WO2012177606A1 - Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors - Google Patents

Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors Download PDF

Info

Publication number
WO2012177606A1
WO2012177606A1 PCT/US2012/043099 US2012043099W WO2012177606A1 WO 2012177606 A1 WO2012177606 A1 WO 2012177606A1 US 2012043099 W US2012043099 W US 2012043099W WO 2012177606 A1 WO2012177606 A1 WO 2012177606A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
pyrazol
pyrrolo
cyanomethyl
pyrimidin
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/US2012/043099
Other languages
English (en)
French (fr)
Inventor
Wenqing Yao
David M. Burns
Jincong Zhuo
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.)
Incyte Corp
Original Assignee
Incyte Corp
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 ES12735369.6T priority Critical patent/ES2560611T3/es
Priority to AU2012273164A priority patent/AU2012273164B2/en
Priority to NZ618982A priority patent/NZ618982B2/en
Priority to JP2014517080A priority patent/JP5876146B2/ja
Priority to PH1/2013/502612A priority patent/PH12013502612A1/en
Priority to CN201280037078.XA priority patent/CN103797010B/zh
Priority to MX2013015087A priority patent/MX344479B/es
Priority to CA2839767A priority patent/CA2839767A1/en
Priority to UAA201400439A priority patent/UA110978C2/uk
Application filed by Incyte Corp filed Critical Incyte Corp
Priority to EA201490042A priority patent/EA201490042A1/ru
Priority to BR112013032720A priority patent/BR112013032720A2/pt
Priority to KR1020147001320A priority patent/KR20140040819A/ko
Priority to EP12735369.6A priority patent/EP2721028B1/en
Priority to HK14110258.0A priority patent/HK1197056B/en
Publication of WO2012177606A1 publication Critical patent/WO2012177606A1/en
Priority to IL230008A priority patent/IL230008A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • Y is CR 7 .
  • R 1 is isopropyl, ethyl, 1 -methylpropyl, 2,2,2-trifluoro- 1-methylethyl, 1-cyclopropylethyl, 1 -cyclohexylethyl, cyclopropyl, 1- trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl, or l-(l-methylpiperidin-4- yl)ethyl.
  • R 1 is isopropyl
  • R 1 is 1 -trifluoromethylcyclopropyl.
  • R 1 is 2,2,2-trifluoroethyl.
  • the compound is a compound of Formula IVa:
  • the compound has Formula Ilia, wherein R 1 , R 2 , R 3 , R 5 , R 6 are defined as in embodiment (a).
  • the compound has Formula IVa, wherein R 1 , R 2 , R 3 , and R 5 are defined as in embodiment (a).
  • the compound has Formula Illb, wherein R 1 , R 2 , R 3 , R 5 , R 6 are defined as in embodiment (b).
  • Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine).
  • Suitable elution solvent composition can be determined by one skilled in the art.
  • Compounds of the invention also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge.
  • amine derivative 8 which can be converted to the corresponding aryl ester 10 by reaction with halo-substituted arylacid ester 9 in the presence of the suitable catalyst such as, but not limited to, ⁇ [2,2'-bis(diphenylphosphino)-l, l 'binaphthalene], Tol- ⁇ [2,2'-bis(di-p-tolylphosphino)-l, l 'binaphthalene], Xanthpos [4,5- bis(diphenylphosphino)-9,9-dimethylxanthene].
  • the suitable catalyst such as, but not limited to, ⁇ [2,2'-bis(diphenylphosphino)-l, l 'binaphthalene], Tol- ⁇ [2,2'-bis(di-p-tolylphosphino)-l, l 'binaphthalene], Xanthpos [4,5- bis(diphenylphosphino)-9,9
  • aryl amide derivatives 12 can be prepared according to the procedures outlined in Scheme 4.
  • the aryl ester 16 can be hydrolyzed to the corresponding acid 19 by using an alkali such as lithium hydroxide, sodium hydroxide or potassium hydroxide.
  • the acid 19 can be transfered to the arylamide 20 by reaction with an appropriate amine in the presence of a suitable coupling reagent such as, but not limited to, BOP, PyOP, HATU, HBTU, EDC, or CDI.
  • Swern oxidation of 20 can produce the corresponding ketone 21 which can be converted to the ⁇ , ⁇ - unsaturated nitrile 22 by Wittig's reaction with diethyl cyanomethylphosphonate.
  • Michael addition of 5 with ⁇ , ⁇ -unsaturated nitrile 21 can afford the adduct 12.
  • the JAK inhibitors described herein can further be used to treat ischemia reperfusion injuries or a disease or condition related to an inflammatory ischemic event such as stroke or cardiac arrest.
  • the JAK inhibitors described herein can further be used to treat endotoxin-driven disease state (e.g., complications after bypass surgery or chronic endotoxin states contributing to chronic cardiac failure).
  • the JAK inhibitors described herein can further be used to treat anorexia, cachexia, or fatigue such as that resulting from or associated with cancer.
  • the JAK inhibitors described herein can further be used to treat restenosis, sclerodermitis, or fibrosis.
  • treating or treatment refers to one or more of (1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and/or symptomatology); and (2) ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and/or symptomatology) such as decreasing the severity of disease.
  • treating or treatment includes preventing the disease; for example, preventing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.
  • Example suitable RAF inhibitors include compounds, and their
  • the selectivity can be at least about 2-fold, at least about 3-fold, at least about 5-fold, at least about 10-fold, at least about 20-fold, at least about 50-fold, or at least about 100-fold. Potency can be measured by one or more in vitro assays, such as the assays provided below in the Examples.
  • the compositions of the invention contain from about 50 mg to about 500 mg of the active ingredient.
  • the active ingredient contains from about 50 mg to about 500 mg of the active ingredient.
  • One having ordinary skill in the art will appreciate that this embodies compounds or compositions containing about 50 mg to about 100 mg, about 100 mg to about 150 mg, about 150 mg to about 200 mg, about 200 mg to about 250 mg, about 250 mg to about 300 mg, about 350 mg to about 400 mg, or about 450 mg to about 500 mg of the active ingredient.
  • liquid forms in which the compounds and compositions of the present invention can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.
  • compositions in can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device can be attached to a face masks tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner.
  • the insert comprises a polymer selected from polyvinylpyrrolidone (PVP), an acrylate or methacrylate polymer or copolymer (e.g., Eudragit® family of polymers from Rohm or Degussa), hydroxymethyl cellulose, polyacrylic acid, poly(amidoamine) dendrimers, poly(dimethyl siloxane), polyethylene oxide, poly(lactide-co-glycolide), poly(2-hydroxyethylmethacrylate), poly(vinyl alcohol), or poly(propylene fumarate).
  • the insert comprises Gelfoam® R.
  • the insert is a polyacrylic acid of 450 kDa-cysteine conjugate.
  • Step 2 tert-butyl 3-(cyanomethylene)azetidine-l-carboxylate
  • Step 3 tert-butyl 3-(cyanomethyl)-3- [4-(l - ⁇ [2-(trimethylsilyl)ethoxy]methyl ⁇ - 1H- pyrrolo[2,3-b]pyridin-4-yl)-lH-pyrazol-l-yl]azetidine-l-carboxylate
  • Step 5 5- ⁇ 3-(cyanomethyl)-3-[4-(l- ⁇ [2-(trimethylsilyl)ethoxy]methyl ⁇ -lH- pyrrolo[2, 3-b]pyridin-4-yl)-lH-pyrazol-l-yl]azetidin-l-yl ⁇ -N-[ ( 1S)-1- cyclopropyle
  • Step 1 methyl 5- ⁇ 3-(cyanomethyl)-3-f4-(7- ⁇ f2-(trimethylsilyl)ethoxyJmethyl ⁇ -7H- pyrrolo[2,3-d]pyrimidin-4-yl)-lH-pyrazol-l-yl]azetidin-l-yl ⁇ pyrazine-2-carboxylate
  • Example 26 4- ⁇ 3-(Cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-lH- pyrazol-l-yl]azetidin-l-yl ⁇ -N-(2,2,2-trifluoro-l-methylethyl)benzamide
  • Step 3 4- ⁇ 3-(cyanomethyl)-3-[ 4-(7H-pyrrolo[2, 3-d]pyrimidin-4-yl)-lH-pyrazol-l- yl]azetidin-l-yl ⁇ -2,5-difluoro-N-[(lS)-2,2,2-trifluoro-l-methylethyl]benzamide
  • N,N-Diisopropylethylamine (0.11 mL, 0.62 mmol) was added to a mixture of ⁇ 3-[4-(7- ⁇ [2-(trimethylsilyl)ethoxy]methyl ⁇ -7H-pyrrolo[2,3-d]pyrimidin-4-yl)-lH- pyrazol-l-yl]azetidin-3-yl ⁇ acetonitrile dihydrochloride (110 mg, 0.22 mmol) and 5- chloro-N-[(lS)-2,2,2-trifluoro-l-methylethyl]pyrazine-2-carboxamide (52 mg, 0.21 mmol) in NMP (3.0 mL).
  • Step 3 5- ⁇ 3-(cyanomethyl)-3-[ 4-(7H-pyrrolo[2, 3-d]pyrimidin-4-yl)-lH-pyrazol-l- yl]azetidin-l-yl ⁇ -N-[(lS)-2,2,2-trifluoro-l-methylethyl]pyrazine-2-carboxamide
  • Step 1 5-chloro-N-[(lS)-l-cyclopropyl-2,2,2-trifluoroethyl]pyrazine-2-carboxamide N,N-Diisopropylethylamine (1.3 mL, 7.5 mmol) was added to a mixture of 5- chloropyrazine-2-carboxylic acid (0.40 g, 2.5 mmol), N,N,N',N'-tetramethyl-0-(7- azabenzotriazol-l-yl)uronium hexafluorophosphate (1.0 g, 2.8 mmol) and (lS)-l- cyclopropyl-2,2,2-trifluoroethanamine hydrochloride (0.44 g, 2.5 mmol) (ASIBA Pharmatech, Cat.#: 70092-HCl) in methylene chloride (10 mL).
  • N,N-Diisopropylethylamine (0.71 mL, 4.1 mmol) was added to a mixture of ⁇ 3-[4-(7- ⁇ [2-(trimethylsilyl)ethoxy]methyl ⁇ -7H-pyrrolo[2,3-d]pyrimidin-4-yl)-lH- pyrazol-l-yl]azetidin-3-yl ⁇ acetonitrile dihydrochloride (0.70 g, 1.4 mmol) and 5- chloro-N-[l-(trifluoromethyl)cyclopropyl]pyrazine-2-carboxamide (0.36 g, 1.4 mmol) in NMP (5.0 mL).
  • the above cell lines can also be used to examine the effects of compounds on phosphorylation of JAK kinases or potential downstream substrates such as STAT proteins, Akt, Shp2, or Erk. These experiments can be performed following an overnight cytokine starvation, followed by a brief preincubation with compound (2 hours or less) and cytokine stimulation of approximately 1 hour or less. Proteins are then extracted from cells and analyzed by techniques familiar to those schooled in the art including Western blotting or ELISAs using antibodies that can differentiate between phosphorylated and total protein. These experiments can utilize normal or cancer cells to investigate the activity of compounds on tumor cell survival biology or on mediators of inflammatory disease.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Neurosurgery (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Pulmonology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
PCT/US2012/043099 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors Ceased WO2012177606A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
UAA201400439A UA110978C2 (uk) 2011-06-20 2012-06-19 Азетидинілфенілові, піридилові або піразинілкарбоксамідні похідні як інгібітори jak
NZ618982A NZ618982B2 (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
EA201490042A EA201490042A1 (ru) 2011-06-20 2012-06-19 Азетидинил-фенил-, пиридил- или пиразинилкарбоксамидные производные как ингибиторы jak
PH1/2013/502612A PH12013502612A1 (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
CN201280037078.XA CN103797010B (zh) 2011-06-20 2012-06-19 作为jak抑制剂的氮杂环丁烷基苯基、吡啶基或吡嗪基甲酰胺衍生物
MX2013015087A MX344479B (es) 2011-06-20 2012-06-19 Derivados de azetidinil fenil, piridil o pirazinil carboxamida como inhibidores de cinasa janus (jak).
CA2839767A CA2839767A1 (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
ES12735369.6T ES2560611T3 (es) 2011-06-20 2012-06-19 Derivados de fenil de azetidinilo, carboxamida de piridilo o pirazinilo como inhibidores de JAK
JP2014517080A JP5876146B2 (ja) 2011-06-20 2012-06-19 Ｊａｋ阻害剤としてのアゼチジニルフェニル、ピリジル、またはピラジニルカルボキサミド誘導体
AU2012273164A AU2012273164B2 (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
BR112013032720A BR112013032720A2 (pt) 2011-06-20 2012-06-19 "derivados de azetidinil fenil, piridil ou pirazinil carboxamida como inibidores de jak, composição e uso dos referidos derivados"
KR1020147001320A KR20140040819A (ko) 2011-06-20 2012-06-19 Ｊａｋ 저해제로서의 아제티디닐 페닐, 피리딜 또는 피라지닐 카르복스아미드 유도체
EP12735369.6A EP2721028B1 (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
HK14110258.0A HK1197056B (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
IL230008A IL230008A (en) 2011-06-20 2013-12-17 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161498942P 2011-06-20 2011-06-20
US61/498,942 2011-06-20
US201261591094P 2012-01-26 2012-01-26
US61/591,094 2012-01-26

Publications (1)

Publication Number Publication Date
WO2012177606A1 true WO2012177606A1 (en) 2012-12-27

Family

ID=46513833

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/043099 Ceased WO2012177606A1 (en) 2011-06-20 2012-06-19 Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors

Country Status (22)

Country Link
US (5) US8691807B2 (https=)
EP (1) EP2721028B1 (https=)
JP (1) JP5876146B2 (https=)
KR (1) KR20140040819A (https=)
CN (1) CN103797010B (https=)
AR (1) AR086983A1 (https=)
AU (1) AU2012273164B2 (https=)
BR (1) BR112013032720A2 (https=)
CA (1) CA2839767A1 (https=)
CL (1) CL2013003647A1 (https=)
CO (1) CO6821966A2 (https=)
CR (1) CR20130668A (https=)
EA (1) EA201490042A1 (https=)
EC (1) ECSP14013148A (https=)
ES (1) ES2560611T3 (https=)
IL (1) IL230008A (https=)
MX (1) MX344479B (https=)
MY (1) MY165963A (https=)
PE (1) PE20140832A1 (https=)
PH (1) PH12013502612A1 (https=)
TW (1) TWI577676B (https=)
WO (1) WO2012177606A1 (https=)

Cited By (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8691807B2 (en) 2011-06-20 2014-04-08 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
WO2014138168A1 (en) * 2013-03-06 2014-09-12 Incyte Corporation Processes and intermediates for making a jak inhibitor
WO2014186706A1 (en) * 2013-05-17 2014-11-20 Incyte Corporation Bipyrazole derivatives as jak inhibitors
US8933085B2 (en) 2010-11-19 2015-01-13 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US8933086B2 (en) 2005-12-13 2015-01-13 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-B]pyridines and pyrrolo[2,3-B]pyrimidines as Janus kinase inhibitors
US9034884B2 (en) 2010-11-19 2015-05-19 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors
WO2015123437A1 (en) 2014-02-13 2015-08-20 Incyte Corporation Cyclopropylamines as lsd1 inhibitors
WO2015123424A1 (en) 2014-02-13 2015-08-20 Incyte Corporation Cyclopropylamines as lsd1 inhibitors
WO2015157257A1 (en) * 2014-04-08 2015-10-15 Incyte Corporation Treatment of b-cell malignancies by a combination jak and pi3k inhibitor
US9193733B2 (en) 2012-05-18 2015-11-24 Incyte Holdings Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US9216984B2 (en) 2009-05-22 2015-12-22 Incyte Corporation 3-[4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane—or heptane-nitrile as JAK inhibitors
US9249145B2 (en) 2009-09-01 2016-02-02 Incyte Holdings Corporation Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9334274B2 (en) 2009-05-22 2016-05-10 Incyte Holdings Corporation N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9359358B2 (en) 2011-08-18 2016-06-07 Incyte Holdings Corporation Cyclohexyl azetidine derivatives as JAK inhibitors
US9464088B2 (en) 2010-03-10 2016-10-11 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US9487521B2 (en) 2011-09-07 2016-11-08 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US9493442B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9498467B2 (en) 2014-05-30 2016-11-22 Incyte Corporation Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1
WO2016196244A1 (en) 2015-05-29 2016-12-08 Incyte Corporation Pyridineamine compounds useful as pim kinase inhibitors
US9550765B2 (en) 2013-01-15 2017-01-24 Incyte Holdings Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as Pim kinase inhibitors
JP2017506659A (ja) * 2014-02-28 2017-03-09 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ 骨髄異形成症候群の治療のためのｊａｋ１阻害剤
WO2017044730A1 (en) 2015-09-09 2017-03-16 Incyte Corporation Salts of a pim kinase inhibitor
WO2017059251A1 (en) 2015-10-02 2017-04-06 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors
US9655854B2 (en) 2013-08-07 2017-05-23 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US9670210B2 (en) 2014-02-13 2017-06-06 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9676750B2 (en) 2013-01-14 2017-06-13 Incyte Corporation Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors
US9695168B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted imidazo[1,5-α]pyridines and imidazo[1,5-α]pyrazines as LSD1 inhibitors
US9695167B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted triazolo[1,5-a]pyridines and triazolo[1,5-a]pyrazines as LSD1 inhibitors
US9695180B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted imidazo[1,2-a]pyrazines as LSD1 inhibitors
US9758523B2 (en) 2014-07-10 2017-09-12 Incyte Corporation Triazolopyridines and triazolopyrazines as LSD1 inhibitors
US9822124B2 (en) 2014-07-14 2017-11-21 Incyte Corporation Bicyclic heteroaromatic carboxamide compounds useful as Pim kinase inhibitors
CN107531695A (zh) * 2015-04-29 2018-01-02 无锡福祈制药有限公司 Jak抑制剂
US9890162B2 (en) 2014-07-14 2018-02-13 Incyte Corporation Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors
US9944647B2 (en) 2015-04-03 2018-04-17 Incyte Corporation Heterocyclic compounds as LSD1 inhibitors
US10000507B2 (en) 2013-08-23 2018-06-19 Incyte Corporation Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors
US10166221B2 (en) 2016-04-22 2019-01-01 Incyte Corporation Formulations of an LSD1 inhibitor
US10166191B2 (en) 2012-11-15 2019-01-01 Incyte Corporation Sustained-release dosage forms of ruxolitinib
US10329255B2 (en) 2015-08-12 2019-06-25 Incyte Corporation Salts of an LSD1 inhibitor
US10596161B2 (en) 2017-12-08 2020-03-24 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
US10758543B2 (en) 2010-05-21 2020-09-01 Incyte Corporation Topical formulation for a JAK inhibitor
US10899736B2 (en) 2018-01-30 2021-01-26 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US10968200B2 (en) 2018-08-31 2021-04-06 Incyte Corporation Salts of an LSD1 inhibitor and processes for preparing the same
US11045455B2 (en) 2015-12-11 2021-06-29 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Azetidine derivative, preparation method therefor, and use thereof
TWI740843B (zh) * 2015-09-25 2021-10-01 中國大陸商迪哲（江蘇）醫藥有限公司 用於抑制ｊａｋ之化合物和方法
US11213528B2 (en) 2007-06-13 2022-01-04 Incyte Holdings Corporation Salts of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US11304949B2 (en) 2018-03-30 2022-04-19 Incyte Corporation Treatment of hidradenitis suppurativa using JAK inhibitors
US11685731B2 (en) 2020-06-02 2023-06-27 Incyte Corporation Processes of preparing a JAK1 inhibitor
US11833152B2 (en) 2018-02-16 2023-12-05 Incyte Corporation JAK1 pathway inhibitors for the treatment of cytokine-related disorders
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
US11957661B2 (en) 2020-12-08 2024-04-16 Incyte Corporation JAK1 pathway inhibitors for the treatment of vitiligo
US12226418B2 (en) 2018-06-01 2025-02-18 Incyte Corporation Dosing regimen for the treatment of PI3K related disorders
US12268667B2 (en) 2021-05-03 2025-04-08 Incyte Corporation JAK1 pathway inhibitors for the treatment of prurigo nodularis

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CL2008001709A1 (es) 2007-06-13 2008-11-03 Incyte Corp Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras.
CA3121743A1 (en) 2009-01-15 2010-07-22 Incyte Holdings Corporation Processes for preparing jak inhibitors and related intermediate compounds
CN104945420A (zh) 2009-06-29 2015-09-30 因塞特公司 作为pi3k抑制剂的嘧啶酮类
EP2655374B1 (en) 2010-12-20 2019-10-23 Incyte Holdings Corporation N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors
CA2827673C (en) 2011-02-18 2020-10-27 Novartis Pharma Ag Mtor/jak inhibitor combination therapy
EP2734205B1 (en) 2011-07-21 2018-03-21 Tolero Pharmaceuticals, Inc. Heterocyclic protein kinase inhibitors
EP2741747A1 (en) 2011-08-10 2014-06-18 Novartis Pharma AG JAK P13K/mTOR COMBINATION THERAPY
KR102507287B1 (ko) 2011-09-02 2023-03-07 인사이트 홀딩스 코포레이션 Ｐｉ３ｋ 억제제로서 헤테로시클릴아민
AR090548A1 (es) 2012-04-02 2014-11-19 Incyte Corp Azaheterociclobencilaminas biciclicas como inhibidores de pi3k
CN104918945B (zh) 2012-11-01 2018-01-05 因赛特公司 作为jak抑制剂的三环稠合噻吩衍生物
CN105555313A (zh) 2013-08-20 2016-05-04 因赛特公司 在c-反应蛋白水平较高的实体肿瘤患者中的存活益处
CN106687462A (zh) 2014-04-30 2017-05-17 因赛特公司 Jak1抑制剂的制备方法以及其新形式
WO2015191677A1 (en) 2014-06-11 2015-12-17 Incyte Corporation Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors
WO2016130501A1 (en) 2015-02-09 2016-08-18 Incyte Corporation Aza-heteroaryl compounds as pi3k-gamma inhibitors
SI3831833T1 (sl) 2015-02-27 2023-03-31 Incyte Holdings Corporation Postopki za pripravo inhibitorja PI3K
US9840503B2 (en) 2015-05-11 2017-12-12 Incyte Corporation Heterocyclic compounds and uses thereof
US9732097B2 (en) 2015-05-11 2017-08-15 Incyte Corporation Process for the synthesis of a phosphoinositide 3-kinase inhibitor
US9988401B2 (en) 2015-05-11 2018-06-05 Incyte Corporation Crystalline forms of a PI3K inhibitor
WO2017027717A1 (en) 2015-08-12 2017-02-16 Incyte Corporation Bicyclic fused pyrimidine compounds as tam inhibitors
US10053465B2 (en) 2015-08-26 2018-08-21 Incyte Corporation Pyrrolopyrimidine derivatives as TAM inhibitors
RS63359B1 (sr) 2015-11-06 2022-07-29 Incyte Corp Heterociklična jedinjenja kao inhibitori pi3k-gama
ES2916874T3 (es) 2015-12-17 2022-07-06 Incyte Corp Derivados de N-fenil-piridina-2-carboxamida y su uso como moduladores de la interacción proteína/proteína PD-1/PD-L1
WO2017120194A1 (en) 2016-01-05 2017-07-13 Incyte Corporation Pyridine and pyridimine compounds as pi3k-gamma inhibitors
MD3436461T2 (ro) 2016-03-28 2024-05-31 Incyte Corp Compuși pirolotriazină ca inhibitori TAM
WO2017223414A1 (en) 2016-06-24 2017-12-28 Incyte Corporation HETEROCYCLIC COMPOUNDS AS PI3K-γ INHIBITORS
EP3558990B1 (en) * 2016-12-22 2022-08-10 Incyte Corporation Tetrahydro imidazo[4,5-c]pyridine derivatives as pd-l1 internalization inducers
WO2018119286A1 (en) 2016-12-22 2018-06-28 Incyte Corporation Bicyclic heteroaromatic compounds as immunomodulators
SI3687996T1 (sl) 2017-09-27 2022-04-29 Incyte Corporation Soli pirolotriazinskih derivatov, ki so uporabne kot zaviralci TAM
KR20240152947A (ko) 2017-10-18 2024-10-22 인사이트 코포레이션 Pi3k-감마 저해제로서의 3차 하이드록시기로 치환된 축합된 이미다졸 유도체
KR20190043437A (ko) 2017-10-18 2019-04-26 씨제이헬스케어 주식회사 단백질 키나제 억제제로서의 헤테로고리 화합물
CN109867676B (zh) * 2017-12-01 2020-10-30 北京普祺医药科技有限公司 一种吡咯并嘧啶衍生的化合物、药物组合物以及其用途
WO2019191679A1 (en) 2018-03-30 2019-10-03 Incyte Corporation Biomarkers for inflammatory skin disease
CN117838695A (zh) 2018-04-13 2024-04-09 住友制药肿瘤公司 用于治疗骨髓增殖性肿瘤和与癌症相关的纤维化的pim激酶抑制剂
CA3097025A1 (en) 2018-04-13 2019-10-17 Incyte Corporation Biomarkers for graft-versus-host disease
CN108484468A (zh) * 2018-05-11 2018-09-04 南京大学 芳基氮杂环丁烷类化合物的制备方法
JP7083203B2 (ja) 2018-06-06 2022-06-10 ジェングル セラピューティクス，インコーポレイテッド ピラゾロピリミジン誘導体、その用途並びに医薬組成物
MD3813800T2 (ro) 2018-06-29 2025-10-31 Incyte Corp Formulări de inhibitor al AXL/MER
CR20250050A (es) 2018-09-05 2025-03-19 Incyte Corp Formas cristalinas de un inhibidor de fosfoinositida 3–quinasa (pi3k) (divisional 2021-0165)
CA3117969A1 (en) 2018-10-31 2020-05-07 Incyte Corporation Combination therapy for treatment of hematological diseases
KR102195348B1 (ko) 2018-11-15 2020-12-24 에이치케이이노엔 주식회사 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물
CA3123596A1 (en) 2018-12-19 2020-06-25 Incyte Corporation Jak1 pathway inhibitors for the treatment of gastrointestinal disease
NZ778055A (en) 2019-02-12 2025-11-28 Sumitomo Pharma America Inc Formulations comprising heterocyclic protein kinase inhibitors
MA55201A (fr) 2019-03-05 2022-01-12 Incyte Corp Inhibiteurs de la voie jak1 pour le traitement d'un dysfonctionnement chronique de l'allogreffe pulmonaire
US11624751B2 (en) 2019-03-19 2023-04-11 Incyte Corporation Biomarkers for vitiligo
CN114761013A (zh) 2019-09-27 2022-07-15 迪斯克医药公司 治疗骨髓纤维化和相关病症的方法
EP4041204A1 (en) 2019-10-10 2022-08-17 Incyte Corporation Biomarkers for graft-versus-host disease
US12360120B2 (en) 2019-10-10 2025-07-15 Incyte Corporation Biomarkers for graft-versus-host disease
WO2021076124A1 (en) 2019-10-16 2021-04-22 Incyte Corporation Use of jak1 inhibitors for the treatment of cutaneous lupus erythematosus and lichen planus (lp)
US11992490B2 (en) 2019-10-16 2024-05-28 Incyte Corporation Use of JAK1 inhibitors for the treatment of cutaneous lupus erythematosus and Lichen planus (LP)
CN115038443A (zh) 2019-11-22 2022-09-09 因西特公司 包含alk2抑制剂和jak2抑制剂的组合疗法
EP4114401A1 (en) 2020-03-06 2023-01-11 Incyte Corporation Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors
WO2021231798A1 (en) 2020-05-13 2021-11-18 Disc Medicine, Inc. Anti-hemojuvelin (hjv) antibodies for treating myelofibrosis
CR20230130A (es) 2020-08-18 2023-07-13 Incyte Corp Proceso e intermedios para preparar un inhibidor de jak1
CA3192099A1 (en) 2020-08-18 2022-02-24 Incyte Corporation Process and intermediates for preparing a jak inhibitor
US11866434B2 (en) 2020-11-06 2024-01-09 Incyte Corporation Process for making a PD-1/PD-L1 inhibitor and salts and crystalline forms thereof
US12005067B2 (en) 2020-12-04 2024-06-11 Incyte Corporation JAK inhibitor with a vitamin D analog for treatment of skin diseases
EP4274578A1 (en) 2021-01-11 2023-11-15 Incyte Corporation Combination therapy comprising jak pathway inhibitor and rock inhibitor
US20240309095A1 (en) 2021-07-07 2024-09-19 Incyte Corporation Anti-b7-h4 antibodies and uses thereof
CN118317946A (zh) 2021-07-12 2024-07-09 因赛特公司 用于制备巴瑞替尼的方法和中间体
US20230272055A1 (en) 2021-12-08 2023-08-31 Incyte Corporation Anti-mutant calreticulin (calr) antibodies and uses thereof
CN114149437A (zh) * 2021-12-24 2022-03-08 安徽大学 一种吡咯并嘧啶五元氮杂环衍生物及其制备方法和用途
IL318652A (en) 2022-08-05 2025-03-01 Incyte Corp Treatment of urticaria with JAK inhibitors
EP4611753A1 (en) 2022-10-31 2025-09-10 Sumitomo Pharma America, Inc. Pim1 inhibitor for treating myeloproliferative neoplasms
TW202438061A (zh) 2023-03-16 2024-10-01 美商英塞特公司 用於治療氣喘之ｊａｋ１路徑抑制劑
WO2025096716A1 (en) 2023-11-01 2025-05-08 Incyte Corporation Anti-mutant calreticulin (calr) antibody-drug conjugates and uses thereof
WO2025226637A1 (en) 2024-04-22 2025-10-30 Incyte Corporation Combination therapy with an anti-colony stimulating factor 1 receptor antibody and a jak inhibitor

Citations (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
WO2000009495A1 (en) 1998-08-11 2000-02-24 Novartis Ag Isoquinoline derivatives with angiogenesis inhibiting activity
WO2000053595A1 (en) 1999-03-06 2000-09-14 Astrazeneca Ab Pyrimidine compounds
WO2001014402A1 (en) 1999-08-19 2001-03-01 Isis Pharmaceuticals, Inc. Antisense modulation of focal adhesion kinase expression
WO2001064655A1 (en) 2000-03-01 2001-09-07 Astrazeneca Ab 2, 4-di(hetero-)arylamino (-oxy)-5-substituted pyrimidines as antineoplastic agents
WO2002000196A2 (en) 2000-06-28 2002-01-03 Smithkline Beecham P.L.C. Wet milling process
WO2003024967A2 (en) 2001-09-19 2003-03-27 Aventis Pharma S.A. Indolizines as kinase protein inhibitors
WO2003037347A1 (en) 2001-10-30 2003-05-08 Novartis Ag Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity
WO2003099771A2 (en) 2002-05-29 2003-12-04 Novartis Ag Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases
WO2004005281A1 (en) 2002-07-05 2004-01-15 Novartis Ag Inhibitors of tyrosine kinases
WO2004046120A2 (en) 2002-11-15 2004-06-03 Vertex Pharmaceuticals Incorporated Diaminotriazoles useful as inhibitors of protein kinases
WO2004056786A2 (en) 2002-12-20 2004-07-08 Pfizer Products Inc. Pyrimidine derivates for the treatment of abnormal cell growth
WO2004080980A1 (en) 2003-03-14 2004-09-23 Novartis Ag 2, 4- di (phenylamino) pyrimidines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders
WO2005028444A1 (en) 2003-09-24 2005-03-31 Novartis Ag 1,4-disubstituted isoquinilone derivatives as raf-kinase inhibitors useful for the treatment of proliferative diseases
WO2006056399A2 (en) 2004-11-24 2006-06-01 Novartis Ag Combinations of jak inhibitors and at least one of bcr-abl, flt-3, fak or raf kinase inhibitors
WO2008022164A2 (en) 2006-08-16 2008-02-21 Boehringer Ingelheim International Gmbh Pyrazine compounds, their use and methods of preparation
WO2008058126A2 (en) 2006-11-06 2008-05-15 Supergen, Inc. Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors
US20080161578A1 (en) 2006-12-29 2008-07-03 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
US20080161559A1 (en) 2006-12-29 2008-07-03 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
WO2008106692A1 (en) 2007-03-01 2008-09-04 Novartis Vaccines And Diagnostics, Inc. Pim kinase inhibitors and methods of their use
WO2008124323A1 (en) 2007-04-03 2008-10-16 Array Biopharma Inc. Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors
WO2009064486A2 (en) 2007-11-15 2009-05-22 Musc Foundation For Research Development Inhibitors of pim protein kinases, compositions, and methods for treating cancer
WO2009109576A1 (en) 2008-03-03 2009-09-11 Novartis Ag Pim kinase inhibitors and methods of their use
US20090233903A1 (en) * 2008-03-11 2009-09-17 Incyte Corporation Azetidine and cyclobutane derivatives as jak inhibitors
WO2010001169A2 (en) 2008-07-02 2010-01-07 Astrazeneca Ab Chemical compounds 251
WO2010000978A1 (fr) 2008-07-03 2010-01-07 Centre National De La Recherche Scientifique NOUVEAUX PYRROLO [2,3-a] CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM
WO2010022081A1 (en) 2008-08-19 2010-02-25 Array Biopharma Inc. Triazolopyridine compounds as pim kinase inhibitors
WO2010022076A1 (en) 2008-08-19 2010-02-25 Array Biopharma Inc. Triazolopyridine compounds as pim kinase inhibitors
WO2010026121A1 (en) 2008-09-02 2010-03-11 Novartis Ag Bicyclic kinase inhibitors
WO2010026122A1 (en) 2008-09-02 2010-03-11 Novartis Ag Heterocyclic pim-kinase inhibitors
WO2010026124A1 (en) 2008-09-02 2010-03-11 Novartis Ag Picolinamide derivatives as kinase inhibitors
US20110059951A1 (en) * 2009-09-01 2011-03-10 Rodgers James D HETEROCYCLIC DERIVATIVES OF PYRAZOL-4-YL-PYRROLO[2,3-d]PYRIMIDINES AS JANUS KINASE INHIBITORS
WO2011029802A1 (en) 2009-09-08 2011-03-17 F. Hoffmann-La Roche Ag 4-substituted pyridin-3-yl-carboxamide compounds and methods of use
WO2011057784A1 (en) 2009-11-11 2011-05-19 Sygnis Bioscience Gmbh & Co. Kg Compounds for pim kinase inhibition and for treating malignancy

Family Cites Families (273)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2985589A (en) 1957-05-22 1961-05-23 Universal Oil Prod Co Continuous sorption process employing fixed bed of sorbent and moving inlets and outlets
US3632836A (en) 1968-10-25 1972-01-04 Dow Chemical Co Solid curable polyepoxides modified with hydrolyzed liquid polyepoxides
US3832460A (en) 1971-03-19 1974-08-27 C Kosti Anesthetic-vasoconstrictor-antihistamine composition for the treatment of hypertrophied oral tissue
US4140755A (en) 1976-02-13 1979-02-20 Hoffmann-La Roche Inc. Sustained release tablet formulations
DE3036390A1 (de) 1980-09-26 1982-05-13 Troponwerke GmbH & Co KG, 5000 Köln Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen
DE3220113A1 (de) 1982-05-28 1983-12-01 Basf Ag, 6700 Ludwigshafen Difluormethoxiphenylthiophosphorsaeureester
US4402832A (en) 1982-08-12 1983-09-06 Uop Inc. High efficiency continuous separation process
US4404335A (en) 1982-08-16 1983-09-13 The Dow Chemical Company Hydrolyzing epoxy resins in absence of solvent and in presence of oxalic acid and a phosphonium compound
US4548990A (en) 1983-08-15 1985-10-22 Ciba-Geigy Corporation Crosslinked, porous polymers for controlled drug delivery
US4498991A (en) 1984-06-18 1985-02-12 Uop Inc. Serial flow continuous separation process
NL8403224A (nl) 1984-10-24 1986-05-16 Oce Andeno Bv Dioxafosforinanen, de bereiding ervan en de toepassing voor het splitsen van optisch actieve verbindingen.
CA1306260C (en) 1985-10-18 1992-08-11 Shionogi & Co., Ltd. Condensed imidazopyridine derivatives
US4921947A (en) 1986-03-31 1990-05-01 Eli Lilly And Company Process for preparing macrolide derivatives
JP2541702B2 (ja) 1989-10-11 1996-10-09 帝人株式会社 二環性ピリミジン誘導体、その製造方法およびそれを有効成分とする医薬製剤
US5403593A (en) 1991-03-04 1995-04-04 Sandoz Ltd. Melt granulated compositions for preparing sustained release dosage forms
IT1258781B (it) 1992-01-16 1996-02-29 Zambon Spa Composizione farmaceutica oftalmica contenente n-acetilcisteina e polivinilalcol
FR2695126B1 (fr) 1992-08-27 1994-11-10 Sanofi Elf Dérivés d'acide thiényl ou pyrrolyl carboxyliques, leur préparation et médicaments les contenant.
AU671491B2 (en) 1992-12-18 1996-08-29 F. Hoffmann-La Roche Ag N-oxycarbonyl substituted 5'-deoxy-5-fluorcytidines
JPH0710876A (ja) 1993-06-24 1995-01-13 Teijin Ltd ４位に環状アミノ基を有するピロロ［２，３―ｄ］ピリミジン
USH1439H (en) 1993-10-18 1995-05-02 The Dow Chemical Company Method to increase the level of α-glycol in liquid epoxy resin
EP0727217A3 (en) 1995-02-10 1997-01-15 Suntory Ltd Pharmaceutical and cosmetic compositions containing God-type ellagitannin as an active ingredient
US5856326A (en) 1995-03-29 1999-01-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
IL117580A0 (en) 1995-03-29 1996-07-23 Merck & Co Inc Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
BR9609613A (pt) 1995-07-05 1999-05-25 Du Pont Composto composição fungicida e método de controle de doenças de plantas
MX9800215A (es) 1995-07-06 1998-03-31 Novartis Ag Pirrolopirimidas y procesos para su preparacion.
US5630943A (en) 1995-11-30 1997-05-20 Merck Patent Gesellschaft Mit Beschrankter Haftung Discontinuous countercurrent chromatographic process and apparatus
GB9604361D0 (en) 1996-02-29 1996-05-01 Pharmacia Spa 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors
CA2250232A1 (en) 1996-04-03 1997-10-09 Allen I. Oliff A method of treating cancer
EP0952842A2 (en) 1996-04-18 1999-11-03 Merck & Co., Inc. A method of treating cancer
US5795909A (en) 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
JP2000508335A (ja) 1996-05-30 2000-07-04 メルク エンド カンパニー インコーポレーテッド 癌の治療方法
US6624138B1 (en) 2001-09-27 2003-09-23 Gp Medical Drug-loaded biological material chemically treated with genipin
AU724216B2 (en) 1997-04-07 2000-09-14 Merck & Co., Inc. A method of treating cancer
US6063284A (en) 1997-05-15 2000-05-16 Em Industries, Inc. Single column closed-loop recycling with periodic intra-profile injection
US6060038A (en) 1997-05-15 2000-05-09 Merck & Co., Inc. Radiolabeled farnesyl-protein transferase inhibitors
CA2295620A1 (en) 1997-08-11 1999-02-18 Boehringer Ingelheim Pharmaceuticals, Inc. 5,6-heteroaryl-dipyrido¬2,3-b:3',2'-f|azepines and their use in the prevention or treatment of hiv infection
US7153845B2 (en) 1998-08-25 2006-12-26 Columbia Laboratories, Inc. Bioadhesive progressive hydration tablets
US6075056A (en) 1997-10-03 2000-06-13 Penederm, Inc. Antifungal/steroid topical compositions
US6025366A (en) 1998-04-02 2000-02-15 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
US6232320B1 (en) 1998-06-04 2001-05-15 Abbott Laboratories Cell adhesion-inhibiting antiinflammatory compounds
CA2333770A1 (en) 1998-06-04 1999-12-09 Abbott Laboratories Cell adhesion-inhibiting antinflammatory compounds
PA8474101A1 (es) 1998-06-19 2000-09-29 Pfizer Prod Inc Compuestos de pirrolo [2,3-d] pirimidina
BR9911365A (pt) 1998-06-19 2001-03-13 Pfizer Prod Inc Compostos pirrolo[2,3-d]pirimidina
JP2000119271A (ja) 1998-08-12 2000-04-25 Hokuriku Seiyaku Co Ltd １ｈ―イミダゾピリジン誘導体
ATE232382T1 (de) 1998-09-10 2003-02-15 Nycomed Danmark As Pharmazeutische zusammensetzungen mit schneller freisetzung von wirkstoffen
US6375839B1 (en) 1998-10-29 2002-04-23 Institut Francais Du Petrole Process and device for separation with variable-length chromatographic zones
FR2785196B1 (fr) 1998-10-29 2000-12-15 Inst Francais Du Petrole Procede et dispositif de separation avec des zones chromatographiques a longueur variable
US6413419B1 (en) 1998-10-29 2002-07-02 Institut Francais Du Petrole Process and device for separation with variable-length chromatographic
WO2000051614A1 (en) 1999-03-03 2000-09-08 Merck & Co., Inc. Inhibitors of prenyl-protein transferases
US6217895B1 (en) 1999-03-22 2001-04-17 Control Delivery Systems Method for treating and/or preventing retinal diseases with sustained release corticosteroids
US6239113B1 (en) 1999-03-31 2001-05-29 Insite Vision, Incorporated Topical treatment or prevention of ocular infections
AU3565999A (en) 1999-04-16 2000-11-02 Coelacanth Chemical Corporation Synthesis of azetidine derivatives
US6921763B2 (en) 1999-09-17 2005-07-26 Abbott Laboratories Pyrazolopyrimidines as therapeutic agents
ATE275141T1 (de) 1999-10-13 2004-09-15 Banyu Pharma Co Ltd Substituierte imidazolin-derivate
US7235258B1 (en) 1999-10-19 2007-06-26 Nps Pharmaceuticals, Inc. Sustained-release formulations for treating CNS-mediated disorders
EP1382339B1 (en) 1999-12-10 2007-12-05 Pfizer Products Inc. Compositions containing pyrrolo ¬2,3-d pyrimidine derivatives
OA12514A (en) 1999-12-24 2006-05-29 Aventis Pharma Ltd Azaindoles.
US7235551B2 (en) 2000-03-02 2007-06-26 Smithkline Beecham Corporation 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
EP1142566B1 (fr) 2000-04-07 2003-10-01 Laboratoire Medidom S.A. Formulations ophtalmiques à base de ciclosporine, d'acide hyaluronique et du polysorbate
WO2001081345A1 (en) 2000-04-20 2001-11-01 Mitsubishi Pharma Corporation Aromatic amide compounds
ES2788383T3 (es) 2000-04-25 2020-10-21 Icos Corp Inhibidores de delta fosfatidilo-inositol 3-quinasa humana
US7498304B2 (en) 2000-06-16 2009-03-03 Curis, Inc. Angiogenesis-modulating compositions and uses
AU2001275495B2 (en) 2000-06-16 2006-08-17 Curis, Inc. Angiogenesis-modulating compositions and uses
US6335342B1 (en) 2000-06-19 2002-01-01 Pharmacia & Upjohn S.P.A. Azaindole derivatives, process for their preparation, and their use as antitumor agents
ES2344831T3 (es) 2000-06-23 2010-09-08 Mitsubishi Tanabe Pharma Corporation Potenciadores de un efecto antitumoral.
IL152771A0 (en) 2000-06-26 2003-06-24 Pfizer Prod Inc PYRROLO(2,3-d) PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS
WO2002016370A1 (en) 2000-08-22 2002-02-28 Hokuriku Seiyaku Co., Ltd. 1h-imidazopyridine derivatives
US20020111353A1 (en) 2000-12-05 2002-08-15 Mark Ledeboer Inhibitors of c-Jun N-terminal kinases (JNK) and other protein kinases
GB0100622D0 (en) 2001-01-10 2001-02-21 Vernalis Res Ltd Chemical compounds V111
WO2002055496A1 (en) 2001-01-15 2002-07-18 Glaxo Group Limited Aryl piperidine and piperazine derivatives as inducers of ldl-receptor expression
US20040102455A1 (en) 2001-01-30 2004-05-27 Burns Christopher John Method of inhibiting kinases
AU2002308748A1 (en) 2001-05-16 2002-11-25 Vertex Pharmaceuticals Incorporated Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases
US7301023B2 (en) 2001-05-31 2007-11-27 Pfizer Inc. Chiral salt resolution
GB0115109D0 (en) 2001-06-21 2001-08-15 Aventis Pharma Ltd Chemical compounds
GB0115393D0 (en) 2001-06-23 2001-08-15 Aventis Pharma Ltd Chemical compounds
EP1414443B1 (en) 2001-08-01 2006-11-15 Merck & Co., Inc. BENZIMIDAZO 4,5-f|ISOQUINOLINONE DERIVATIVES
US6429231B1 (en) 2001-09-24 2002-08-06 Bradley Pharmaceuticals, Inc. Compositions containing antimicrobials and urea for the treatment of dermatological disorders and methods for their use
JP2003155285A (ja) 2001-11-19 2003-05-27 Toray Ind Inc 環状含窒素誘導体
EP1460059A4 (en) 2001-11-30 2005-01-05 Teijin Ltd PROCESS FOR PRODUCING 5- (3-CYANOPHENYL) -3-FORMYLBENZOIC ACID COMPOUND
PY0228255A (es) 2001-12-06 2004-06-01 Pfizer Prod Inc Compuestos cristalinos novedosos
US6995144B2 (en) 2002-03-14 2006-02-07 Eisai Co., Ltd. Nitrogen containing heterocyclic compounds and medicines containing the same
EA007156B1 (ru) 2002-04-15 2006-08-25 Адамс Лэборетриз, Инк. Замедленно высвобождающие лекарственные композиции гвайфенезина
TW200403058A (en) 2002-04-19 2004-03-01 Bristol Myers Squibb Co Heterocyclo inhibitors of potassium channel function
AU2003237121A1 (en) 2002-04-26 2003-11-10 Vertex Pharmaceuticals Incorporated Pyrrole derivatives as inhibitors of erk2 and uses thereof
WO2003092595A2 (en) 2002-05-02 2003-11-13 Merck & Co., Inc Tyrosine kinase inhibitors
WO2003094888A1 (en) 2002-05-07 2003-11-20 Control Delivery Systems, Inc. Processes for forming a drug delivery device
DE60317198T2 (de) 2002-05-23 2008-12-04 Cytopia Research Pty. Ltd., Richmond Proteinkinaseinhibitoren
EP1535934A4 (en) 2002-06-26 2005-11-02 Idemitsu Kosan Co HYDROGENATED COPOLYMER, METHOD FOR THE PRODUCTION THEREOF AND THIS CONTAINING HOTMELT ADHESIVE COMPOSITION
GB0215844D0 (en) 2002-07-09 2002-08-14 Novartis Ag Organic compounds
US20060004010A1 (en) 2002-07-10 2006-01-05 Hiromu Habashita Ccr4 antagonist and medical use thereof
CA2497977A1 (en) 2002-09-20 2004-04-01 Alcon, Inc. Use of cytokine synthesis inhibitors for the treatment of dry eye disorders
US20040204404A1 (en) 2002-09-30 2004-10-14 Robert Zelle Human N-type calcium channel blockers
EP1562938B1 (en) 2002-11-04 2007-08-29 Vertex Pharmaceuticals Incorporated Heteroaryl-pyrimidine derivatives as jak inhibitors
US8034831B2 (en) 2002-11-06 2011-10-11 Celgene Corporation Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies
US20040099204A1 (en) 2002-11-25 2004-05-27 Nestor John J. Sheet, page, line, position marker
NZ539901A (en) 2002-11-26 2007-09-28 Pfizer Prod Inc Method of treatment of transplant rejection
UY28126A1 (es) 2002-12-24 2004-06-30 Alcon Inc Uso de glucocorticoides selectivos para la superficie ocular en el tratamiento de la sequedad ocular
TW200418806A (en) 2003-01-13 2004-10-01 Fujisawa Pharmaceutical Co HDAC inhibitor
US7444183B2 (en) 2003-02-03 2008-10-28 Enteromedics, Inc. Intraluminal electrode apparatus and method
JP2006518381A (ja) 2003-02-07 2006-08-10 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 プロテインキナーゼのインヒビターとして有用なヘテロアリール置換ピロール
WO2004092154A1 (en) 2003-04-03 2004-10-28 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of protein kinases
SE0301373D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
SE0301372D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
FR2857454B1 (fr) 2003-07-08 2006-08-11 Aventis Pasteur Dosage des acides techoiques des bacteries gram+
US20050043346A1 (en) 2003-08-08 2005-02-24 Pharmacia Italia S.P.A. Pyridylpyrrole derivatives active as kinase inhibitors
EP1663204B1 (en) 2003-08-29 2014-05-07 Exelixis, Inc. C-kit modulators and methods of use
WO2005026129A1 (en) 2003-09-15 2005-03-24 Gpc Biotech Ag Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases
CN1870997B (zh) 2003-10-24 2011-05-04 参天制药株式会社 角膜结膜病变的治疗剂
US7387793B2 (en) 2003-11-14 2008-06-17 Eurand, Inc. Modified release dosage forms of skeletal muscle relaxants
MY141220A (en) 2003-11-17 2010-03-31 Astrazeneca Ab Pyrazole derivatives as inhibitors of receptor tyrosine kinases
JP2007512316A (ja) 2003-11-25 2007-05-17 ファイザー・プロダクツ・インク アテローム性動脈硬化症の治療方法
JP2007514729A (ja) 2003-12-17 2007-06-07 ファイザー・プロダクツ・インク 移植拒絶反応の治療方法
MXPA06007076A (es) 2003-12-19 2006-08-31 Pharmacopeia Drug Discovery Tiadiazoles como ligandos del receptor cxc y cc-quimiocina.
CA2550361C (en) 2003-12-19 2014-04-29 Prabha Ibrahim Compounds and methods for development of ret modulators
BRPI0418078A8 (pt) 2003-12-23 2018-01-02 Astex Therapeutics Ltd composto ou um seu sal, solvato, tautômero ou n-óxido, uso de um composto, métodos para a profilaxia ou tratamento de um estado ou condição doentia mediada pela proteína quinase b e mediada pela proteína quinase a, para tratar uma doença ou condição, para inibir uma proteína quinase b e uma proteína quinase a, para modular um processo celular, para tratar um distúrbio imune em um mamífero e para induzir apoptose em uma célula cancerosa, composição farmacêutica, e, processo para a preparação de um composto
WO2005067546A2 (en) 2004-01-13 2005-07-28 Ambit Biosciences Corporation Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases
CA2559285A1 (en) 2004-03-18 2005-09-29 Brigham And Women's Hospital, Inc. Methods for the treatment of synucleinopathies
TWI372624B (en) 2004-03-30 2012-09-21 Vertex Pharma Azaindoles useful as inhibitors of jak and other protein kinases
WO2005117909A2 (en) 2004-04-23 2005-12-15 Exelixis, Inc. Kinase modulators and methods of use
WO2005105814A1 (en) 2004-04-28 2005-11-10 Incyte Corporation Tetracyclic inhibitors of janus kinases
US7558717B2 (en) 2004-04-28 2009-07-07 Vertex Pharmaceuticals Incorporated Crystal structure of human JAK3 kinase domain complex and binding pockets thereof
AU2005237254B2 (en) 2004-05-03 2010-02-04 Novartis Ag Combinations comprising a S1P receptor agonist and a JAK3 kinase inhibitor
EP1753428A4 (en) 2004-05-14 2010-09-15 Abbott Lab INHIBITORS OF KINASES AS THERAPEUTIC AGENTS
PE20060426A1 (es) 2004-06-02 2006-06-28 Schering Corp DERIVADOS DE ACIDO TARTARICO COMO INHIBIDORES DE MMPs, ADAMs, TACE Y TNF-alfa
JP4688876B2 (ja) 2004-06-10 2011-05-25 アイアールエム・リミテッド・ライアビリティ・カンパニー タンパク質キナーゼ阻害剤としての化合物および組成物
EP1760071A4 (en) 2004-06-23 2008-03-05 Ono Pharmaceutical Co COMPOUND WITH S1P RECEPTOR BINDING ABILITY AND USE THEREOF
WO2006004984A1 (en) 2004-06-30 2006-01-12 Vertex Pharmaceuticals Incorporated Azaindoles useful as inhibitors of protein kinases
US7138423B2 (en) 2004-07-20 2006-11-21 Bristol-Myers Squibb Company Arylpyrrolidine derivatives as NK-1 /SSRI antagonists
FR2873691B1 (fr) 2004-07-29 2006-10-06 Sanofi Synthelabo Derives d'amino-piperidine, leur preparation et leur application en therapeutique
WO2006013114A1 (en) 2004-08-06 2006-02-09 Develogen Aktiengesellschaft Use of a timp-2 secreted protein product for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome
CN101006186A (zh) 2004-08-23 2007-07-25 财团法人牧岩生命工学研究所 用于检测sars冠状病毒的引物和探针，包括该引物和/或探针的试剂盒及其检测方法
US20070054916A1 (en) 2004-10-01 2007-03-08 Amgen Inc. Aryl nitrogen-containing bicyclic compounds and methods of use
WO2006040036A1 (en) 2004-10-13 2006-04-20 F. Hoffmann-La Roche Ag Disubstituted pyrazolobenzodiazepines useful as inhibitors for cdk2 and angiogesis, and for the treatment of breast, colon, lung and prostate cancer
UY29177A1 (es) 2004-10-25 2006-05-31 Astex Therapeutics Ltd Derivados sustituidos de purina, purinona y deazapurina, composiciones que los contienen métodos para su preparación y sus usos
MY179032A (en) 2004-10-25 2020-10-26 Cancer Research Tech Ltd Ortho-condensed pyridine and pyrimidine derivatives (e.g.purines) as protein kinase inhibitors
ATE482213T1 (de) 2004-11-04 2010-10-15 Vertex Pharma Als inhibitoren von proteinkinasen geeignete pyrazoloä1,5-aüpyrimidine
US7517870B2 (en) 2004-12-03 2009-04-14 Fondazione Telethon Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization
WO2006065916A1 (en) 2004-12-14 2006-06-22 Alcon, Inc. Method of treating dry eye disorders using 13(s)-hode and its analogs
AR053992A1 (es) 2004-12-22 2007-05-30 Astrazeneca Ab Compuestos quimicos con actividad anticancerosa, un procedimiento para su preparacion, su uso en la preparacion de medicamentos y composicion farmaceutica.
AR054416A1 (es) 2004-12-22 2007-06-27 Incyte Corp Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas.
EP1844037A1 (en) 2005-01-20 2007-10-17 Pfizer Limited Chemical compounds
CA2596830A1 (en) 2005-02-03 2006-09-14 Vertex Pharmaceuticals Incorporated Pyrrolopyrimidines useful as inhibitors of protein kinase
WO2007044050A2 (en) 2005-02-04 2007-04-19 Bristol-Myers Squibb Company 1h-imidazo[4,5-d]thieno[3,2-b]pyridine based tricyclic compounds and pharmaceutical compositions comprising same
CA2600144A1 (en) 2005-03-15 2006-09-28 Irm Llc Compounds and compositions as protein kinase inhibitors
NZ562468A (en) 2005-04-05 2009-10-30 Pharmacopeia Inc Purine and imidazopyridine derivatives for immunosuppression
GB0510139D0 (en) 2005-05-18 2005-06-22 Addex Pharmaceuticals Sa Novel compounds B1
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
WO2006127587A1 (en) 2005-05-20 2006-11-30 Vertex Pharmaceuticals Incorporated Pyrrolopyridines useful as inhibitors of protein kinase
WO2006133426A2 (en) 2005-06-08 2006-12-14 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
WO2006136823A1 (en) 2005-06-21 2006-12-28 Astex Therapeutics Limited Heterocyclic containing amines as kinase b inhibitors
CN102206216B (zh) 2005-06-22 2014-11-12 普莱希科公司 作为蛋白质激酶抑制剂的吡咯并[2,3-b]吡啶衍生物
EP2251341A1 (en) 2005-07-14 2010-11-17 Astellas Pharma Inc. Heterocyclic Janus kinase 3 inhibitors
FR2889662B1 (fr) 2005-08-11 2011-01-14 Galderma Res & Dev Emulsion de type huile-dans-eau pour application topique en dermatologie
WO2007025090A2 (en) 2005-08-25 2007-03-01 Kalypsys, Inc. Heterobicyclic and - tricyclic inhibitors of mapk/erk kinase
EP2270014A1 (en) 2005-09-22 2011-01-05 Incyte Corporation Azepine inhibitors of janus kinases
ZA200802685B (en) 2005-09-30 2009-10-28 Vertex Pharma Deazapurines useful as inhibitors of janus kinases
WO2007044894A2 (en) 2005-10-11 2007-04-19 Chembridge Research Laboratories, Inc. Cell-free protein expression systems and methods of use thereof
PT1937664E (pt) 2005-10-14 2011-07-07 Sumitomo Chemical Co Composto de hidrazida e utilização pesticida do mesmo
WO2007049041A1 (en) 2005-10-28 2007-05-03 Astrazeneca Ab 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer
CN103626742B (zh) 2005-11-01 2017-04-26 塔格根公司 激酶的联-芳基间-嘧啶抑制剂
WO2007062459A1 (en) 2005-11-29 2007-06-07 Cytopia Research Pty Ltd Selective kinase inhibitors based on pyridine scaffold
US20130137681A1 (en) 2005-12-13 2013-05-30 Incyte Corporation HETEROARYL SUBSTITUTED PYRROLO[2,3-b]PYRIDINES AND PYRROLO[2,3-b]PYRIMIDINES AS JANUS KINASE INHIBITORS
EP2455382B1 (en) 2005-12-13 2016-10-26 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
WO2007076423A2 (en) 2005-12-22 2007-07-05 Smithkline Beecham Corporation INHIBITORS OF Akt ACTIVITY
SI1962830T1 (sl) 2005-12-23 2013-07-31 Glaxosmithkline Llc Azaindolni inhibitorji kinaz Aurora
JP4643455B2 (ja) 2006-01-12 2011-03-02 株式会社ユニバーサルエンターテインメント 遊技システム
CN102532133A (zh) 2006-01-17 2012-07-04 沃泰克斯药物股份有限公司 适用作詹纳斯激酶抑制剂的吖吲哚类
US20070208053A1 (en) 2006-01-19 2007-09-06 Arnold Lee D Fused heterobicyclic kinase inhibitors
WO2007090141A2 (en) 2006-02-01 2007-08-09 Smithkline Beecham Corporation Pyrrolo [2, 3, b] pyridine derivatives useful as raf kinase inhibitors
US7745477B2 (en) 2006-02-07 2010-06-29 Hoffman-La Roche Inc. Heteroaryl and benzyl amide compounds
CA2642340A1 (en) 2006-02-24 2007-08-30 Teva Pharmaceutical Industries Ltd. Metoprolol succinate e.r. tablets and methods for their preparation
KR20090008217A (ko) 2006-03-10 2009-01-21 오노 야꾸힝 고교 가부시키가이샤 질소 함유 복소환 유도체 및 이들을 유효 성분으로 하는 약제
MX2008012738A (es) 2006-04-03 2009-02-06 Astellas Pharma Inc Heterocompuesto.
JP2009532475A (ja) 2006-04-05 2009-09-10 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 ヤヌスキナーゼの阻害剤として有用なデアザプリン
US20090124636A1 (en) 2006-04-12 2009-05-14 Pfizer Inc. Chemical compounds
WO2007129195A2 (en) 2006-05-04 2007-11-15 Pfizer Products Inc. 4-pyrimidine-5-amino-pyrazole compounds
AU2007252994A1 (en) 2006-05-18 2007-11-29 Bayer Healthcare Ag Pharmaceutical compositions comprising implitapide and methods of using same
US7691811B2 (en) 2006-05-25 2010-04-06 Bodor Nicholas S Transporter-enhanced corticosteroid activity and methods and compositions for treating dry eye
TWI398252B (zh) 2006-05-26 2013-06-11 諾華公司 吡咯并嘧啶化合物及其用途
NZ573174A (en) 2006-06-01 2012-01-12 Msd Consumer Care Inc Sustained release pharmaceutical dosage form containing phenylephrine
EP2044061A2 (en) 2006-07-20 2009-04-08 Mehmet Kahraman Benzothiophene inhibitors of rho kinase
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
US8492378B2 (en) 2006-08-03 2013-07-23 Takeda Pharmaceutical Company Limited GSK-3β inhibitor
PE20080769A1 (es) 2006-09-08 2008-08-14 Novartis Ag Derivados de biaril-sulfonamida
WO2008035376A2 (en) 2006-09-19 2008-03-27 Council Of Scientific & Industrial Research A novel bio-erodible insert for ophthalmic applications and a process for the preparation thereof
TW200831104A (en) 2006-10-04 2008-08-01 Pharmacopeia Inc 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression
TW200837064A (en) 2006-10-04 2008-09-16 Pharmacopeia Inc 8-substituted 2-(benzimidazolyl)purine derivatives for immunosuppression
US20120225057A1 (en) 2006-10-11 2012-09-06 Deciphera Pharmaceuticals, Llc Methods and compositions for the treatment of myeloproliferative diseases and other proliferative diseases
US20080119496A1 (en) 2006-11-16 2008-05-22 Pharmacopeia Drug Discovery, Inc. 7-Substituted Purine Derivatives for Immunosuppression
ME02372B (me) 2006-11-22 2016-06-20 Incyte Holdings Corp Imidazotriazini i imidazopiramidini kao inhibitori kinaze
WO2008067119A2 (en) 2006-11-27 2008-06-05 Smithkline Beecham Corporation Novel compounds
SG177221A1 (en) 2006-12-15 2012-01-30 Abbott Lab Novel oxadiazole compounds
WO2008079292A1 (en) 2006-12-20 2008-07-03 Amgen Inc. Heterocyclic compounds and their use in treating inflammation, angiogenesis and cancer
EP2125781A2 (en) 2006-12-20 2009-12-02 Amgen Inc. Substituted heterocycles and methods of use
WO2008077712A1 (en) 2006-12-22 2008-07-03 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Gel useful for the delivery of ophthalmic drugs
EP2121692B1 (en) 2006-12-22 2013-04-10 Incyte Corporation Substituted heterocycles as janus kinase inhibitors
KR20080062876A (ko) 2006-12-29 2008-07-03 주식회사 대웅제약 신규한 항진균성 트리아졸 유도체
US8188178B2 (en) 2007-05-07 2012-05-29 3M Innovative Properties Company Cold shrinkable article including an epichlorohydrin composition
GB0709031D0 (en) 2007-05-10 2007-06-20 Sareum Ltd Pharmaceutical compounds
CA2687931C (en) 2007-05-31 2016-05-24 Boehringer Ingelheim International Gmbh Ccr2 receptor antagonists and uses thereof
GB0710528D0 (en) 2007-06-01 2007-07-11 Glaxo Group Ltd Novel compounds
CL2008001709A1 (es) 2007-06-13 2008-11-03 Incyte Corp Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras.
EP3070090B1 (en) 2007-06-13 2018-12-12 Incyte Holdings Corporation Use of salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h- pyrazol-1-yl)-3- cyclopentylpropanenitrile
US8541426B2 (en) 2007-07-11 2013-09-24 Pfizer Inc. Pharmaceutical compositions and methods of treating dry eye disorders
BRPI0815042A2 (pt) 2007-08-01 2015-02-10 Pfizer Compostos de pirazol
WO2009049028A1 (en) 2007-10-09 2009-04-16 Targegen Inc. Pyrrolopyrimidine compounds and their use as janus kinase modulators
WO2009064835A1 (en) 2007-11-16 2009-05-22 Incyte Corporation 4-pyrazolyl-n-arylpyrimidin-2-amines and 4-pyrazolyl-n-heteroarylpyrimidin-2-amines as janus kinase inhibitors
GB0723815D0 (en) 2007-12-05 2008-01-16 Glaxo Group Ltd Compounds
CN101977923B (zh) 2008-01-18 2014-10-08 捷克有机化学和生物化学研究院 抑制细胞生长的7-脱氮嘌呤核苷
MX2010008376A (es) 2008-02-04 2011-02-22 Mercury Therapeutics Inc Moduladores ampk.
AU2009227013B2 (en) 2008-03-21 2013-01-10 Novartis Ag Novel heterocyclic compounds and uses therof
WO2009155156A1 (en) 2008-06-18 2009-12-23 Merck & Co., Inc. Inhibitors of janus kinases
MX379265B (es) 2008-06-26 2025-03-11 Anterios Inc Aplicacion dérmica de toxina botulínica en nanoemulsiones para usarse en el tratamiento de trastornos de la piel.
JP4884570B2 (ja) 2008-08-20 2012-02-29 ファイザー・インク ピロロ［２，３−ｄ］ピリミジン化合物
CL2009001884A1 (es) 2008-10-02 2010-05-14 Incyte Holdings Corp Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco.
AU2009304508A1 (en) * 2008-10-17 2010-04-22 Merck Frosst Canada Ltd. Azetidine derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase
CA3121743A1 (en) 2009-01-15 2010-07-22 Incyte Holdings Corporation Processes for preparing jak inhibitors and related intermediate compounds
EP2210890A1 (en) 2009-01-19 2010-07-28 Almirall, S.A. Oxadiazole derivatives as S1P1 receptor agonists
US8263601B2 (en) 2009-02-27 2012-09-11 Concert Pharmaceuticals, Inc. Deuterium substituted xanthine derivatives
SG176111A1 (en) 2009-05-22 2011-12-29 Incyte Corp 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors
JP5775070B2 (ja) 2009-05-22 2015-09-09 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ ヤヌスキナーゼ阻害剤としてのピラゾール−４−イル−ピロロ［２，３−ｄ］ピリミジンおよびピロール−３−イル−ピロロ［２，３−ｄ］ピリミジンのＮ−（ヘテロ）アリール−ピロリジン誘導体
UA110324C2 (en) 2009-07-02 2015-12-25 Genentech Inc Jak inhibitory compounds based on pyrazolo pyrimidine
US9346809B2 (en) 2009-07-08 2016-05-24 Leo Pharma A/S Heterocyclic compounds as JAK receptor and protein tyrosine kinase inhibitors
US20120157500A1 (en) 2009-08-24 2012-06-21 Weikang Tao Jak inhibition blocks rna interference associated toxicities
TW201111385A (en) 2009-08-27 2011-04-01 Biocryst Pharm Inc Heterocyclic compounds as janus kinase inhibitors
EP2305660A1 (en) 2009-09-25 2011-04-06 Almirall, S.A. New thiadiazole derivatives
KR101921850B1 (ko) 2009-10-09 2018-11-23 인사이트 홀딩스 코포레이션 3-（4-（7Ｈ-피롤로〔2,3-ｄ〕피리미딘-4-일）-1Ｈ-피라졸-1-일）-3-사이클로펜틸프로판니트릴의 하이드록실, 케토 및 글루쿠로나이드 유도체
US9242987B2 (en) 2009-10-20 2016-01-26 Cellzome Limited Heterocyclyl pyrazolopyrimidine analogues as JAK inhibitors
US8671402B2 (en) 2009-11-09 2014-03-11 Bank Of America Corporation Network-enhanced control of software updates received via removable computer-readable medium
WO2011066374A2 (en) 2009-11-24 2011-06-03 Alder Biopharmaceuticals, Inc. Antagonists of il-6 to prevent or treat cachexia, weakness, fatigue, and/or fever
US20130129675A1 (en) 2009-12-04 2013-05-23 Board Of Regents, The University Of Texas System Interferon therapies in combination with blockade of stat3 activation
ES2461967T3 (es) 2009-12-18 2014-05-21 Pfizer Inc. Compuestos de pirrolo[2,3-d]pirimidina
EP2523957A1 (en) 2010-01-12 2012-11-21 F. Hoffmann-La Roche AG Tricyclic heterocyclic compounds, compositions and methods of use thereof
SA111320200B1 (ar) 2010-02-17 2014-02-16 ديبيوفارم اس ايه مركبات ثنائية الحلقة واستخداماتها كمثبطات c-src/jak مزدوجة
EP2536729A1 (en) 2010-02-18 2012-12-26 Incyte Corporation Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors
PT3354652T (pt) 2010-03-10 2020-07-20 Incyte Holdings Corp Derivados de piperidin-4-ilazetidina como inibidores de jak1
KR20130094710A (ko) 2010-04-14 2013-08-26 어레이 바이오파마 인크. Ｊａｋ 키나아제의 억제제로서 5,7-치환된-이미다조［1,2-ｃ］피리미딘
EP2390252A1 (en) 2010-05-19 2011-11-30 Almirall, S.A. New pyrazole derivatives
RS54824B1 (sr) 2010-05-21 2016-10-31 Incyte Holdings Corp Topikalna formulacija za inhibiciju jak-a
US8637529B2 (en) 2010-06-11 2014-01-28 AbbYie Inc. Pyrazolo[3,4-d]pyrimidine compounds
WO2012003457A1 (en) 2010-07-01 2012-01-05 Mtm Research Llc Anti-fibroblastic fluorochemical emulsion therapies
WO2012045020A1 (en) 2010-09-30 2012-04-05 Portola Pharmaceuticals, Inc. Combinations of 4-(cyclopropylamino)-2-(4-(4-(ethylsulfonyl)piperazin-1-yl)phenylamino)pyrimidine-5-carboxamide and fludarabine
CA2818542A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
WO2012068440A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors
WO2012071612A1 (en) 2010-12-03 2012-06-07 Ym Biosciences Australia Pty Ltd Treatment of jak2-mediated conditions
CA2827673C (en) 2011-02-18 2020-10-27 Novartis Pharma Ag Mtor/jak inhibitor combination therapy
CN102247368B (zh) 2011-05-19 2013-05-29 安徽永生堂药业有限责任公司 一种复方阿伐斯汀缓释片及其制备方法
CN102218042A (zh) 2011-05-26 2011-10-19 青岛黄海制药有限责任公司 富马酸喹硫平组合物的缓释片剂及其制备方法
MY165963A (en) 2011-06-20 2018-05-18 Incyte Holdings Corp Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
WO2013007768A1 (en) 2011-07-13 2013-01-17 F. Hoffmann-La Roche Ag Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors
WO2013007765A1 (en) 2011-07-13 2013-01-17 F. Hoffmann-La Roche Ag Fused tricyclic compounds for use as inhibitors of janus kinases
EP2741747A1 (en) 2011-08-10 2014-06-18 Novartis Pharma AG JAK P13K/mTOR COMBINATION THERAPY
TW201313721A (zh) 2011-08-18 2013-04-01 Incyte Corp 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物
UA111854C2 (uk) 2011-09-07 2016-06-24 Інсайт Холдінгс Корпорейшн Способи і проміжні сполуки для отримання інгібіторів jak
TW201406761A (zh) 2012-05-18 2014-02-16 Incyte Corp 做爲ｊａｋ抑制劑之哌啶基環丁基取代之吡咯并吡啶及吡咯并嘧啶衍生物
US10155987B2 (en) 2012-06-12 2018-12-18 Dana-Farber Cancer Institute, Inc. Methods of predicting resistance to JAK inhibitor therapy
AU2013274030B2 (en) 2012-06-15 2016-07-07 Sun Pharmaceutical Industries, Inc. Deuterated derivatives of ruxolitinib
US20150246043A1 (en) 2012-07-27 2015-09-03 Ratiopharm Gmbh Oral dosage forms for modified release comprising ruxolitinib
CN102772384A (zh) 2012-08-07 2012-11-14 四川百利药业有限责任公司 一种盐酸米诺环素缓释片及其制备方法
JP2015526520A (ja) 2012-08-31 2015-09-10 プリンシピア バイオファーマ インコーポレイテッド Ｉｔｋ阻害剤としてのベンズイミダゾール誘導体
CN104918945B (zh) 2012-11-01 2018-01-05 因赛特公司 作为jak抑制剂的三环稠合噻吩衍生物
CN113384546A (zh) 2012-11-15 2021-09-14 因赛特公司 鲁索利替尼的缓释剂型
WO2014138168A1 (en) 2013-03-06 2014-09-12 Incyte Corporation Processes and intermediates for making a jak inhibitor
SMT201900223T1 (it) 2013-05-17 2019-07-11 Incyte Corp Sale di bipirazolo come inibitore di jak
SG10201801069QA (en) 2013-08-07 2018-03-28 Incyte Corp Sustained release dosage forms for a jak1 inhibitor
CN105555313A (zh) 2013-08-20 2016-05-04 因赛特公司 在c-反应蛋白水平较高的实体肿瘤患者中的存活益处
JP6576941B2 (ja) 2014-02-28 2019-09-18 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ 骨髄異形成症候群の治療のためのｊａｋ１阻害剤
PH12020552277A1 (en) 2014-04-08 2023-07-17 Incyte Holdings Corp Treatment of b-cell malignancies by a combination jak and pi3k inhibitor
CN106687462A (zh) 2014-04-30 2017-05-17 因赛特公司 Jak1抑制剂的制备方法以及其新形式
EP3148545B1 (en) 2014-05-28 2023-03-15 Onco Tracker, Inc. Anti-cancer effects of jak2 inhibitors in combination with thalidomide derivatives and glucocorticoids
US9498467B2 (en) 2014-05-30 2016-11-22 Incyte Corporation Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1
US10766900B2 (en) 2017-12-29 2020-09-08 Formosa Laboratories, Inc. Baricitinib intermediate, method for forming Baricitinib intermediate, and method for preparing Baricitinib or pharmaceutically acceptable salt thereof
KR20260019028A (ko) 2019-02-06 2026-02-09 썬 파마슈티칼 인더스트리즈 인코포레이티드 거울상 이성질체 풍부한 jak 억제제를 제조하는 방법

Patent Citations (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
WO2000009495A1 (en) 1998-08-11 2000-02-24 Novartis Ag Isoquinoline derivatives with angiogenesis inhibiting activity
WO2000053595A1 (en) 1999-03-06 2000-09-14 Astrazeneca Ab Pyrimidine compounds
WO2001014402A1 (en) 1999-08-19 2001-03-01 Isis Pharmaceuticals, Inc. Antisense modulation of focal adhesion kinase expression
WO2001064655A1 (en) 2000-03-01 2001-09-07 Astrazeneca Ab 2, 4-di(hetero-)arylamino (-oxy)-5-substituted pyrimidines as antineoplastic agents
WO2002000196A2 (en) 2000-06-28 2002-01-03 Smithkline Beecham P.L.C. Wet milling process
WO2003024967A2 (en) 2001-09-19 2003-03-27 Aventis Pharma S.A. Indolizines as kinase protein inhibitors
WO2003037347A1 (en) 2001-10-30 2003-05-08 Novartis Ag Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity
WO2003099771A2 (en) 2002-05-29 2003-12-04 Novartis Ag Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases
WO2004005281A1 (en) 2002-07-05 2004-01-15 Novartis Ag Inhibitors of tyrosine kinases
WO2004046120A2 (en) 2002-11-15 2004-06-03 Vertex Pharmaceuticals Incorporated Diaminotriazoles useful as inhibitors of protein kinases
WO2004056786A2 (en) 2002-12-20 2004-07-08 Pfizer Products Inc. Pyrimidine derivates for the treatment of abnormal cell growth
WO2004080980A1 (en) 2003-03-14 2004-09-23 Novartis Ag 2, 4- di (phenylamino) pyrimidines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders
WO2005028444A1 (en) 2003-09-24 2005-03-31 Novartis Ag 1,4-disubstituted isoquinilone derivatives as raf-kinase inhibitors useful for the treatment of proliferative diseases
WO2006056399A2 (en) 2004-11-24 2006-06-01 Novartis Ag Combinations of jak inhibitors and at least one of bcr-abl, flt-3, fak or raf kinase inhibitors
WO2008022164A2 (en) 2006-08-16 2008-02-21 Boehringer Ingelheim International Gmbh Pyrazine compounds, their use and methods of preparation
US20100210627A1 (en) 2006-08-16 2010-08-19 Boehringer Ingelheim International Gmbh Pyrazine compounds, their use and methods of preparation
WO2008058126A2 (en) 2006-11-06 2008-05-15 Supergen, Inc. Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors
US7750007B2 (en) 2006-11-06 2010-07-06 Supergen, Inc. Imidazo[1,2-beta]pyridazine and pyrazolo[1,5-alpha]pyrimidine derivatives and their use as protein kinase inhibitors
WO2008082839A2 (en) 2006-12-29 2008-07-10 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
WO2008082840A1 (en) 2006-12-29 2008-07-10 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
US20080161578A1 (en) 2006-12-29 2008-07-03 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
US20080161559A1 (en) 2006-12-29 2008-07-03 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
WO2008106692A1 (en) 2007-03-01 2008-09-04 Novartis Vaccines And Diagnostics, Inc. Pim kinase inhibitors and methods of their use
US20100029633A1 (en) 2007-04-03 2010-02-04 Array Biopharma Inc. Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors
WO2008124323A1 (en) 2007-04-03 2008-10-16 Array Biopharma Inc. Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors
WO2009064486A2 (en) 2007-11-15 2009-05-22 Musc Foundation For Research Development Inhibitors of pim protein kinases, compositions, and methods for treating cancer
WO2009109576A1 (en) 2008-03-03 2009-09-11 Novartis Ag Pim kinase inhibitors and methods of their use
US20090233903A1 (en) * 2008-03-11 2009-09-17 Incyte Corporation Azetidine and cyclobutane derivatives as jak inhibitors
WO2009114512A1 (en) 2008-03-11 2009-09-17 Incyte Corporation Azetidine and cyclobutane derivatives as jak inhibitors
WO2010001169A2 (en) 2008-07-02 2010-01-07 Astrazeneca Ab Chemical compounds 251
WO2010000978A1 (fr) 2008-07-03 2010-01-07 Centre National De La Recherche Scientifique NOUVEAUX PYRROLO [2,3-a] CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM
WO2010022081A1 (en) 2008-08-19 2010-02-25 Array Biopharma Inc. Triazolopyridine compounds as pim kinase inhibitors
WO2010022076A1 (en) 2008-08-19 2010-02-25 Array Biopharma Inc. Triazolopyridine compounds as pim kinase inhibitors
WO2010026121A1 (en) 2008-09-02 2010-03-11 Novartis Ag Bicyclic kinase inhibitors
WO2010026122A1 (en) 2008-09-02 2010-03-11 Novartis Ag Heterocyclic pim-kinase inhibitors
WO2010026124A1 (en) 2008-09-02 2010-03-11 Novartis Ag Picolinamide derivatives as kinase inhibitors
US20110059951A1 (en) * 2009-09-01 2011-03-10 Rodgers James D HETEROCYCLIC DERIVATIVES OF PYRAZOL-4-YL-PYRROLO[2,3-d]PYRIMIDINES AS JANUS KINASE INHIBITORS
WO2011029802A1 (en) 2009-09-08 2011-03-17 F. Hoffmann-La Roche Ag 4-substituted pyridin-3-yl-carboxamide compounds and methods of use
WO2011057784A1 (en) 2009-11-11 2011-05-19 Sygnis Bioscience Gmbh & Co. Kg Compounds for pim kinase inhibition and for treating malignancy

Non-Patent Citations (43)

* Cited by examiner, † Cited by third party
Title
"Remington's Pharmaceutical Sciences", 1985, MACK PUBLISHING COMPANY, pages: 1418
ADV PHARMACOL., vol. 47, 2000, pages 113 - 74
AGENTS ACTIONS., vol. 38, no. 1-2, January 1993 (1993-01-01), pages 116 - 2 1
ARTHRITIS AND RHEUMATISM, vol. 58, no. 11, pages 1674 - 1686
BARABINO ET AL., EXPERIMENTAL EYE RESEARCH, vol. 79, 2004, pages 613 - 621
BOUDNY, V.; KOVARIK, J., NEOPLASM, vol. 49, 2002, pages 349 - 355
BOWMAN, T. ET AL., ONCOGENE, vol. 19, 2000, pages 2474 - 2488
BURGER, R. ET AL., HEMATOL J., vol. 2, 2001, pages 42 - 53
COLIGAN, J.E. ET AL.: "Current Protocols in Immunology", vol. 3, WILEY PRESS.
DUDLEY, A.C. ET AL., BIOCHEM. J, vol. 390, 2005, pages 427 - 36
FLEX E. ET AL., J EXP MED., vol. 205, 2008, pages 751 - 8
FONESCA, J.E. ET AL., AUTOIMMUNITY REVIEWS, vol. 8, 2009, pages 538 - 42
GRONEBERG, D.A. ET AL., ALLERGY, vol. 58, 2003, pages 1101 - 1113
GUSCHIN, D., N. ET AL., EMBO J, vol. 14, 1995, pages 1421
IMMUNOL TODAY, vol. 19, no. L, January 1998 (1998-01-01), pages 3 7 - 44
JAMES, C. ET AL., NATURE, vol. 434, pages 1144 - 1148
JCI, vol. 113, pages 1664 - 1675
JOURNAL OFPHARMACEUTICAL SCIENCE, vol. 66, 1977, pages 2
K. BLOM: "Two-Pump At Column Dilution Configuration for Preparative LC-MS", J COMBI. CHEM., vol. 4, 2002, pages 295
K. BLOM; B. GLASS; R. SPARKS; A. COMBS: "Preparative LCMS Purification: Improved Compound Specific Method Optimization", J COMB. CHEM., vol. 6, 2004, pages 874 - 883
K. BLOM; B. GLASS; R. SPARKS; A. COMBS: "Preparative LCMS Purification: Improved Compound Specific Method Optimization", J. COMB. CHEM., vol. 6, 2004, pages 874 - 883
K. BLOM; B. GLASS; R. SPARKS; A. COMBS: "Preparative LC-MS Purification: Improved Compound Specific Method Optimization", J. COMBI. CHEM., vol. 6, 2004, pages 874 - 883
K. BLOM; R. SPARKS; J. DOUGHTY; G. EVERLOF; T. HAQUE; A. COMBS: "Optimizing Preparative LC-MS Configurations and Methods for Parallel Synthesis Purification", J. COMBI. CHEM., vol. 5, 2003, pages 670
KAUSHANSKY K, NEJM, vol. 354, 2006, pages 2034 - 45
LEMP: "The Definition and Classification of Dry Eye Disease: Report of the Definition and Classification Subcommittee of the International Dry Eye Workshop", THE OCULAR SURFACE, vol. 5, no. 2, April 2007 (2007-04-01), pages 75 - 92
LEVIN ET AL., CANCER CELL, vol. 7, 2005, pages 387 - 397
MACCHI P ET AL., NATURE, vol. 377, 1995, pages 65 - 8
MINEGISHI, Y ET AL., IMMUNITY, vol. 25, 2006, pages 745 - 55
MULLIGHAN CG, PROC NATL ACAD SCI U S A., vol. 106, 2009, pages 9414 - 8
ORTMANN, R. A.; T. CHENG ET AL., ARTHRITIS RES, vol. 2, no. 1, 2000, pages 16 - 32
PARGANAS E ET AL., CELL, vol. 93, 1998, pages 385 - 95
PARK ET AL., ANALYTICAL BIOCHEMISTRY, vol. 269, 1999, pages 94 - 104
RODIG, S. J.; M. A. MERAZ ET AL., CELL, vol. 93, no. 3, 1998, pages 373 - 83
SCHRADER ET AL.: "Developmental Opthalmology", vol. 41, 2008, KARGER, pages: 298 - 312
SMITH ET AL., IMMUNOLOGY AND CELL BIOLOGY, vol. 76, 1998, pages 497 - 512
SMOLEN, J. S. ET AL., LANCET, vol. 371, 2008, pages 987
SRIRAM, K. ET AL., J BIOL. CHEM., vol. 279, no. 19, 2 March 2004 (2004-03-02), pages 19936 - 47
STAERK, J. ET AL., JBC, vol. 280, pages 41893 - 41899
W.S.S. JEE; W. YAO, J MUSCULOSKEL. NUERON. INTERACT., vol. 1, no. 3, 2001, pages 193 - 207
WAGH ET AL.: "Polymers used in ocular dosage form and drug delivery systems", ASIAN J. PHARM., January 2008 (2008-01-01), pages 12 - 17
WINYARD, P.G.; WILLOUGHBY, D.A.: "Methods in Molecular Biology", vol. 225, 2003, HUMANA PRESS
WUTS; GREENE: "Protective Groups in Organic Synthesis", 2007, JOHN WILEY & SONS
YAO ET AL., ARTHRITIS AND RHEUMATISM, vol. 58, no. 6, 2008, pages 3485 - 3497

Cited By (190)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10639310B2 (en) 2005-12-13 2020-05-05 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
US9206187B2 (en) 2005-12-13 2015-12-08 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as Janus kinase
US11744832B2 (en) 2005-12-13 2023-09-05 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
US9814722B2 (en) 2005-12-13 2017-11-14 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as janus kinase inhibitors
US8933086B2 (en) 2005-12-13 2015-01-13 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-B]pyridines and pyrrolo[2,3-B]pyrimidines as Janus kinase inhibitors
US8946245B2 (en) 2005-12-13 2015-02-03 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
US9974790B2 (en) 2005-12-13 2018-05-22 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as janus kinase inhibitors
US9662335B2 (en) 2005-12-13 2017-05-30 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as janus kinase inhibitors
US10398699B2 (en) 2005-12-13 2019-09-03 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors
US9079912B2 (en) 2005-12-13 2015-07-14 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as Janus kinase inhibitors
US11331320B2 (en) 2005-12-13 2022-05-17 Incyte Holdings Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
US11213528B2 (en) 2007-06-13 2022-01-04 Incyte Holdings Corporation Salts of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US9334274B2 (en) 2009-05-22 2016-05-10 Incyte Holdings Corporation N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9216984B2 (en) 2009-05-22 2015-12-22 Incyte Corporation 3-[4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane—or heptane-nitrile as JAK inhibitors
US9623029B2 (en) 2009-05-22 2017-04-18 Incyte Holdings Corporation 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane- or heptane-nitrile as JAK inhibitors
US9249145B2 (en) 2009-09-01 2016-02-02 Incyte Holdings Corporation Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
US9999619B2 (en) 2010-03-10 2018-06-19 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US9464088B2 (en) 2010-03-10 2016-10-11 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US10695337B2 (en) 2010-03-10 2020-06-30 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US11285140B2 (en) 2010-03-10 2022-03-29 Incyte Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US11219624B2 (en) 2010-05-21 2022-01-11 Incyte Holdings Corporation Topical formulation for a JAK inhibitor
US11571425B2 (en) 2010-05-21 2023-02-07 Incyte Corporation Topical formulation for a JAK inhibitor
US10758543B2 (en) 2010-05-21 2020-09-01 Incyte Corporation Topical formulation for a JAK inhibitor
US10869870B2 (en) 2010-05-21 2020-12-22 Incyte Corporation Topical formulation for a JAK inhibitor
US12226419B2 (en) 2010-05-21 2025-02-18 Incyte Corporation Topical formulation for a JAK inhibitor
US11590136B2 (en) 2010-05-21 2023-02-28 Incyte Corporation Topical formulation for a JAK inhibitor
US12544381B2 (en) 2010-05-21 2026-02-10 Incyte Corporation Topical formulation for JAK inhibitor
US12564593B2 (en) 2010-05-21 2026-03-03 Incyte Corporation Topical formulation for a JAK inhibitor
US9034884B2 (en) 2010-11-19 2015-05-19 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors
US10640506B2 (en) 2010-11-19 2020-05-05 Incyte Holdings Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidines derivatives as JAK inhibitors
US8933085B2 (en) 2010-11-19 2015-01-13 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US8691807B2 (en) 2011-06-20 2014-04-08 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US11214573B2 (en) 2011-06-20 2022-01-04 Incyte Holdings Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US10513522B2 (en) 2011-06-20 2019-12-24 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US9611269B2 (en) 2011-06-20 2017-04-04 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US9359358B2 (en) 2011-08-18 2016-06-07 Incyte Holdings Corporation Cyclohexyl azetidine derivatives as JAK inhibitors
US9718834B2 (en) 2011-09-07 2017-08-01 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US9487521B2 (en) 2011-09-07 2016-11-08 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US9193733B2 (en) 2012-05-18 2015-11-24 Incyte Holdings Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US11576865B2 (en) 2012-11-15 2023-02-14 Incyte Corporation Sustained-release dosage forms of ruxolitinib
US11576864B2 (en) 2012-11-15 2023-02-14 Incyte Corporation Sustained-release dosage forms of ruxolitinib
US10874616B2 (en) 2012-11-15 2020-12-29 Incyte Corporation Sustained-release dosage forms of ruxolitinib
US11337927B2 (en) 2012-11-15 2022-05-24 Incyte Holdings Corporation Sustained-release dosage forms of ruxolitinib
US10166191B2 (en) 2012-11-15 2019-01-01 Incyte Corporation Sustained-release dosage forms of ruxolitinib
US11896717B2 (en) 2012-11-15 2024-02-13 Incyte Holdings Corporation Sustained-release dosage forms of ruxolitinib
US9676750B2 (en) 2013-01-14 2017-06-13 Incyte Corporation Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors
US9550765B2 (en) 2013-01-15 2017-01-24 Incyte Holdings Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as Pim kinase inhibitors
US11229631B2 (en) 2013-01-15 2022-01-25 Incyte Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as Pim kinase inhibitors
US10828290B2 (en) 2013-01-15 2020-11-10 Incyte Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as pim kinase inhibitors
US10265307B2 (en) 2013-01-15 2019-04-23 Incyte Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as Pim kinase inhibitors
US10517858B2 (en) 2013-01-15 2019-12-31 Incyte Holdings Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as PIM kinase inhibitors
US9849120B2 (en) 2013-01-15 2017-12-26 Incyte Holdings Corporation Thiazolecarboxamides and pyridinecarboxamide compounds useful as Pim kinase inhibitors
EP3985008A1 (en) * 2013-03-06 2022-04-20 Incyte Holdings Corporation Processes and intermediates for making a jak inhibitor
US9714233B2 (en) 2013-03-06 2017-07-25 Incyte Corporation Processes and intermediates for making a JAK inhibitor
CN105189509A (zh) * 2013-03-06 2015-12-23 因赛特公司 用于制备jak抑制剂的方法及中间体
TWI634121B (zh) * 2013-03-06 2018-09-01 英塞特控股公司 用於製備ｊａｋ抑制劑之方法及中間物
CN105189509B (zh) * 2013-03-06 2017-12-19 因赛特公司 用于制备jak抑制剂的方法及中间体
KR102366356B1 (ko) 2013-03-06 2022-02-23 인사이트 홀딩스 코포레이션 Jak 저해제를 제조하기 위한 방법 및 중간생성물
EP3489239A1 (en) * 2013-03-06 2019-05-29 Incyte Holdings Corporation Processes and intermediates for making a jak inhibitor
JP2016512196A (ja) * 2013-03-06 2016-04-25 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤の製造方法及びその中間体
JP2019023190A (ja) * 2013-03-06 2019-02-14 インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤の製造方法及びその中間体
US9221845B2 (en) 2013-03-06 2015-12-29 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
KR20210038705A (ko) * 2013-03-06 2021-04-07 인사이트 홀딩스 코포레이션 Jak 저해제를 제조하기 위한 방법 및 중간생성물
KR20150140287A (ko) * 2013-03-06 2015-12-15 인사이트 코포레이션 Jak 저해제를 제조하기 위한 방법 및 중간생성물
US8987443B2 (en) 2013-03-06 2015-03-24 Incyte Corporation Processes and intermediates for making a JAK inhibitor
KR102236232B1 (ko) * 2013-03-06 2021-04-05 인사이트 홀딩스 코포레이션 Jak 저해제를 제조하기 위한 방법 및 중간생성물
WO2014138168A1 (en) * 2013-03-06 2014-09-12 Incyte Corporation Processes and intermediates for making a jak inhibitor
EA030705B1 (ru) * 2013-03-06 2018-09-28 Инсайт Холдингс Корпорейшн Способы и промежуточные соединения при получении ингибитора jak
AU2014225938B2 (en) * 2013-03-06 2018-07-19 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
AU2022263454B2 (en) * 2013-05-17 2024-01-18 Incyte Holdings Corporation Bipyrazole derivatives as jak inhibitors
KR20220127371A (ko) * 2013-05-17 2022-09-19 인사이트 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
WO2014186706A1 (en) * 2013-05-17 2014-11-20 Incyte Corporation Bipyrazole derivatives as jak inhibitors
AU2014265279B2 (en) * 2013-05-17 2018-09-27 Incyte Holdings Corporation Bipyrazole derivatives as JAK inhibitors
KR102341908B1 (ko) 2013-05-17 2021-12-23 인사이트 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
KR20210120120A (ko) * 2013-05-17 2021-10-06 인사이트 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
KR20160019905A (ko) * 2013-05-17 2016-02-22 인사이트 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
EA039660B1 (ru) * 2013-05-17 2022-02-24 Инсайт Корпорейшн Твердая форма производного бипиразола
JP2016519147A (ja) * 2013-05-17 2016-06-30 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤としてのビピラゾール誘導体
EP4275756A3 (en) * 2013-05-17 2024-02-07 Incyte Holdings Corporation Bipyrazole derivatives as jak inhibitors
US9926301B2 (en) 2013-05-17 2018-03-27 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
US9382231B2 (en) 2013-05-17 2016-07-05 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
JP2019011364A (ja) * 2013-05-17 2019-01-24 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤としてのビピラゾール誘導体
US11905275B2 (en) 2013-05-17 2024-02-20 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
PH12018502125A1 (en) * 2013-05-17 2019-03-25 Incyte Corp Bipyrazole derivatives as jak inhibitors
KR20240063187A (ko) * 2013-05-17 2024-05-10 인사이트 홀딩스 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
US11001571B2 (en) 2013-05-17 2021-05-11 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
KR102663357B1 (ko) 2013-05-17 2024-05-14 인사이트 홀딩스 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
US11591318B2 (en) 2013-05-17 2023-02-28 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
CN105452239B (zh) * 2013-05-17 2017-11-21 因赛特公司 作为jak抑制剂的联吡唑衍生物
EP3527263A1 (en) * 2013-05-17 2019-08-21 Incyte Corporation Bipyrazole derivatives as jak inhibitors
AU2020202000B2 (en) * 2013-05-17 2021-03-11 Incyte Holdings Corporation Bipyrazole derivatives as jak inhibitors
US10435392B2 (en) 2013-05-17 2019-10-08 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
KR102729910B1 (ko) 2013-05-17 2024-11-15 인사이트 홀딩스 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
EP3231801A1 (en) * 2013-05-17 2017-10-18 Incyte Corporation Bipyrazole salt as jak inhibitor
EP3786162A1 (en) * 2013-05-17 2021-03-03 Incyte Corporation Bipyrazole derivatives as jak inhibitors
JP2021008493A (ja) * 2013-05-17 2021-01-28 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤としてのビピラゾール誘導体
AU2018223058B2 (en) * 2013-05-17 2020-01-02 Incyte Holdings Corporation Bipyrazole derivatives as jak inhibitors
US12247020B2 (en) 2013-05-17 2025-03-11 Incyte Corporation Bipyrazole derivatives as JAK inhibitors
EA036448B1 (ru) * 2013-05-17 2020-11-11 Инсайт Корпорейшн Производные бипиразола в качестве ингибиторов jak
AU2021202685B2 (en) * 2013-05-17 2022-11-17 Incyte Holdings Corporation Bipyrazole derivatives as jak inhibitors
EP4620528A3 (en) * 2013-05-17 2025-11-26 Incyte Holdings Corporation Bipyrazole derivatives as jak inhibitors
JP2022163162A (ja) * 2013-05-17 2022-10-25 インサイト・ホールディングス・コーポレイション Ｊａｋ阻害剤としてのビピラゾール誘導体
JP7126741B2 (ja) 2013-05-17 2022-08-29 インサイト・ホールディングス・コーポレイション Ｊａｋ阻害剤としてのビピラゾール誘導体
KR102442747B1 (ko) 2013-05-17 2022-09-14 인사이트 코포레이션 Ｊａｋ 저해제로서 비피라졸 유도체
US9655854B2 (en) 2013-08-07 2017-05-23 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US11045421B2 (en) 2013-08-07 2021-06-29 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US12151026B2 (en) 2013-08-07 2024-11-26 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US10561616B2 (en) 2013-08-07 2020-02-18 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US10000507B2 (en) 2013-08-23 2018-06-19 Incyte Corporation Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors
US9994546B2 (en) 2014-02-13 2018-06-12 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US11155532B2 (en) 2014-02-13 2021-10-26 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US11247992B2 (en) 2014-02-13 2022-02-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
EP3626714A1 (en) 2014-02-13 2020-03-25 Incyte Corporation Cyclopropylamines as lsd1 inhibitors
US10717737B2 (en) 2014-02-13 2020-07-21 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US10300051B2 (en) 2014-02-13 2019-05-28 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9527835B2 (en) 2014-02-13 2016-12-27 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9670210B2 (en) 2014-02-13 2017-06-06 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
WO2015123424A1 (en) 2014-02-13 2015-08-20 Incyte Corporation Cyclopropylamines as lsd1 inhibitors
US10513493B2 (en) 2014-02-13 2019-12-24 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US10676457B2 (en) 2014-02-13 2020-06-09 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
WO2015123437A1 (en) 2014-02-13 2015-08-20 Incyte Corporation Cyclopropylamines as lsd1 inhibitors
US9493450B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US10174030B2 (en) 2014-02-13 2019-01-08 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9493442B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
JP2017506659A (ja) * 2014-02-28 2017-03-09 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ 骨髄異形成症候群の治療のためのｊａｋ１阻害剤
KR20230044320A (ko) * 2014-04-08 2023-04-03 인사이트 코포레이션 Ｊａｋ 및 ｐｉ3ｋ 억제제 조합에 의한 ｂ-세포 악성종양의 치료
KR102396717B1 (ko) * 2014-04-08 2022-05-11 인사이트 코포레이션 Ｊａｋ 및 ｐｉ3ｋ 억제제 조합에 의한 ｂ-세포 악성종양의 치료
JP2023040142A (ja) * 2014-04-08 2023-03-22 インサイト・ホールディングス・コーポレイション Ｊａｋ及びｐｉ３ｋ阻害剤併用によるｂ細胞悪性腫瘍の処置
IL288231B2 (en) * 2014-04-08 2023-06-01 Incyte Corp An inhibitor of jak1/2 or a pharmaceutical salt derived from it and an inhibitor of pi3k or a pharmaceutical salt derived from it, for use in the treatment of myelofibroblasts.
KR102717075B1 (ko) * 2014-04-08 2024-10-15 인사이트 홀딩스 코포레이션 Ｊａｋ 및 ｐｉ3ｋ 억제제 조합에 의한 ｂ-세포 악성종양의 치료
KR20160146778A (ko) * 2014-04-08 2016-12-21 인사이트 코포레이션 Ｊａｋ 및 ｐｉ3ｋ 억제제 조합에 의한 ｂ-세포 악성종양의 치료
EP4501409A3 (en) * 2014-04-08 2025-05-14 Incyte Holdings Corporation Treatment of b-cell malignancies by a combination jak and pi3k inhibitor
WO2015157257A1 (en) * 2014-04-08 2015-10-15 Incyte Corporation Treatment of b-cell malignancies by a combination jak and pi3k inhibitor
JP2017510615A (ja) * 2014-04-08 2017-04-13 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ及びｐｉ３ｋ阻害剤併用によるｂ細胞悪性腫瘍の処置
US10675284B2 (en) 2014-04-08 2020-06-09 Incyte Corporation Treatment of B-cell malignancies by a combination JAK and PI3K inhibitors
US10064866B2 (en) 2014-04-08 2018-09-04 Incyte Corporation Treatment of B-cell malignancies by a combination JAK and PI3K inhibitors
US9498467B2 (en) 2014-05-30 2016-11-22 Incyte Corporation Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1
US9695167B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted triazolo[1,5-a]pyridines and triazolo[1,5-a]pyrazines as LSD1 inhibitors
US10640503B2 (en) 2014-07-10 2020-05-05 Incyte Corporation Imidazopyridines and imidazopyrazines as LSD1 inhibitors
US9695168B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted imidazo[1,5-α]pyridines and imidazo[1,5-α]pyrazines as LSD1 inhibitors
US9695180B2 (en) 2014-07-10 2017-07-04 Incyte Corporation Substituted imidazo[1,2-a]pyrazines as LSD1 inhibitors
US9758523B2 (en) 2014-07-10 2017-09-12 Incyte Corporation Triazolopyridines and triazolopyrazines as LSD1 inhibitors
US10556908B2 (en) 2014-07-10 2020-02-11 Incyte Corporation Substituted imidazo[1,2-a]pyrazines as LSD1 inhibitors
US10968221B2 (en) 2014-07-10 2021-04-06 Incyte Corporation Substituted [1,2,4]triazolo[1,5-a]pyrazines as LSD1 inhibitors
US10047086B2 (en) 2014-07-10 2018-08-14 Incyte Corporation Imidazopyridines and imidazopyrazines as LSD1 inhibitors
US10138249B2 (en) 2014-07-10 2018-11-27 Incyte Corporation Triazolopyridines and triazolopyrazines as LSD1 inhibitors
US10125133B2 (en) 2014-07-10 2018-11-13 Incyte Corporation Substituted [1,2,4]triazolo[1,5-a]pyridines and substituted [1,2,4]triazolo[1,5-a]pyrazines as LSD1 inhibitors
US10112950B2 (en) 2014-07-10 2018-10-30 Incyte Corporation Substituted imidazo[1,2-a]pyrazines as LSD1 inhibitors
US9822124B2 (en) 2014-07-14 2017-11-21 Incyte Corporation Bicyclic heteroaromatic carboxamide compounds useful as Pim kinase inhibitors
US9890162B2 (en) 2014-07-14 2018-02-13 Incyte Corporation Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors
US9944647B2 (en) 2015-04-03 2018-04-17 Incyte Corporation Heterocyclic compounds as LSD1 inhibitors
US10800779B2 (en) 2015-04-03 2020-10-13 Incyte Corporation Heterocyclic compounds as LSD1 inhibitors
US11401272B2 (en) 2015-04-03 2022-08-02 Incyte Corporation Heterocyclic compounds as LSD1 inhibitors
CN107531695B (zh) * 2015-04-29 2020-03-27 无锡福祈制药有限公司 Jak抑制剂
CN107531695A (zh) * 2015-04-29 2018-01-02 无锡福祈制药有限公司 Jak抑制剂
EP3290418A4 (en) * 2015-04-29 2018-10-17 Wuxi Fortune Pharmaceutical Co., Ltd Jak inhibitors
WO2016196244A1 (en) 2015-05-29 2016-12-08 Incyte Corporation Pyridineamine compounds useful as pim kinase inhibitors
US9540347B2 (en) 2015-05-29 2017-01-10 Incyte Corporation Pyridineamine compounds useful as Pim kinase inhibitors
US9802918B2 (en) 2015-05-29 2017-10-31 Incyte Corporation Pyridineamine compounds useful as Pim kinase inhibitors
US10723700B2 (en) 2015-08-12 2020-07-28 Incyte Corporation Salts of an LSD1 inhibitor
US10329255B2 (en) 2015-08-12 2019-06-25 Incyte Corporation Salts of an LSD1 inhibitor
US11498900B2 (en) 2015-08-12 2022-11-15 Incyte Corporation Salts of an LSD1 inhibitor
US11066387B2 (en) 2015-09-09 2021-07-20 Incyte Corporation Salts of a Pim kinase inhibitor
US11505540B2 (en) 2015-09-09 2022-11-22 Incyte Corporation Salts of a Pim kinase inhibitor
WO2017044730A1 (en) 2015-09-09 2017-03-16 Incyte Corporation Salts of a pim kinase inhibitor
US12043614B2 (en) 2015-09-09 2024-07-23 Incyte Corporation Salts of a Pim kinase inhibitor
US10336728B2 (en) 2015-09-09 2019-07-02 Incyte Corporation Salts of a Pim kinase inhibitor
US9862705B2 (en) 2015-09-09 2018-01-09 Incyte Corporation Salts of a pim kinase inhibitor
TWI740843B (zh) * 2015-09-25 2021-10-01 中國大陸商迪哲（江蘇）醫藥有限公司 用於抑制ｊａｋ之化合物和方法
US9920032B2 (en) 2015-10-02 2018-03-20 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors
WO2017059251A1 (en) 2015-10-02 2017-04-06 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors
US10450296B2 (en) 2015-10-02 2019-10-22 Incyte Corporation Heterocyclic compounds useful as Pim kinase inhibitors
US11053215B2 (en) 2015-10-02 2021-07-06 Incyte Corporation Heterocyclic compounds useful as Pim kinase inhibitors
US11045455B2 (en) 2015-12-11 2021-06-29 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Azetidine derivative, preparation method therefor, and use thereof
US10166221B2 (en) 2016-04-22 2019-01-01 Incyte Corporation Formulations of an LSD1 inhibitor
US11278541B2 (en) 2017-12-08 2022-03-22 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
US10596161B2 (en) 2017-12-08 2020-03-24 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
US10899736B2 (en) 2018-01-30 2021-01-26 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US12336998B2 (en) 2018-02-16 2025-06-24 Incyte Corporation JAK1 pathway inhibitors for the treatment of cytokine-related disorders
US11833152B2 (en) 2018-02-16 2023-12-05 Incyte Corporation JAK1 pathway inhibitors for the treatment of cytokine-related disorders
US12280054B2 (en) 2018-03-30 2025-04-22 Incyte Corporation Treatment of hidradenitis suppurativa using JAK inhibitors
US11304949B2 (en) 2018-03-30 2022-04-19 Incyte Corporation Treatment of hidradenitis suppurativa using JAK inhibitors
US12226418B2 (en) 2018-06-01 2025-02-18 Incyte Corporation Dosing regimen for the treatment of PI3K related disorders
US10968200B2 (en) 2018-08-31 2021-04-06 Incyte Corporation Salts of an LSD1 inhibitor and processes for preparing the same
US11512064B2 (en) 2018-08-31 2022-11-29 Incyte Corporation Salts of an LSD1 inhibitor and processes for preparing the same
US11685731B2 (en) 2020-06-02 2023-06-27 Incyte Corporation Processes of preparing a JAK1 inhibitor
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
US12440495B2 (en) 2020-06-03 2025-10-14 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
US11957661B2 (en) 2020-12-08 2024-04-16 Incyte Corporation JAK1 pathway inhibitors for the treatment of vitiligo
US12268667B2 (en) 2021-05-03 2025-04-08 Incyte Corporation JAK1 pathway inhibitors for the treatment of prurigo nodularis

Also Published As

Publication number Publication date
US20140171409A1 (en) 2014-06-19
CO6821966A2 (es) 2013-12-31
TW201311686A (zh) 2013-03-16
US20200079783A1 (en) 2020-03-12
ES2560611T3 (es) 2016-02-22
JP5876146B2 (ja) 2016-03-02
US20150225411A1 (en) 2015-08-13
CN103797010B (zh) 2016-02-24
KR20140040819A (ko) 2014-04-03
US20170253598A1 (en) 2017-09-07
EP2721028B1 (en) 2015-11-04
HK1197056A1 (zh) 2015-01-02
TWI577676B (zh) 2017-04-11
CN103797010A (zh) 2014-05-14
AU2012273164B2 (en) 2015-05-28
EA201490042A1 (ru) 2014-10-30
PE20140832A1 (es) 2014-07-14
CL2013003647A1 (es) 2014-07-04
EP2721028A1 (en) 2014-04-23
ECSP14013148A (es) 2015-03-31
AU2012273164A1 (en) 2013-05-02
US9023840B2 (en) 2015-05-05
CA2839767A1 (en) 2012-12-27
AR086983A1 (es) 2014-02-05
CR20130668A (es) 2014-03-31
US20130018034A1 (en) 2013-01-17
MY165963A (en) 2018-05-18
MX344479B (es) 2016-12-16
NZ618982A (en) 2015-08-28
JP2014520146A (ja) 2014-08-21
US9611269B2 (en) 2017-04-04
IL230008A (en) 2016-10-31
PH12013502612A1 (en) 2014-04-28
US8691807B2 (en) 2014-04-08
US11214573B2 (en) 2022-01-04
MX2013015087A (es) 2014-02-11
US10513522B2 (en) 2019-12-24
BR112013032720A2 (pt) 2016-09-13

Similar Documents

Publication Publication Date Title
US11214573B2 (en) Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US11001571B2 (en) Bipyrazole derivatives as JAK inhibitors
EP2640725B1 (en) Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors
DK3050882T3 (en) PIPERIDIN-4-YL-AZETIDINE DERIVATIVES AS JAK1 INHIBITORS
HK40103736A (en) Bipyrazole derivatives as jak inhibitors
HK40103736B (en) Bipyrazole derivatives as jak inhibitors
HK1197056B (en) Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
HK40049209A (en) Bipyrazole derivatives as jak inhibitors
NZ618982B2 (en) Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
HK1189877B (en) Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors

Legal Events

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

Ref document number: 201280037078.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: 12735369

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2012273164

Country of ref document: AU

Date of ref document: 20120619

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2839767

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: CR2013-000668

Country of ref document: CR

WWE Wipo information: entry into national phase

Ref document number: MX/A/2013/015087

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2014517080

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2013003647

Country of ref document: CL

Ref document number: 13296752

Country of ref document: CO

Ref document number: 002852-2013

Country of ref document: PE

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2012735369

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 20147001320

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: A201400439

Country of ref document: UA

Ref document number: 201490042

Country of ref document: EA

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112013032720

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112013032720

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20131219

WWW Wipo information: withdrawn in national office

Ref document number: 618982

Country of ref document: NZ