WO2010054398A1 - Compounds useful as inhibitors of atr kinase - Google Patents

Compounds useful as inhibitors of atr kinase Download PDF

Info

Publication number
WO2010054398A1
WO2010054398A1 PCT/US2009/063922 US2009063922W WO2010054398A1 WO 2010054398 A1 WO2010054398 A1 WO 2010054398A1 US 2009063922 W US2009063922 W US 2009063922W WO 2010054398 A1 WO2010054398 A1 WO 2010054398A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
aliphatic
alkyl
optionally substituted
ring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2009/063922
Other languages
English (en)
French (fr)
Inventor
Jean-Damien Charrier
Steven Durrant
David Kay
Michael O'donnell
Ronald Knegtel
Somhairle Maccormick
Joanne Pinder
Anisa Virani
Stephen Young
Hayley Binch
Thomas Cleveland
Lev T.D. Fanning
Dennis Hurley
Pramod Joshi
Urvi Sheth
Alina Silina
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vertex Pharmaceuticals Inc
Original Assignee
Vertex Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to CA2743134A priority Critical patent/CA2743134A1/en
Priority to HK12102078.7A priority patent/HK1161260B/xx
Priority to JP2011535772A priority patent/JP5702293B2/ja
Priority to RU2011123647/04A priority patent/RU2011123647A/ru
Priority to AU2009313198A priority patent/AU2009313198B2/en
Priority to KR1020177002740A priority patent/KR20170015566A/ko
Priority to KR1020117013234A priority patent/KR101712576B1/ko
Priority to MX2011004953A priority patent/MX2011004953A/es
Priority to EP09756203A priority patent/EP2370424A1/en
Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Priority to NZ593316A priority patent/NZ593316A/xx
Priority to CN200980152891.XA priority patent/CN102264721B/zh
Publication of WO2010054398A1 publication Critical patent/WO2010054398A1/en
Priority to ZA2011/03411A priority patent/ZA201103411B/en
Anticipated expiration legal-status Critical
Priority to IL212817A priority patent/IL212817A/en
Priority to US13/104,291 priority patent/US8410112B2/en
Priority to US13/742,948 priority patent/US20140113005A1/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

Definitions

  • R 1 is a 5-membered ring optionally fused to another ring.
  • R 1 is a monocyclic 5-membered ring containing 1-3 heteroatoms selected from oxygen, nitrogen, or sulfur.
  • R 1 is a 5-membered ring and is selected from the following:
  • R is H or Ci_ 4 alkyl wherein said Ci_ 4 alkyl is optionally substituted with 1-4 halo.
  • J is fluoro or a moiety containing a hydrogen bond acceptor
  • V 1 is Ci_6 aliphatic chain wherein up to three methylene unit of the aliphatic chain may be optionally replaced with -NR'-, -O-, -S-, -C(O)-, -S(O)-, or -S(O) 2 -; wherein the first or second methylene group away from the point of attachment is replaced with CO, SO, SO 2 , S, or O; R' is H or Ci_ 4 alkyl;
  • V is a Ci_ioaliphatic chain wherein 0-3 methylene units are optionally replaced with -NR-, -O-,
  • Q 2 is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 2 is optionally substituted with 1-5 J Q2 ;
  • V is O, O(C 1-6 alkyl), (C 1-4 alkyl)O, C(O)O, C(O)O(Ci. ealkyl), C(O)O(Ci_ 6 alkyl)O(Ci_ 6 alkyl), C(O)(C i_ 6 alkyl), C(O)(Ci_ 6 alkyl)N, C(O)(Ci. 6 alkyl)NH(Ci. 6 alkyl), C(O)(Ci_ 6 alkyl)C(O)O, C(O)(Ci_ 6 alkyl)O, C(O)(Ci. 6 alkyl)O(Ci. 6 alkyl), C(O)(Ci. 6 alkyl)NH(Ci. 6 alkyl),
  • Q 2 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, imidazolyl, thienyl, thiazolyl, furanyl, pyrazolyl, triazolyl, tetrazolyl, pyrrolyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, thiomorpholinyl, or tetrahydropyranyl; wherein said Q 2 is optionally substituted with Ci_ 6 alkyl, CN, halo, haloCi_ 4 alkyl, NH(C M alkyl), N(Ci_ 4 alkyl) 2 , or O(C 1-6 alkyl).
  • J is selected from, oxo, -OH, -NHC(O)(C i_ 4 alkyl), -C(O)(Ci. 4 alkyl), -C(O)NH 2 , -C(O)NH(Ci_ 4 alkyl), -C(O)NH(C i_ 4 alkyl) 2 , -S(O) 2 (Ci_ 4 alkyl), -S(O) 2 NH(Ci. 4 alkyl), or -S(O) 2 N(Ci_ 4 alkyl) 2 .
  • cycloaliphatic refers to a monocyclic C3-C8 hydrocarbon or bicyclic Cs-Ci 2 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule wherein any individual ring in said bicyclic ring system has 3-7 members.
  • cycloaliphatic groups include, but are not limited to, cycloalkyl and cycloalkenyl groups. Specific examples include, but are not limited to, cyclohexyl, cyclopropenyl, and cyclobutyl.
  • the pharmaceutical compositions of this invention may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include, but are not limited to, cocoa butter, beeswax and polyethylene glycols.
  • a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug.
  • Such materials include, but are not limited to, cocoa butter, beeswax and polyethylene glycols.
  • the pharmaceutical compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs.
  • Topical application for the lower intestinal tract can be effected in a rectal
  • additional drugs which are normally administered to treat or prevent that condition, may be administered together with the compounds of this invention.
  • an "effective amount" of the compound or pharmaceutically acceptable composition is that amount effective in order to treat said disease.
  • the compounds and compositions, according to the method of the present invention may be administered using any amount and any route of administration effective for treating or lessening the severity of said disease.
  • Pyrimidine family include Cytarabine, gemcitabine, 5-Fluorouracil (5FU) and relatives.
  • Some other specific examples of antimetabolites include Aminopterin, Methotrexate, Pemetrexed,
  • the bromine atom in iii.3 can then be used as a handle for nucleophilic displacement with a cyclic amine to generate compounds vi of this invention where R 2 is linked to the aminopyrazine moiety through a nitrogen atom.
  • the bromine atom in iii.3 can also be used as a handle for metal-catalyzed cross-coupling (e.g., palladium catalyzed coupling with a boronic acid) to generate compounds x of this invention where R 2 is linked to the aminopyrazine moiety through a carbon atom.
  • Step 3 4-(5-amino-6-(6-methyl-lH-benzo[d]imidazol-2-yl)pyrazin-2-yl)-N,N-dimethyl-5,6- dihydropyridine-l(2H)-sulfonamide (Compound 1-23)
  • Compound 1-16 was prepared using Method A, Steps 1-3 followed by Method P, Steps 1-3.
  • Compound 1-73 was also prepared using Method A, Step 1 followed by Method B, Steps 1-4 followed by Method S, Steps 1-2 followed by Method T, Step 1.
  • Compound 1-73 (E)-l-(3-amino-6-(4-(ethylsulfonyl)piperazin-l-yl)pyrazin-2-yl)-3-phenylprop- 2-en-l-one; IH NMR (400.0 MHz, DMSO) d 1.21 (t, 3H), 3.13 (q, 2H), 3.35-3.37 (m, 4H), 3.54- 3.57 (m, 4H), 7.47-7.51 (m, 3H), 7.55 (br s, 2H), 7.72 (d, IH), 7.79-7.81 (m, 2H), 8.28 (d, IH), 8.41 (s, IH) ppm; MS (ES + ) 402.01
  • Step 7 3-(l-(4-aminophenyl)-lH-l,2,3-triazol-4-yl)-5-(4- (ethylsulfonyl)piperazin-l-yl)pyrazin-2-amine

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • AIDS & HIV (AREA)
  • Biotechnology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
PCT/US2009/063922 2008-11-10 2009-11-10 Compounds useful as inhibitors of atr kinase Ceased WO2010054398A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
EP09756203A EP2370424A1 (en) 2008-11-10 2009-11-10 Compounds useful as inhibitors of atr kinase
JP2011535772A JP5702293B2 (ja) 2008-11-10 2009-11-10 Ａｔｒキナーゼの阻害剤として有用な化合物
NZ593316A NZ593316A (en) 2008-11-10 2009-11-10 Pyrazine compounds useful as inhibitors of atr kinase
AU2009313198A AU2009313198B2 (en) 2008-11-10 2009-11-10 Compounds useful as inhibitors of ATR kinase
KR1020177002740A KR20170015566A (ko) 2008-11-10 2009-11-10 Ａｔｒ 키나제의 억제제로서 유용한 화합물
KR1020117013234A KR101712576B1 (ko) 2008-11-10 2009-11-10 Ａｔｒ 키나제의 억제제로서 유용한 화합물
MX2011004953A MX2011004953A (es) 2008-11-10 2009-11-10 Compuestos utiles como inhibidores de cinasa atr.
CA2743134A CA2743134A1 (en) 2008-11-10 2009-11-10 Compounds useful as inhibitors of atr kinase
RU2011123647/04A RU2011123647A (ru) 2008-11-10 2009-11-10 Соединения, полезные в качестве ингибиторов atr киназы
HK12102078.7A HK1161260B (en) 2008-11-10 2009-11-10 Compounds useful as inhibitors of atr kinase
CN200980152891.XA CN102264721B (zh) 2008-11-10 2009-11-10 用作atr激酶抑制剂的化合物
ZA2011/03411A ZA201103411B (en) 2008-11-10 2011-05-10 Compounds useful as inhibitors of atr kinase
IL212817A IL212817A (en) 2008-11-10 2011-05-11 Atr kinase suppressants, preparations containing them and their uses
US13/104,291 US8410112B2 (en) 2008-11-10 2011-10-27 Compounds useful as inhibitors of ATR kinase
US13/742,948 US20140113005A1 (en) 2008-11-10 2013-01-16 Compounds useful as inhibitors of atr kinase

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US11290608P 2008-11-10 2008-11-10
US61/112,906 2008-11-10
US11420408P 2008-11-13 2008-11-13
US61/114,204 2008-11-13
US14646309P 2009-01-22 2009-01-22
US61/146,463 2009-01-22
US16365509P 2009-03-26 2009-03-26
US61/163,655 2009-03-26

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/104,291 Continuation US8410112B2 (en) 2008-11-10 2011-10-27 Compounds useful as inhibitors of ATR kinase

Publications (1)

Publication Number Publication Date
WO2010054398A1 true WO2010054398A1 (en) 2010-05-14

Family

ID=41650104

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/063922 Ceased WO2010054398A1 (en) 2008-11-10 2009-11-10 Compounds useful as inhibitors of atr kinase

Country Status (13)

Country Link
US (2) US8410112B2 (https=)
EP (1) EP2370424A1 (https=)
JP (3) JP5702293B2 (https=)
KR (2) KR20170015566A (https=)
CN (1) CN102264721B (https=)
AU (2) AU2009313198B2 (https=)
CA (1) CA2743134A1 (https=)
IL (1) IL212817A (https=)
MX (1) MX2011004953A (https=)
NZ (1) NZ593316A (https=)
RU (1) RU2011123647A (https=)
WO (1) WO2010054398A1 (https=)
ZA (1) ZA201103411B (https=)

Cited By (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011143426A1 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143399A1 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143419A1 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Pyrazines useful as inhibitors of atr kinase
WO2011163527A1 (en) * 2010-06-23 2011-12-29 Vertex Pharmaceuticals Incorporated Pyrrolo- pyrazine derivatives useful as inhibitors of atr kinase
WO2011143425A3 (en) * 2010-05-12 2012-02-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143423A3 (en) * 2010-05-12 2012-03-01 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011149993A3 (en) * 2010-05-25 2012-04-05 Abbott Laboratories SUBSTITUTED OCTAHYDROCYCLOPENTA[c]PYRROLES AS CALCIUM CHANNEL MODULATORS
US8198285B2 (en) 2010-01-19 2012-06-12 Astrazeneca Ab Pyrazine derivatives
US8410112B2 (en) 2008-11-10 2013-04-02 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013049859A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Treating pancreatic cancer and non-small cell lung cancer with atr inhibitors
WO2013049719A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2013049720A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2013071094A1 (en) * 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8691865B2 (en) 2008-11-26 2014-04-08 Abbvie Inc. Substituted octahydrocyclopenta[C]pyrrol-4-amines as calcium channel blockers
WO2014055756A1 (en) 2012-10-04 2014-04-10 Vertex Pharmaceuticals Incorporated Method for measuring atr inhibition mediated increases in dna damage
CN103946221A (zh) * 2011-09-16 2014-07-23 诺华股份有限公司 用于治疗囊性纤维化的杂环化合物
CN103987709A (zh) * 2011-09-30 2014-08-13 沃泰克斯药物股份有限公司 用于制备可用作atr激酶抑制剂的化合物的方法
US8822469B2 (en) 2011-06-22 2014-09-02 Vertex Pharmaceuticals Incorporated Pyrrolo[2,3-B]pyrazines useful as inhibitors of ATR kinase
US8841450B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841449B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841337B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841308B2 (en) 2008-12-19 2014-09-23 Vertex Pharmaceuticals Incorporated Pyrazin-2-amines useful as inhibitors of ATR kinase
US8846686B2 (en) 2011-09-30 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8846917B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8877759B2 (en) 2011-04-05 2014-11-04 Vertex Pharnaceuticals Incorporated Aminopyrazines as ATR kinase inhibitors
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8962623B2 (en) 2011-03-04 2015-02-24 Locus Pharmaceuticals, Inc. Aminopyrazine compounds
US9056867B2 (en) 2011-09-16 2015-06-16 Novartis Ag N-substituted heterocyclyl carboxamides
US9096584B2 (en) 2010-05-12 2015-08-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9096602B2 (en) 2011-06-22 2015-08-04 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-B]pyrazines as ATR kinase inhibitors
US9156831B2 (en) 2013-01-23 2015-10-13 Astrazeneca Ab Chemical compounds
WO2015185531A1 (de) 2014-06-05 2015-12-10 Bayer Cropscience Aktiengesellschaft Bicyclische verbindungen als schädlingsbekämpfungsmittel
US9309250B2 (en) 2011-06-22 2016-04-12 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors
US9340546B2 (en) 2012-12-07 2016-05-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2016094688A1 (en) * 2014-12-10 2016-06-16 Massachusetts Institute Of Technology Fused 1,3-azole derivatives useful for the treatment of proliferative diseases
US9549932B2 (en) 2014-08-04 2017-01-24 Bayer Pharma Aktiengesellschaft 2-(morpholin-4-yl)-1,7-naphthyridines
WO2017059357A1 (en) 2015-09-30 2017-04-06 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of dna damaging agents and atr inhibitors
US9663519B2 (en) 2013-03-15 2017-05-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9670215B2 (en) 2014-06-05 2017-06-06 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
EP3364967A2 (en) * 2015-10-23 2018-08-29 Vifor (International) AG Ferroportin inhibitors
WO2018153968A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft An inhibitor of atr kinase for use in a method of treating a hyper-proliferative disease
WO2018153969A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with radium-223 salt
WO2018153972A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors and antiandrogens
US10106555B2 (en) 2016-02-16 2018-10-23 Massachusetts Institute Of Technology Max binders as MYC modulators and uses thereof
WO2018206547A1 (en) 2017-05-12 2018-11-15 Bayer Pharma Aktiengesellschaft Combination of bub1 and atr inhibitors
US10160760B2 (en) 2013-12-06 2018-12-25 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2019025440A1 (en) 2017-08-04 2019-02-07 Bayer Pharma Aktiengesellschaft COMBINATION OF ATR KINASE INHIBITORS AND PD-1 / PD-L1 INHIBITORS
EP3461480A1 (en) 2017-09-27 2019-04-03 Onxeo Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer
WO2019110586A1 (en) 2017-12-08 2019-06-13 Bayer Aktiengesellschaft Predictive markers for atr kinase inhibitors
US10478430B2 (en) 2012-04-05 2019-11-19 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase and combination therapies thereof
WO2020028706A1 (en) * 2018-08-01 2020-02-06 Araxes Pharma Llc Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer
WO2020064971A1 (en) 2018-09-26 2020-04-02 Merck Patent Gmbh Combination of a pd-1 antagonist, an atr inhibitor and a platinating agent for the treatment of cancer
WO2020078788A1 (en) 2018-10-16 2020-04-23 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with 2,3-dihydroimidazo[1,2-c]quinazoline compounds
WO2020078905A1 (en) 2018-10-15 2020-04-23 Merck Patent Gmbh Combination therapy utilizing dna alkylating agents and atr inhibitors
US11028076B2 (en) 2016-01-11 2021-06-08 Celator Pharmaceuticals, Inc. Inhibiting ataxia telangiectasia and Rad3-related protein (ATR)
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
US11129820B2 (en) 2017-04-18 2021-09-28 Vifor (International) Ag Ferroportin-inhibitor salts
US11179394B2 (en) 2014-06-17 2021-11-23 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of Chk1 and ATR inhibitors
US11926616B2 (en) 2018-03-08 2024-03-12 Incyte Corporation Aminopyrazine diol compounds as PI3K-γ inhibitors
WO2025247379A1 (zh) * 2024-05-30 2025-12-04 深圳微芯生物科技股份有限公司 一种苯并咪唑类化合物、其制备方法及应用

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR085607A1 (es) 2011-03-04 2013-10-16 Lexicon Pharmaceuticals Inc Inhibidores de la mst1 quinasa y metodos para su utilizacion
JP6321673B2 (ja) * 2012-12-20 2018-05-09 ルゥ チーン−ビン 放射線と組み合わせて使用するための放射線増感剤化合物
UY35464A (es) 2013-03-15 2014-10-31 Araxes Pharma Llc Inhibidores covalentes de kras g12c.
TWI659021B (zh) 2013-10-10 2019-05-11 亞瑞克西斯製藥公司 Ｋｒａｓ ｇ１２ｃ之抑制劑
JO3517B1 (ar) * 2014-01-17 2020-07-05 Novartis Ag ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2
CN105899493B (zh) * 2014-01-17 2019-03-29 诺华股份有限公司 用于抑制shp2活性的1-(三嗪-3-基/哒嗪-3-基)-哌(-嗪)啶衍生物及其组合物
CZ306322B6 (cs) 2014-12-17 2016-11-30 Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Substituovaný 2-(2-fenylhydrazinyl)pyrazin, způsob jeho přípravy, jeho použití a farmaceutický přípravek ho obsahující
WO2018140599A1 (en) 2017-01-26 2018-08-02 Araxes Pharma Llc Benzothiophene and benzothiazole compounds and methods of use thereof
WO2018140514A1 (en) 2017-01-26 2018-08-02 Araxes Pharma Llc 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds as kras g12c inhibitors for the treatment of cancer
JP7050792B2 (ja) * 2017-01-26 2022-04-08 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ベンジルオキシピラジニルシクロプロパンカルボン酸、その医薬組成物及び使用
CN110382482A (zh) 2017-01-26 2019-10-25 亚瑞克西斯制药公司 稠合的杂-杂二环化合物及其使用方法
EP3573954A1 (en) 2017-01-26 2019-12-04 Araxes Pharma LLC Fused bicyclic benzoheteroaromatic compounds and methods of use thereof
WO2018140513A1 (en) 2017-01-26 2018-08-02 Araxes Pharma Llc 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer
EP3573959B1 (en) * 2017-01-26 2021-07-28 Boehringer Ingelheim International GmbH Benzylaminopyrazinylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
AU2018271990A1 (en) 2017-05-25 2019-12-12 Araxes Pharma Llc Covalent inhibitors of KRAS
US11639346B2 (en) 2017-05-25 2023-05-02 Araxes Pharma Llc Quinazoline derivatives as modulators of mutant KRAS, HRAS or NRAS
HUE066043T2 (hu) * 2017-07-13 2024-07-28 Univ Texas A TR kináz beterociklusos inhibitorai
CN109232533A (zh) * 2017-09-28 2019-01-18 北京越之康泰生物医药科技有限公司 氮杂环类衍生物、其制备方法及其医药用途
JP7508593B2 (ja) * 2020-05-20 2024-07-01 北京泰徳製薬股▲フン▼有限公司 Ａｔｒキナーゼ阻害剤としての２，４，６－トリ置換ピリミジン化合物
WO2022065962A1 (ko) * 2020-09-28 2022-03-31 한국화학연구원 Mlkl 결합 또는 분해용 화합물 및 이들의 의약 용도
CN116063307B (zh) 2021-10-29 2025-08-19 中国药科大学 Shp2与cdk4/6双靶点抑制化合物合成及其制备方法与应用
CN116514801B (zh) * 2022-01-20 2024-11-08 四川大学 2-苯基-[1,2,4]三唑并[1,5-a]吡啶类化合物、其氮氧化物及用途
TW202517268A (zh) * 2023-07-14 2025-05-01 美商塞萊托藥品股份有限公司 包含ａｔｒ抑制劑之脂質體組合物之使用方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060211709A1 (en) * 2002-05-03 2006-09-21 Buhr Chris A Protein kinase modulators and methods of use
WO2007111904A2 (en) * 2006-03-22 2007-10-04 Vertex Pharmaceuticals Incorporated C-met protein kinase inhibitors for the treatment of proliferative disorders

Family Cites Families (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4309430A (en) 1980-06-27 1982-01-05 Merck & Co., Inc. Pyrazinyl-1,2,4-oxadiazole-5-ones, for treatment of edema, and processes for preparing same
US5329012A (en) 1987-10-29 1994-07-12 The Research Foundation Of State University Of New York Bis(acyloxmethyl)imidazole compounds
JP2597917B2 (ja) 1990-04-26 1997-04-09 富士写真フイルム株式会社 新規な色素形成カプラー及びそれを用いたハロゲン化銀カラー写真感光材料
JP2002241379A (ja) 1997-03-21 2002-08-28 Dainippon Pharmaceut Co Ltd ３−オキサジアゾリルキノキサリン誘導体
EP1097933A4 (en) 1998-07-16 2001-11-07 Shionogi & Co PYRIMIDINE DERIVATIVES HAVING ANTI-TUMOR ACTIVITY
US6660753B2 (en) 1999-08-19 2003-12-09 Nps Pharmaceuticals, Inc. Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
EP1237880B1 (en) 1999-12-17 2008-01-23 Novartis Vaccines and Diagnostics, Inc. Pyrazine based inhibitors of glycogen synthase kinase 3
US6849660B1 (en) 2000-08-01 2005-02-01 Isis Pharmaceuticals, Inc. Antimicrobial biaryl compounds
EP1217000A1 (en) 2000-12-23 2002-06-26 Aventis Pharma Deutschland GmbH Inhibitors of factor Xa and factor VIIa
CA2446380A1 (en) 2001-05-08 2002-11-14 Yale University Proteomimetic compounds and methods
SE0102438D0 (sv) * 2001-07-05 2001-07-05 Astrazeneca Ab New compounds
SE0102439D0 (sv) 2001-07-05 2001-07-05 Astrazeneca Ab New compounds
US6992087B2 (en) 2001-11-21 2006-01-31 Pfizer Inc Substituted aryl 1,4-pyrazine derivatives
AU2002343557A1 (en) 2001-11-21 2003-06-10 Pharmacia And Upjohn Company Substituted aryl 1,4-pyrazine derivatives
EP1472245A2 (en) 2002-02-06 2004-11-03 Vertex Pharmaceuticals Incorporated Heteroaryl compounds useful as inhibitors of gsk-3
ES2306859T3 (es) 2002-03-13 2008-11-16 Janssen Pharmaceutica Nv Derivados de sulfonil como nuevos inhibidores de histona deacetilasa.
GB0206860D0 (en) 2002-03-22 2002-05-01 Glaxo Group Ltd Compounds
TWI319387B (en) 2002-04-05 2010-01-11 Astrazeneca Ab Benzamide derivatives
GB0209715D0 (en) 2002-04-27 2002-06-05 Astrazeneca Ab Chemical compounds
EP1501514B1 (en) * 2002-05-03 2012-12-19 Exelixis, Inc. Protein kinase modulators and methods of use
CA2482838A1 (en) 2002-05-31 2003-12-11 Eisai Co., Ltd. Pyrazole compounds and pharmaceutical compositions containing the compound
US7015227B2 (en) 2002-06-21 2006-03-21 Cgi Pharmaceuticals, Inc. Certain amino-substituted monocycles as kinase modulators
WO2004033431A2 (en) 2002-10-04 2004-04-22 Arena Pharmaceuticals, Inc. Hydroxypyrazoles for use against metabolic-related disorders
SE0203752D0 (sv) 2002-12-17 2002-12-17 Astrazeneca Ab New compounds
SE0203754D0 (sv) 2002-12-17 2002-12-17 Astrazeneca Ab New compounds
CA2517720A1 (en) 2003-03-11 2004-09-23 Pfizer Products Inc. Pyrazine compounds as transforming growth factor (tgf) inhibitors
JP2006520794A (ja) 2003-03-21 2006-09-14 スミスクライン ビーチャム コーポレーション 化合物
WO2004084824A2 (en) 2003-03-24 2004-10-07 Merck & Co., Inc. Biaryl substituted 6-membered heterocyles as sodium channel blockers
GB2400101A (en) 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
US20060252741A1 (en) 2003-05-15 2006-11-09 Colandrea Vincent J 3-(2-amino-1-azacyclyl)-5-aryl-1,2,4-oxadiazoles as s1p receptor agonists
AR045595A1 (es) 2003-09-04 2005-11-02 Vertex Pharma Composiciones utiles como inhibidores de proteinas quinasas
US7807696B2 (en) 2003-10-07 2010-10-05 The Feinstein Institute For Medical Research Isoxazole and isothiazole compounds useful in the treatment of inflammation
EP1715867A4 (en) 2004-02-12 2009-04-15 Merck & Co Inc BIPYRIDYLAMIDE AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR-5
WO2005123672A2 (en) 2004-06-14 2005-12-29 Takeda San Diego, Inc. Kinase inhibitors
MX2007001126A (es) 2004-07-27 2007-09-25 Sgx Pharmaceuticals Inc Moduladores de heterociclo cinasa de anillo fusionado.
US7626021B2 (en) 2004-07-27 2009-12-01 Sgx Pharmaceuticals, Inc. Fused ring heterocycle kinase modulators
WO2006053342A2 (en) 2004-11-12 2006-05-18 Osi Pharmaceuticals, Inc. Integrin antagonists useful as anticancer agents
EP1814883A1 (en) 2004-11-22 2007-08-08 Vertex Pharmaceuticals Incorporated Bicyclic inhibitors or rho kinase
GB0428235D0 (en) 2004-12-23 2005-01-26 Glaxo Group Ltd Novel compounds
WO2006071548A2 (en) 2004-12-27 2006-07-06 Alcon, Inc. Aminopyrazine analogs for treating glaucoma and other rho kinase-mediated diseases
GB0500492D0 (en) 2005-01-11 2005-02-16 Cyclacel Ltd Compound
US7622583B2 (en) 2005-01-14 2009-11-24 Chemocentryx, Inc. Heteroaryl sulfonamides and CCR2
GB0501999D0 (en) 2005-02-01 2005-03-09 Sentinel Oncology Ltd Pharmaceutical compounds
CA2598456A1 (en) 2005-02-16 2006-08-24 Schering Corporation Heterocyclic substituted piperazines with cxcr3 antagonist activity
JP5033119B2 (ja) 2005-04-25 2012-09-26 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング キナーゼ阻害剤としての新規アザ複素環化合物
WO2007015632A1 (en) 2005-08-04 2007-02-08 Cgk Co., Ltd. Atm and atr inhibitor
TW200736260A (en) 2005-11-10 2007-10-01 Smithkline Beecham Corp Inhibitors of Akt activity
WO2007063012A1 (en) 2005-12-01 2007-06-07 F. Hoffmann-La Roche Ag Heteroaryl substituted piperidine derivatives as l-cpt1 inhibitors
EP1970377A4 (en) 2005-12-09 2013-02-27 Meiji Seika Kaisha LINCOMYCIN DERIVATIVE AND ANTIBACTERIAL AGENT CONTAINING THIS AS AN ACTIVE SUBSTANCE
EP1962853A1 (en) 2005-12-22 2008-09-03 Alcon Research, Ltd. (indazol-5-yl)-pyrazines and (1,3-dihydro-indol-2-one)- pyrazines for treating rho kinase-mediated diseases and conditions
ITMI20060311A1 (it) 2006-02-21 2007-08-22 Btsr Int Spa Dispositivo perfezionato di alimentazione di filo o filatio ad una macchina tessile e metodo per attuare tale alimentazione
GB0603684D0 (en) 2006-02-23 2006-04-05 Novartis Ag Organic compounds
WO2007096764A2 (en) 2006-02-27 2007-08-30 Glenmark Pharmaceuticals S.A. Bicyclic heteroaryl derivatives as cannabinoid receptor modulators
TW200800203A (en) 2006-03-08 2008-01-01 Astrazeneca Ab New use
CN101454314A (zh) 2006-03-31 2009-06-10 先灵公司 激酶抑制剂
CA2654358A1 (en) 2006-06-22 2007-12-27 Biovitrum Ab (Publ) Pyridine and pyrazine derivatives as mnk kinase inhibitors
JP2009541323A (ja) 2006-06-22 2009-11-26 マリンクロット インコーポレイテッド 拡張された共役を有するピラジン誘導体およびその使用
WO2008037477A1 (en) 2006-09-29 2008-04-03 Novartis Ag Pyrazolopyrimidines as p13k lipid kinase inhibitors
GB0619342D0 (en) 2006-09-30 2006-11-08 Vernalis R&D Ltd New chemical compounds
EP2450350A1 (en) 2006-10-04 2012-05-09 F. Hoffmann-La Roche AG 3-Pyridinecarboxamide and 2-pyrazinecarboxamide derivatives as HDL-cholesterol raising agents
WO2008060907A2 (en) 2006-11-10 2008-05-22 Bristol-Myers Squibb Company Pyrrolo-pyridine kinase inhibitors
EP2125808A2 (en) 2006-12-15 2009-12-02 Bayer Schering Pharma Aktiengesellschaft 3-h-pyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same
EP2125781A2 (en) 2006-12-20 2009-12-02 Amgen Inc. Substituted heterocycles and methods of use
PE20081581A1 (es) 2006-12-21 2008-11-12 Plexxikon Inc COMPUESTOS PIRROLO[2,3-b]PIRIDINAS COMO MODULADORES DE QUINASA
GB0625659D0 (en) 2006-12-21 2007-01-31 Cancer Rec Tech Ltd Therapeutic compounds and their use
AU2008219166B2 (en) 2007-02-16 2013-05-16 Amgen Inc. Nitrogen-containing heterocyclyl ketones and their use as c-Met inhibitors
MX2009009304A (es) 2007-03-01 2009-11-18 Novartis Ag Inhibidores de cinasa pim y metodos para su uso.
PE20090288A1 (es) 2007-05-10 2009-04-03 Smithkline Beecham Corp Derivados de quinoxalina como inhibidores de la pi3 quinasa
PE20090717A1 (es) 2007-05-18 2009-07-18 Smithkline Beecham Corp Derivados de quinolina como inhibidores de la pi3 quinasa
UY31137A1 (es) 2007-06-14 2009-01-05 Smithkline Beecham Corp Derivados de quinazolina como inhibidores de la pi3 quinasa
EP2157090A4 (en) 2007-06-21 2011-09-07 Taisho Pharmaceutical Co Ltd PYRAZINAMIDE COMPOUND
CN101784269A (zh) 2007-06-26 2010-07-21 莱西肯医药有限公司 治疗由5-羟色胺介导的疾病和病症的方法
GB0713259D0 (en) 2007-07-09 2007-08-15 Astrazeneca Ab Pyrazine derivatives 954
RS54303B1 (sr) 2007-07-19 2016-02-29 Lundbeck, H., A/S 5-člani heterociklični amidi i srodna jedinjenja
JP5241834B2 (ja) 2007-07-19 2013-07-17 メルク・シャープ・アンド・ドーム・コーポレーション プロテインキナーゼ阻害剤としての複素環アミド化合物
BRPI0815042A2 (pt) 2007-08-01 2015-02-10 Pfizer Compostos de pirazol
WO2009024825A1 (en) 2007-08-21 2009-02-26 Astrazeneca Ab 2-pyrazinylbenzimidazole derivatives as receptor tyrosine kinase inhibitors
WO2009037247A1 (en) 2007-09-17 2009-03-26 Neurosearch A/S Pyrazine derivatives and their use as potassium channel modulators
ATE523508T1 (de) 2007-10-25 2011-09-15 Astrazeneca Ab Für die behandlung von zellproliferativen erkrankungen geeignete pyridin- und pyrazinderivate
ATE522536T1 (de) 2008-02-25 2011-09-15 Hoffmann La Roche Pyrrolopyrazin-kinasehemmer
CA2716223A1 (en) 2008-02-25 2009-09-03 F. Hoffmann-La Roche Ag Pyrrolopyrazine kinase inhibitors
JP5368485B2 (ja) 2008-02-25 2013-12-18 エフ．ホフマン−ラ ロシュ アーゲー ピロロピラジンキナーゼインヒビター
AU2009218609A1 (en) 2008-02-25 2009-09-03 F. Hoffmann-La Roche Ag Pyrrolopyrazine kinase inhibitors
TW200940537A (en) 2008-02-26 2009-10-01 Astrazeneca Ab Heterocyclic urea derivatives and methods of use thereof
US8110576B2 (en) 2008-06-10 2012-02-07 Plexxikon Inc. Substituted pyrrolo[2,3b]pyrazines and methods for treatment of raf protein kinase-mediated indications
GB0814364D0 (en) 2008-08-05 2008-09-10 Eisai London Res Lab Ltd Diazaindole derivatives and their use in the inhibition of c-Jun N-terminal kinase
JP2012506381A (ja) 2008-10-21 2012-03-15 バーテックス ファーマシューティカルズ インコーポレイテッド ｃ−ＭＥＴタンパク質キナーゼ阻害剤
KR20170015566A (ko) * 2008-11-10 2017-02-08 버텍스 파마슈티칼스 인코포레이티드 Ａｔｒ 키나제의 억제제로서 유용한 화합물
CA2744498C (en) 2008-11-25 2017-10-24 University Of Rochester Mlk inhibitors and methods of use
KR101361858B1 (ko) 2008-12-05 2014-02-12 에프. 호프만-라 로슈 아게 피롤로피라지닐 우레아 키나아제 저해제
ES2663222T3 (es) 2008-12-19 2018-04-11 Vertex Pharmaceuticals Incorporated Derivados de pirazina útiles como inhibidores de la quinasa ATR
CA2740193A1 (en) 2008-12-23 2010-07-01 Abbott Laboratories Anti-viral compounds
KR20110132564A (ko) 2009-02-11 2011-12-08 선오비온 파마슈티컬스 인코포레이티드 히스타민 ｈ3 역 작용제 및 길항제, 및 이의 사용 방법
US20120065247A1 (en) 2009-03-27 2012-03-15 Discoverybiomed, Inc. Modulating ires-mediated translation
JP2013526539A (ja) 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用なピラジン
US8969356B2 (en) 2010-05-12 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
JP2013526540A (ja) 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
JP2013529200A (ja) 2010-05-12 2013-07-18 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
US9630956B2 (en) 2010-05-12 2017-04-25 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
JP5856151B2 (ja) 2010-05-12 2016-02-09 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ Ａｔｒキナーゼ阻害剤として有用な２−アミノピリジン誘導体
CN102311396B (zh) 2010-07-05 2015-01-07 暨南大学 一种吡嗪类衍生物和其制备方法及在制药中的应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060211709A1 (en) * 2002-05-03 2006-09-21 Buhr Chris A Protein kinase modulators and methods of use
WO2007111904A2 (en) * 2006-03-22 2007-10-04 Vertex Pharmaceuticals Incorporated C-met protein kinase inhibitors for the treatment of proliferative disorders

Cited By (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8410112B2 (en) 2008-11-10 2013-04-02 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8691865B2 (en) 2008-11-26 2014-04-08 Abbvie Inc. Substituted octahydrocyclopenta[C]pyrrol-4-amines as calcium channel blockers
US10479784B2 (en) 2008-12-19 2019-11-19 Vertex Pharmaceuticals Incorporated Substituted pyrazin-2-amines as inhibitors of ATR kinase
US8841308B2 (en) 2008-12-19 2014-09-23 Vertex Pharmaceuticals Incorporated Pyrazin-2-amines useful as inhibitors of ATR kinase
US9365557B2 (en) 2008-12-19 2016-06-14 Vertex Pharmaceuticals Incorporated Substituted pyrazin-2-amines as inhibitors of ATR kinase
JP2015024996A (ja) * 2008-12-19 2015-02-05 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ Ａｔｒキナーゼのインヒビターとして有用なピラジン誘導体
US10961232B2 (en) 2008-12-19 2021-03-30 Vertex Pharmaceuticals Incorporated Substituted pyrazines as ATR kinase inhibitors
US9701674B2 (en) 2008-12-19 2017-07-11 Vertex Pharmaceuticals Incorporated Substituted pyrazines as ATR kinase inhibitors
US8198285B2 (en) 2010-01-19 2012-06-12 Astrazeneca Ab Pyrazine derivatives
US9630956B2 (en) 2010-05-12 2017-04-25 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9096584B2 (en) 2010-05-12 2015-08-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2011143423A3 (en) * 2010-05-12 2012-03-01 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143426A1 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
JP2013526541A (ja) * 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
US8962631B2 (en) 2010-05-12 2015-02-24 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2011143425A3 (en) * 2010-05-12 2012-02-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8969356B2 (en) 2010-05-12 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9062008B2 (en) 2010-05-12 2015-06-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2011143399A1 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2011143419A1 (en) * 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Pyrazines useful as inhibitors of atr kinase
US9334244B2 (en) 2010-05-12 2016-05-10 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8796470B2 (en) 2010-05-25 2014-08-05 Abbvie Inc. Substituted octahydrocyclopenta[c]pyrroles as calcium channel modulators
WO2011149993A3 (en) * 2010-05-25 2012-04-05 Abbott Laboratories SUBSTITUTED OCTAHYDROCYCLOPENTA[c]PYRROLES AS CALCIUM CHANNEL MODULATORS
WO2011163527A1 (en) * 2010-06-23 2011-12-29 Vertex Pharmaceuticals Incorporated Pyrrolo- pyrazine derivatives useful as inhibitors of atr kinase
US8623869B2 (en) 2010-06-23 2014-01-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8962623B2 (en) 2011-03-04 2015-02-24 Locus Pharmaceuticals, Inc. Aminopyrazine compounds
US8877759B2 (en) 2011-04-05 2014-11-04 Vertex Pharnaceuticals Incorporated Aminopyrazines as ATR kinase inhibitors
US8822469B2 (en) 2011-06-22 2014-09-02 Vertex Pharmaceuticals Incorporated Pyrrolo[2,3-B]pyrazines useful as inhibitors of ATR kinase
US9309250B2 (en) 2011-06-22 2016-04-12 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors
US9096602B2 (en) 2011-06-22 2015-08-04 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-B]pyrazines as ATR kinase inhibitors
CN103946221A (zh) * 2011-09-16 2014-07-23 诺华股份有限公司 用于治疗囊性纤维化的杂环化合物
CN103946221B (zh) * 2011-09-16 2016-08-03 诺华股份有限公司 用于治疗囊性纤维化的杂环化合物
US9056867B2 (en) 2011-09-16 2015-06-16 Novartis Ag N-substituted heterocyclyl carboxamides
US8765751B2 (en) 2011-09-30 2014-07-01 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
CN106496173A (zh) * 2011-09-30 2017-03-15 沃泰克斯药物股份有限公司 用于制备可用作atr激酶抑制剂的化合物的方法
US8853217B2 (en) 2011-09-30 2014-10-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013049719A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US9035053B2 (en) 2011-09-30 2015-05-19 Vertex Pharmaceuticals Incorporated Processes for making compounds useful as inhibitors of ATR kinase
WO2013049720A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8846686B2 (en) 2011-09-30 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
RU2648507C2 (ru) * 2011-09-30 2018-03-26 Вертекс Фармасьютикалз Инкорпорейтед Лечение рака поджелудочной железы и немелкоклеточного рака легкого ингибиторами atr
EP3733185A1 (en) * 2011-09-30 2020-11-04 Vertex Pharmaceuticals Incorporated Treating non-small cell lung cancer with atr inhibitors
US10208027B2 (en) 2011-09-30 2019-02-19 Vertex Pharmaceuticals Incorporated Processes for preparing ATR inhibitors
CN108464983A (zh) * 2011-09-30 2018-08-31 沃泰克斯药物股份有限公司 用atr抑制剂治疗胰腺癌和非小细胞肺癌
US10822331B2 (en) 2011-09-30 2020-11-03 Vertex Pharmaceuticals Incorporated Processes for preparing ATR inhibitors
CN103987709A (zh) * 2011-09-30 2014-08-13 沃泰克斯药物股份有限公司 用于制备可用作atr激酶抑制剂的化合物的方法
WO2013049859A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Treating pancreatic cancer and non-small cell lung cancer with atr inhibitors
CN103957917A (zh) * 2011-09-30 2014-07-30 沃泰克斯药物股份有限公司 用atr抑制剂治疗胰腺癌和非小细胞肺癌
US9862709B2 (en) 2011-09-30 2018-01-09 Vertex Pharmaceuticals Incorporated Processes for making compounds useful as inhibitors of ATR kinase
CN108685922A (zh) * 2011-09-30 2018-10-23 沃泰克斯药物股份有限公司 用atr抑制剂治疗胰腺癌和非小细胞肺癌
CN103987709B (zh) * 2011-09-30 2016-09-28 沃泰克斯药物股份有限公司 用于制备可用作atr激酶抑制剂的化合物的方法
US10813929B2 (en) 2011-09-30 2020-10-27 Vertex Pharmaceuticals Incorporated Treating cancer with ATR inhibitors
US8841450B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841449B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8841337B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071094A1 (en) * 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8846918B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8846917B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10478430B2 (en) 2012-04-05 2019-11-19 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase and combination therapies thereof
US11110086B2 (en) 2012-04-05 2021-09-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase and combination therapies thereof
US9791456B2 (en) 2012-10-04 2017-10-17 Vertex Pharmaceuticals Incorporated Method for measuring ATR inhibition mediated increases in DNA damage
WO2014055756A1 (en) 2012-10-04 2014-04-10 Vertex Pharmaceuticals Incorporated Method for measuring atr inhibition mediated increases in dna damage
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9718827B2 (en) 2012-12-07 2017-08-01 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9650381B2 (en) 2012-12-07 2017-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US11117900B2 (en) 2012-12-07 2021-09-14 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10787452B2 (en) 2012-12-07 2020-09-29 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US11370798B2 (en) 2012-12-07 2022-06-28 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9340546B2 (en) 2012-12-07 2016-05-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US12187731B2 (en) 2012-12-07 2025-01-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10392391B2 (en) 2012-12-07 2019-08-27 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9657008B2 (en) 2013-01-23 2017-05-23 Astrazeneca Ab Chemical compounds
US9156831B2 (en) 2013-01-23 2015-10-13 Astrazeneca Ab Chemical compounds
US9663519B2 (en) 2013-03-15 2017-05-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10160760B2 (en) 2013-12-06 2018-12-25 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US11485739B2 (en) 2013-12-06 2022-11-01 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10815239B2 (en) 2013-12-06 2020-10-27 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10800781B2 (en) 2014-06-05 2020-10-13 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2015185531A1 (de) 2014-06-05 2015-12-10 Bayer Cropscience Aktiengesellschaft Bicyclische verbindungen als schädlingsbekämpfungsmittel
US9670215B2 (en) 2014-06-05 2017-06-06 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US10093676B2 (en) 2014-06-05 2018-10-09 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US11179394B2 (en) 2014-06-17 2021-11-23 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of Chk1 and ATR inhibitors
US9993484B2 (en) 2014-08-04 2018-06-12 Bayer Pharma Aktiengesellschaft 2-(morpholin-4-yl)-1,7-naphthyridines
US10772893B2 (en) 2014-08-04 2020-09-15 Bayer Pharma Aktiengesellschaft 2-(morpholin-4-yl)-1,7-naphthyridines
US9549932B2 (en) 2014-08-04 2017-01-24 Bayer Pharma Aktiengesellschaft 2-(morpholin-4-yl)-1,7-naphthyridines
EP3395818A1 (en) 2014-08-04 2018-10-31 Bayer Pharma Aktiengesellschaft 2-(morpholin-4-yl)-1,7-naphthyridines
US11529356B2 (en) 2014-08-04 2022-12-20 Bayer Pharma Aktiengesellschaft 2-(morpholin-4-yl)-1,7-naphthyridines
US10017520B2 (en) 2014-12-10 2018-07-10 Massachusetts Institute Of Technology Myc modulators and uses thereof
WO2016094688A1 (en) * 2014-12-10 2016-06-16 Massachusetts Institute Of Technology Fused 1,3-azole derivatives useful for the treatment of proliferative diseases
WO2017059357A1 (en) 2015-09-30 2017-04-06 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of dna damaging agents and atr inhibitors
US11464774B2 (en) 2015-09-30 2022-10-11 Vertex Pharmaceuticals Incorporated Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors
US11066399B2 (en) 2015-10-23 2021-07-20 Vifor (International) Ag Ferroportin inhibitors
US11001579B2 (en) 2015-10-23 2021-05-11 Vifor (International) Ag Ferroportin inhibitors
EP3364967A2 (en) * 2015-10-23 2018-08-29 Vifor (International) AG Ferroportin inhibitors
US11028076B2 (en) 2016-01-11 2021-06-08 Celator Pharmaceuticals, Inc. Inhibiting ataxia telangiectasia and Rad3-related protein (ATR)
US11787781B2 (en) 2016-01-11 2023-10-17 Celator Pharmaceuticals, Inc. Inhibiting ataxia telangiectasia and RAD3-related protein (ATR)
US10865213B2 (en) 2016-02-16 2020-12-15 Massachusetts Institute Of Technology Max binders as MYC modulators and uses thereof
US10106555B2 (en) 2016-02-16 2018-10-23 Massachusetts Institute Of Technology Max binders as MYC modulators and uses thereof
WO2018153969A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with radium-223 salt
WO2018153972A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors and antiandrogens
WO2018153968A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft An inhibitor of atr kinase for use in a method of treating a hyper-proliferative disease
US11129820B2 (en) 2017-04-18 2021-09-28 Vifor (International) Ag Ferroportin-inhibitor salts
WO2018206547A1 (en) 2017-05-12 2018-11-15 Bayer Pharma Aktiengesellschaft Combination of bub1 and atr inhibitors
WO2019025440A1 (en) 2017-08-04 2019-02-07 Bayer Pharma Aktiengesellschaft COMBINATION OF ATR KINASE INHIBITORS AND PD-1 / PD-L1 INHIBITORS
EP3461480A1 (en) 2017-09-27 2019-04-03 Onxeo Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer
WO2019110586A1 (en) 2017-12-08 2019-06-13 Bayer Aktiengesellschaft Predictive markers for atr kinase inhibitors
US11926616B2 (en) 2018-03-08 2024-03-12 Incyte Corporation Aminopyrazine diol compounds as PI3K-γ inhibitors
US12365668B2 (en) 2018-03-08 2025-07-22 Incyte Corporation Aminopyrazine diol compounds as PI3K-y inhibitors
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
US12421197B2 (en) 2018-07-02 2025-09-23 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
AU2019312670B2 (en) * 2018-08-01 2025-01-02 Araxes Pharma Llc Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer
WO2020028706A1 (en) * 2018-08-01 2020-02-06 Araxes Pharma Llc Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer
WO2020064971A1 (en) 2018-09-26 2020-04-02 Merck Patent Gmbh Combination of a pd-1 antagonist, an atr inhibitor and a platinating agent for the treatment of cancer
WO2020078905A1 (en) 2018-10-15 2020-04-23 Merck Patent Gmbh Combination therapy utilizing dna alkylating agents and atr inhibitors
WO2020078788A1 (en) 2018-10-16 2020-04-23 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with 2,3-dihydroimidazo[1,2-c]quinazoline compounds
WO2025247379A1 (zh) * 2024-05-30 2025-12-04 深圳微芯生物科技股份有限公司 一种苯并咪唑类化合物、其制备方法及应用

Also Published As

Publication number Publication date
CN102264721A (zh) 2011-11-30
AU2009313198B2 (en) 2016-03-24
JP5702293B2 (ja) 2015-04-15
JP5972942B2 (ja) 2016-08-17
KR20170015566A (ko) 2017-02-08
IL212817A0 (en) 2011-07-31
EP2370424A1 (en) 2011-10-05
JP2012508260A (ja) 2012-04-05
KR20110084527A (ko) 2011-07-25
JP2014240410A (ja) 2014-12-25
ZA201103411B (en) 2012-09-26
CN102264721B (zh) 2015-12-09
IL212817A (en) 2015-05-31
JP2016216495A (ja) 2016-12-22
KR101712576B1 (ko) 2017-03-06
US20120040020A1 (en) 2012-02-16
US8410112B2 (en) 2013-04-02
NZ593316A (en) 2013-06-28
AU2009313198A1 (en) 2011-06-30
MX2011004953A (es) 2011-12-14
AU2016203414A1 (en) 2016-06-23
HK1161260A1 (zh) 2012-08-24
RU2011123647A (ru) 2012-12-20
CA2743134A1 (en) 2010-05-14
US20140113005A1 (en) 2014-04-24

Similar Documents

Publication Publication Date Title
AU2009313198B2 (en) Compounds useful as inhibitors of ATR kinase
EP1951716B1 (en) Aminopyrimidines useful as kinase inhibitors
US8268811B2 (en) Thiazoles and pyrazoles useful as kinase inhibitors
US20100137305A1 (en) Aminopyrimidines useful as kinase inhibitors
EP2152696B1 (en) Aminopyrimidines useful as kinase inhibitors
US8455507B2 (en) Aminopyrimidines useful as kinase inhibitors
CA2687966A1 (en) Thiazoles and pyrazoles useful as kinase inhibitors
AU2012240030A1 (en) Aminopyrazine compounds useful as inhibitors of TRA kinase
EP4534538A2 (en) Compounds useful as inhibitors of atr kinase
BRPI0619704A2 (pt) composto, composição, método para inibir a atividade da proteìna aurora quinase numa amostra biológica, método para tratar um distúrbio proliferativo e método para tratar cáncer
EP2155730A2 (en) Aminopyrimidines useful as kinase inhibitors
HK40050074A (en) Pyrazolo[1,5-a]pyrimidines useful as inhibitors of atr kinase for the treatment of cancer diseases
HK40050074B (en) Pyrazolo[1,5-a]pyrimidines useful as inhibitors of atr kinase for the treatment of cancer diseases
HK40008986A (en) 2-amino-n-(piperidin-1-yl-pyridin-3-yl) pyrazolo[1,5alpha]pyrimidine-3-carboxamid as inhibitor of atr kinase
HK1125107A (en) Aminopyrimidines useful as kinase inhibitors

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200980152891.X

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09756203

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2743134

Country of ref document: CA

Ref document number: 2011535772

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: MX/A/2011/004953

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 212817

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 2014/KOLNP/2011

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2009756203

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 593316

Country of ref document: NZ

ENP Entry into the national phase

Ref document number: 20117013234

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2011123647

Country of ref document: RU

ENP Entry into the national phase

Ref document number: 2009313198

Country of ref document: AU

Date of ref document: 20091110

Kind code of ref document: A