITORS OF SHP2
MX2020006273A (es) 2017-12-15 2020-09-14 Revolution Medicines Inc Compuestos policiclicos como inhibidores alostericos de shp2.
WO2019165073A1 (en) 2018-02-21 2019-08-29 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
TW202003471A (zh) 2018-03-21 2020-01-16 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
CN112203689A (zh) 2018-04-10 2021-01-08 锐新医药公司 治疗癌症的shp2抑制剂组合物和方法

Also Published As

Publication number Publication date
KR20230028581A (ko) 2023-02-28
CY1121155T1 (el) 2020-05-29
CR20200617A (es) 2021-02-11
PE20170011A1 (es) 2017-03-25
JP2017502993A (ja) 2017-01-26
JO3517B1 (ar) 2020-07-05
TWI657083B (zh) 2019-04-21
MX2016009223A (es) 2016-10-05
CA2935695A1 (en) 2015-07-23
HRP20181832T1 (hr) 2019-01-11
US10077276B2 (en) 2018-09-18
PT3094628T (pt) 2018-11-21
CN105916845B (zh) 2019-11-12
EA031573B1 (ru) 2019-01-31
CU24424B1 (es) 2019-06-04
PH12016501336A1 (en) 2016-08-15
GT201600147A (es) 2018-11-27
AU2015207757B2 (en) 2017-04-06
EP3094628B1 (en) 2018-08-08
MY176357A (en) 2020-08-03
US10336774B2 (en) 2019-07-02
UY35957A (es) 2015-08-31
CN105916845A (zh) 2016-08-31
EP3094628A1 (en) 2016-11-23
EA201691442A1 (ru) 2016-12-30
ECSP16067692A (es) 2017-10-31
RS57757B1 (sr) 2018-12-31
CR20160328A (es) 2016-11-10
JP6534389B2 (ja) 2019-06-26
BR112016016432A2 (es) 2017-08-08
AU2015207757A8 (en) 2017-05-11
NZ721598A (en) 2018-08-31
MA39282A1 (fr) 2018-06-29
SI3094628T1 (sl) 2018-11-30
CL2016001790A1 (es) 2016-12-30
KR102501558B1 (ko) 2023-02-20
US20220396585A1 (en) 2022-12-15
AP2016009299A0 (en) 2016-06-30
PH12016501336B1 (en) 2016-08-15
US20170015680A1 (en) 2017-01-19
IL246436A0 (en) 2016-08-31
BR112016016432B1 (pt) 2022-11-29
US20180201623A1 (en) 2018-07-19
SG11201605272SA (en) 2016-08-30
AU2015207757B8 (en) 2017-05-11
HUE039869T2 (hu) 2019-02-28
NI201600101A (es) 2016-09-06
DK3094628T3 (en) 2018-12-03
US20220073537A1 (en) 2022-03-10
MX356895B (es) 2018-06-19
KR20160103137A (ko) 2016-08-31
MA39282B1 (fr) 2018-10-31
WO2015107495A1 (en) 2015-07-23
PL3094628T3 (pl) 2019-01-31
US10968235B2 (en) 2021-04-06
US20210371429A1 (en) 2021-12-02
CA2935695C (en) 2022-08-30
LT3094628T (lt) 2018-10-25
IL246436B (en) 2019-10-31
AU2015207757A1 (en) 2016-07-07
US11952386B2 (en) 2024-04-09
AR100033A1 (es) 2016-09-07
US20200181168A1 (en) 2020-06-11
ES2695242T3 (es) 2019-01-02
DOP2016000177A (es) 2016-09-30
TW201612170A (en) 2016-04-01
TN2016000268A1 (en) 2017-10-06

Similar Documents

Publication Publication Date Title
SV2016005245A (es) Compuestos derivados y composiciones de n-azaspirocicloalcano n-heteroaril sustituido para inhibir la actividad de shp2
UY36308A (es) Inhibidores de histona acetiltransferasas espirocíclicas (hat) y métodos para su uso
ZA201802657B (en) Crystal forms of beta-nicotinamide mononucleotide
CL2016001579A1 (es) Nuevas indazolcarboxamidas, procedimientos para su preparación, preparaciones farmacéuticas que las contienen, así como su uso para la preparación de medicamentos.
CR20160205A (es) Inhibidores de kras g12c
NI201600049A (es) Inhibidores de kras g12c
CL2017000902A1 (es) Dihidropirrolopiridinas inhibidoras de ror-gamma
CL2016003293A1 (es) Inhibidores de mnk y método relacionado al mismo
EA201691582A1 (ru) Новые фармацевтические препараты
SV2016005153A (es) Compuestos y composiciones como inhibidores de la mek
ECSP13013021A (es) Compuestos de benzotiazol y su uso farmacéutico
UY32809A (es) Compuestos y composiciones como inhibidores de cinasa s y k
CO2017004714A2 (es) Formas cristalinas de 5-cloro-n4-[2-(dimetilfosforil)fenil]-n2-{2-metoxi-4-[4-(4-metilpiperazin-1-il)piperidin-1-il]pirimidina-2,4-diamina
CR20140175A (es) Compuestos y métodos para mejorar las respuestas inmunitarias innatas
UY33885A (es) Inhibición de la il17 y del ifn-gamma para el tratamiento de las inflamaciones autoinmunes
AR100306A1 (es) Análogos de glucagón estables y uso para el tratamiento de la hipoglucemia
DOP2016000297A (es) Composiciones farmacéuticas útiles para tratar enfermedades infecciosas
ECSP18003372A (es) Compuestos tricíclicos y su uso como inhibidores de la fosfodiesterasa
MX2016008841A (es) Moduladores heterociclicos de la sintesis de lipidos para su uso contra el cancer e infecciones virales.
CR20160527A (es) Derivados de carboxamida
CO2018007610A2 (es) Derivados de indano y su uso en terapias