WO1998034915A1 - Derives du n-hxdroxy-beta-sulfonyl-propionamide et leur utilisation comme inhibiteurs des metalloproteases matrices - Google Patents

Derives du n-hxdroxy-beta-sulfonyl-propionamide et leur utilisation comme inhibiteurs des metalloproteases matrices Download PDF

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Publication number
WO1998034915A1
WO1998034915A1 PCT/IB1998/000101 IB9800101W WO9834915A1 WO 1998034915 A1 WO1998034915 A1 WO 1998034915A1 IB 9800101 W IB9800101 W IB 9800101W WO 9834915 A1 WO9834915 A1 WO 9834915A1
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Prior art keywords
alkyl
aryl
alkoxy
aryloxy
heteroaryl
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PCT/IB1998/000101
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English (en)
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Ralph Pelton Robinson
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Pfizer Inc.
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Priority to AU54935/98A priority Critical patent/AU5493598A/en
Priority to CA002279863A priority patent/CA2279863A1/fr
Priority to EP98900334A priority patent/EP0966438A1/fr
Priority to BR9807824-0A priority patent/BR9807824A/pt
Priority to JP10534044A priority patent/JP2000507975A/ja
Publication of WO1998034915A1 publication Critical patent/WO1998034915A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
    • C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
    • 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

Definitions

  • the present invention relates to arylsulfonylamino hydroxamic acid derivatives which are inhibitors of matrix metalloproteinases or the production of tumor necrosis factor (TNF) and as such are useful in the treatment of a condition selected from the group consisting of arthritis,
  • the compounds of the present invention may be used in combination therapy with standard non- steroidal anti-inflammatory drugs (hereinafter NSAID'S) and analgesics for the treatment of
  • cytotoxic drugs such as ad ⁇ amycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and alkaloids, such as vinc ⁇ stine, in the treatment of cancer
  • This invention also relates to a method of using such compounds in the treatment of the above diseases in mammals, especially humans, and to pharmaceutical compositions useful therefor 20
  • Matrix-degrading metalloproteinases such as gelatmase, stromelysin and collagenase, are involved in tissue matrix degradation (e g collagen collapse) and have been implicated in many pathological conditions involving abnormal connective tissue and basement membrane matrix metabolism, such as arthritis (e . 25 osteoarth ⁇ tis and rheumatoid arthritis), tissue uiceration (e g .
  • Tumor necrosis factor is recognized to be involved in many infectious and auto-immune 30 diseases (W Fiers, FEBS Letters. 1991, 285, 199) Furthermore, it has been shown that TNF is the prime mediator of the inflammatory response seen in sepsis and septic shock (C E Spooner et al , Clinical Immunology and Immunopatholo ⁇ v. 1992, 62 S11) Summarv of the Invention
  • the present invention relates to a compound of the formula
  • R 2 is hydrogen or (C r C 6 )alkyl
  • R 3 and R 4 are independently selected from the group consisting of hydrogen, (C 1 -C ⁇ )alkyl, trifluoromethyl, tnfluoromethyl(C r C 6 )alkyl, (C r C 6 )alkyl(d ⁇ fluoromethylene), (C 1 -C 3 )alkyl(d ⁇ fluoromethylene)(C 1 -C 3 )alkyl, (C 6 -C 10 )aryl, (C 2 -C 9 )heteroaryl,
  • any of the carbon atoms of said ring, capable of forming an additional bond may be optionally substituted by a substituent (preferably zero to three substituents) independently selected from the group consisting of fluoro, chloro, bromo, (C 1 -C 6 )alkyl, (C r C 6 )alkoxy, perfluoro(C r C 3 )alkyl, perfluoro(C 1 -C 3 )alkoxy and (C 6 -C 10 )aryloxy, R is R O or R R N wherein R 6 and R 7 are each independently selected from the group consisting of hydrogen, (C C 6 )alkyl, (C 6 -C 10 )aryl(C C 6 )alkyl or (C 2 -C 9 )heteroaryl(C r C 6 )alkyl, wherein each of said (C 6 -C 10 )aryl and (C 2 -C 9 )heteroaryl moieties of said (C 6 -
  • R 8 is piperazinyl, (C 1 -C 6 )alkylp ⁇ peraz ⁇ nyl, (C 6 -C 10 )arylp ⁇ peraz ⁇ nyl,
  • Q is (C r C 6 )alkyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 - C 10 )aryl(C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryloxy(C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryl, (C 2 - C 9 )heteroaryl(C 2 -C 9 )heteroaryl, (C 1 -C 6 )alkyl(C 6 -C 10 )aryl, (C 1 -C 6 )alkoxy(C 6 -C 10 )aryl, (C 6 - C 10 )aryl(C r C 6 )alkoxy(C 6 -
  • the present invention also relates to the pharmaceutically acceptable acid addition salts of compounds of the formula I
  • the acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned base compounds of this invention are those which form non-toxic acid addition salts, ]_ ⁇ _, salts containing pharmacologically acceptable anions, such as the hydrochlonde, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate []_e_, 1 ,1'-methylene-b ⁇ s-(2-hydroxy-3- naphthoate)]saltsaltsaltsalt
  • the invention also relates to base addition salts of formula I
  • the chemical bases that may be used as reagents to prepare pharmaceutically acceptable base salts of those compounds of formula I that are acidic in nature are those that form non-toxic base salts with such compounds
  • Such non-toxic base salts include, but are not limited to those derived from such pharmacologically acceptable cations such as alkali metal cations (e g . potassium and sodium) and alkaline earth metal cations (e g .
  • ammonium or water- soluble amine addition salts such as N-methylglucam ⁇ ne-(meglum ⁇ ne), t ⁇ methyl-ammonium or diethylammonium, and the lower alkanolammonium salts such t ⁇ s-(hydroxymethyl)- methylammonium and other base salts of pharmaceutically acceptable organic amines
  • alkyl as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, branched or cyclic moieties or combinations thereof
  • alkoxy includes O-alkyl groups wherein “alkyl” is defined above
  • aryl as used herein, unless otherwise indicated, includes an organic radical derived from an aromatic hydrocarbon by removal of one hydrogen, such as phenyl or naphthyl
  • heteroaryl includes an organic radical derived from an aromatic heterocyclic compound by removal of one hydrogen, such as pyridyl, furyl, pyroyi, thienyl, isothiazolyl, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, py ⁇ midyl, quinolyl, isoquinoly., benzofuryl, isobenzofuryl, benzothienyl, pyrazolyl, indolyl, isoindolyl, punnyl, carbazolyl, isoxazolyl, thiazolyl, oxazolyl, benzthiazolyl or benzoxazolyl
  • acyl as used herein, unless otherwise indicated, includes a radical of the general formula RCO wherein R is alkyl, alkoxy, aryl, arylalkyl or arylalkoxy
  • acyloxy includes O-acyl groups wherein "acyl” is defined above
  • the compound of formula I may have chiral centers and therefore exist in different diaste ⁇ ome ⁇ c or enantiome ⁇ c forms
  • This invention relates to all optical isomers and stereoisomers of the compounds of formula I and mixtures thereof
  • Preferred compounds of formula I include those wherein R 1 is OH and R 2 is hydrogen
  • Other preferred compounds of formula I include those wherein both R 3 and R 4 are (C r C 6 )alkyl or R 3 and R 4 are taken together to form an optionally substituted (C 3 -C 6 )cycloalkyl ring or a benzo-fused(C 3 -C 6 )cycloalkyl ring or a group of the formula
  • Other preferred compounds of formula I include those wherein R 1 is hydroxy
  • Other preferred compounds of formula I include those wherein Q is (C 6 -C 10 )aryl or (C ⁇ - C 10 )aryloxy(C 6 -C 10 )aryl, wherein each (C 6 -C 10 )aryl moieties of said is (C 6 -C 10 )aryl or (C 6 - C 10 )aryloxy(C 6 -C 10 )aryl groups may be optionally substituted with one or more substituents independently selected from fluoro, chloro, bromo, (C r C ⁇ )alkyl, (C r C 6 )alkoxy or perfluoro(C 1 - C 3 )alkyl
  • More preferred compounds of formula I include those wherein Q is phenyl or phenoxyphenyl optionally substituted with one or more substituents independently selected from fluoro, chloro, bromo, (C r C 6 )alkyl, (C r C 6 )alkoxy or perfluoro(C 1 -C 3 )alkyl, more preferably the substituents are selected from fluoro, chloro, (C r C 6 )alkoxy or (C r C 6 )alkyl, most preferably the substituent is in the 4-pos ⁇ t ⁇ on
  • Specific preferred compounds of formula I include the following (2S)-2,N-d ⁇ hydroxy-3-(4-methoxybenzenesulfonyl)prop ⁇ onam ⁇ de, 3-[4-(4-fluorophenoxy)phenylsulfonyl]-2,N-d ⁇ hydroxyprop ⁇ onam ⁇ de, 2,N-d ⁇ hydroxy-2-[1-(4-methoxybenzenesulfonyl)cyclobutyl]acetam ⁇ de
  • the present invention also relates to a pharmaceutical composition for (a) the treatment of a condition selected from the group consisting of arthritis, osteoporosis, cancer, synergy with cytotoxic anticancer agents, tissue uiceration, macular degeneration, restenosis, pe ⁇ odontal disease, epidermolysis bullosa, sclentis, in combination with standard NSAID'S and analgesics and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of
  • the present invention also relates to a method for treating a condition selected from the group consisting of arthritis, osteoporosis, cancer, tissue uiceration, macular degeneration, restenosis, pe ⁇ odontal disease, epidermolysis bullosa, sclentis, compounds of formula I may be used in combination with standard NSAID'S and analgesics and in combination with cytotoxic anticancer agents, and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of tumor necrosis factor (TNF) in a mammal, including a human, comprising administering to said mammal an amount of a compound of formula I or a pharmaceutically acceptable salt thereof effective in treating such a condition
  • TNF tumor necrosis factor
  • Scheme 1 refers to the preparation of compounds of the formula I, wherein R 3 and R 4 are hydrogen
  • a compound of the formula i is prepared from a compound of the formula II by hydrogenolysis under an atmosphere of hydrogen in the presence of a catalyst in a reaction inert solvent
  • Suitable catalysts include 5% palladium on barium sulfate or 5% palladium on carbon, preferably 5% palladium on barium sulfate
  • Suitable solvents include an alcohol such as ethanol, methanol or isopropanol, preferably methanol
  • the aforesaid reaction may be performed at a pressure from about 1 to about 5 atmospheres, preferably about 3 atmospheres
  • Suitable temperatures for the aforesaid reaction range from about 20°C (room temperature) to about 60°C, preferably the temperature may range from about 20°C to about 25°C (i e room temperature)
  • the reaction is complete within about 0 5 hours to about 5 hours, preferably about 3 hours
  • the compound of formula II is prepared from a compound of formula III by reaction with O-benzylhydroxylamine hydrochlo ⁇ de, an activating agent, and a base in a reaction inert solvent
  • Suitable activating agents include (benzot ⁇ azol-l-yloxy)t ⁇ s(d ⁇ methylam ⁇ no) phosphonium hexafluorophosphate or 1-(3-(d ⁇ methylam ⁇ nopropyl)-3-ethylcarbod ⁇ m ⁇ de hydrochlonde, preferably (benzot ⁇ azol-l-yloxy)t ⁇ s(d ⁇ methylam ⁇ no) phosphonium hexafluorophosphate
  • Suitable bases include tertiary amines such as triethylamine, diisopropylethylamine or 4-N,N-d ⁇ methylam ⁇ nopy ⁇ d ⁇ ne, preferably triethylamine
  • the temperature of the aforesaid reaction may range from about 0°
  • the compound of formula III is prepared from a compound of formula IV by hydrogenolysis under an atmosphere of hydrogen in the presence of a catalyst in a reaction inert solvent
  • Suitable catalysts include palladium or 5-10% palladium on activated charcoal, preferably 10% palladium on activated charcoal
  • Suitable solvents include acetic acid, alcohols such as ethanol, methanol, or isopropanol, preferably ethanol
  • the aforesaid reaction may be performed at a pressure from about 1 to about 5 atmospheres, preferably about 3 atmospheres Suitable temperatures for the aforesaid reaction range from about 20°C (room temperature) to about 60°C, preferably the temperature may range from about 20°C to about 25°C (i e room temperature)
  • the reaction is complete within about 0 5 hours to about 24 hours, preferably about 3 hours
  • Suitable oxidants include meta- chloroperbenzoic acid, hydrogen peroxide or sodium perborate, preferably meta- chloroperbenzoic acid
  • Suitable solvents include halogenated solvents such as methylene chloride or chloroform, preferably methylene chloride
  • Suitable temperatures for the aforesaid reaction range from about 0°C to about 60°C, preferably the temperature may range from about 20°C to about 25°C (i e room temperature) The reaction is complete within about 0 5 hours to about 24 hours, preferably about 3 hours
  • Compounds of the formula V, wherein R 1 is hydroxy can be prepared from compounds of the formula VI by reaction with a Gngnard reagent and a thiol of the formula QSH in a reaction inert solvent
  • Gngnard reagents include ethyl magnesium bromide or phenyl magnesium bromide, preferably ethyl magnesium bromide
  • Suitable solvents include ethers such as diethy 1 ether, tetrahydrofuran or 1 ,2-d ⁇ methoxyethane, preferably the solvent is a mixture of tetrahydrofuran and diethyl ether
  • Suitable temperatures for the aforesaid reaction are from about -78°C to about 50°C , preferably from about 0°C to about 25°C (i e room temperature) The reaction is complete in about 1 to about 24 hours, preferably about 3 hours Compounds of the formula V, wherein R 1 is (C 6 -C 10 )aryl(C
  • Compounds of the formula VI can be prepared by methods well known to those of ordinary skill in the art Compounds of the formula VI can also be prepared by peracid oxidation (e g , meta-chloroperbenzoic acid) of the corresponding , ⁇ -unsaturated benzyl esters as described in Jerry March, Advanced Organic Chemistry. 735 (3rd ed , 1985)
  • the corresponding , ⁇ -unsaturated benzyl esters may be prepared by Knovenagel condensation between a malonate monobenzyl ester and paraformaldehyde in the presence of pipendine as described in H O House, Modern Synthetic Reactions. 649-651 (2nd ed , WA Benjamin, Menlo Park, California, 1972)
  • Scheme 2 refers to the preparation of compounds of the formula I, wherein R 2 is hydrogen and R 1 is OH
  • compounds of formula I can be prepared from compounds of the formula VII by hydrogenolysis under an atmosphere of hydrogen in the presence of a catalyst in a reaction inert solvent
  • Suitable catalysts include 5% palladium on barium sulfate or 5% palladium on carbon, preferably 5% palladium on barium sulfate
  • Suitable solvents include an alcohol such as ethanol, methanol or isopropanol, preferably methanol
  • the aforesaid reaction may be performed at a pressure from about 1 to about 5 atmospheres, preferably about 3 atmospheres
  • Suitable temperatures for the aforesaid reaction range from about 20°C (room temperature) to about 60°C, preferably the temperature may range from about 20°C to about 25°C (i e room temperature)
  • the reaction is complete within about 0 5 hours to about 5 hours, preferably about 3 hours
  • the compound of formula IX is prepared from a compound of the formula X by reaction with an excess of sodium pe ⁇ odate in the presence of catalytic ruthenium trichloride hydrate
  • the aforesaid reaction is conducted at a temperature from about 0°C to about 35°C, preferably from about 20°C to about 25°C (i e room temperature)
  • Suitable solvents include acetone or a mixture of acetonitnle, carbon tetrachlo ⁇ de and water, preferably a 1 1 2 mixture of acetonitile, carbon tetrachlonde and water
  • the reaction is conducted from about 0 5 to about 2 hours, preferably about 1 25 hours
  • the compound of the formula X wherein "P" is pivaloyl, acetyl or benzoyl, is prepared by reaction of a compound of the formula XI with a protecting group reagent in the presence of a base in a reaction inert solvent
  • Suitable protecting group reagents include pivaloyl chloride, pivaloic anhydride, acetyl chloride, acetic anhydride, benzoyl clo ⁇ de or benzoic anhydride, preferably acetic anhydride
  • Suitable bases include tertiary amine bases such as pyridine or 4-N,N-d ⁇ methylam ⁇ nopyr ⁇ d ⁇ ne, preferably 4-N, N-dimethylaminopy ⁇ dine
  • the temperature of the aforesaid reaction is from about 0°C to about 30°C, preferably from about 20°C to about 25°C (i e room temperature)
  • Suitable solvents include halogenated solvents such as methylene chlor
  • the compound of formula XI is prepared from a compound of the formula XII by reaction with 2-furaldehyde and a strong base in a polar aprotic solvent
  • Suitable bases include potassium-tert -butoxide, lithium diisopropylamide, and butyl lithium, preferably 2 5 M n- butyllithium in hexane
  • the temperature of the aforesaid reaction is from about -78°C to about 0°C, preferably about -78°C
  • Suitable solvents include diethyl ether, tetrahydrofuran, or 1,2- dimethoxyethane, preferably the solvent is tetrahydrofuran
  • the reaction is conducted from about 0 25 hours to about 6 hours, preferably about 0 33 hours
  • the compound of formula XII is prepared from a compound of the formula XIII by reaction with an oxidant in a reaction inert solvent Suitable oxidants include meta- chloroperbenzoic acid
  • the compound of the formula XIII is prepared from a compound of the formula XIV by reaction with a thiol of the formula QSH in the presence of a base in an aprotic solvent
  • bases include sodium hydride, ethyl magnesium bromide, lithium diisopropyl amide, potassium hydride, or sodium methoxide, preferably sodium hydride
  • the temperature of the aforesaid reaction is from about 0°C to about 60°C, preferably 20°C to about 25°C (i e room temperature)
  • Suitable solvents include aprotic solvents such as methylene chloride, tetrahydrofuran or N,N-d ⁇ methylformam ⁇ de, preferably N,N-d ⁇ methylformam ⁇ de
  • the reaction is conducted for about 1 hour to about 48 hours, preferably about 16 hours
  • Compounds of the formula XIV and QSH are commercially available or can be made by methods well known to those of ordinary skill in the art
  • Compounds of the formula QSH can also be prepared by reaction of an alkyl or aryl halide with sodium sulfhyd ⁇ de as described in Jerry March, Advanced Organic Chemistry. 360 and 589 (3rd ed , 1985)
  • compounds of the formula QSH can also be prepared by reaction of an aryl diazonium salt with sodium sulfhydnde as described in March ⁇ d_ at 601
  • compounds of the formula QSH can also be prepared by reaction of a Gngnard reagent with sulfur as described in March id.
  • compounds of the formula QSH can also be prepared by reduction of a sulfonyl chloride, sulfonic acid or disulfide as described in March ⁇ d_ at 1107 and 1110
  • Scheme 3 refers to the preparation of compounds of the formula I, wherein R 1 is other than hydroxy and R 2 is hydrogen
  • compounds of the formula I are prepared from compounds of the formula XVII by hydrogenolysis according to methods analogous to the methods described for converting compounds of formula VII to compounds of formula I in Scheme 2
  • compounds of the formula XVII are prepared from compounds of the formula XVI by reaction with O-benzylhydroxylamine hydrochlo ⁇ de in the presence of a catalyst and a base in a reaction inert solvent according to methods analogous to the conversion of compounds of the formula IX to formula VIII as described above in Scheme 2
  • Compounds of the formula XVI are prepared from compounds of the formula XV by reaction with an excess of sodium periodate in the presence of a catalyst according to methods analogous to those used for the conversion of compounds of the formula X to formula IX as described above in Scheme 2.
  • R 1 is (C 6 -C 10 )aryl(C C 6 )alkoxy or (C,-C e )alkoxy
  • R 1a L is a leaving group and R 1a is (C 6 -C 10 )aryl(C 1 -C 6 )alkyl or (C 1 -C ⁇ )alky1, in the presence of a strong base in an aprotic polar solvent.
  • Suitable leaving groups include chloro, fluoro, bromo, mesylate, triflate or tosylate.
  • the leaving group is iodo.
  • Suitable bases include lithium dialkyi amides such as lithium N-isopropyl-N-cyclohexylamide or lithium diisopropyl amide, potassium t-butoxide, sodium amide, potassium hydride or sodium hydride, preferably sodium hydride.
  • Suitable solvents include ethers (such as THF, diethyl ether or 1 ,2-dimethoxyethane), preferably THF. The aforesaid reaction is conducted at about -78°C to about 0°C, preferably at about 0°C.
  • Suitable leaving groups include chloro, fluoro, bromo or (R b )0- (i.e. an anhydride).
  • the leaving group is chloro.
  • Suitable bases include tertiary amine bases such as triethylamine, pyridine or 4-dimethylaminopyridine, preferably triethylamine.
  • the temperature of the aforesaid reaction is from about 0°C to about 30°C, preferably from about 20°C to about 25°C (i.e. room temperature).
  • Suitable solvents include halogenated solvents such as methylene chloride or chloroform, preferably methylene chloride. The reaction is conducted from about 1 hour to about 24 hours, preferably for about 2 hours.
  • Scheme 4 refers to the preparation of compounds of the formula I, wherein R 2 is other than hydrogen and R 3 and R 4 are other than hydrogen.
  • compounds of the formula I are prepared from compounds of the formula XXIII by hydrogenolysis under an atmosphere of hydrogen in the presence of a catalyst in a reaction inert solvent.
  • Suitable catalysts include 5% palladium on barium sulfate or 5% palladium on carbon, preferably 5% palladium on barium sulfate.
  • Suitable solvents include an alcohol such as ethanol, methanol or isopropanol, preferably methanol
  • the aforesaid reaction may be performed at a pressure from about 1 to about 5 atmospheres, preferably about 3 atmospheres
  • Suitable temperatures for the aforesaid reaction range from about 20°C (room temperature) to about 60°C, preferably the temperature may range from about 20°C to about 25°C (i e room temperature)
  • the reaction is complete within about U 5 hours to about 5 hours, preferably about 3 hours
  • the compound of the formula XXIII is prepared from a compound of the formula XXII by reaction with O-benzylhydroxylamine hydrochlonde in the presence of a catalyst and a base in a reaction inert solvent
  • Suitable catalysts include (benzotr ⁇ azol-1- yloxy)t ⁇ s(d ⁇ methylam ⁇ no)phosphon ⁇ um hexafluorophosphate or 1-(3-(d ⁇ methylam ⁇ nopropyl)-3- ethylcarbodiimide hydrochlonde, preferably (benzot ⁇ azol-l-yloxy)tr ⁇ s(d ⁇ methylam ⁇ no) phosphonium hexafluorophosphate
  • Suitable bases include tertiary amines such as triethylamine diisopropylethylamine or dimethylaminopy ⁇ dine, preferably triethylamine
  • the aforesaid reaction temperature is from about 0° C to about
  • the compound of the formula XXII can be prepared by deprotection of a compound of the formula XXI by reaction with an alkali metal hydroxide in a polar solvent
  • Suitable alkali metal hydroxides include lithium hydroxide, sodium hydroxide or potassium hydroxide, preferably lithium hydroxide, most preferably about 5 equivalents of the alkali metal hydroxide
  • the aforesaid reaction may conducted at a temperature from about 0°C to about 60°C, preferably from about 20°C to about 25°C (i e room temperature)
  • Suitable solvents include a mixture of water and an alcohol such as methanol or ethanol and, optionally an water miscible ether such as tetrahydrofuran or 1 ,2-d ⁇ methoxyethane
  • the solvent system is methanol/water/tetrahydrofuran
  • the reaction is conducted from about 1 to about 72 hours, preferably about 24 hours
  • Suitable bases include sodium hydride (NaH), potassium-tert -butoxide, lithium d ⁇ sopropylamide, and butyl lithium, preferably 2 5 M n-butyllithium in hexane
  • NaH sodium hydride
  • potassium-tert -butoxide lithium d ⁇ sopropylamide
  • butyl lithium preferably 2 5 M n-butyllithium in hexane
  • the temperature of the aforesaid reaction is from about -78°C to about 0°C, preferably about -78°C
  • Suitable solvents include diethyl ether, tetrahydrofuran, or 1 ,2-d ⁇ methoxyethane, preferably the solvent is tetrahydrofuran
  • the reaction is conducted from about 0 25 hours to about 6 hours, preferably about 0 33 hours
  • compounds of the formula I wherein R 1 is other than hydroxy, R 2 is other than hydrogen and R and R 4 are other than hydrogen, can be prepared from compounds of the formula XXV by methods analogous to the conversion of compounds of the formula XXII to compounds of formula I, as described above in Scheme 4 Compounds of the formula XXV can be prepared from compounds of the formula
  • Suitable catalysts include palladium or 5- 10% palladium on activated charcoal, preferably 10% palladium on activated charcoal
  • Suitable solvents include acetic acid, alcohols such as ethanol, methanol, or isopropanol, preferably ethanol
  • the aforesaid reaction may be performed at a pressure from about 1 to about 5 atmospheres, preferably about 3 atmospheres Suitable temperatures for the aforesaid reaction range from about 20°C (room temperature) to about 60°C, preferably the temperature may range from about 20°C to about 25°C (i e room temperature)
  • the reaction is complete within about 0 5 hours to about 24 hours, preferably about 3 hours
  • (C r C 6 )alkoxy can be prepared from compounds of the formula XXI by reaction with an arylalkyl or alkyl halide in the presence of a base in an aprotic solvent
  • bases include sodium hydride, ethyl magnesium bromide, lithium diisopropyl amide, potassium hydride, or sodium methoxide, preferably sodium hydride
  • the temperature of the aforesaid reaction is from about 0°C to about 60°C, preferably 20°C to about 25°C (i e room temperature)
  • Suitable solvents include aprotic solvents such as methylene chloride, tetrahydrofuran or N,N- dimethylformamide, preferably N,N-d ⁇ methylformam ⁇ de
  • the reaction is conducted for about 1 hour to about 48 hours, preferably about 16 hours
  • Suitable bases include tertiary amines such as triethylamine, dnsopropylethylamine or 4-N,N-d ⁇ methylam ⁇ nopyr ⁇ d ⁇ ne, preferably triethylamine
  • the temperature of the aforesaid reaction may range from about 0°C to about 60°C, preferably about 20°C (room temperature)
  • Suitable solvents include halogenated solvents such as methylene chloride or chloroform, or ethers such as THF or diethyl ether, preferably the solvent is methylene chloride
  • the acids which are used to prepare the pharmaceutically acceptable acid addition salts of the base compounds of this invention are those which form non-toxic acid addition salts, ]_ ⁇ _, salts containing pharmacologically acceptable anions, such as hydrochlonde, hydrobromide, hydroiodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate and pamoate [ ⁇ _e_, 1 ,1'-methylene-b ⁇ s-(2-hydroxy-3- naphthoate)] salts
  • pharmacologically acceptable anions such as hydrochlonde, hydrobromide, hydroiodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate
  • Those compounds of the formula I which are also acidic in nature, are capable of forming base salts with various pharmacologically acceptable cations
  • examples of such salts include the alkali metal or alkaline-earth metal salts and particularly, the sodium and potassium salts
  • These salts are all prepared by conventional techniques
  • the chemical bases which are used as reagents to prepare the pharmaceutically acceptable base salts of this invention are those which form non-toxic base salts with the herein described acidic compounds of formula I
  • These non-toxic base salts include those derived from such pharmacologically acceptable cations as sodium, potassium, calcium and magnesium, etc
  • These salts can easily be prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations, and then evaporating the resulting solution to dryness, preferably under reduced pressure Alternatively, they may also be prepared by mixing lower alkanolic solutions of the acidic compounds and the desired alkali metal alkoxide together, and then evaporating
  • the compounds of formula I or their pharmaceutically acceptable salts (hereinafter also referred to as the compounds of the present invention) to inhibit matrix metalloproteinases or the production of tumor necrosis factor (TNF) and, consequently, demonstrate their effectiveness for treating diseases characterized by matrix metalloproteinase or the production of tumor necrosis factor is shown by the following yjtro assay tests
  • MMP-1 Human Colla ⁇ enase
  • Human recombinant collagenase is activated with trypsin using the following ratio 10 mg trypsin per 100 mg of collagenase
  • the trypsin and collagenase are incubated at room temperature for 10 minutes then a five fold excess (50 mg/10 mg trypsin) of soybean trypsin inhibitor is added 10 mM stock solutions of inhibitors are made up in dimethyl sulfoxide and then diluted using the following Scheme
  • Collagenase is diluted to 400 ng/ml and 25 ml is then added to appropriate wells of the microfluor plate Final concentration of collagenase in the assay is 100 ng/ml
  • Substrate (DNP-Pro-Cha-Gly-Cys(Me)-H ⁇ s-Ala-Lys(NMA)-NH 2 ) is made as a 5 mM stock in dimethyl sulfoxide and then diluted to 20 mM in assay buffer The assay is initiated by the addition of 50 ml substrate per well of the microfluor plate to give a final concentration of 10 mM
  • Fluorescence readings (360 nM excitation, 460 nm emission) were taken at time 0 and then at 20 minute intervals The assay is conducted at room temperature with a typical assay time of 3 hours
  • Fluorescence vs time is then plotted for both the blank and collagenase containing samples (data from triplicate determinations is averaged)
  • a time point that provides a good signal (the blank) and that is on a linear part of the curve (usually around 120 minutes) is chosen to determine IC 50 values
  • the zero time is used as a blank for each compound at each concentration and these values are subtracted from the 120 minute data
  • Data is plotted as inhibitor concentration vs % control (inhibitor fluorescence divided by fluorescence of collagenase alone x 100)
  • IC 50 's are determined from the concentration of inhibitor that gives a signal that is 50% of the control
  • IC 50 's are reported to be ⁇ 0 03 mM then the inhibitors are assayed at concentrations of 0 3 mM, 0 03 mM, 0 03 mM and 0 003 mM
  • MMP-2 Inhibition of Gelatmase activity is assayed using the Dnp-Pro-Cha-Gly-Cys(Me)-H ⁇ s-Ala- Lys(NMA)-NH 2 substrate (10 mM) under the same conditions as inhibition of human collagenase (MMP-1)
  • 72kD gelatmase is activated with 1 mM APMA (p-aminophenyl mercuric acetate) for 15 hours at 4°C and is diluted to give a final concentration in the assay of 100 mg/ml
  • Inhibitors are diluted as for inhibition of human collagenase (MMP-1) to give final concentrations in the assay of 30 mM, 3 mM, 0 3 mM and 0 03 mM Each concentration is done in triplicate
  • Fluorescence readings (360 nm excitation, 460 emission) are taken at time zero and then at 20 minutes intervals for 4 hours
  • IC 50 's are determined as per inhibition of human collagenase (MMP-1 ) If IC 50 's are reported to be less than 0 03 mM, then the inhibitors are assayed at final concentrations of 0 3 mM, 0 03 mM, 0 003 mM and 0 003 mM
  • MMP-3 Inhibition of Stromelysin Activity
  • Inhibition of stromelysin activity is based on a modified spectrophotometric assay described by Weingarten and Feder (Wemberg, H and Feder, J , Spectrophotometric Assay for Vertebrate Collagenase, Anal Biochem 147, 437-440 (1985))
  • Hydrolysis of the thio peptolide substrate [Ac-Pro-Leu-Gly-SCH[CH 2 CH(CH 3 ) 2 ]CO-Leu-Gly-OC 2 H 5 ] yields a mercaptan fragment that can be monitored in the presence of Ellman's reagent
  • Human recombinant prostromelysin is activated with trypsin using a ratio of 1 ml of a 10 mg/ml trypsin stock per 26 mg of stromelysin The trypsin and stromeiysin are incubated at 37°C for 15 minutes followed by 10
  • Assays are conducted in a total volume of 250 ml of assay buffer (200 mM sodium chloride, 50 mM MES, and 10 mM calcium chloride, pH 6 0) in 96-well microliter plates
  • Activated stromelysin is diluted in assay buffer to 25 mg/ml
  • Ellman's reagent (3-Carboxy-4- nitrophenyl disulfide) is made as a 1M stock in dimethyl formamide and diluted to 5 mM in assay buffer with 50 ml per well yielding at 1 mM final concentration 10 mM stock solutions of inhibitors are made in dimethyl sulfoxide and diluted serially in assay buffer such that addition of 50 mL to the appropriate wells yields final concentrations of 3 mM, 0 3 mM, 0 003 mM, and 0 0003 mM All conditions are completed in triplicate
  • a 300 mM dimethyl sulfoxide stock solution of the peptide substrate is diluted to 15 mM in assay buffer and the assay is initiated by addition of 50 ml to each well to give a final concentration of 3 mM substrate Blanks consist of the peptide substrate and Ellman's reagent without the enzyme Product formation was monitored at 405 nm with a Molecular Devices
  • MMP-13 Human recombinant MMP-13 is activated with 2mM APMA (p-aminophenyl mercuric acetate) for 1 5 hours, at 37°C and is diluted to 400 mg/ml in assay buffer (50 mM Tns, pH 7 5, 200 mM sodium chloride, 5mM cal ⁇ um chloride, 20mM zinc chloride, 0 02% b ⁇ j) Twenty-five microliters of diluted enzyme is added per well of a 96 well microfluor plate The enzyme is then diluted in a 1 4 ratio in the assay by the addition of inhibitor and substrate to give a final concentration in the assay of 100 mg/ml
  • assay buffer 50 mM Tns, pH 7 5, 200 mM sodium chloride, 5mM cal ⁇ um chloride, 20mM zinc chloride, 0 02% b ⁇ j
  • 10 mM stock solutions of inhibitors are made up in dimethyl sulfoxide and then diluted in assay buffer as per the inhibitor dilution scheme for inhibition of human collagenase (MMP-1) Twenty-five microliters of each concentration is added in triplicate to the microfluor plate The final concentrations in the assay are 30 mM, 3mM, 0 3 mM, and 0 03 mM Substrate (Dnp-Pro-Cha-Gly-Cys(Me)-H ⁇ s-Ala-Lys(NMA)-NH 2 ) is prepared as for inhibition of human collagenase (MMP-1) and 50 ml is added to each well to give a final assay concentration of 10 mM Fluorescence readings (360 nM excitation, 450 emission) are taken at time 0 and every 5 minutes for 1 hour
  • Positive controls consist of enzyme and substrate with no inhibitor and blanks consist of substrate only
  • IC 50 's are determined as per inhibition of human collagenase (MMP-1) If IC 50 's are reported to be less than 0 03 mM, inhibitors are then assayed at final concentrations of 0 3 mM, 0 03 mM, 0 003 mM and 0 0003 mM
  • the active compound will be administered at dosages between about 0 1 and 25 mg/kg body weight of the subject to be treated per day, preferably from about 0 3 to 5 mg/kg
  • the active compound will be administered orally or parenterally
  • some variation in dosage will necessarily occur depending on the condition of the subject being treated
  • the person responsible for administration will, in any event, determine the appropriate dose for the individual subject
  • the compounds of the present invention can be administered in a wide variety of different dosage forms, in general, the therapeutically effective compounds of this invention are present in such dosage forms at concentration levels ranging from about 5 0% to about 70% by weight
  • tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and glycine may be employed along with various disintegrants such as starch (and preferably corn, potato or tapioca starch), alginic acid and certain complex silicates, together with granulation binders like polyvinylpyrro done, sucrose, gelation and acacia Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tablettmg purposes
  • Solid compositions of a similar type may also be employed as fillers in gelatin capsules, preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols
  • the active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes and, if so desired, emulsifying and/or suspending agents as well
  • a sterile mjectable solution of the active ingredient is usually prepared Solutions of a therapeutic compound of the present invention in either sesame or peanut oil or in aqueous propylene glycol may be employed The aqueous solutions should be suitably adjusted and buffered, preferably at a pH of greater than 8, if necessary and the liquid diluent first rendered isotonic These aqueous solutions are suitable intravenous injection purposes
  • the oily solutions are suitable for intraarticular, intramuscular and subcutaneous injection purposes
  • the preparation of all these solutions under sterile conditions is readily accomplished by standard pharmaceutical techniques well known to those skilled in the art
  • compounds can be administered intramuscularly or subcutaneously at dosage levels of about 0 1 to 50 mg/kg/day, advantageously 0 2 to 10 mg/kg/day given in a single dose or up to 3 divided doses
  • the active compounds of the invention may also be formulated in rectal compositions such as supposi
  • the active compounds of the invention are conveniently delivered in the form of a solution or suspension from a pump spray container that is squeezed or pumped by the patient or as an aerosol spray presentation from a pressurized container or a nebulizer, with the use of a suitable propellant, e g .
  • the dosage unit may be determined by providing a valve to deliver a metered amount
  • the pressurized container or nebulizer may contain a solution or suspension of the active compound
  • Capsules and cartridges made, for example, from gelatin
  • an inhaler or insufflator may be formulated containing a powder mix of a compound of the invention and a suitable powder base such as lactose or starch
  • Example 4 2.N-DIHYDROXY-2-f1-(4-METHOXYBENZENESULFONYL)CYCLOPENTYL1ACETAMlDE 2,N-Dihydroxy-2-[1-(4-methoxybenzenesulfonyl)cyclopentyl]acetamide was prepared by a method analogous to that described in Example 3 using 4-methoxybenzenethiol and cyclopentyl bromide as startinc* materials. MS m/z 328 (M-1).
  • DIHYDROXYACETAMIDE 2- ⁇ 1-[4-(4-Fluorophenoxy)benzenesulfonyl]cyclobutyl ⁇ -2,N-dihydroxyacetamide was prepared by a method analogous to that described in Example 3 using 4-(4- fluorophenoxy)benzenethiol and cyclobutyl bromide as starting materials. MS m/z 394 (M-1).
  • 4-(4-Fluorophenoxy)benzenethiol was obtained as follows. Chlorosulfonic acid (26 mL, 0.392 mole) was added dropwise to ice-cooled 4-fluorophenoxybenzene (36.9 grams, 0.196 mole) with mechanical stirring. When addition was complete, the mixture was stirred at room temperature for 4 hours. The mixture was then poured into ice water. The product, 4-
  • DIHYDROXYACETAMIDE 2- ⁇ 1-[4-(4-Fluorophenoxy)benzenesulfonyl]cyclopentyl ⁇ -2,N-d ⁇ hydroxyacetam ⁇ de was prepared by a method analogous to that described in Example 3 using (4- fluorophenoxy)benzeneth ⁇ ol and cyclopentyl bromide as starting materials MS m/z 408 (M-1)

Abstract

L'invention porte sur un composé de formule (I) dans laquelle R?1, R2, R3, R4¿ et Q sont définis dans la description, sur des préparations pharmaceutiques le contenant, et sur leur utilisation à des fins médicales comme inhibiteurs des métalloprotéases matrices et générateurs du facteur de nécrose tumorale (TNF).
PCT/IB1998/000101 1997-02-07 1998-01-27 Derives du n-hxdroxy-beta-sulfonyl-propionamide et leur utilisation comme inhibiteurs des metalloproteases matrices WO1998034915A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU54935/98A AU5493598A (en) 1997-02-07 1998-01-27 N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases
CA002279863A CA2279863A1 (fr) 1997-02-07 1998-01-27 Derives du n-hxdroxy-beta-sulfonyl-propionamide et leur utilisation comme inhibiteurs des metalloproteases matrices
EP98900334A EP0966438A1 (fr) 1997-02-07 1998-01-27 Derives du n-hxdroxy-beta-sulfonyl-propionamide et leur utilisation comme inhibiteurs des metalloproteases matrices
BR9807824-0A BR9807824A (pt) 1997-02-07 1998-01-27 Derivados de n-hidróxi-beta-sulfonil-propionamida e seu uso como inibidores de metaloproteinases de matriz
JP10534044A JP2000507975A (ja) 1997-02-07 1998-01-27 Ｎ−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用

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US3740297P 1997-02-07 1997-02-07
US60/037,402 1997-02-07

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JP (1) JP2000507975A (fr)
AP (1) AP9801169A0 (fr)
AR (1) AR011116A1 (fr)
AU (1) AU5493598A (fr)
BR (1) BR9807824A (fr)
CA (1) CA2279863A1 (fr)
HR (1) HRP980062A2 (fr)
MA (1) MA26472A1 (fr)
PA (1) PA8446001A1 (fr)
TN (1) TNSN98022A1 (fr)
WO (1) WO1998034915A1 (fr)
ZA (1) ZA98970B (fr)

Cited By (255)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0984959A1 (fr) * 1997-03-04 2000-03-15 Monsanto Company Composes aromatiques d'acide sulfonyle alpha-hydroxy hydroxamique
US6191300B1 (en) 1999-04-16 2001-02-20 Eastman Chemical Company Process for the preparation of cyclopropylacetonitrile
US6362183B1 (en) * 1997-03-04 2002-03-26 G. D. Searle & Company Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds
US6437177B1 (en) 1997-11-21 2002-08-20 Martha A. Warpehoski α-hydroxy, -amino, and halo derivatives of β-sulfonyl hydroxamic acids as matrix metallopropteinases inhibitors
US6833456B2 (en) 2002-03-01 2004-12-21 Agouron Pharmaceuticals, Inc. Indolyl-urea derivatives of thienopyridines useful as antiangiogenic agents, and methods for their use
WO2005023759A2 (fr) 2003-09-03 2005-03-17 Array Biopharma Inc. Inhibiteurs heterocycliques de mek et procedes d'utilisation associes
US6869962B2 (en) 2002-06-14 2005-03-22 Agouron Pharmaceuticals, Inc. Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use
WO2005051300A2 (fr) 2003-11-19 2005-06-09 Array Biopharma Inc. Inhibiteurs bicycliques de mek et leurs procedes de production
US6995171B2 (en) 2001-06-21 2006-02-07 Agouron Pharmaceuticals, Inc. Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents
US7037498B2 (en) 2001-01-05 2006-05-02 Abgenix, Inc. Antibodies to insulin-like growth factor I receptor
US7053107B2 (en) 2002-12-19 2006-05-30 Agouron Pharmaceuticals, Inc. Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
WO2007035744A1 (fr) 2005-09-20 2007-03-29 Osi Pharmaceuticals, Inc. Marqueurs biologiques predictifs d'une reaction anticancereuse aux inhibiteurs kinase du recepteur du facteur de croissance 1 analogue a l'insuline
WO2007044084A2 (fr) 2005-05-18 2007-04-19 Array Biopharma Inc. Inhibiteurs heterocycliques de mek et leurs procedes d'utilisation
US7208500B2 (en) 2003-08-29 2007-04-24 Agouron Pharmaceuticals, Inc. Thienopyridine-phenylacetamides and their derivatives useful as new anti-angiogenic agents
WO2007076245A2 (fr) 2005-12-21 2007-07-05 Array Biopharma Inc. Nouveau sel hydrogenosulfate
WO2008075196A1 (fr) 2006-12-15 2008-06-26 Pfizer Products Inc. Dérivés du benzamidazole
US7429667B2 (en) 2005-01-20 2008-09-30 Ardea Biosciences, Inc. Phenylamino isothiazole carboxamidines as MEK inhibitors
WO2008129380A1 (fr) 2007-04-18 2008-10-30 Pfizer Products Inc. Dérivés de sulfonyle amide pour le traitement d'une croissance cellulaire anormale
WO2009018238A1 (fr) 2007-07-30 2009-02-05 Ardea Biosciences, Inc. Combinaisons d'inhibiteurs de mek et d'inhibiteurs de raf kinase et leurs utilisations
WO2009082687A1 (fr) 2007-12-21 2009-07-02 Genentech, Inc. Azaindolizines et procédés d'utilisation
WO2009114870A2 (fr) 2008-03-14 2009-09-17 Intellikine, Inc. Inhibiteurs de kinases, et procédés d’utilisation associés
EP2130536A1 (fr) 2002-03-13 2009-12-09 Array Biopharma, Inc. Dérivés de benzimidazole d'alkylat N3 en tant qu'inhibiteurs de Mek
WO2010045495A2 (fr) 2008-10-16 2010-04-22 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Anticorps entièrement humains dirigés contre un antigène associé au mélanome de masse moléculaire élevée et leurs utilisations
WO2010051043A1 (fr) 2008-11-03 2010-05-06 Intellikine, Inc. Inhibiteurs de la benzoxazole kinase et procédés d'utilisation
US7759518B2 (en) 2005-07-21 2010-07-20 Ardea Biosciences Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK
WO2010090764A1 (fr) 2009-02-09 2010-08-12 Supergen, Inc. Inhibiteurs pyrrolopyrimidinyle de l'axi kinase
WO2010091150A1 (fr) 2009-02-05 2010-08-12 Immunogen, Inc. Nouveaux dérivés de benzodiazépine
WO2010099363A1 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010098866A1 (fr) 2009-02-27 2010-09-02 Supergen, Inc. Inhibiteurs cyclopentathiophène/cyclohexathiophène de l'adn méthyltransférase
WO2010099138A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Procédés pour l'identification d'agents qui inhibent les cellules tumorales de type mésenchymateuses ou leur formation
WO2010099137A2 (fr) 2009-02-26 2010-09-02 Osi Pharmaceuticals, Inc. Procédés in situ pour surveiller l'état emt de cellules tumorales in vivo
WO2010099139A2 (fr) 2009-02-25 2010-09-02 Osi Pharmaceuticals, Inc. Thérapie anti-cancer combinée
WO2010099364A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010108652A1 (fr) 2009-03-27 2010-09-30 Ardea Biosciences Inc. Dihydropyridine-sulfonamides et dihydropyridine-sulfamides en tant qu'inhibiteurs de mek
US7820664B2 (en) 2007-01-19 2010-10-26 Bayer Schering Pharma Ag Inhibitors of MEK
WO2010129816A2 (fr) 2009-05-07 2010-11-11 Intellikine, Inc. Composés hétérocycliques et leurs utilisations
US7842836B2 (en) 2006-04-11 2010-11-30 Ardea Biosciences N-aryl-N'alkyl sulfamides as MEK inhibitors
US7858643B2 (en) 2004-08-26 2010-12-28 Agouron Pharmaceuticals, Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
WO2011014726A1 (fr) 2009-07-31 2011-02-03 Osi Pharmaceuticals, Inc. Polythérapie par inhibiteur de mtor et inhibiteur de l’angiogenèse
WO2011022439A1 (fr) 2009-08-17 2011-02-24 Intellikine, Inc. Composés hétérocycliques et leurs utilisations
US7897624B2 (en) 2006-04-18 2011-03-01 Ardea Biosciences Pyridone sulfonamides and pyridone sulfamides as MEK inhibitors
EP2292233A2 (fr) 1999-11-11 2011-03-09 OSI Pharmaceuticals, Inc. Utilisations pharmaceutiques de N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine
WO2011027249A2 (fr) 2009-09-01 2011-03-10 Pfizer Inc. Dérivés de benzimidazole
WO2011049625A1 (fr) 2009-10-20 2011-04-28 Mansour Samadpour Procédé de criblage d'aflatoxine dans des produits
EP2322551A2 (fr) 2004-12-22 2011-05-18 Amgen, Inc Compositions conprenant anti-IGF-1R Anticorps et Méthodes pour leur Production
EP2343086A2 (fr) 2001-11-09 2011-07-13 Pfizer Products Inc. Anticorps contre CD40
WO2011098971A1 (fr) 2010-02-12 2011-08-18 Pfizer Inc. Sels et polymorphes de la 8-fluoro-2-{4-[(méthylamino}méthyl]phényl}-1,3,4,5-tétrahydro-6h-azépino[5,4,3-cd]indol-6-one
WO2011100403A1 (fr) 2010-02-10 2011-08-18 Immunogen, Inc Anticorps anti-cd20 et utilisations de ceux-ci
WO2011109584A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011109572A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011145035A1 (fr) 2010-05-17 2011-11-24 Indian Incozen Therapeutics Pvt. Ltd. Nouveau composés de 3,5-disubstitués-3h-imidazo[4,5-b]pyridine et 3,5- disubstitués -3h-[1,2,3]triazolo[4,5-b] pyridine utilisés comme modulateurs des protéines kinases
WO2011146882A1 (fr) 2010-05-21 2011-11-24 Intellikine, Inc. Composés chimiques, compositions et procédés pour modulation de kinases
WO2012052948A1 (fr) 2010-10-20 2012-04-26 Pfizer Inc. Dérivés de pyridine-2 en tant que modulateurs des récepteurs smoothened
WO2012064973A2 (fr) 2010-11-10 2012-05-18 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et utilisations de ceux-ci
EP2476667A2 (fr) 2003-02-26 2012-07-18 Sugen, Inc. Composés d'aminohétéroaryle utilisés en tant qu'inhibiteurs de protéine kinase
WO2012097000A1 (fr) 2011-01-10 2012-07-19 Pingda Ren Procédés de préparation d'isoquinolinones et de formes solides d'isoquinolinones
WO2012106556A2 (fr) 2011-02-02 2012-08-09 Amgen Inc. Méthodes et compositions associées à l'inhibition d'igf-1r
WO2012112708A1 (fr) 2011-02-15 2012-08-23 Immunogen, Inc. Dérivés de benzodiazépine cytotoxiques et procédés de préparation
WO2012116040A1 (fr) 2011-02-22 2012-08-30 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de la kinase du récepteur du facteur de croissance 1 analogue à l'insuline dans le carcinome hépatocellulaire
WO2012116237A2 (fr) 2011-02-23 2012-08-30 Intellikine, Llc Composés hétérocycliques et leurs utilisations
WO2012142164A1 (fr) 2011-04-12 2012-10-18 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Anticorps monoclonaux humains qui se lient aux facteurs de croissance insulinomimétique (igf) de type i et ii
WO2012145183A2 (fr) 2011-04-19 2012-10-26 Pfizer Inc. Combinaisons d'anticorps anti-4-1bb et d'anticorps induisant une cytotoxicité à médiation cellulaire dépendante d'un anticorps (adcc) pour le traitement du cancer
WO2012149014A1 (fr) 2011-04-25 2012-11-01 OSI Pharmaceuticals, LLC Utilisation de signatures de gènes de tem dans la découverte de médicaments contre le cancer, diagnostics et traitement du cancer
WO2012151525A1 (fr) 2011-05-04 2012-11-08 Rhizen Pharmaceuticals Sa Nouveaux composés en tant que modulateurs de protéines kinases
WO2013012918A1 (fr) 2011-07-19 2013-01-24 Infinity Pharmaceuticals Inc. Composés hétérocycliques et leurs utilisations
WO2013012915A1 (fr) 2011-07-19 2013-01-24 Infinity Pharmaceuticals Inc. Composés hétérocycliques et leurs utilisations
WO2013032591A1 (fr) 2011-08-29 2013-03-07 Infinity Pharmaceuticals Inc. Composés hétérocycliques et leurs utilisations
WO2013042006A1 (fr) 2011-09-22 2013-03-28 Pfizer Inc. Dérivés de pyrrolopyrimidine et de purine
WO2013049332A1 (fr) 2011-09-29 2013-04-04 Infinity Pharmaceuticals, Inc. Inhibiteurs de monoacylglycérol lipase et procédés de leur utilisation
WO2013050725A1 (fr) 2011-10-04 2013-04-11 King's College London Anticorps ige anti-hmw-maa
WO2013068902A1 (fr) 2011-11-08 2013-05-16 Pfizer Inc. Procédés de traitement de troubles inflammatoires utilisant des anticorps anti-m-csf
WO2013126617A1 (fr) 2012-02-22 2013-08-29 The Regents Of The University Of Colorado, A Body Corporate Dérivés de bouvardine et leurs utilisations thérapeutiques
US8530463B2 (en) 2007-05-07 2013-09-10 Hale Biopharma Ventures Llc Multimodal particulate formulations
WO2013144737A2 (fr) 2012-03-30 2013-10-03 Rhizen Pharmaceuticals Sa Nouveaux composés 3,5-disubstitués-3h-imidazo[4,5-b]pyridines et 3,5-disubstitués-3h-[1,2,3]triazolo[4,5-b]pyridines en tant que modulateurs des protéines kinases c-met
WO2013152252A1 (fr) 2012-04-06 2013-10-10 OSI Pharmaceuticals, LLC Polythérapie antinéoplasique
WO2013154878A1 (fr) 2012-04-10 2013-10-17 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
WO2013185115A1 (fr) 2012-06-08 2013-12-12 Sutro Biopharma, Inc. Anticorps comprenant des résidus d'acides aminés non endogènes spécifiques d'un site, leurs procédés de préparation et leurs procédés d'utilisation
EP2690101A1 (fr) 2007-12-19 2014-01-29 Genentech, Inc. 5-anilinoimidazopyridines et procédés d'utilisation
WO2014031566A1 (fr) 2012-08-22 2014-02-27 Immunogen, Inc. Dérivés de benzodiazépine cytotoxique
WO2014036492A1 (fr) 2012-08-31 2014-03-06 Sutro Biopharma, Inc. Acides aminés modifiés comprenant un groupe azido
WO2014071109A1 (fr) 2012-11-01 2014-05-08 Infinity Pharmaceuticals, Inc. Traitement de cancers à l'aide de modulateurs d'isoforme de pi3 kinase
WO2014134486A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
WO2014134483A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
WO2014143659A1 (fr) 2013-03-15 2014-09-18 Araxes Pharma Llc Inhibiteurs covalents irréversibles de la gtpase k-ras g12c
WO2014151147A1 (fr) 2013-03-15 2014-09-25 Intellikine, Llc Combinaison d'inhibiteurs de kinase et ses utilisations
WO2014152588A1 (fr) 2013-03-15 2014-09-25 Araxes Pharma Llc Inhibiteurs covalents de k-ras g12c
WO2014151386A1 (fr) 2013-03-15 2014-09-25 Infinity Pharmaceuticals, Inc. Sels et formes solides d'isoquinolinones et compositions les comprenant et procédés pour les utiliser
US8895546B2 (en) 2009-03-27 2014-11-25 Hale Biopharma Ventures, Llc Administration of benzodiazepine compositions
WO2014194030A2 (fr) 2013-05-31 2014-12-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire et des agents cytotoxiques
WO2014194254A1 (fr) 2013-05-30 2014-12-04 Infinity Pharmaceuticals, Inc. Traitement anticancer au moyen de modulateurs isoformes de la kinase p13
WO2015006555A2 (fr) 2013-07-10 2015-01-15 Sutro Biopharma, Inc. Anticorps comprenant plusieurs résidus d'acides aminés non naturels site-spécifiques, des procédés permettant leur préparation et leurs méthodes d'utilisation
WO2015051341A1 (fr) 2013-10-03 2015-04-09 Araxes Pharma Llc Inhibiteurs d'erk et méthodes d'utilisation
WO2015051244A1 (fr) 2013-10-04 2015-04-09 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
WO2015051241A1 (fr) 2013-10-04 2015-04-09 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
WO2015054572A1 (fr) 2013-10-10 2015-04-16 Araxes Pharma Llc Inhibiteurs de k-ras g12c
WO2015054658A1 (fr) 2013-10-11 2015-04-16 Sutro Biopharma, Inc. Acides aminés modifiés comprenant des groupes fonctionnels de tétrazine, procédés de préparation et procédés d'utilisation associés
WO2015061204A1 (fr) 2013-10-21 2015-04-30 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
US9034861B2 (en) 2009-10-13 2015-05-19 Allomek Therapeutics Llc MEK inhibitors useful in the treatment of diseases
WO2015075598A1 (fr) 2013-11-21 2015-05-28 Pfizer Inc. Dérivés de purine substitués en positions 2 et 6, et leur utilisation dans le traitement des désordres prolifératifs
EP2918589A1 (fr) 2009-07-15 2015-09-16 Intellikine, LLC Dérivé d'adenine comme inhibiteur de pi3k
WO2015155624A1 (fr) 2014-04-10 2015-10-15 Pfizer Inc. Dérivés de dihydropyrrolopyrimidine
WO2015168079A1 (fr) 2014-04-29 2015-11-05 Infinity Pharmaceuticals, Inc. Dérivés de pyrimidine ou de pyridine utiles en tant qu'inhibiteurs de pi3k
WO2015166373A1 (fr) 2014-04-30 2015-11-05 Pfizer Inc. Dérivés de dihétérocycle liés à cycloalkyle
US9227978B2 (en) 2013-03-15 2016-01-05 Araxes Pharma Llc Covalent inhibitors of Kras G12C
WO2016001789A1 (fr) 2014-06-30 2016-01-07 Pfizer Inc. Dérivés de pyrimidine en tant qu'inhibiteurs de pi3k destinés à être utilisés dans le traitement du cancer
WO2016019280A1 (fr) 2014-07-31 2016-02-04 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Anticorps monoclonaux humains dirigés contre l'epha4 et leur utilisation
EP3009436A1 (fr) 2008-07-08 2016-04-20 Intellikine, LLC Inhibiteurs de kinases et procédés d'utilisation
WO2016097918A1 (fr) 2014-12-18 2016-06-23 Pfizer Inc. Dérivés de pyrimidine et de triazine, et leur utilisation comme inhibiteurs d'axl
EP3050876A2 (fr) 2009-11-05 2016-08-03 Rhizen Pharmaceuticals S.A. Modulateurs de kinase
US9452215B2 (en) 2012-02-22 2016-09-27 The Regents Of The University Of Colorado Bourvadin derivatives and therapeutic uses thereof
WO2016178876A2 (fr) 2015-05-01 2016-11-10 Cocrystal Pharma, Inc. Analogues de nucléosides à utiliser pour le traitement d'infections par des virus de la famille des flaviviridae et du cancer
WO2017009751A1 (fr) 2015-07-15 2017-01-19 Pfizer Inc. Dérivés de pyrimidine
EP3135692A1 (fr) 2010-06-16 2017-03-01 University of Pittsburgh of the Commonwealth System of Higher Education Anticorps dirigés contre l'endoplasmine et leur utilisation
EP3135690A1 (fr) 2012-06-26 2017-03-01 Sutro Biopharma, Inc. Proteines fc modifiees contenant des residus specifiques d'acides amines non naturels, leurs conjugues, leurs procedes de preparation et leurs procedes d'utilisation
WO2017058792A1 (fr) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibiteurs de protéines kras portant la mutation g12c
WO2017058768A1 (fr) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibiteurs de protéines kras portant la mutation g12c
EP3170840A1 (fr) 2003-09-10 2017-05-24 Warner-Lambert Company LLC Anticorps dirigés contre le m-csf
WO2017087528A1 (fr) 2015-11-16 2017-05-26 Araxes Pharma Llc Composés quinazoline substitués en position 2 comprenant un groupe hétérocyclique substitué et leur méthode d'utilisation
WO2017096165A1 (fr) 2015-12-03 2017-06-08 Agios Pharmaceuticals, Inc. Inhibiteurs de mat2a pour le traitement du cancer n'exprimant pas mtap
WO2017132617A1 (fr) 2016-01-27 2017-08-03 Sutro Biopharma, Inc. Conjugués d'anticorps anti-cd74, compositions comprenant des conjugués d'anticorps anti-cd74 et méthodes d'utilisations desdits conjugués d'anticorps anti-cd74
WO2017161002A1 (fr) 2016-03-16 2017-09-21 Kura Oncology, Inc. Inhibiteurs bicycliques pontés de ménine-mll et méthodes d'utilisation
WO2017161028A1 (fr) 2016-03-16 2017-09-21 Kura Oncology, Inc. Inhibiteurs substitués de ménine-mll et méthodes d'utilisation
US9810690B2 (en) 2015-10-19 2017-11-07 Araxes Pharma Llc Method for screening inhibitors of Ras
WO2017197240A1 (fr) 2016-05-12 2017-11-16 The Regents Of The University Of Michigan Inhibiteurs de ash1l et méthodes de traitement au moyen de ceux-ci
US9840516B2 (en) 2013-10-10 2017-12-12 Araxes Pharma Llc Substituted quinazolines as inhibitors of KRAS G12C
WO2017214269A1 (fr) 2016-06-08 2017-12-14 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
US9862701B2 (en) 2014-09-25 2018-01-09 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
WO2018045379A1 (fr) 2016-09-02 2018-03-08 Dana-Farber Cancer Institute, Inc. Composition et méthodes de traitement des déreglements des lymphocytes b
WO2018064510A1 (fr) 2016-09-29 2018-04-05 Araxes Pharma Llc Inhibiteurs de protéines mutantes kras g12c
WO2018068017A1 (fr) 2016-10-07 2018-04-12 Araxes Pharma Llc Composés hétérocycliques en tant qu'inhibiteurs de ras et leurs procédés d'utilisation
WO2018098352A2 (fr) 2016-11-22 2018-05-31 Jun Oishi Ciblage d'expression du point de contrôle immunitaire induit par kras
US9988357B2 (en) 2015-12-09 2018-06-05 Araxes Pharma Llc Methods for preparation of quinazoline derivatives
WO2018119183A2 (fr) 2016-12-22 2018-06-28 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US10011600B2 (en) 2014-09-25 2018-07-03 Araxes Pharma Llc Methods and compositions for inhibition of Ras
WO2018140514A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Dérivés de 1-(6-(3-hydroxynaphtalen-1-yl)quinazolin-2-yl)azétidin-1-yl)prop-2-en-1-one et composés similaires utilisés en tant qu'inhibiteurs de kras g12c pour le traitement du cancer
WO2018140598A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés n-hétérocycliques fusionnés et leurs procédés d'utilisation
WO2018140512A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés benzohétéroaromatiques bicycliques fusionnés et leurs procédés d'utilisation
WO2018140600A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés hétéro-hétéro-bicycliques fusionnés et leurs procédés d'utilisation
WO2018140599A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés à base de benzothiophène et de benzothiazole et leurs procédés d'utilisation
WO2018140513A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Dérivés de 1-(3-(6-(3-hydroxynaphtalen-1-yl)benzofuran-2-yl)azétidin-1yl)prop-2-en-1-one et composés similaires utilisés en tant que modulateurs de kras g12c pour le traitement du cancer
WO2018175746A1 (fr) 2017-03-24 2018-09-27 Kura Oncology, Inc. Méthodes de traitement d'hémopathies malignes et du sarcome d'ewing
US10111874B2 (en) 2014-09-18 2018-10-30 Araxes Pharma Llc Combination therapies for treatment of cancer
WO2018217651A1 (fr) 2017-05-22 2018-11-29 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
WO2018218069A1 (fr) 2017-05-25 2018-11-29 Araxes Pharma Llc Dérivés de quinazoline utilisés en tant que modulateurs de kras, hras ou nras mutants
WO2018218071A1 (fr) 2017-05-25 2018-11-29 Araxes Pharma Llc Composés et leurs procédés d'utilisation pour le traitement du cancer
WO2018218070A2 (fr) 2017-05-25 2018-11-29 Araxes Pharma Llc Inhibiteurs covalents de kras
US10144724B2 (en) 2015-07-22 2018-12-04 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
EP3409669A1 (fr) 2014-06-19 2018-12-05 ARIAD Pharmaceuticals, Inc. Composés hétéroaryles pour inhibition de kinase
EP3409278A1 (fr) 2011-07-21 2018-12-05 Tolero Pharmaceuticals, Inc. Inhibiteurs de protéine kinase hétérocycliques
WO2019023316A1 (fr) 2017-07-26 2019-01-31 Sutro Biopharma, Inc. Méthodes d'utilisation d'anticorps anti-cd74 et de conjugués d'anticorps dans le traitement d'un lymphome à cellules t
WO2019051291A1 (fr) 2017-09-08 2019-03-14 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
WO2019055909A1 (fr) 2017-09-18 2019-03-21 Sutro Biopharma, Inc. Conjugués anticorps-récepteur alpha anti-folate et leurs utilisations
US10246424B2 (en) 2015-04-10 2019-04-02 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
WO2019075367A1 (fr) 2017-10-13 2019-04-18 Tolero Pharmaceuticals, Inc. Activateurs de pkm2 en combinaison avec des espèces réactives de l'oxygène pour le traitement du cancer
WO2019094772A1 (fr) 2017-11-10 2019-05-16 The Regents Of The University Of Michigan Agents de dégradation de ash1l et méthodes de traitement au moyen de ceux-ci
WO2019113469A1 (fr) 2017-12-07 2019-06-13 The Regents Of The University Of Michigan Inhibiteurs de la famille nsd et méthodes de traitement comprenant ces derniers
US10422788B2 (en) 2016-12-19 2019-09-24 Tolero Pharmaceuticals, Inc. Profiling peptides and methods for sensitivity profiling
US10428064B2 (en) 2015-04-15 2019-10-01 Araxes Pharma Llc Fused-tricyclic inhibitors of KRAS and methods of use thereof
WO2019213516A1 (fr) 2018-05-04 2019-11-07 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
WO2019213526A1 (fr) 2018-05-04 2019-11-07 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
WO2019217691A1 (fr) 2018-05-10 2019-11-14 Amgen Inc. Inhibiteurs de kras g12c pour le traitement du cancer
WO2019232419A1 (fr) 2018-06-01 2019-12-05 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
WO2019236957A1 (fr) 2018-06-07 2019-12-12 The Regents Of The University Of Michigan Inhibiteurs de prc1 et méthodes de traitement comprenant ces derniers
WO2019241157A1 (fr) 2018-06-11 2019-12-19 Amgen Inc. Inhibiteurs de kras g12c pour le traitement du cancer
EP3590932A1 (fr) 2013-03-14 2020-01-08 Tolero Pharmaceuticals, Inc. Inhibiteurs jak2 et alk2 et leurs procédés d'utilisation
WO2020028706A1 (fr) 2018-08-01 2020-02-06 Araxes Pharma Llc Composés hétérocycliques spiro et procédés d'utilisation correspondants pour le traitement du cancer
US10562925B2 (en) 2015-05-18 2020-02-18 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs having increased bioavailability
US10568887B2 (en) 2015-08-03 2020-02-25 Tolero Pharmaceuticals, Inc. Combination therapies for treatment of cancer
EP3613743A1 (fr) 2008-01-04 2020-02-26 Intellikine, LLC Procédés de préparation de dérivés de 1h-pyrazolo[3,4-d]pyrimidin-4-amine
WO2020050890A2 (fr) 2018-06-12 2020-03-12 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US10588907B2 (en) 2015-06-04 2020-03-17 Kura Oncology, Inc. Methods and compositions for inhibiting the interaction of menin with MLL proteins
WO2020060944A1 (fr) 2018-09-17 2020-03-26 Sutro Biopharma, Inc. Polythérapies avec des conjugués d'anticorps anti-récepteur du folate
US10624880B2 (en) 2015-04-20 2020-04-21 Tolero Pharmaceuticals, Inc. Predicting response to alvocidib by mitochondrial profiling
WO2020086739A1 (fr) 2018-10-24 2020-04-30 Araxes Pharma Llc Dérivés de 2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(1h-indazol-4-yl)-benzonitrile et composés apparentés en tant qu'inhibiteurs de protéine kras g12c mutante pour l'inhibition de métastase tumorale
US10646488B2 (en) 2016-07-13 2020-05-12 Araxes Pharma Llc Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
WO2020102730A1 (fr) 2018-11-16 2020-05-22 Amgen Inc. Synthèse améliorée d'un intermédiaire clé du composé inhibiteur de kras g12c
WO2020106647A2 (fr) 2018-11-19 2020-05-28 Amgen Inc. Polythérapie comprenant un inhibiteur de krasg12c et un ou plusieurs principes pharmaceutiquement actifs supplémentaires pour le traitement de cancers
WO2020106640A1 (fr) 2018-11-19 2020-05-28 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
WO2020113071A1 (fr) 2018-11-29 2020-06-04 Araxes Pharma Llc Composés et procédés d'utilisation associés pour le traitement du cancer
US10689356B2 (en) 2015-09-28 2020-06-23 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
WO2020132649A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a
WO2020132648A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Inhibiteurs de kif18a
WO2020132651A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Inhibiteurs de kif18a
WO2020132653A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a
US10730867B2 (en) 2015-09-28 2020-08-04 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
US10766865B2 (en) 2012-10-16 2020-09-08 Sumitomo Dainippon Pharma Oncology, Inc. PKM2 modulators and methods for their use
WO2020180768A1 (fr) 2019-03-01 2020-09-10 Revolution Medicines, Inc. Composés hétéroaryle bicycliques et leurs utilisations
WO2020180770A1 (fr) 2019-03-01 2020-09-10 Revolution Medicines, Inc. Composés hétérocyclyle bicycliques et leurs utilisations
WO2020198077A1 (fr) 2019-03-22 2020-10-01 Sumitomo Dainippon Pharma Oncology, Inc. Compositions comprenant des modulateurs de pkm2 et méthodes de traitement les utilisant
US10822312B2 (en) 2016-03-30 2020-11-03 Araxes Pharma Llc Substituted quinazoline compounds and methods of use
WO2020227105A1 (fr) 2019-05-03 2020-11-12 Sutro Biopharma, Inc. Conjugués d'anticorps anti-bcma
US10858343B2 (en) 2015-09-28 2020-12-08 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
WO2021003417A1 (fr) 2019-07-03 2021-01-07 Sumitomo Dainippon Pharma Oncology, Inc. Inhibiteurs de tyrosine kinase non récepteur 1 (tnk1) et leurs utilisations
WO2021026098A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Inhibiteurs de kif18a
WO2021026099A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Inhibiteurs de kif18a
WO2021026100A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Dérivés de pyridine en tant qu'inhibiteurs de kif18a
WO2021026101A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Inhibiteurs de kif18a
WO2021067215A1 (fr) 2019-09-30 2021-04-08 Agios Pharmaceuticals, Inc. Composés de pipéridine utilisés en tant qu'inhibiteurs de ménine
US10975071B2 (en) 2015-09-28 2021-04-13 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
WO2021081212A1 (fr) 2019-10-24 2021-04-29 Amgen Inc. Dérivés de pyridopyrimidine utiles en tant qu'inhibiteurs de kras g12c et de kras g12d dans le traitement du cancer
WO2021086833A1 (fr) 2019-10-28 2021-05-06 Merck Sharp & Dohme Corp. Inhibiteurs à petites molécules de mutant de kras g12c
WO2021085653A1 (fr) 2019-10-31 2021-05-06 Taiho Pharmaceutical Co., Ltd. Dérivés de 4-aminobut-2-enamide et sels de ces derniers
WO2021092115A1 (fr) 2019-11-08 2021-05-14 Revolution Medicines, Inc. Composés hétéroaryles bicycliques et leurs utilisations
WO2021091967A1 (fr) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2021091982A1 (fr) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2021091956A1 (fr) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2021097212A1 (fr) 2019-11-14 2021-05-20 Amgen Inc. Synthèse améliorée de composé inhibiteur de kras g12c
WO2021097207A1 (fr) 2019-11-14 2021-05-20 Amgen Inc. Synthèse améliorée de composés inhibiteurs de kras g12c
US11013741B1 (en) 2018-04-05 2021-05-25 Sumitomo Dainippon Pharma Oncology, Inc. AXL kinase inhibitors and use of the same
WO2021107160A1 (fr) 2019-11-29 2021-06-03 Taiho Pharmaceutical Co., Ltd. Composé ayant une activité inhibitrice contre la mutation kras g12d
WO2021108683A1 (fr) 2019-11-27 2021-06-03 Revolution Medicines, Inc. Inhibiteurs de ras covalents et leurs utilisations
US11034710B2 (en) 2018-12-04 2021-06-15 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11040038B2 (en) 2018-07-26 2021-06-22 Sumitomo Dainippon Pharma Oncology, Inc. Methods for treating diseases associated with abnormal ACVR1 expression and ACVR1 inhibitors for use in the same
WO2021142026A1 (fr) 2020-01-07 2021-07-15 Revolution Medicines, Inc. Dosage d'inhibiteurs de shp2 et méthodes de traitement du cancer
WO2021155006A1 (fr) 2020-01-31 2021-08-05 Les Laboratoires Servier Sas Inhibiteurs de kinases dépendantes des cyclines et leurs utilisations
WO2021178597A1 (fr) 2020-03-03 2021-09-10 Sutro Biopharma, Inc. Anticorps comprenant des étiquettes de glutamine spécifiques à un site, leurs procédés de préparation et d'utilisation
US11118233B2 (en) 2016-05-18 2021-09-14 The University Of Chicago BTK mutation and ibrutinib resistance
WO2021207310A1 (fr) 2020-04-08 2021-10-14 Agios Pharmaceuticals, Inc. Inhibiteurs de la ménine et procédés d'utilisation pour le traitement du cancer
WO2021204159A1 (fr) 2020-04-08 2021-10-14 Agios Pharmaceuticals, Inc. Inhibiteurs de ménine et procédés d'utilisation pour le traitement du cancer
WO2021215544A1 (fr) 2020-04-24 2021-10-28 Taiho Pharmaceutical Co., Ltd. Inhibiteurs de protéine kras g12d
WO2021215545A1 (fr) 2020-04-24 2021-10-28 Taiho Pharmaceutical Co., Ltd. Polythérapie anticancéreuse avec un inhibiteur de n-(1-acryloyl-azétidin-3-yl)-2-((1h-indazol-3-yl) amino) méthyl)-1 h-imidazole-5-carboxamide de kras-g12c
WO2021257736A1 (fr) 2020-06-18 2021-12-23 Revolution Medicines, Inc. Méthodes de retardement, de prévention et de traitement de la résistance acquise aux inhibiteurs de ras
WO2022014640A1 (fr) 2020-07-15 2022-01-20 大鵬薬品工業株式会社 Combinaison contenant un composé pyrimidine destinée à être utilisée dans le traitement de tumeurs
US11236091B2 (en) 2019-05-21 2022-02-01 Amgen Inc. Solid state forms
US11241414B2 (en) 2008-03-28 2022-02-08 Neurelis, Inc. Administration of benzodiazepine compositions
US11267885B2 (en) 2017-01-26 2022-03-08 Zlip Holding Limited CD47 antigen binding unit and uses thereof
US11279694B2 (en) 2016-11-18 2022-03-22 Sumitomo Dainippon Pharma Oncology, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
WO2022060583A1 (fr) 2020-09-03 2022-03-24 Revolution Medicines, Inc. Utilisation d'inhibiteurs de sos1 pour traiter des malignités à mutations de shp2
WO2022060836A1 (fr) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Dérivés d'indole servant d'inhibiteurs dans le traitement du cancer
EP4006030A2 (fr) 2015-06-04 2022-06-01 Kura Oncology, Inc. Procédés et compositions d'inhibition de l'interaction de ménine avec des protéines mll
WO2022140427A1 (fr) 2020-12-22 2022-06-30 Qilu Regor Therapeutics Inc. Inhibiteurs de sos1 et utilisations associées
US11426404B2 (en) 2019-05-14 2022-08-30 Amgen Inc. Dosing of KRAS inhibitor for treatment of cancers
US11471456B2 (en) 2019-02-12 2022-10-18 Sumitomo Pharma Oncology, Inc. Formulations comprising heterocyclic protein kinase inhibitors
WO2022221227A1 (fr) 2021-04-13 2022-10-20 Nuvalent, Inc. Hétérocycles amino-substitués pour le traitement de cancers avec des mutations egfr
WO2022235866A1 (fr) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Inhibiteurs de ras covalents et leurs utilisations
WO2022235864A1 (fr) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Inhibiteurs de ras
WO2022235870A1 (fr) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Inhibiteurs de ras pour le traitement du cancer
US11497756B2 (en) 2017-09-12 2022-11-15 Sumitomo Pharma Oncology, Inc. Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib
WO2022250170A1 (fr) 2021-05-28 2022-12-01 Taiho Pharmaceutical Co., Ltd. Petites molécules inhibitrices de protéines mutées par kras
US11542248B2 (en) 2017-06-08 2023-01-03 Kura Oncology, Inc. Methods and compositions for inhibiting the interaction of menin with MLL proteins
WO2023056589A1 (fr) 2021-10-08 2023-04-13 Servier Pharmaceuticals Llc Inhibiteurs de ménine et procédés d'utilisation pour le traitement du cancer
WO2023060253A1 (fr) 2021-10-08 2023-04-13 Revolution Medicines, Inc. Inhibiteurs de ras
US11649251B2 (en) 2017-09-20 2023-05-16 Kura Oncology, Inc. Substituted inhibitors of menin-MLL and methods of use
WO2023114954A1 (fr) 2021-12-17 2023-06-22 Genzyme Corporation Composés pyrazolopyrazine utilisés comme inhibiteurs de la shp2
EP4227307A1 (fr) 2022-02-11 2023-08-16 Genzyme Corporation Composés pyrazolopyrazine en tant qu'inhibiteurs de shp2
US11746103B2 (en) 2020-12-10 2023-09-05 Sumitomo Pharma Oncology, Inc. ALK-5 inhibitors and uses thereof
WO2023172940A1 (fr) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Méthodes de traitement du cancer du poumon réfractaire immunitaire
US11793802B2 (en) 2019-03-20 2023-10-24 Sumitomo Pharma Oncology, Inc. Treatment of acute myeloid leukemia (AML) with venetoclax failure
WO2023211812A1 (fr) 2022-04-25 2023-11-02 Nested Therapeutics, Inc. Dérivés hétérocycliques en tant qu'inhibiteurs de protéine kinase activée par mitogène (mek)
WO2023240263A1 (fr) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Inhibiteurs de ras macrocycliques
US11858925B2 (en) 2020-07-10 2024-01-02 The Regents Of The University Of Michigan GAS41 inhibitors and methods of use thereof
WO2024006542A1 (fr) 2022-06-30 2024-01-04 Sutro Biopharma, Inc. Anticorps anti-ror1 et conjugués d'anticorps, compositions comprenant des anticorps anti-ror1 ou des conjugués d'anticorps, et méthodes de fabrication et d'utilisation d'anticorps anti-ror1 et de conjugués d'anticorps
WO2024010925A2 (fr) 2022-07-08 2024-01-11 Nested Therapeutics, Inc. Inhibiteurs de protéine kinase activée par mitogène (mek)
US11931420B2 (en) 2021-04-30 2024-03-19 Celgene Corporation Combination therapies using an anti-BCMA antibody drug conjugate (ADC) in combination with a gamma secretase inhibitor (GSI)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03294252A (ja) * 1990-04-13 1991-12-25 Yamanouchi Pharmaceut Co Ltd アミド化合物又はその塩
WO1993020047A1 (fr) * 1992-04-07 1993-10-14 British Bio-Technology Limited Inhibiteurs de la collagenase et de la cytokine a base d'acide hydroxamique
WO1995009841A1 (fr) * 1993-10-07 1995-04-13 British Biotech Pharmaceuticals Limited Derives d'acide hyroxamique utilises comme inhibiteurs de production de cytokine
EP0780386A1 (fr) * 1995-12-20 1997-06-25 F. Hoffmann-La Roche Ag Inhibiteurs de métalloprotéases matricielles
WO1997024117A1 (fr) * 1996-01-02 1997-07-10 Rhone-Poulenc Rorer Pharmaceuticals Inc. Composes d'acide (aryle, heteroaryle, arylmethyle ou heteroarylmethyle) hydroxamique substitues

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03294252A (ja) * 1990-04-13 1991-12-25 Yamanouchi Pharmaceut Co Ltd アミド化合物又はその塩
WO1993020047A1 (fr) * 1992-04-07 1993-10-14 British Bio-Technology Limited Inhibiteurs de la collagenase et de la cytokine a base d'acide hydroxamique
WO1995009841A1 (fr) * 1993-10-07 1995-04-13 British Biotech Pharmaceuticals Limited Derives d'acide hyroxamique utilises comme inhibiteurs de production de cytokine
EP0780386A1 (fr) * 1995-12-20 1997-06-25 F. Hoffmann-La Roche Ag Inhibiteurs de métalloprotéases matricielles
WO1997024117A1 (fr) * 1996-01-02 1997-07-10 Rhone-Poulenc Rorer Pharmaceuticals Inc. Composes d'acide (aryle, heteroaryle, arylmethyle ou heteroarylmethyle) hydroxamique substitues

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 9207, Derwent World Patents Index; AN 92-051997, XP002063103, "Amide cpds. which inhibit collagenase - useful for treating bone resorption diseases, epidermolysis bullosa, etc." *

Cited By (394)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0984959A4 (fr) * 1997-03-04 2001-05-02 Monsanto Co Composes aromatiques d'acide sulfonyle alpha-hydroxy hydroxamique
US6362183B1 (en) * 1997-03-04 2002-03-26 G. D. Searle & Company Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds
US6716844B2 (en) 1997-03-04 2004-04-06 Pharmacia Corporation Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds
EP0984959A1 (fr) * 1997-03-04 2000-03-15 Monsanto Company Composes aromatiques d'acide sulfonyle alpha-hydroxy hydroxamique
US6437177B1 (en) 1997-11-21 2002-08-20 Martha A. Warpehoski α-hydroxy, -amino, and halo derivatives of β-sulfonyl hydroxamic acids as matrix metallopropteinases inhibitors
US6191300B1 (en) 1999-04-16 2001-02-20 Eastman Chemical Company Process for the preparation of cyclopropylacetonitrile
EP2292233A2 (fr) 1999-11-11 2011-03-09 OSI Pharmaceuticals, Inc. Utilisations pharmaceutiques de N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine
EP3100730A1 (fr) 1999-11-11 2016-12-07 OSI Pharmaceuticals, LLC N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine pour traiter nsclc
EP2194067A2 (fr) 2001-01-05 2010-06-09 Pfizer Inc. Anticorps anti-récepteur de croissance I analogue à l'insuline (IGF-IR)
EP2796468A2 (fr) 2001-01-05 2014-10-29 Pfizer Inc Anticorps contre le récepteur du facteur de croissance 1 analogue à l'insuline
US7037498B2 (en) 2001-01-05 2006-05-02 Abgenix, Inc. Antibodies to insulin-like growth factor I receptor
US9234041B2 (en) 2001-01-05 2016-01-12 Pfizer Inc. Antibodies to insulin-like growth factor I receptor
US6995171B2 (en) 2001-06-21 2006-02-07 Agouron Pharmaceuticals, Inc. Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents
EP2343086A2 (fr) 2001-11-09 2011-07-13 Pfizer Products Inc. Anticorps contre CD40
US6833456B2 (en) 2002-03-01 2004-12-21 Agouron Pharmaceuticals, Inc. Indolyl-urea derivatives of thienopyridines useful as antiangiogenic agents, and methods for their use
EP3000810A1 (fr) 2002-03-13 2016-03-30 Array Biopharma, Inc. Dérivé de benzimidazole d'alkylat n3 en tant qu'inhibiteur de mek
EP2130537A1 (fr) 2002-03-13 2009-12-09 Array Biopharma, Inc. Dérivés de benzimidazole d'alkylat N3 en tant qu'inhibiteurs de Mek
EP2275102A1 (fr) 2002-03-13 2011-01-19 Array Biopharma, Inc. Dérivés de benzimidazole d'alkylat N3 en tant qu'inhibiteurs de Mek
EP2130536A1 (fr) 2002-03-13 2009-12-09 Array Biopharma, Inc. Dérivés de benzimidazole d'alkylat N3 en tant qu'inhibiteurs de Mek
US6869962B2 (en) 2002-06-14 2005-03-22 Agouron Pharmaceuticals, Inc. Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use
US7045528B2 (en) 2002-06-14 2006-05-16 Agouron Pharmaceuticals, Inc. Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use
US7053107B2 (en) 2002-12-19 2006-05-30 Agouron Pharmaceuticals, Inc. Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
EP2476667A2 (fr) 2003-02-26 2012-07-18 Sugen, Inc. Composés d'aminohétéroaryle utilisés en tant qu'inhibiteurs de protéine kinase
US7208500B2 (en) 2003-08-29 2007-04-24 Agouron Pharmaceuticals, Inc. Thienopyridine-phenylacetamides and their derivatives useful as new anti-angiogenic agents
WO2005023759A2 (fr) 2003-09-03 2005-03-17 Array Biopharma Inc. Inhibiteurs heterocycliques de mek et procedes d'utilisation associes
US10280219B2 (en) 2003-09-10 2019-05-07 Amgen Fremont Inc. Antibodies to M-CSF
US9718883B2 (en) 2003-09-10 2017-08-01 Amgen Fremont Inc. Antibodies to M-CSF
EP3170840A1 (fr) 2003-09-10 2017-05-24 Warner-Lambert Company LLC Anticorps dirigés contre le m-csf
EP2251327A2 (fr) 2003-11-19 2010-11-17 Array Biopharma, Inc. Inhibiteurs hétérocycliques de MEK et leurs procédés d'utilisation
WO2005051300A2 (fr) 2003-11-19 2005-06-09 Array Biopharma Inc. Inhibiteurs bicycliques de mek et leurs procedes de production
US7858643B2 (en) 2004-08-26 2010-12-28 Agouron Pharmaceuticals, Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
US8785632B2 (en) 2004-08-26 2014-07-22 Agouron Pharmaceuticals, Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
EP2322551A2 (fr) 2004-12-22 2011-05-18 Amgen, Inc Compositions conprenant anti-IGF-1R Anticorps et Méthodes pour leur Production
EP2322550A1 (fr) 2004-12-22 2011-05-18 Amgen, Inc Compositions conprenant anti-IGF-1R anticorps et méthodes pour leur production
US7429667B2 (en) 2005-01-20 2008-09-30 Ardea Biosciences, Inc. Phenylamino isothiazole carboxamidines as MEK inhibitors
US7652047B2 (en) 2005-01-20 2010-01-26 Ardea Biosciences, Inc. Phenylamino isothiazole carboxamidines as MEK inhibitors
WO2007044084A2 (fr) 2005-05-18 2007-04-19 Array Biopharma Inc. Inhibiteurs heterocycliques de mek et leurs procedes d'utilisation
EP2361905A1 (fr) 2005-05-18 2011-08-31 Array Biopharma Inc. Inhibiteurs hétérocycliques de MEK et leurs utilisation
EP2364973A1 (fr) 2005-05-18 2011-09-14 Array Biopharma, Inc. Inhibiteurs hétérocycliques de MEK et ses procédés d'utilisation
US8829052B2 (en) 2005-07-21 2014-09-09 Ardea Biosciences, Inc. Derivatives of N-(arylamino)sulfonamides as inhibitors of MEK
US7759518B2 (en) 2005-07-21 2010-07-20 Ardea Biosciences Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK
US8101799B2 (en) 2005-07-21 2012-01-24 Ardea Biosciences Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK
WO2007035744A1 (fr) 2005-09-20 2007-03-29 Osi Pharmaceuticals, Inc. Marqueurs biologiques predictifs d'une reaction anticancereuse aux inhibiteurs kinase du recepteur du facteur de croissance 1 analogue a l'insuline
EP2372363A1 (fr) 2005-09-20 2011-10-05 OSI Pharmaceuticals, Inc. Marqueurs biologiques prédictifs d'une réaction anticancéreuse aux inhibiteurs kinase du récepteur du facteur de croissance 1 analogue à l'insuline
WO2007076245A2 (fr) 2005-12-21 2007-07-05 Array Biopharma Inc. Nouveau sel hydrogenosulfate
US7842836B2 (en) 2006-04-11 2010-11-30 Ardea Biosciences N-aryl-N'alkyl sulfamides as MEK inhibitors
US7897624B2 (en) 2006-04-18 2011-03-01 Ardea Biosciences Pyridone sulfonamides and pyridone sulfamides as MEK inhibitors
US8716318B2 (en) 2006-04-18 2014-05-06 Ardea Biosciences Pyridone sulfonamides and pyridone sulfamides as MEK inhibitors
WO2008075196A1 (fr) 2006-12-15 2008-06-26 Pfizer Products Inc. Dérivés du benzamidazole
US8063049B2 (en) 2007-01-19 2011-11-22 Ardea Biosciences, Inc. Inhibitors of MEK
US7820664B2 (en) 2007-01-19 2010-10-26 Bayer Schering Pharma Ag Inhibitors of MEK
WO2008129380A1 (fr) 2007-04-18 2008-10-30 Pfizer Products Inc. Dérivés de sulfonyle amide pour le traitement d'une croissance cellulaire anormale
US8530463B2 (en) 2007-05-07 2013-09-10 Hale Biopharma Ventures Llc Multimodal particulate formulations
WO2009018238A1 (fr) 2007-07-30 2009-02-05 Ardea Biosciences, Inc. Combinaisons d'inhibiteurs de mek et d'inhibiteurs de raf kinase et leurs utilisations
EP2690101A1 (fr) 2007-12-19 2014-01-29 Genentech, Inc. 5-anilinoimidazopyridines et procédés d'utilisation
WO2009082687A1 (fr) 2007-12-21 2009-07-02 Genentech, Inc. Azaindolizines et procédés d'utilisation
US11433065B2 (en) 2008-01-04 2022-09-06 Intellikine Llc Certain chemical entities, compositions and methods
EP3613743A1 (fr) 2008-01-04 2020-02-26 Intellikine, LLC Procédés de préparation de dérivés de 1h-pyrazolo[3,4-d]pyrimidin-4-amine
WO2009114870A2 (fr) 2008-03-14 2009-09-17 Intellikine, Inc. Inhibiteurs de kinases, et procédés d’utilisation associés
US11241414B2 (en) 2008-03-28 2022-02-08 Neurelis, Inc. Administration of benzodiazepine compositions
US9763876B2 (en) 2008-03-28 2017-09-19 Hale Biopharma Ventures, Llc Administration of benzodiazepine compositions
US11793786B2 (en) 2008-03-28 2023-10-24 Neurelis, Inc. Administration of benzodiazepine compositions
EP3009436A1 (fr) 2008-07-08 2016-04-20 Intellikine, LLC Inhibiteurs de kinases et procédés d'utilisation
WO2010045495A2 (fr) 2008-10-16 2010-04-22 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Anticorps entièrement humains dirigés contre un antigène associé au mélanome de masse moléculaire élevée et leurs utilisations
WO2010051043A1 (fr) 2008-11-03 2010-05-06 Intellikine, Inc. Inhibiteurs de la benzoxazole kinase et procédés d'utilisation
EP3153023A1 (fr) 2008-11-03 2017-04-12 Intellikine, LLC Inhibiteurs de kinase de benzoxazole et leurs procédés d'utilisation
EP3360879A1 (fr) 2009-02-05 2018-08-15 ImmunoGen, Inc. Dérivés de benzodiazépine en tant qu'agents cytotoxiques
WO2010091150A1 (fr) 2009-02-05 2010-08-12 Immunogen, Inc. Nouveaux dérivés de benzodiazépine
EP3100745A1 (fr) 2009-02-05 2016-12-07 Immunogen, Inc. Nouveaux dérivés de benzodiazépine
WO2010090764A1 (fr) 2009-02-09 2010-08-12 Supergen, Inc. Inhibiteurs pyrrolopyrimidinyle de l'axi kinase
WO2010099139A2 (fr) 2009-02-25 2010-09-02 Osi Pharmaceuticals, Inc. Thérapie anti-cancer combinée
WO2010099137A2 (fr) 2009-02-26 2010-09-02 Osi Pharmaceuticals, Inc. Procédés in situ pour surveiller l'état emt de cellules tumorales in vivo
WO2010099363A1 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010098866A1 (fr) 2009-02-27 2010-09-02 Supergen, Inc. Inhibiteurs cyclopentathiophène/cyclohexathiophène de l'adn méthyltransférase
WO2010099138A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Procédés pour l'identification d'agents qui inhibent les cellules tumorales de type mésenchymateuses ou leur formation
WO2010099364A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
US8895546B2 (en) 2009-03-27 2014-11-25 Hale Biopharma Ventures, Llc Administration of benzodiazepine compositions
WO2010108652A1 (fr) 2009-03-27 2010-09-30 Ardea Biosciences Inc. Dihydropyridine-sulfonamides et dihydropyridine-sulfamides en tant qu'inhibiteurs de mek
WO2010129816A2 (fr) 2009-05-07 2010-11-11 Intellikine, Inc. Composés hétérocycliques et leurs utilisations
EP3441392A1 (fr) 2009-07-15 2019-02-13 Intellikine, LLC Composition pharmaceutique pour administration orale
EP2918589A1 (fr) 2009-07-15 2015-09-16 Intellikine, LLC Dérivé d'adenine comme inhibiteur de pi3k
WO2011014726A1 (fr) 2009-07-31 2011-02-03 Osi Pharmaceuticals, Inc. Polythérapie par inhibiteur de mtor et inhibiteur de l’angiogenèse
WO2011022439A1 (fr) 2009-08-17 2011-02-24 Intellikine, Inc. Composés hétérocycliques et leurs utilisations
WO2011027249A2 (fr) 2009-09-01 2011-03-10 Pfizer Inc. Dérivés de benzimidazole
US9034861B2 (en) 2009-10-13 2015-05-19 Allomek Therapeutics Llc MEK inhibitors useful in the treatment of diseases
WO2011049625A1 (fr) 2009-10-20 2011-04-28 Mansour Samadpour Procédé de criblage d'aflatoxine dans des produits
EP3050876A2 (fr) 2009-11-05 2016-08-03 Rhizen Pharmaceuticals S.A. Modulateurs de kinase
EP3444242A2 (fr) 2009-11-05 2019-02-20 Rhizen Pharmaceuticals S.A. Nouveaux modulateurs de benzopyran dekinase
WO2011100403A1 (fr) 2010-02-10 2011-08-18 Immunogen, Inc Anticorps anti-cd20 et utilisations de ceux-ci
EP3597651A1 (fr) 2010-02-12 2020-01-22 Pfizer Inc Sels et polymorphes de 8-fluoro-2-{4-[(méthylamino} méthyl] phényl}-1 ,3,4,5-tetrahydro-6h-azepino[5,4,3- cd]indol-6-one
WO2011098971A1 (fr) 2010-02-12 2011-08-18 Pfizer Inc. Sels et polymorphes de la 8-fluoro-2-{4-[(méthylamino}méthyl]phényl}-1,3,4,5-tétrahydro-6h-azépino[5,4,3-cd]indol-6-one
EP4166558A1 (fr) 2010-02-12 2023-04-19 Pfizer Inc. Sels et polymorphes de 8-fluoro-2-{4-[(méthylamino} méthyl] phényl}-1 ,3,4,5-tetrahydro-6h-azepino[5,4,3- cd]indol-6-one
EP3150610A1 (fr) 2010-02-12 2017-04-05 Pfizer Inc Sels et polymorphes de 8-fluoro-2-{4-[(méthylamino} méthyl] phényl} -1,3,4,5-tetrahydro-6h-azepino [5,4,3-cd] indol-6-one
WO2011109584A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
WO2011109572A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
EP3450432A1 (fr) 2010-05-17 2019-03-06 Incozen Therapeutics Pvt. Ltd. Nouveaux composés 3,5 disubstitués-3h-imidazo[4,5-b] pyridine et 3,5-disubstitués-3h-[1,2,3]triazolo[4,5-b] pyridine utilisés comme modulateurs de kinases de protéine
WO2011145035A1 (fr) 2010-05-17 2011-11-24 Indian Incozen Therapeutics Pvt. Ltd. Nouveau composés de 3,5-disubstitués-3h-imidazo[4,5-b]pyridine et 3,5- disubstitués -3h-[1,2,3]triazolo[4,5-b] pyridine utilisés comme modulateurs des protéines kinases
WO2011146882A1 (fr) 2010-05-21 2011-11-24 Intellikine, Inc. Composés chimiques, compositions et procédés pour modulation de kinases
EP3135692A1 (fr) 2010-06-16 2017-03-01 University of Pittsburgh of the Commonwealth System of Higher Education Anticorps dirigés contre l'endoplasmine et leur utilisation
WO2012052948A1 (fr) 2010-10-20 2012-04-26 Pfizer Inc. Dérivés de pyridine-2 en tant que modulateurs des récepteurs smoothened
WO2012064973A2 (fr) 2010-11-10 2012-05-18 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et utilisations de ceux-ci
EP3581574A1 (fr) 2011-01-10 2019-12-18 Infinity Pharmaceuticals, Inc. Composition pour administration orale à utiliser dans le traitement du cancer, d'une maladie inflammatoire ou d'une maladie auto-immune
US9290497B2 (en) 2011-01-10 2016-03-22 Infinity Pharmaceuticals, Inc. Processes for preparing isoquinolinones and solid forms of isoquinolinones
US10550122B2 (en) 2011-01-10 2020-02-04 Infinity Pharmaceuticals, Inc. Solid forms of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one and methods of use thereof
EP3238722A1 (fr) 2011-01-10 2017-11-01 Infinity Pharmaceuticals, Inc. Formes solides d'isoquinolinones
USRE46621E1 (en) 2011-01-10 2017-12-05 Infinity Pharmaceuticals, Inc. Processes for preparing isoquinolinones and solid forms of isoquinolinones
US11312718B2 (en) 2011-01-10 2022-04-26 Infinity Pharmaceuticals, Inc. Formulations of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one
WO2012097000A1 (fr) 2011-01-10 2012-07-19 Pingda Ren Procédés de préparation d'isoquinolinones et de formes solides d'isoquinolinones
US9840505B2 (en) 2011-01-10 2017-12-12 Infinity Pharmaceuticals, Inc. Solid forms of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1 (2H)-one and methods of use thereof
WO2012106556A2 (fr) 2011-02-02 2012-08-09 Amgen Inc. Méthodes et compositions associées à l'inhibition d'igf-1r
WO2012128868A1 (fr) 2011-02-15 2012-09-27 Immunogen, Inc. Dérivés cytotoxiques de benzodiazépine
EP3666289A1 (fr) 2011-02-15 2020-06-17 ImmunoGen, Inc. Dérivés de benzodiazépine cytotoxique
WO2012112708A1 (fr) 2011-02-15 2012-08-23 Immunogen, Inc. Dérivés de benzodiazépine cytotoxiques et procédés de préparation
EP3053600A1 (fr) 2011-02-15 2016-08-10 ImmunoGen, Inc. Dérivés de benzodiazépine cytotoxique
WO2012116040A1 (fr) 2011-02-22 2012-08-30 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de la kinase du récepteur du facteur de croissance 1 analogue à l'insuline dans le carcinome hépatocellulaire
WO2012116237A2 (fr) 2011-02-23 2012-08-30 Intellikine, Llc Composés hétérocycliques et leurs utilisations
US9127000B2 (en) 2011-02-23 2015-09-08 Intellikine, LLC. Heterocyclic compounds and uses thereof
WO2012142164A1 (fr) 2011-04-12 2012-10-18 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Anticorps monoclonaux humains qui se lient aux facteurs de croissance insulinomimétique (igf) de type i et ii
EP3536708A1 (fr) 2011-04-19 2019-09-11 Pfizer Inc Combinaisons d'anticorps anti-4-1bb et d'anticorps induisant une cytotoxicité à médiation cellulaire dépendante d'un anticorps (adcc) pour le traitement du cancer
WO2012145183A2 (fr) 2011-04-19 2012-10-26 Pfizer Inc. Combinaisons d'anticorps anti-4-1bb et d'anticorps induisant une cytotoxicité à médiation cellulaire dépendante d'un anticorps (adcc) pour le traitement du cancer
WO2012149014A1 (fr) 2011-04-25 2012-11-01 OSI Pharmaceuticals, LLC Utilisation de signatures de gènes de tem dans la découverte de médicaments contre le cancer, diagnostics et traitement du cancer
WO2012151525A1 (fr) 2011-05-04 2012-11-08 Rhizen Pharmaceuticals Sa Nouveaux composés en tant que modulateurs de protéines kinases
WO2013012918A1 (fr) 2011-07-19 2013-01-24 Infinity Pharmaceuticals Inc. Composés hétérocycliques et leurs utilisations
WO2013012915A1 (fr) 2011-07-19 2013-01-24 Infinity Pharmaceuticals Inc. Composés hétérocycliques et leurs utilisations
US10875864B2 (en) 2011-07-21 2020-12-29 Sumitomo Dainippon Pharma Oncology, Inc. Substituted imidazo[1,2-B]pyridazines as protein kinase inhibitors
EP3812387A1 (fr) 2011-07-21 2021-04-28 Sumitomo Dainippon Pharma Oncology, Inc. Inhibiteurs de protéine kinase hétérocycliques
EP3409278A1 (fr) 2011-07-21 2018-12-05 Tolero Pharmaceuticals, Inc. Inhibiteurs de protéine kinase hétérocycliques
WO2013032591A1 (fr) 2011-08-29 2013-03-07 Infinity Pharmaceuticals Inc. Composés hétérocycliques et leurs utilisations
WO2013042006A1 (fr) 2011-09-22 2013-03-28 Pfizer Inc. Dérivés de pyrrolopyrimidine et de purine
US9630979B2 (en) 2011-09-29 2017-04-25 Infinity Pharmaceuticals, Inc. Inhibitors of monoacylglycerol lipase and methods of their use
WO2013049332A1 (fr) 2011-09-29 2013-04-04 Infinity Pharmaceuticals, Inc. Inhibiteurs de monoacylglycérol lipase et procédés de leur utilisation
EP3275902A1 (fr) 2011-10-04 2018-01-31 IGEM Therapeutics Limited Anticorps ige anti-hmw-maa
WO2013050725A1 (fr) 2011-10-04 2013-04-11 King's College London Anticorps ige anti-hmw-maa
WO2013068902A1 (fr) 2011-11-08 2013-05-16 Pfizer Inc. Procédés de traitement de troubles inflammatoires utilisant des anticorps anti-m-csf
US9452215B2 (en) 2012-02-22 2016-09-27 The Regents Of The University Of Colorado Bourvadin derivatives and therapeutic uses thereof
US10259846B2 (en) 2012-02-22 2019-04-16 The Regents Of The University Of Colorado Bouvardin derivatives and therapeutic uses thereof
WO2013126617A1 (fr) 2012-02-22 2013-08-29 The Regents Of The University Of Colorado, A Body Corporate Dérivés de bouvardine et leurs utilisations thérapeutiques
EP3345624A1 (fr) 2012-02-22 2018-07-11 The Regents Of The University Of Colorado Dérivés de bouvardin et leurs utilisations thérapeutiques
WO2013144737A2 (fr) 2012-03-30 2013-10-03 Rhizen Pharmaceuticals Sa Nouveaux composés 3,5-disubstitués-3h-imidazo[4,5-b]pyridines et 3,5-disubstitués-3h-[1,2,3]triazolo[4,5-b]pyridines en tant que modulateurs des protéines kinases c-met
WO2013152252A1 (fr) 2012-04-06 2013-10-10 OSI Pharmaceuticals, LLC Polythérapie antinéoplasique
WO2013154878A1 (fr) 2012-04-10 2013-10-17 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
EP3505534A1 (fr) 2012-06-08 2019-07-03 Sutro Biopharma, Inc. Anticorps comprenant des résidus d'acides aminés non endogènes spécifiques d'un site, leurs procédés de préparation et leurs procédés d'utilisation
WO2013185115A1 (fr) 2012-06-08 2013-12-12 Sutro Biopharma, Inc. Anticorps comprenant des résidus d'acides aminés non endogènes spécifiques d'un site, leurs procédés de préparation et leurs procédés d'utilisation
EP3135690A1 (fr) 2012-06-26 2017-03-01 Sutro Biopharma, Inc. Proteines fc modifiees contenant des residus specifiques d'acides amines non naturels, leurs conjugues, leurs procedes de preparation et leurs procedes d'utilisation
WO2014031566A1 (fr) 2012-08-22 2014-02-27 Immunogen, Inc. Dérivés de benzodiazépine cytotoxique
EP4074728A1 (fr) 2012-08-31 2022-10-19 Sutro Biopharma, Inc. Peptides modifiés comprenant un groupe azido
WO2014036492A1 (fr) 2012-08-31 2014-03-06 Sutro Biopharma, Inc. Acides aminés modifiés comprenant un groupe azido
EP3584255A1 (fr) 2012-08-31 2019-12-25 Sutro Biopharma, Inc. Acides aminés modifiés comprenant un groupe azido
US10766865B2 (en) 2012-10-16 2020-09-08 Sumitomo Dainippon Pharma Oncology, Inc. PKM2 modulators and methods for their use
WO2014071109A1 (fr) 2012-11-01 2014-05-08 Infinity Pharmaceuticals, Inc. Traitement de cancers à l'aide de modulateurs d'isoforme de pi3 kinase
EP3566750A2 (fr) 2013-02-28 2019-11-13 ImmunoGen, Inc. Conjugués comprenant des agents de liaison cellulaire et des agents cytotoxiques
WO2014134483A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
WO2014134486A2 (fr) 2013-02-28 2014-09-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire (cba) et des agents cytotoxiques
EP3590932A1 (fr) 2013-03-14 2020-01-08 Tolero Pharmaceuticals, Inc. Inhibiteurs jak2 et alk2 et leurs procédés d'utilisation
US10752594B2 (en) 2013-03-14 2020-08-25 Sumitomo Dainippon Pharma Oncology, Inc. JAK1 and ALK2 inhibitors and methods for their use
WO2014152588A1 (fr) 2013-03-15 2014-09-25 Araxes Pharma Llc Inhibiteurs covalents de k-ras g12c
US10919850B2 (en) 2013-03-15 2021-02-16 Araxes Pharma Llc Covalent inhibitors of KRas G12C
EP3401314A1 (fr) 2013-03-15 2018-11-14 Araxes Pharma LLC Inhibiteurs covalents de kras g12c
WO2014143659A1 (fr) 2013-03-15 2014-09-18 Araxes Pharma Llc Inhibiteurs covalents irréversibles de la gtpase k-ras g12c
WO2014151147A1 (fr) 2013-03-15 2014-09-25 Intellikine, Llc Combinaison d'inhibiteurs de kinase et ses utilisations
US9227978B2 (en) 2013-03-15 2016-01-05 Araxes Pharma Llc Covalent inhibitors of Kras G12C
US9745319B2 (en) 2013-03-15 2017-08-29 Araxes Pharma Llc Irreversible covalent inhibitors of the GTPase K-Ras G12C
US9926267B2 (en) 2013-03-15 2018-03-27 Araxes Pharma Llc Covalent inhibitors of K-Ras G12C
WO2014151386A1 (fr) 2013-03-15 2014-09-25 Infinity Pharmaceuticals, Inc. Sels et formes solides d'isoquinolinones et compositions les comprenant et procédés pour les utiliser
US10273207B2 (en) 2013-03-15 2019-04-30 Araxes Pharma Llc Covalent inhibitors of kras G12C
WO2014194254A1 (fr) 2013-05-30 2014-12-04 Infinity Pharmaceuticals, Inc. Traitement anticancer au moyen de modulateurs isoformes de la kinase p13
EP3811974A1 (fr) 2013-05-30 2021-04-28 Infinity Pharmaceuticals, Inc. Traitement anticancer au moyen de modulateurs isoformes de la kinase p13
WO2014194030A2 (fr) 2013-05-31 2014-12-04 Immunogen, Inc. Conjugués comprenant des agents de liaison cellulaire et des agents cytotoxiques
WO2015006555A2 (fr) 2013-07-10 2015-01-15 Sutro Biopharma, Inc. Anticorps comprenant plusieurs résidus d'acides aminés non naturels site-spécifiques, des procédés permettant leur préparation et leurs méthodes d'utilisation
EP3336103A1 (fr) 2013-07-10 2018-06-20 Sutro Biopharma, Inc. Anticorps comprenant plusieurs résidus d'acides aminés non naturels sitespécifiques, des procédés permettant leur préparation et leurs méthodes d'utilisation
WO2015051341A1 (fr) 2013-10-03 2015-04-09 Araxes Pharma Llc Inhibiteurs d'erk et méthodes d'utilisation
WO2015051241A1 (fr) 2013-10-04 2015-04-09 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
EP3964507A1 (fr) 2013-10-04 2022-03-09 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
WO2015051244A1 (fr) 2013-10-04 2015-04-09 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
US11878985B2 (en) 2013-10-10 2024-01-23 Araxes Pharma Llc Substituted quinazolines as inhibitors of KRAS G12C
US10370386B2 (en) 2013-10-10 2019-08-06 Araxes Pharma Llc Substituted quinolines as inhibitors of KRAS G12C
EP3636639A1 (fr) 2013-10-10 2020-04-15 Araxes Pharma LLC Inhibiteurs de kras g12c
US10927125B2 (en) 2013-10-10 2021-02-23 Araxes Pharma Llc Substituted cinnolines as inhibitors of KRAS G12C
WO2015054572A1 (fr) 2013-10-10 2015-04-16 Araxes Pharma Llc Inhibiteurs de k-ras g12c
US9840516B2 (en) 2013-10-10 2017-12-12 Araxes Pharma Llc Substituted quinazolines as inhibitors of KRAS G12C
WO2015054658A1 (fr) 2013-10-11 2015-04-16 Sutro Biopharma, Inc. Acides aminés modifiés comprenant des groupes fonctionnels de tétrazine, procédés de préparation et procédés d'utilisation associés
WO2015061204A1 (fr) 2013-10-21 2015-04-30 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
WO2015075598A1 (fr) 2013-11-21 2015-05-28 Pfizer Inc. Dérivés de purine substitués en positions 2 et 6, et leur utilisation dans le traitement des désordres prolifératifs
WO2015155624A1 (fr) 2014-04-10 2015-10-15 Pfizer Inc. Dérivés de dihydropyrrolopyrimidine
WO2015168079A1 (fr) 2014-04-29 2015-11-05 Infinity Pharmaceuticals, Inc. Dérivés de pyrimidine ou de pyridine utiles en tant qu'inhibiteurs de pi3k
WO2015166373A1 (fr) 2014-04-30 2015-11-05 Pfizer Inc. Dérivés de dihétérocycle liés à cycloalkyle
EP3556757A1 (fr) 2014-04-30 2019-10-23 Pfizer Inc Dérivés de dihétérocycle liés à cycloalkyle
EP3778584A1 (fr) 2014-06-19 2021-02-17 ARIAD Pharmaceuticals, Inc. Procédé de préparation de dérivés de 2-chloro-4-hétéroaryl-pyridimidines
EP3409669A1 (fr) 2014-06-19 2018-12-05 ARIAD Pharmaceuticals, Inc. Composés hétéroaryles pour inhibition de kinase
WO2016001789A1 (fr) 2014-06-30 2016-01-07 Pfizer Inc. Dérivés de pyrimidine en tant qu'inhibiteurs de pi3k destinés à être utilisés dans le traitement du cancer
EP3473271A1 (fr) 2014-07-31 2019-04-24 The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services Anticorps monoclonaux humains dirigés contre epha4 et leur utilisation
WO2016019280A1 (fr) 2014-07-31 2016-02-04 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Anticorps monoclonaux humains dirigés contre l'epha4 et leur utilisation
US10934360B2 (en) 2014-07-31 2021-03-02 The Hong Kong University Of Science And Technology Human monoclonal antibodies against EPHA4 and their use
US10111874B2 (en) 2014-09-18 2018-10-30 Araxes Pharma Llc Combination therapies for treatment of cancer
US9862701B2 (en) 2014-09-25 2018-01-09 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
US10011600B2 (en) 2014-09-25 2018-07-03 Araxes Pharma Llc Methods and compositions for inhibition of Ras
WO2016097918A1 (fr) 2014-12-18 2016-06-23 Pfizer Inc. Dérivés de pyrimidine et de triazine, et leur utilisation comme inhibiteurs d'axl
US9593097B2 (en) 2014-12-18 2017-03-14 Pfizer Inc. Axl inhibitors
US10829458B2 (en) 2015-04-10 2020-11-10 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
US10246424B2 (en) 2015-04-10 2019-04-02 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
US10624880B2 (en) 2015-04-20 2020-04-21 Tolero Pharmaceuticals, Inc. Predicting response to alvocidib by mitochondrial profiling
WO2016178876A2 (fr) 2015-05-01 2016-11-10 Cocrystal Pharma, Inc. Analogues de nucléosides à utiliser pour le traitement d'infections par des virus de la famille des flaviviridae et du cancer
US10562925B2 (en) 2015-05-18 2020-02-18 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs having increased bioavailability
EP4006030A2 (fr) 2015-06-04 2022-06-01 Kura Oncology, Inc. Procédés et compositions d'inhibition de l'interaction de ménine avec des protéines mll
US10588907B2 (en) 2015-06-04 2020-03-17 Kura Oncology, Inc. Methods and compositions for inhibiting the interaction of menin with MLL proteins
WO2017009751A1 (fr) 2015-07-15 2017-01-19 Pfizer Inc. Dérivés de pyrimidine
US10144724B2 (en) 2015-07-22 2018-12-04 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
US10351550B2 (en) 2015-07-22 2019-07-16 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
US10835537B2 (en) 2015-08-03 2020-11-17 Sumitomo Dainippon Pharma Oncology, Inc. Combination therapies for treatment of cancer
US10682356B2 (en) 2015-08-03 2020-06-16 Tolero Pharmaceuticals, Inc. Combination therapies for treatment of cancer
US10568887B2 (en) 2015-08-03 2020-02-25 Tolero Pharmaceuticals, Inc. Combination therapies for treatment of cancer
WO2017058768A1 (fr) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibiteurs de protéines kras portant la mutation g12c
WO2017058792A1 (fr) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibiteurs de protéines kras portant la mutation g12c
US10730867B2 (en) 2015-09-28 2020-08-04 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
US10689356B2 (en) 2015-09-28 2020-06-23 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
US10858343B2 (en) 2015-09-28 2020-12-08 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
US10882847B2 (en) 2015-09-28 2021-01-05 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
US9810690B2 (en) 2015-10-19 2017-11-07 Araxes Pharma Llc Method for screening inhibitors of Ras
US10414757B2 (en) 2015-11-16 2019-09-17 Araxes Pharma Llc 2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof
WO2017087528A1 (fr) 2015-11-16 2017-05-26 Araxes Pharma Llc Composés quinazoline substitués en position 2 comprenant un groupe hétérocyclique substitué et leur méthode d'utilisation
US11021470B2 (en) 2015-11-16 2021-06-01 Araxes Pharma Llc 2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof
WO2017096165A1 (fr) 2015-12-03 2017-06-08 Agios Pharmaceuticals, Inc. Inhibiteurs de mat2a pour le traitement du cancer n'exprimant pas mtap
US9988357B2 (en) 2015-12-09 2018-06-05 Araxes Pharma Llc Methods for preparation of quinazoline derivatives
WO2017132615A1 (fr) 2016-01-27 2017-08-03 Sutro Biopharma, Inc. Conjugués d'anticorps anti-cd74, compositions comprenant des conjugués d'anticorps anti-cd74 et méthodes d'utilisations desdits conjugués d'anticorps anti-cd74
WO2017132617A1 (fr) 2016-01-27 2017-08-03 Sutro Biopharma, Inc. Conjugués d'anticorps anti-cd74, compositions comprenant des conjugués d'anticorps anti-cd74 et méthodes d'utilisations desdits conjugués d'anticorps anti-cd74
US10781218B2 (en) 2016-03-16 2020-09-22 Kura Oncology, Inc. Substituted inhibitors of menin-MLL and methods of use
WO2017161028A1 (fr) 2016-03-16 2017-09-21 Kura Oncology, Inc. Inhibiteurs substitués de ménine-mll et méthodes d'utilisation
WO2017161002A1 (fr) 2016-03-16 2017-09-21 Kura Oncology, Inc. Inhibiteurs bicycliques pontés de ménine-mll et méthodes d'utilisation
US11555041B2 (en) 2016-03-16 2023-01-17 Kura Oncology, Inc. Bridged bicyclic inhibitors of menin-MLL and methods of use
US11673898B2 (en) 2016-03-16 2023-06-13 Kura Oncology, Inc. Substituted inhibitors of menin-MLL and methods of use
EP4219449A2 (fr) 2016-03-16 2023-08-02 Kura Oncology, Inc. Dérivés indoliques substitués et leurs procédés de préparation
US10752639B2 (en) 2016-03-16 2020-08-25 Kura Oncology, Inc. Bridged bicyclic inhibitors of menin-MLL and methods of use
US10822312B2 (en) 2016-03-30 2020-11-03 Araxes Pharma Llc Substituted quinazoline compounds and methods of use
WO2017197240A1 (fr) 2016-05-12 2017-11-16 The Regents Of The University Of Michigan Inhibiteurs de ash1l et méthodes de traitement au moyen de ceux-ci
US11883381B2 (en) 2016-05-12 2024-01-30 The Regents Of The University Of Michigan ASH1L inhibitors and methods of treatment therewith
US11118233B2 (en) 2016-05-18 2021-09-14 The University Of Chicago BTK mutation and ibrutinib resistance
WO2017214269A1 (fr) 2016-06-08 2017-12-14 Infinity Pharmaceuticals, Inc. Composés hétérocycliques et leurs utilisations
US10646488B2 (en) 2016-07-13 2020-05-12 Araxes Pharma Llc Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
US10870694B2 (en) 2016-09-02 2020-12-22 Dana Farber Cancer Institute, Inc. Composition and methods of treating B cell disorders
WO2018045379A1 (fr) 2016-09-02 2018-03-08 Dana-Farber Cancer Institute, Inc. Composition et méthodes de traitement des déreglements des lymphocytes b
US10723738B2 (en) 2016-09-29 2020-07-28 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
US10280172B2 (en) 2016-09-29 2019-05-07 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
WO2018064510A1 (fr) 2016-09-29 2018-04-05 Araxes Pharma Llc Inhibiteurs de protéines mutantes kras g12c
WO2018068017A1 (fr) 2016-10-07 2018-04-12 Araxes Pharma Llc Composés hétérocycliques en tant qu'inhibiteurs de ras et leurs procédés d'utilisation
US10377743B2 (en) 2016-10-07 2019-08-13 Araxes Pharma Llc Inhibitors of RAS and methods of use thereof
US11279694B2 (en) 2016-11-18 2022-03-22 Sumitomo Dainippon Pharma Oncology, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
WO2018098352A2 (fr) 2016-11-22 2018-05-31 Jun Oishi Ciblage d'expression du point de contrôle immunitaire induit par kras
US10422788B2 (en) 2016-12-19 2019-09-24 Tolero Pharmaceuticals, Inc. Profiling peptides and methods for sensitivity profiling
US11285135B2 (en) 2016-12-22 2022-03-29 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2018119183A2 (fr) 2016-12-22 2018-06-28 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US10532042B2 (en) 2016-12-22 2020-01-14 Amgen Inc. KRAS G12C inhibitors and methods of using the same
EP4001269A1 (fr) 2016-12-22 2022-05-25 Amgen Inc. Dérivés de benzoisothiazole, isothiazolo[3,4-b]pyridine, quinazoline, phthalazine, pyrido[2,3-d]pyridazine et pyrido[2,3-d]pyrimidine en tant qu'inhibiteurs de kras g12c pour le traitement de cancer du poumon, du pancréas ou de l'intestin
WO2018140512A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés benzohétéroaromatiques bicycliques fusionnés et leurs procédés d'utilisation
WO2018140600A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés hétéro-hétéro-bicycliques fusionnés et leurs procédés d'utilisation
WO2018140514A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Dérivés de 1-(6-(3-hydroxynaphtalen-1-yl)quinazolin-2-yl)azétidin-1-yl)prop-2-en-1-one et composés similaires utilisés en tant qu'inhibiteurs de kras g12c pour le traitement du cancer
WO2018140598A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés n-hétérocycliques fusionnés et leurs procédés d'utilisation
US11358959B2 (en) 2017-01-26 2022-06-14 Araxes Pharma Llc Benzothiophene and benzothiazole compounds and methods of use thereof
US11059819B2 (en) 2017-01-26 2021-07-13 Janssen Biotech, Inc. Fused hetero-hetero bicyclic compounds and methods of use thereof
US11279689B2 (en) 2017-01-26 2022-03-22 Araxes Pharma Llc 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1 yl)prop-2-en-1-one derivatives and similar compounds as KRAS G12C modulators for treating cancer
US11267885B2 (en) 2017-01-26 2022-03-08 Zlip Holding Limited CD47 antigen binding unit and uses thereof
US11136308B2 (en) 2017-01-26 2021-10-05 Araxes Pharma Llc Substituted quinazoline and quinazolinone compounds and methods of use thereof
WO2018140599A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Composés à base de benzothiophène et de benzothiazole et leurs procédés d'utilisation
WO2018140513A1 (fr) 2017-01-26 2018-08-02 Araxes Pharma Llc Dérivés de 1-(3-(6-(3-hydroxynaphtalen-1-yl)benzofuran-2-yl)azétidin-1yl)prop-2-en-1-one et composés similaires utilisés en tant que modulateurs de kras g12c pour le traitement du cancer
US11274093B2 (en) 2017-01-26 2022-03-15 Araxes Pharma Llc Fused bicyclic benzoheteroaromatic compounds and methods of use thereof
US11944627B2 (en) 2017-03-24 2024-04-02 Kura Oncology, Inc. Methods for treating hematological malignancies and Ewing's sarcoma
WO2018175746A1 (fr) 2017-03-24 2018-09-27 Kura Oncology, Inc. Méthodes de traitement d'hémopathies malignes et du sarcome d'ewing
US11905281B2 (en) 2017-05-22 2024-02-20 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2018217651A1 (fr) 2017-05-22 2018-11-29 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US10519146B2 (en) 2017-05-22 2019-12-31 Amgen Inc. KRAS G12C inhibitors and methods of using the same
EP3974429A1 (fr) 2017-05-22 2022-03-30 Amgen Inc. Précurseurs d'inhibiteurs de kras g12c
WO2018218070A2 (fr) 2017-05-25 2018-11-29 Araxes Pharma Llc Inhibiteurs covalents de kras
WO2018218071A1 (fr) 2017-05-25 2018-11-29 Araxes Pharma Llc Composés et leurs procédés d'utilisation pour le traitement du cancer
WO2018218069A1 (fr) 2017-05-25 2018-11-29 Araxes Pharma Llc Dérivés de quinazoline utilisés en tant que modulateurs de kras, hras ou nras mutants
US11639346B2 (en) 2017-05-25 2023-05-02 Araxes Pharma Llc Quinazoline derivatives as modulators of mutant KRAS, HRAS or NRAS
US11377441B2 (en) 2017-05-25 2022-07-05 Araxes Pharma Llc Covalent inhibitors of KRAS
US10745385B2 (en) 2017-05-25 2020-08-18 Araxes Pharma Llc Covalent inhibitors of KRAS
US10736897B2 (en) 2017-05-25 2020-08-11 Araxes Pharma Llc Compounds and methods of use thereof for treatment of cancer
US11542248B2 (en) 2017-06-08 2023-01-03 Kura Oncology, Inc. Methods and compositions for inhibiting the interaction of menin with MLL proteins
WO2019023316A1 (fr) 2017-07-26 2019-01-31 Sutro Biopharma, Inc. Méthodes d'utilisation d'anticorps anti-cd74 et de conjugués d'anticorps dans le traitement d'un lymphome à cellules t
WO2019051291A1 (fr) 2017-09-08 2019-03-14 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11306087B2 (en) 2017-09-08 2022-04-19 Amgen Inc. Inhibitors of KRAS G12C and methods of using the same
US10640504B2 (en) 2017-09-08 2020-05-05 Amgen Inc. Inhibitors of KRAS G12C and methods of using the same
EP4141005A1 (fr) 2017-09-08 2023-03-01 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11497756B2 (en) 2017-09-12 2022-11-15 Sumitomo Pharma Oncology, Inc. Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib
WO2019055909A1 (fr) 2017-09-18 2019-03-21 Sutro Biopharma, Inc. Conjugués anticorps-récepteur alpha anti-folate et leurs utilisations
US11649251B2 (en) 2017-09-20 2023-05-16 Kura Oncology, Inc. Substituted inhibitors of menin-MLL and methods of use
WO2019075367A1 (fr) 2017-10-13 2019-04-18 Tolero Pharmaceuticals, Inc. Activateurs de pkm2 en combinaison avec des espèces réactives de l'oxygène pour le traitement du cancer
US11833210B2 (en) 2017-11-10 2023-12-05 The Regents Of The University Of Michigan ASH1L inhibitors and methods of treatment therewith
WO2019094773A1 (fr) 2017-11-10 2019-05-16 The Regents Of The University Of Michigan Inhibiteurs de ash1l et méthodes de traitement comprenant ces derniers
US11110177B2 (en) 2017-11-10 2021-09-07 The Regents Of The University Of Michigan ASH1L degraders and methods of treatment therewith
US11147885B2 (en) 2017-11-10 2021-10-19 The Regents Of The University Of Michigan ASH1L inhibitors and methods of treatment therewith
WO2019094772A1 (fr) 2017-11-10 2019-05-16 The Regents Of The University Of Michigan Agents de dégradation de ash1l et méthodes de traitement au moyen de ceux-ci
US11786602B2 (en) 2017-11-10 2023-10-17 The Regents Of The University Of Michigan ASH1L degraders and methods of treatment therewith
US10632209B2 (en) 2017-11-10 2020-04-28 The Regents Of The University Of Michigan ASH1L inhibitors and methods of treatment therewith
WO2019113469A1 (fr) 2017-12-07 2019-06-13 The Regents Of The University Of Michigan Inhibiteurs de la famille nsd et méthodes de traitement comprenant ces derniers
US11013741B1 (en) 2018-04-05 2021-05-25 Sumitomo Dainippon Pharma Oncology, Inc. AXL kinase inhibitors and use of the same
US11400091B2 (en) 2018-04-05 2022-08-02 Sumitomo Pharma Oncology, Inc. AXL kinase inhibitors and use of the same
US11090304B2 (en) 2018-05-04 2021-08-17 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2019213526A1 (fr) 2018-05-04 2019-11-07 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11045484B2 (en) 2018-05-04 2021-06-29 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2019213516A1 (fr) 2018-05-04 2019-11-07 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11766436B2 (en) 2018-05-04 2023-09-26 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2019217691A1 (fr) 2018-05-10 2019-11-14 Amgen Inc. Inhibiteurs de kras g12c pour le traitement du cancer
US10988485B2 (en) 2018-05-10 2021-04-27 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2019232419A1 (fr) 2018-06-01 2019-12-05 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11096939B2 (en) 2018-06-01 2021-08-24 Amgen Inc. KRAS G12C inhibitors and methods of using the same
WO2019236957A1 (fr) 2018-06-07 2019-12-12 The Regents Of The University Of Michigan Inhibiteurs de prc1 et méthodes de traitement comprenant ces derniers
EP4155293A1 (fr) 2018-06-07 2023-03-29 The Regents of The University of Michigan Inhibiteurs de prc1 et méthodes de traitement comprenant ces derniers
US11319302B2 (en) 2018-06-07 2022-05-03 The Regents Of The University Of Michigan PRC1 inhibitors and methods of treatment therewith
WO2019241157A1 (fr) 2018-06-11 2019-12-19 Amgen Inc. Inhibiteurs de kras g12c pour le traitement du cancer
EP4268898A2 (fr) 2018-06-11 2023-11-01 Amgen Inc. Inhibiteurs de kras g12c pour le traitement du cancer
WO2020050890A2 (fr) 2018-06-12 2020-03-12 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11285156B2 (en) 2018-06-12 2022-03-29 Amgen Inc. Substituted piperazines as KRAS G12C inhibitors
US11040038B2 (en) 2018-07-26 2021-06-22 Sumitomo Dainippon Pharma Oncology, Inc. Methods for treating diseases associated with abnormal ACVR1 expression and ACVR1 inhibitors for use in the same
WO2020028706A1 (fr) 2018-08-01 2020-02-06 Araxes Pharma Llc Composés hétérocycliques spiro et procédés d'utilisation correspondants pour le traitement du cancer
WO2020060944A1 (fr) 2018-09-17 2020-03-26 Sutro Biopharma, Inc. Polythérapies avec des conjugués d'anticorps anti-récepteur du folate
WO2020086739A1 (fr) 2018-10-24 2020-04-30 Araxes Pharma Llc Dérivés de 2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(1h-indazol-4-yl)-benzonitrile et composés apparentés en tant qu'inhibiteurs de protéine kras g12c mutante pour l'inhibition de métastase tumorale
WO2020102730A1 (fr) 2018-11-16 2020-05-22 Amgen Inc. Synthèse améliorée d'un intermédiaire clé du composé inhibiteur de kras g12c
US11299491B2 (en) 2018-11-16 2022-04-12 Amgen Inc. Synthesis of key intermediate of KRAS G12C inhibitor compound
EP4234546A2 (fr) 2018-11-16 2023-08-30 Amgen Inc. Synthèse améliorée d'un intermédiaire clé du composé inhibiteur de kras g12c
US11053226B2 (en) 2018-11-19 2021-07-06 Amgen Inc. KRAS G12C inhibitors and methods of using the same
US11439645B2 (en) 2018-11-19 2022-09-13 Amgen Inc. Combination therapy including a KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers
WO2020106647A2 (fr) 2018-11-19 2020-05-28 Amgen Inc. Polythérapie comprenant un inhibiteur de krasg12c et un ou plusieurs principes pharmaceutiquement actifs supplémentaires pour le traitement de cancers
WO2020106640A1 (fr) 2018-11-19 2020-05-28 Amgen Inc. Inhibiteurs de kras g12c et leurs procédés d'utilisation
US11918584B2 (en) 2018-11-19 2024-03-05 Amgen Inc. Combination therapy including a KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers
WO2020113071A1 (fr) 2018-11-29 2020-06-04 Araxes Pharma Llc Composés et procédés d'utilisation associés pour le traitement du cancer
US11530231B2 (en) 2018-12-04 2022-12-20 Sumitomo Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11034710B2 (en) 2018-12-04 2021-06-15 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11236069B2 (en) 2018-12-20 2022-02-01 Amgen Inc. KIF18A inhibitors
WO2020132649A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a
WO2020132648A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Inhibiteurs de kif18a
WO2020132651A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Inhibiteurs de kif18a
WO2020132653A1 (fr) 2018-12-20 2020-06-25 Amgen Inc. Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a
US11471456B2 (en) 2019-02-12 2022-10-18 Sumitomo Pharma Oncology, Inc. Formulations comprising heterocyclic protein kinase inhibitors
WO2020180768A1 (fr) 2019-03-01 2020-09-10 Revolution Medicines, Inc. Composés hétéroaryle bicycliques et leurs utilisations
WO2020180770A1 (fr) 2019-03-01 2020-09-10 Revolution Medicines, Inc. Composés hétérocyclyle bicycliques et leurs utilisations
US11793802B2 (en) 2019-03-20 2023-10-24 Sumitomo Pharma Oncology, Inc. Treatment of acute myeloid leukemia (AML) with venetoclax failure
US11712433B2 (en) 2019-03-22 2023-08-01 Sumitomo Pharma Oncology, Inc. Compositions comprising PKM2 modulators and methods of treatment using the same
WO2020198077A1 (fr) 2019-03-22 2020-10-01 Sumitomo Dainippon Pharma Oncology, Inc. Compositions comprenant des modulateurs de pkm2 et méthodes de traitement les utilisant
WO2020227105A1 (fr) 2019-05-03 2020-11-12 Sutro Biopharma, Inc. Conjugués d'anticorps anti-bcma
US11426404B2 (en) 2019-05-14 2022-08-30 Amgen Inc. Dosing of KRAS inhibitor for treatment of cancers
US11236091B2 (en) 2019-05-21 2022-02-01 Amgen Inc. Solid state forms
US11827635B2 (en) 2019-05-21 2023-11-28 Amgen Inc. Solid state forms
US11529350B2 (en) 2019-07-03 2022-12-20 Sumitomo Pharma Oncology, Inc. Tyrosine kinase non-receptor 1 (TNK1) inhibitors and uses thereof
WO2021003417A1 (fr) 2019-07-03 2021-01-07 Sumitomo Dainippon Pharma Oncology, Inc. Inhibiteurs de tyrosine kinase non récepteur 1 (tnk1) et leurs utilisations
WO2021026098A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Inhibiteurs de kif18a
WO2021026100A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Dérivés de pyridine en tant qu'inhibiteurs de kif18a
WO2021026101A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Inhibiteurs de kif18a
WO2021026099A1 (fr) 2019-08-02 2021-02-11 Amgen Inc. Inhibiteurs de kif18a
WO2021067215A1 (fr) 2019-09-30 2021-04-08 Agios Pharmaceuticals, Inc. Composés de pipéridine utilisés en tant qu'inhibiteurs de ménine
WO2021081212A1 (fr) 2019-10-24 2021-04-29 Amgen Inc. Dérivés de pyridopyrimidine utiles en tant qu'inhibiteurs de kras g12c et de kras g12d dans le traitement du cancer
WO2021086833A1 (fr) 2019-10-28 2021-05-06 Merck Sharp & Dohme Corp. Inhibiteurs à petites molécules de mutant de kras g12c
WO2021085653A1 (fr) 2019-10-31 2021-05-06 Taiho Pharmaceutical Co., Ltd. Dérivés de 4-aminobut-2-enamide et sels de ces derniers
WO2021091967A1 (fr) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2021091956A1 (fr) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2021091982A1 (fr) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2021092115A1 (fr) 2019-11-08 2021-05-14 Revolution Medicines, Inc. Composés hétéroaryles bicycliques et leurs utilisations
WO2021097212A1 (fr) 2019-11-14 2021-05-20 Amgen Inc. Synthèse améliorée de composé inhibiteur de kras g12c
WO2021097207A1 (fr) 2019-11-14 2021-05-20 Amgen Inc. Synthèse améliorée de composés inhibiteurs de kras g12c
WO2021108683A1 (fr) 2019-11-27 2021-06-03 Revolution Medicines, Inc. Inhibiteurs de ras covalents et leurs utilisations
WO2021107160A1 (fr) 2019-11-29 2021-06-03 Taiho Pharmaceutical Co., Ltd. Composé ayant une activité inhibitrice contre la mutation kras g12d
WO2021142026A1 (fr) 2020-01-07 2021-07-15 Revolution Medicines, Inc. Dosage d'inhibiteurs de shp2 et méthodes de traitement du cancer
WO2021155006A1 (fr) 2020-01-31 2021-08-05 Les Laboratoires Servier Sas Inhibiteurs de kinases dépendantes des cyclines et leurs utilisations
WO2021178597A1 (fr) 2020-03-03 2021-09-10 Sutro Biopharma, Inc. Anticorps comprenant des étiquettes de glutamine spécifiques à un site, leurs procédés de préparation et d'utilisation
WO2021204159A1 (fr) 2020-04-08 2021-10-14 Agios Pharmaceuticals, Inc. Inhibiteurs de ménine et procédés d'utilisation pour le traitement du cancer
WO2021207310A1 (fr) 2020-04-08 2021-10-14 Agios Pharmaceuticals, Inc. Inhibiteurs de la ménine et procédés d'utilisation pour le traitement du cancer
WO2021215544A1 (fr) 2020-04-24 2021-10-28 Taiho Pharmaceutical Co., Ltd. Inhibiteurs de protéine kras g12d
WO2021215545A1 (fr) 2020-04-24 2021-10-28 Taiho Pharmaceutical Co., Ltd. Polythérapie anticancéreuse avec un inhibiteur de n-(1-acryloyl-azétidin-3-yl)-2-((1h-indazol-3-yl) amino) méthyl)-1 h-imidazole-5-carboxamide de kras-g12c
WO2021257736A1 (fr) 2020-06-18 2021-12-23 Revolution Medicines, Inc. Méthodes de retardement, de prévention et de traitement de la résistance acquise aux inhibiteurs de ras
US11858925B2 (en) 2020-07-10 2024-01-02 The Regents Of The University Of Michigan GAS41 inhibitors and methods of use thereof
WO2022014640A1 (fr) 2020-07-15 2022-01-20 大鵬薬品工業株式会社 Combinaison contenant un composé pyrimidine destinée à être utilisée dans le traitement de tumeurs
WO2022060583A1 (fr) 2020-09-03 2022-03-24 Revolution Medicines, Inc. Utilisation d'inhibiteurs de sos1 pour traiter des malignités à mutations de shp2
WO2022060836A1 (fr) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Dérivés d'indole servant d'inhibiteurs dans le traitement du cancer
US11746103B2 (en) 2020-12-10 2023-09-05 Sumitomo Pharma Oncology, Inc. ALK-5 inhibitors and uses thereof
WO2022140427A1 (fr) 2020-12-22 2022-06-30 Qilu Regor Therapeutics Inc. Inhibiteurs de sos1 et utilisations associées
WO2022221227A1 (fr) 2021-04-13 2022-10-20 Nuvalent, Inc. Hétérocycles amino-substitués pour le traitement de cancers avec des mutations egfr
US11931420B2 (en) 2021-04-30 2024-03-19 Celgene Corporation Combination therapies using an anti-BCMA antibody drug conjugate (ADC) in combination with a gamma secretase inhibitor (GSI)
WO2022235870A1 (fr) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Inhibiteurs de ras pour le traitement du cancer
WO2022235866A1 (fr) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Inhibiteurs de ras covalents et leurs utilisations
WO2022235864A1 (fr) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Inhibiteurs de ras
WO2022250170A1 (fr) 2021-05-28 2022-12-01 Taiho Pharmaceutical Co., Ltd. Petites molécules inhibitrices de protéines mutées par kras
WO2023060253A1 (fr) 2021-10-08 2023-04-13 Revolution Medicines, Inc. Inhibiteurs de ras
WO2023056589A1 (fr) 2021-10-08 2023-04-13 Servier Pharmaceuticals Llc Inhibiteurs de ménine et procédés d'utilisation pour le traitement du cancer
WO2023114954A1 (fr) 2021-12-17 2023-06-22 Genzyme Corporation Composés pyrazolopyrazine utilisés comme inhibiteurs de la shp2
EP4227307A1 (fr) 2022-02-11 2023-08-16 Genzyme Corporation Composés pyrazolopyrazine en tant qu'inhibiteurs de shp2
WO2023172940A1 (fr) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Méthodes de traitement du cancer du poumon réfractaire immunitaire
WO2023211812A1 (fr) 2022-04-25 2023-11-02 Nested Therapeutics, Inc. Dérivés hétérocycliques en tant qu'inhibiteurs de protéine kinase activée par mitogène (mek)
WO2023240263A1 (fr) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Inhibiteurs de ras macrocycliques
WO2024006542A1 (fr) 2022-06-30 2024-01-04 Sutro Biopharma, Inc. Anticorps anti-ror1 et conjugués d'anticorps, compositions comprenant des anticorps anti-ror1 ou des conjugués d'anticorps, et méthodes de fabrication et d'utilisation d'anticorps anti-ror1 et de conjugués d'anticorps
WO2024010925A2 (fr) 2022-07-08 2024-01-11 Nested Therapeutics, Inc. Inhibiteurs de protéine kinase activée par mitogène (mek)

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TNSN98022A1 (fr) 2005-03-15
AP9801169A0 (en) 1999-08-05
EP0966438A1 (fr) 1999-12-29
CA2279863A1 (fr) 1998-08-13
AU5493598A (en) 1998-08-26
JP2000507975A (ja) 2000-06-27
MA26472A1 (fr) 2004-12-20
BR9807824A (pt) 2000-03-08
HRP980062A2 (en) 1998-12-31
PA8446001A1 (es) 2000-05-24
AR011116A1 (es) 2000-08-02

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