WO1999065908A1 - PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS - Google Patents

PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS Download PDF

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Publication number
WO1999065908A1
WO1999065908A1 PCT/IB1999/001100 IB9901100W WO9965908A1 WO 1999065908 A1 WO1999065908 A1 WO 1999065908A1 IB 9901100 W IB9901100 W IB 9901100W WO 9965908 A1 WO9965908 A1 WO 9965908A1
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Prior art keywords
alkyl
amιno
alkoxy
pyrrolo
aryl
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PCT/IB1999/001100
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English (en)
French (fr)
Inventor
Todd Andrew Blumenkopf
Mark Edward Flanagan
Matthew Frank Brown
Paul Steven Changelian
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Pfizer Products Inc
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Pfizer Products Inc
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Priority to HR20000885A priority Critical patent/HRP20000885B1/xx
Priority to HU0102574A priority patent/HUP0102574A3/hu
Priority to JP2000554733A priority patent/JP4666762B2/ja
Priority to HK01107744.3A priority patent/HK1036801B/xx
Priority to UA2000127300A priority patent/UA64792C2/uk
Priority to AU39518/99A priority patent/AU3951899A/en
Priority to EP99922454A priority patent/EP1087970B1/en
Priority to DK99922454T priority patent/DK1087970T3/da
Priority to AT99922454T priority patent/ATE265458T1/de
Priority to BR9911365-1A priority patent/BR9911365A/pt
Priority to PL345123A priority patent/PL198640B1/pl
Priority to EA200001203A priority patent/EA005852B1/ru
Priority to CA002335492A priority patent/CA2335492C/en
Application filed by Pfizer Products Inc filed Critical Pfizer Products Inc
Priority to IL13958699A priority patent/IL139586A0/xx
Priority to SI9930579T priority patent/SI1087970T1/xx
Priority to DE69916833T priority patent/DE69916833T2/de
Priority to SK1898-2000A priority patent/SK286640B6/sk
Priority to APAP/P/1999/001584A priority patent/AP1021A/en
Publication of WO1999065908A1 publication Critical patent/WO1999065908A1/en
Priority to NZ518444A priority patent/NZ518444A/en
Priority to IS5721A priority patent/IS2395B/is
Priority to NO20006453A priority patent/NO318784B1/no
Anticipated expiration legal-status Critical
Priority to AU2003234874A priority patent/AU2003234874B2/en
Priority to NO20050202A priority patent/NO20050202L/no
Priority to FR14C0019C priority patent/FR14C0019I2/fr
Priority to NO2014012C priority patent/NO2014012I1/no
Ceased legal-status Critical Current

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    • 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
    • A—HUMAN NECESSITIES
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • A—HUMAN NECESSITIES
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    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
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    • A61P17/00—Drugs for dermatological disorders
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    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • 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
    • 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
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • 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
    • 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
    • A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones

Definitions

  • the present invention relates to pyrrolo[2,3-d]pyr ⁇ m ⁇ d ⁇ ne compounds which are inhibitors of protein tyrosine kinases, such as the enzyme Janus Kinase 3 (hereinafter also referred to as JAK3) and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arth ⁇ tis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other indications where immunosuppression would be desirable
  • This invention also relates to a method of using such compounds in the treatment of the above indications in mammals, especially humans, and the phamaceutical compositions useful therefor
  • JAK3 is a member of the Janus family of protein tyrosine kinases Although the other members of this family are expressed by essentially all tissues, JAK3 expression is limited to hematopoetic cells This is consistent with its essential role in signaling through the receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 by non-covalent association of JAK3 with the gamma chain common to these multichain receptors XSCID patient populations have been identified with severely reduced levels of JAK3 protein or with genetic defects to the common gamma chain, suggesting that immunosuppression should result from blocking signaling through the JAK3 pathway Animal studies have suggested that JAK3 not only plays a critical role in B and T lymphocyte maturation, but that JAK3 is constitutively required to maintain T cell function Modulation of immune activity through this novel mechanism can prove useful in the treatment of T cell proliferative disorders such as transplant rejection and autoimmune diseases
  • R 1 is a group of the formula wherein y is 0, 1 or 2
  • R 4 ⁇ s selected from the group consisting of hydrogen, (C C ⁇ alkyl, (C 2 -C 6 )alkenyl, (C 2 - C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, ammo, tnfluoromethyl, (C 1 -C 4 )alkoxy, (C 1 -C 6 )acyloxy, (C,-C 6 )alkylam ⁇ no, ((C 1 -C 6 )alkyl) 2 am ⁇ no, cyano, nitro, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (CrC ⁇ acylammo, or R 4 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, ammo, tnfluoromethyl,
  • F, K and P are each independently oxygen, S(0) d wherein d is 0, 1 or 2, NR 6 or CR 7 R S ,
  • R 6 is selected from the group consisting of hydrogen, (C r C 6 )alkyl, tnfluoromethyl, t ⁇ fluoromethyl(C 1 -C 6 )alkyl, (C r Cg)alkyl (difluoromethylene), (C 1 -C 3 )alkyl(d ⁇ fluoromethylene)(C 1 - C 3 )alkyl, (CrCgJalkoxyCCrCgJacyl, (CrCgJalkylaminoCCrCgJacyl, ((C 1 -C 6 )alkyl) 2 am ⁇ no(C 1 - C 6 )acyl, (C 6 -C 10 )aryl, (C 6 -C 9 )heteroaryl, (C 6 -C 10 )aryl(C l -C 6 )alkyl, (C ⁇ -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10
  • R 7 and R 8 are each independently selected from the group consisting of hydrogen, (C r C 6 )alkyl, ammo, hydroxy, (C r C 6 )alkoxy, (C 1 -C 6 )alkylam ⁇ no, ((C 1 -Cg)alkyl)am ⁇ no, (C r C 6 )acylam ⁇ no, (C C ⁇ acy C T C ⁇ alkylammo, carboxy, (C r C 6 )alkoxyacyl, (C 1 -C 6 )alkylam ⁇ noacyl, ((C r C 6 )alkyl) 2 am ⁇ noacyl, aminoacyl, tnfluoromethyl, t ⁇ fluoromethy C rCeJalkyl, (C r C 6 )alkyl (difluoromethylene), (C 1 -C 3 )alkyl(d ⁇ fluoromethylene)(C 1 -C 3 )alkyl, (C
  • Z is hydroxy, (C r C 6 )alkoxy or NR 1 R 2 wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, piperidyl, (C r C 6 )alkylp ⁇ per ⁇ dyl, (C 6 - C 10 )arylp ⁇ pe ⁇ dyl, (C 5 -C 9 )heteroarylp ⁇ pe ⁇ dyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylp ⁇ per ⁇ dyl, (C 5 -
  • R 6 (C r C 6 )alkyl, (C 1 -C 6 )alkyl(CHR 6 )(C 1 -C 6 )alkyl wherein R 6 is piperidyl, (C 6 - C 10 )arylp ⁇ per ⁇ dyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylp ⁇ per ⁇ dyl, (C 5 -C 9 )heteroarylp ⁇ per ⁇ dyl or (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl, or R 1 is defined as OR 9 or S(0) q R 9 wherein q is 0, 1 or 2, and
  • R 9 is selected from the group consisting of t ⁇ fluoromethyl(C 1 -C 6 )alkyl, (C r C 3 )alkyl(d ⁇ fluoromethylene)(C 1 -C 3 )alkyl, (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, ammo, hydroxy, (C r C 6 ) alkoxy, halo, (C,- C 6 )alkyl S(0) m wherein m is 0, 1 or 2, R 15 R 15 NS(0) m wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or (C.,-C 6 )alkyl, (C r C 6 )acyl, (C.
  • F, K and P are each independently oxygen, S(0) d wherein d is 0, 1 or 2, NR 6 or CR 7 R 8 wherein R 6 , R 7 and R 8 are as defined above,
  • R 2 and R 3 are each independently selected from the group consisting of hydrogen, deuterium, ammo, halo, hydoxy, nitro, carboxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, tnfluoromethyl, t ⁇ fluoromethoxy, (C 1 -C 6 )alkyl, (C r C 6 )alkoxy wherein the alkyl or alkoxy groups are optionally substittued by one to three groups selected from halo, hydroxy, carboxy, ammo (C,- C 6 )alkylth ⁇ o, (C 1 -C 6 )alkylam ⁇ no, ((C 1 -C 6 )alkyl) 2 am ⁇ no, (C 5 -C 9 )heteroaryl, (C 2 - C 9 )heterocycloalkyl, (C 3 -C 9 )cycloalkyl or (C
  • the invention also relates to base addition salts of formula I
  • the chemical bases that may be used as reagents to prepare pharmaceutically acceptable base salts of those compounds of formula I that are acidic in nature are those that form non-toxic base salts with such compounds
  • Such non-toxic base salts include, but are not limited to those derived from such pharmacologically acceptable cations such as alkali metal cations (e_g_, potassium and sodium) and alkaline earth metal cations (e_g_, calcium and magnesium), ammonium or water- soluble amine addition salts such as N-methylglucam ⁇ ne-(meglum ⁇ ne), and the lower alkanolammomum and other base salts of pharmaceutically acceptable organic amines
  • alkyl as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, branched or cyclic moieties or combinations thereof
  • alkoxy includes O-alkyl groups wherein “alkyl” is defined above
  • halo as used herein, unless otherwise indicated, includes fluoro, chloro, bromo or lodo
  • the compounds of this invention may contain double bonds When such bonds are present, the compounds of the invention exist as cis and trans configurations and as mixtures thereof
  • alkyl and alkenyl groups referred to herein, as well as the alkyl moieties of other groups referred to herein (e_g_, alkoxy), may be linear or branched, and they may also be cyclic (e_g_, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl) or be linear or branched and contain cyclic moieties Unless otherwise indicated, halogen includes fluorine, chlorine, bromine, and iodine
  • (C 3 -C 10 )Cycloalkyl when used herein refers to cycloalkyl groups containing zero to two levels of unsaturation such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl cyclohexenyl, 1,3-cyclohexad ⁇ ene, cycloheptyl, cyclohepten l, b ⁇ cyclo[3 2 1]octane, norbomanyl etc (C 2 -C 9 )Heterocycloalkyl when used herein refers to pyrrolidmyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, azi ⁇ dinyl, oxiranyl, methylenedioxyl, chromenyl, isoxazolidmyl, 1 ,3-oxazol ⁇ d ⁇ n
  • (C 2 -C 9 )Heteroaryl when used herein refers to furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, t ⁇ azolyl, tetrazolyl, imidazolyl, 1,3,5-oxad ⁇ azolyl, 1 ,2,4- oxadiazolyl, 1,2,3-oxad ⁇ azolyl, 1,3,5-th ⁇ ad ⁇ azolyl, 1,2,3-th ⁇ ad ⁇ azolyl, 1,2,4-th ⁇ ad ⁇ azolyl, pyridyl, py ⁇ midyl, pyrazmyl, pyridazmyl, 1 ,2,4-tr ⁇ az ⁇ nyl, 1,2,3-t ⁇ az ⁇ nyl, 1,3,5-tr ⁇ az ⁇ nyl, pyrazolo[3,4- b
  • Compounds of formula (I) may be administered in a pharmaceutically acceptable form either alone or in combination with one or more additional agents which modulate a mammalian immune system or with antimflammatory agents
  • agents may include but are not limited to cyclosponn A (e g Sand ⁇ mmune lt:
  • agents may be administered as part of the same or separate dosage forms, via the same or different routes of administration, and on the same or different
  • the compounds of this invention include all conformational isomers (e_g_, cis and trans isomers) and all optical isomers of compounds of the formula I (e_g_, enantiomers and diastereomers), as well as racemic, diastereome ⁇ c and other mixtures of such isomers
  • Preferred compounds of formula I include those wherein R 1 is NR 4 R 5
  • Other preferred compounds of formula I include those wherein R 4 is hydrogen, (C r C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by hydroxy, ammo, tnfluoromethyl, (C 1 -C 6 )acyloxy, ((C 1 -C 6 )alkyl) 2 am ⁇ no or (C 1 -C 6 )acylam ⁇ no, or R 4 is (C 3 -C
  • R 5 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five deuterium, hydroxy, tnfluoromethyl, halo, (C r C 6 )alkyl, hydroxy(C r C 6 )alkyl, (C r C 6 )acyl, (C 1 -C 6 )alkylam ⁇ no(C 1 - C 6 )acyl, ((C 1 -C 6 )alkyl) 2 am ⁇ no(C 1 -C 6 )acyl, (C 1 -C 6 )acylam ⁇ no, (C T C ⁇ alkoxy-CO-NH, (C C 6 )alkylam ⁇ no-CO-, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, (C 1
  • R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, ⁇ -C ⁇ alky!, (C 2 - C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 3 -C 10 )cycloalkoxy, (C 2 - C 9 )heterocycloalkyl, (C 5 -Cg)heteroaryl or (C 6 -C 10 )aryl
  • Specific preferred compounds of formula I include the following 2- ⁇ 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyr ⁇ m ⁇ d ⁇ n-4-yl)-am ⁇ no]-cyclohexyl ⁇ -propan-2- ol, 2- ⁇ 3-[(2-Hydroxy-ethyl)-(7H-pyrrolo[2,3-d]pyr ⁇ m ⁇ d ⁇ n-4-yl)-am ⁇ no]-4-methyl-cyclohexyl ⁇ - propan-2-ol,
  • the present invention also relates to a pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases or (b) the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, effective in such disorders or conditions and a pharmaceutically acceptable carrier
  • the present invention also relates to a pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases or (b) the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human comprising an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with T-cell immunosuppressant or antimflammatory agents, effective in such disorders or conditions and a pharmaceutically acceptable carrier
  • the present invention also relates to a method for the inhibition of protein typrosme kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering
  • the present invention also relates to a method for treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, effective in treating such a condition
  • the present invention also relates to a method for the inhibition of protein typrosme kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with T-cell immunosuppressant or antimflammatory agents
  • the present invention also relates to a method for treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with T-cell immunosuppressant or antiinflammatory agents, effective in treating such a condition.
  • a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia
  • XVII is converted to the corresponding compound of formula XVI, wherein R is benzenesulfonyl or benzyl, by treating XVII with benzenesulfonyl chloride, benzylchlo ⁇ de or benzylbromide in the presence of a base, such as sodium hydride or potassium carbonate, and a polar aprotic solvent, such as dimethylformamide or tetra hydrofu ran The reaction mixture is stirred at a temperature between about 0°C to about 70°C, preferably about 30°C, for a time period between about 1 hour to about 3 hours, preferably about 2 hours
  • reaction 2 of Scheme 1_ the 4-chloropyrrolo[2,3-d]pyr ⁇ m ⁇ d ⁇ ne compound of formula XVI is converted to the corresponding 4-am ⁇ nopyrrolo[2,3-d]pyr ⁇ m ⁇ d ⁇ ne compound of formula XV by coupling XVI with an amine of the formula HNR R 5
  • the reaction is carried out in an alcohol solvent, such as tert-butanol, methanol or ethanol, or other high boiling organic solvents, such as dimethylformamide, 1 ,4-d ⁇ oxane or 1 ,2-d ⁇ chloroethane, at a temperature between about 60°C to about 120°C, preferably about 80°C
  • Typical reaction times are between about 2 hours to about 48 hours, preferably about 16 hours
  • reaction 3 of Scheme 1_ removal of the protecting group from the compound of formula XV, wherein R is benzenesulfonyl, to give the corresponding compound of formula I, is carried out by treating XV with an alkali base, such as sodium hydroxide or potassium hydroxide, in an alcohol solvent, such as methanol or ethanol, or mixed solvents, such as alcohol/tetrahydrofuran or alcohol/water The reaction is carried out at room temperature for a time period between about 15 minutes to about 1 hour, preferably 30 minutes
  • Removal of the protecting group from the compound of formula XV wherein R is benzyl is conducted by treating XV with sodium in ammonia at a temperature of about -78°C for a time period between about 15 minutes to about 1 hour
  • the compound of formula XIX is converted to the corresponding compound of formula XVI by treating XIX with N-butyllithium, lithium diisopropylam e or sodium hydride, at a temperature of about -78°C, in the presence of a polar aprotic solvent, such as tetra hydrofu ran
  • the anionic intermediate so formed is further reacted with (a) alkylhahde or benzylhalide, at a temperature between about -78°C to room temperature, preferably -78 °C, when R 3 is alkyl or benzyl, (b) an aldehyde or ketone, at a temperature between about -78°C to room temperature, preferably -78°C, when R 3 is alkoxy, and (c) zinc chloride, at a temperature between about -78°C to room temperature, preferably - 78°C, and the corresponding organozmc intermediate so formed is then reacted with
  • reaction 3 of Scheme 4 the compound of formula XXIII is converted to the corresponding compound of formula XV, according to the procedure described above in reaction 3 of Scheme 2
  • XVI is converted the to the corresponding compound of formula XXV by coupling XVI with a compound of the formula, R 9 OH, in the presence of sodium hydroxide
  • the reaction is carried out in a polar aprotic solvent, such as tetrahydrofuran, and heated to reflux for a time period between about 2 hours to about 4 hours, preferably about 3 hours Removal of the protecting group is carried out according to the procedure described above in reaction 3 of Scheme 1_
  • XVII is converted to the corresponding compound of formula XXVI by coupling XVII with a compound of the formula, SR 9 , in the presence of potassium tert-butoxide and a polar aprotic solvent, such as tetrahydrofuran
  • a polar aprotic solvent such as tetrahydrofuran
  • the resulting reaction mixture is heated to reflux for a time period between about 2 5 hours to about 5 hours, preferably about 3 5 hours
  • the compound of formula XXVI may be further reacted with an oxidizing agent known to one of ordinary skill in the art, such as hydrogen peroxide, oxone, 3-chloroperoxybenzo ⁇ c acid or tert-butylperoxide to generate the corresponding 4- R 9 sulfinylpyrrolo[2,3-d]py ⁇ m ⁇ d ⁇ ne or 4- R 9 sulfonylpyrrolo compounds
  • the compounds of the present invention that are basic in nature are capable of forming a wide variety of different salts with various inorganic and organic acids Although such salts must be pharmaceutically acceptable for administration to animals, it is often desirable in practice to initially isolate the compound of the present invention from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert the latter back to the free base compound by treatment with an alkaline reagent and subsequently convert the latter free base to a pharmaceutically acceptable acid addition salt
  • the acid addition salts of the base compounds of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol Upon careful evaporation of the solvent, the desired solid salt is readily obtained
  • the desired acid salt can also be precipitated from a solution of the free base in an organic solvent by adding to the solution an appropriate mineral or organic acid
  • Those compounds of the present invention that are acidic in nature are capable of forming base salts with various pharmacologically acceptable cations
  • examples of such salts include the alkali metal or alkaline-earth metal salts and particularly, the sodium and potassium salts
  • the chemical bases which are used as reagents to prepare the pharmaceutically acceptable base salts of this invention are those which form non-toxic base salts with the acidic compounds of the present invention
  • Such non-toxic base salts include those derived from such pharmacologically acceptable cations as sodium, potassium calcium and magnesium, etc
  • These salts can easily be prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations, and then evaporating the resulting solution to dryness, preferably under reduced pressure Alternatively, they may also be prepared by mixing lower alkanolic solutions of the acidic compounds and the desired alkali metal alkoxide together, and then evaporating the resulting solution to dryness in the same manner as before In either
  • compositions of the present invention may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers
  • the active compounds of the invention may be formulated for oral, buccal, intranasal, parenteral (e g , intravenous, intramuscular or subcutaneous) or rectal administration or in a form suitable for administration by inhalation or insufflation
  • the active compounds of the invention may also be formulated for sustained delivery
  • the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e g , pregelatinized maize starch, polyvinylpyrro done or hydroxypropyl methylcellulose), fillers (e g , lactose, microcrystalline cellulose or calcium phosphate), lubricants (e g , magnesium stearate, talc or silica), dismtegrants (e g , potato starch or sodium starch glycolate), or wetting agents (e_g_, sodium lauryl sulphate)
  • binding agents e g , pregelatinized maize starch, polyvinylpyrro done or hydroxypropyl methylcellulose
  • fillers e g , lactose, microcrystalline cellulose or calcium phosphate
  • lubricants e g , magnesium stearate, talc or silica
  • dismtegrants e g
  • composition may take the form of tablets or lozenges formulated in conventional manner
  • the active compounds of the invention may be formulated for parenteral administration by injection, including using conventional cathete ⁇ zation techniques or infusion Formulations for injection may be presented in unit dosage form, e_g_, in ampules or in multi-dose containers, with an added preservative
  • the compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulating agents such as suspending, stabilizing and/or dispersing agents
  • the active ingredient may be in powder form for reconstitution with a suitable vehicle, e g , sterile pyrogen-free water, before use
  • the active compounds of the invention may also be formulated in rectal compositions such as suppositories or retention enemas, e_g_, containing conventional suppository bases such as cocoa butter or other glycendes
  • the active compounds of the invention are conveniently delivered in the form of a solution or suspension from a pump spray container that is squeezed or pumped by the patient or as an aerosol spray presentation from a pressurized container or a nebulizer, with the use of a suitable propellant, e g , dichlorodifluoromethane, t ⁇ chlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas
  • a suitable propellant e g
  • dichlorodifluoromethane t ⁇ chlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas
  • the dosage unit may be determined by providing a valve to deliver a metered amount
  • the pressurized container or nebulizer may contain a solution or suspension of the active compound Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator may be formulated containing a powder mix
  • a proposed dose of the active compounds of the invention for oral, parenteral or buccal administration to the average adult human for the treatment of the conditions referred to above is 0 1 to 1000 mg of the active ingredient per unit dose which could be administered, for example, 1 to 4 times per day
  • Aerosol formulations for treatment of the conditions referred to above are preferably arranged so that each metered dose or "puff of aerosol contains 20 ⁇ g to 1000 ⁇ g of the compound of the invention
  • the overall daily dose with an aerosol will be within the range 0 1 mg to 1000 mg Administration may be several times daily, for example 2, 3, 4 or 8 times, giving for example, 1 , 2 or 3 doses each time
  • a compound of formula (I) administered in a pharmaceutically acceptable form either alone or in combination with one or more additional agents which modulate a mammhan immune system or with antimflammatory agents agents which may include but are not limited to cyclosponn A (e g Sandimmune' 11 or Neoral , rapamycm, FK-506 (tacro mus), leflunomide, deoxyspergua n, mycophenolate (e g Cellcept , azathiop ⁇ ne (e g Imuran ), daclizumab (e g
  • Zenapax ' e g Orthocolone r '
  • OKT3 e g Orthocolone r '
  • AtGarn aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, and antiinflmmatory steroids (e g prednisolone or dexamethasone), and such agents may be administered as part of the same or separate dosage forms, via the same or different routes of administration, and on the same or different administration schedules according to standard pharmaceutical practice
  • FK506 (Tacrohmus) is given orally at 0 10-0 15 mg/kg body weight, every 12 hours, within first 48 hours postoperative Does is monitored by serum Tacrohmus trough levels
  • Cyclosponn A (Sandimmune oral or intravenous formulation, or Neoral , oral solution or capsules) is given orally at 5 mg/kg body weight, every 12 hours within 48 hours postoperative
  • the active agents can be formulated for sustained delivery according to methods well known to those of ordinary skill in the art Examples of such formulations can be found in United States Patents 3,538,214, 4,060,598, 4,173,626, 3,119,742, and 3,492,397
  • JAK3 JH1 GST Enzymatic Assay
  • the JAK3 kinase assay utilizes a protein expressed in baculovirus-mfected SF9 cells (a fusion protein of GST and the catalytic domain of human JAK3) purified by affinity chromatography on glutathione-Sepaharose
  • the substrate for the reaction is poly-Glutamic acid-Tyrosme (PGT (4 1), Sigma catalog # P0275), coated onto Nunc Maxi Sorp plates at 100 ⁇ g/ml overnight at 37°C
  • PPT poly-Glutamic acid-Tyrosme
  • the plates are washed three times and JAK3 is added to the wells containing 100 ⁇ l of kinase buffer (50 mM HEPES, pH 7 3, 125 mM NaCI, 24 mM MgCI2)+ 0 2 uM ATP + 1 mM Na orthovanadate )
  • the reaction proceeds for 30 minutes at room temperature and the plates is washed three
  • DND 39/IL-4 Cellular Assay for JAK3 kinase Inhibitors
  • the DND 39/IL-4 assay is designed to find inhibitors of JAK3 kinase activity which would be prime candidates for immunosupressive and/or allergy
  • the assay uses a B-cell line called DND39 which has had the luciferase gene driven by the germ line IgE promoter stably integrated into one of the chromosomes
  • the kinase JAK3 which is associated with the IL-4 receptor, phosphorylates the signal transducer STAT6 STAT6 then blinds to the germ ne IgE promoter and starts transcription of the luciferase gene Luciferase is measured in a lysate of these cells using the Promega luciferase assay reagent system
  • DND39 cells are grown in RPMI 1640 supplemented with 10% heat inactivated FCS, 2 mM L-Glutamme, and 100 units/ml Pen /Strep The cells are maintained from 1x10 s to 1x10 6 cells/ml Split to 1x10 5 on Friday, cells will be at about 1x10 6 on Monday Then split 1 2 during the week keeping 200 ml in a flask as needed 3x10 5 DND39 cells are plated in 100 ⁇ l of RPMI 1640 supplemented with 1 % heat inactivated FCS, 2 mM L-glutamine, and 100 units/ml Pen/Step in a 96 well Vee bottom plate (Nunc) Compounds are diluted serially 1 2 in DMSO starting at 4mM to 1 9 ⁇ M In a 96 well polypropylene plate, changing tips after each dilution Then 5 ⁇ l of each dilution are added to 500 ⁇ l of RPMI/1% serum in a 96 tube rack
  • EXAMPLE 70 4-[Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-cyclohexanecarboxylic acid ethyl ester 4-[Methylamino]cyclohexanecarboxylic acid. LRMS: 303. EXAMPLE 71
  • Example 86 The title compound of Example 86 was prepared by a method analogous to that described in Example 85 EXAMPLE 86
  • Example 88 The title compound of Example 88 were prepared by a method analogous to that described in Example 87

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EA200001203A EA005852B1 (ru) 1998-06-19 1999-06-14 ПИРРОЛО[2,3-d]ПИРИМИДИНЫ
IL13958699A IL139586A0 (en) 1998-06-19 1999-06-14 PYRROLO [2,3-d] PYRIMIDINE COMPOUNDS
JP2000554733A JP4666762B2 (ja) 1998-06-19 1999-06-14 ピロロ［２．３−ｄ］ピリミジン化合物
HK01107744.3A HK1036801B (en) 1998-06-19 1999-06-14 Pyrrolo(2,3-d)pyrimidine compounds, composition and use there of
UA2000127300A UA64792C2 (en) 1998-06-19 1999-06-14 Pyrrole [2,3-d]pyrimidine derivatives, a pharmaceutical composition (variants), a method for inhibition of protein tyrosine kinase or janus kinase 3 of mammals (variants) and a method for treatment (variants)
AU39518/99A AU3951899A (en) 1998-06-19 1999-06-14 Pyrrolo(2,3-d)pyrimidine compounds
EP99922454A EP1087970B1 (en) 1998-06-19 1999-06-14 PYRROLO 2,3-d]PYRIMIDINE COMPOUNDS
DK99922454T DK1087970T3 (da) 1998-06-19 1999-06-14 Pyrrol[2,3-d]pyrimidin forbindelser
AT99922454T ATE265458T1 (de) 1998-06-19 1999-06-14 Pyrrolo(2,3-d)pyrimidin-verbindungen
BR9911365-1A BR9911365A (pt) 1998-06-19 1999-06-14 Compostos pirrolo[2,3-d]pirimidina
PL345123A PL198640B1 (pl) 1998-06-19 1999-06-14 Związki pirolo[2,3-d]pirymidynowe, środek farmaceutyczny i zastosowanie tych związków
HU0102574A HUP0102574A3 (en) 1998-06-19 1999-06-14 Pyrrolo[2,3-d]pyrimidine compounds
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DE69916833T DE69916833T2 (de) 1998-06-19 1999-06-14 Pyrrolo(2,3-d)pyrimidin-verbindungen
SK1898-2000A SK286640B6 (sk) 1998-06-19 1999-06-14 Pyrol [2,3-d] pyrimidínová zlúčenina, jej použitie na výrobu liečiva, farmaceutická kompozícia s jej obsahom, použitie jej kombinácie s ďalšími činidlami a súpravy s jej obsahom na výrobu liečiva
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APAP/P/1999/001584A AP1021A (en) 1998-06-19 1999-06-17 Pyrrolo [2,3-d] pyrimidine compounds.
NZ518444A NZ518444A (en) 1998-06-19 2000-11-08 Pyrrolo[2,3-d] pyrimidine compounds
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NO20006453A NO318784B1 (no) 1998-06-19 2000-12-18 Pyrrolo(2,3-d)pyrimidinforbindelser samt anvendelse derav og farmasoytisk sammensetning
AU2003234874A AU2003234874B2 (en) 1998-06-19 2003-08-13 Pyrrolo[2,3-d]pyrimidine Compounds
NO20050202A NO20050202L (no) 1998-06-19 2005-01-13 Pyrrolo(2,3-d)pyrimidinforbindelser
FR14C0019C FR14C0019I2 (fr) 1998-06-19 2014-03-07 COMPOSES DE PYRROLO 2,3d]PYRIMIDINE
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Cited By (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001042246A3 (en) * 1999-12-10 2001-11-22 Pfizer Prod Inc PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS
WO2002000661A1 (en) * 2000-06-26 2002-01-03 Pfizer Products Inc. PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS
DE10063294A1 (de) * 2000-12-19 2002-07-04 Aventis Pharma Gmbh Substituierte Heterocyclo-Norbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
WO2002096909A1 (en) * 2001-05-31 2002-12-05 Pfizer Products Inc. Optical resolution of (1-benzyl-4-methylpiperidin-3-yl) -methylamine and the use thereof for the preparation of pyrrolo 2,3-pyrimidine derivatives as protein kinases inhibitors
WO2003000695A1 (en) * 2001-06-23 2003-01-03 Aventis Pharmaceuticals Inc Pyrrolopyrimidines as protein kinase inhibitors
WO2003066632A1 (en) * 2002-02-05 2003-08-14 Glaxo Group Limited Sulphonyl compounds with 5 -ht6 receptor affinity
WO2003004007A3 (en) * 2001-06-29 2003-08-28 Ab Science Use of tyrosine kinase inhibitors for treating inflammatory bowel diseases (ibd)
US6635762B1 (en) 1998-06-19 2003-10-21 Pfizer Inc. Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use
EP1388541A1 (en) * 2002-08-09 2004-02-11 Centre National De La Recherche Scientifique (Cnrs) Pyrrolopyrazines as kinase inhibitors
WO2003002109A3 (en) * 2001-06-29 2004-05-27 Ab Science Use of tyrosine kinase inhibitors for treating autoimmune diseases
WO2005051393A1 (en) * 2003-11-25 2005-06-09 Pfizer Products Inc. Method of treatment of atherosclerosis
US6924290B2 (en) 2002-01-23 2005-08-02 Bayer Pharmaceuticals Corporation Rho-kinase inhibitors
JP2005523251A (ja) * 2002-01-10 2005-08-04 バイエル・ヘルスケア・アクチェンゲゼルシャフト Ｒｈｏ−キナーゼ阻害剤
US6943172B2 (en) 2002-01-23 2005-09-13 Bayer Pharmaceuticals Corporation Rho-kinase inhibitors
US6965027B2 (en) 2001-12-06 2005-11-15 Pfizer Inc. Crystalline 3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile citrate
WO2005095357A3 (en) * 2004-03-30 2006-01-19 Taisho Pharmaceutical Co Ltd Pyrimidine derivatives and methods of treatment related to the use thereof
WO2006004703A3 (en) * 2004-06-29 2006-03-09 Amgen Inc PYRROLO[2,3-d]PYRIMIDINES THAT MODULATE ACK1 AND LCK ACTIVITY
WO2006091450A1 (en) * 2005-02-18 2006-08-31 Lexicon Genetics Incorporated 4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine compounds
US7169794B2 (en) 2001-02-12 2007-01-30 Roche Palo Alto Llc 6-substituted pyrido-pyrimidines
WO2007077949A1 (en) 2005-12-28 2007-07-12 Astellas Pharma Inc. Heterocyclic janus kinase 3 inhibitors
US7244729B2 (en) 2001-08-07 2007-07-17 Novartis Ag 4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives
US7250420B2 (en) 2002-11-26 2007-07-31 Pfizer Inc. Method of treatment of transplant rejection
EP1474126A4 (en) * 2002-01-18 2007-08-08 Massachusetts Inst Technology TREATMENTS FOR NEUROTOXICITY IN ALZHEIMER DISEASE
US7323469B2 (en) 2001-08-07 2008-01-29 Novartis Ag 7H-pyrrolo[2,3-d]pyrimidine derivatives
US7335667B2 (en) 2004-12-22 2008-02-26 Incyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-4-yl-amines as Janus kinase inhibitors
WO2008084861A1 (ja) 2007-01-12 2008-07-17 Astellas Pharma Inc. 縮合ピリジン化合物
WO2008119792A1 (en) * 2007-04-02 2008-10-09 Palau Pharma, S. A. Pyrrolopyrimidine derivatives as jak3 inhibitors
DE102007027800A1 (de) 2007-06-16 2008-12-18 Bayer Healthcare Ag Substituierte bicyclische Heteroaryl-Verbindungen und ihre Verwendung
US7547702B2 (en) 2000-09-20 2009-06-16 Ortho-Mcneil Pharmaceutical, Inc. 4-amino-quinazolines
US7598257B2 (en) 2005-12-13 2009-10-06 Incyte Corporation Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors
WO2007041130A3 (en) * 2005-09-30 2010-01-21 Vertex Pharmaceuticals Incorporated Deazapurines useful as inhibitors of janus kinases
WO2009115084A3 (de) * 2008-03-20 2010-04-08 Schebo Biotech Ag Pyrrolopyrimidin-derivate und deren verwendungen
US7700610B2 (en) 2001-06-29 2010-04-20 Ab Science Use of tyrosine kinase inhibitors for treating allergic diseases
US7727731B2 (en) 2001-06-29 2010-06-01 Ab Science Potent, selective and non toxic c-kit inhibitors
US7741335B2 (en) 2001-06-29 2010-06-22 Ab Science Use of tyrosine kinase inhibitors for treating inflammatory diseases
US7829566B2 (en) 2001-09-17 2010-11-09 Werner Mederski 4-amino-quinazolines
US7834022B2 (en) 2007-06-13 2010-11-16 Incyte Corporation Metabolites of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
WO2011003418A1 (en) 2009-07-08 2011-01-13 Leo Pharma A/S Heterocyclic compounds as jak receptor and protein tyrosine kinase inhibitors
WO2011045702A1 (en) 2009-10-15 2011-04-21 Pfizer Inc. Pyrrolo[2,3-d] pyrimidine compounds
WO2011075334A1 (en) 2009-12-18 2011-06-23 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
WO2011097087A1 (en) 2010-02-05 2011-08-11 Pfizer Inc. Pyrrolo [ 2, 3 - d] pyrimidine urea compounds as jak inhibitors
WO2011031554A3 (en) * 2009-08-27 2011-09-15 Biocryst Pharmaceuticals, Inc. Heterocyclic compounds as janus kinase inhibitors
US8133899B2 (en) 2008-08-20 2012-03-13 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US8158616B2 (en) 2008-03-11 2012-04-17 Incyte Corporation Azetidine and cyclobutane derivatives as JAK inhibitors
US8163767B2 (en) 2005-07-14 2012-04-24 Astellas Pharma Inc. Heterocyclic Janus Kinase 3 inhibitors
US8183248B2 (en) 2005-05-13 2012-05-22 Irm Llc Substituted pyrrolo[2,3-d]pyrimidines and compositions as protein kinase inhibitors
WO2012093169A1 (en) 2011-01-07 2012-07-12 Leo Pharma A/S Novel sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use thereof
WO2012127506A1 (en) 2011-03-22 2012-09-27 Advinus Therapeutics Limited Substituted fused tricyclic compounds, compositions and medicinal applications thereof
US8299084B2 (en) 2009-04-20 2012-10-30 Auspex Pharmaceuticals, Inc. Piperidine inhibitors of Janus kinase 3
EP2007373A4 (en) * 2006-03-29 2012-12-19 Foldrx Pharmaceuticals Inc INHIBITION OF ALPHA SYNUCLEINE TOXICITY
CN102985425A (zh) * 2010-07-09 2013-03-20 利奥制药有限公司 作为蛋白酪氨酸激酶抑制剂的新的高哌嗪衍生物及其医药用途
US8420657B2 (en) 2008-02-06 2013-04-16 Novartis Ag Pyrrolo[2,3-D]pyrimidines and use thereof as tyrosine kinase inhibitors
EP2583678A2 (en) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Small molecule immunopotentiators and assays for their detection
US8513270B2 (en) 2006-12-22 2013-08-20 Incyte Corporation Substituted heterocycles as Janus kinase inhibitors
US8546407B2 (en) 2004-10-25 2013-10-01 Astex Therapeutics Limited Ortho-condensed pyridine and pyrimidine derivatives (e.g., purines) as protein kinases inhibitors
US8563541B2 (en) 2005-09-22 2013-10-22 Incyte Corporation Azepine inhibitors of Janus kinases
US8609647B2 (en) 2009-07-31 2013-12-17 Japan Tobacco Inc. Nitrogen-containing spirocyclic compounds and pharmaceutical uses thereof
WO2014001973A1 (en) * 2012-06-29 2014-01-03 Pfizer Inc. NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-d]PYRIMIDINES AS LRRK2 INHIBITORS
WO2014044691A1 (en) * 2012-09-20 2014-03-27 Bayer Pharma Aktiengesellschaft Substituted pyrrolopyrimidinylamino-benzothiazolones as mknk kinase inhibitors
US8691807B2 (en) 2011-06-20 2014-04-08 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US8722693B2 (en) 2007-06-13 2014-05-13 Incyte Corporation Salts of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US8796293B2 (en) 2006-04-25 2014-08-05 Astex Therapeutics Limited Purine and deazapurine derivatives as pharmaceutical compounds
WO2014123332A1 (ko) * 2013-02-07 2014-08-14 한국과학기술연구원 ＪＡＫ-3 저해제로 유용한 ７Ｈ-피롤로[2,3-ｄ]피리미딘-4-싸이올 유도체
WO2014128591A1 (en) 2013-02-22 2014-08-28 Pfizer Inc. Pyrrolo [2, 3 -d]pyrimidine derivatives as inhibitors of janus- related kinases (jak)
WO2014139388A1 (en) * 2013-03-14 2014-09-18 Merck Sharp & Dohme Corp. Novel indole derivatives useful as anti-diabetic agents
US8933085B2 (en) 2010-11-19 2015-01-13 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US8987443B2 (en) 2013-03-06 2015-03-24 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US9034884B2 (en) 2010-11-19 2015-05-19 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors
EP2796460A4 (en) * 2011-12-21 2015-05-20 Jiangsu Hengrui Medicine Co SULFUR PYRROL-HETEROARYL RING DERIVATIVE, METHOD OF MANUFACTURING THEREOF AND MEDICAL USES THEREOF
WO2015083028A1 (en) 2013-12-05 2015-06-11 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
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
WO2016024185A1 (en) 2014-08-12 2016-02-18 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine derivatives useful for inhibiting janus kinase
US9296757B2 (en) 2012-05-21 2016-03-29 Bayer Pharma Aktiengesellschaft Substituted benzothienopyrimidines
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
US9358229B2 (en) 2011-08-10 2016-06-07 Novartis Pharma Ag JAK PI3K/mTOR combination therapy
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
WO2016178110A1 (en) 2015-05-01 2016-11-10 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof
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
US9512161B2 (en) 2009-10-09 2016-12-06 Incyte Corporation Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
WO2017034245A1 (ko) * 2015-08-21 2017-03-02 양지화학 주식회사 야누스 키나제 1 선택적 억제제 및 그 의약 용도
US9593115B2 (en) 2012-09-21 2017-03-14 Advinus Therapeutics Ltd. Substituted fused tricyclic compounds, compositions, and medicinal applications thereof
US9655854B2 (en) 2013-08-07 2017-05-23 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US9695171B2 (en) 2013-12-17 2017-07-04 Pfizer Inc. 3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazines as LRRK2 inhibitors
WO2017142740A1 (en) 2016-02-16 2017-08-24 Zoetis Services Llc Process for preparing 7h-pyrrolo [2, 3-d] pyrimidine compounds
CN107098908A (zh) * 2016-02-23 2017-08-29 欣凯医药科技(上海)有限公司 一种吡咯并嘧啶类化合物的制备方法和应用
US9993480B2 (en) 2011-02-18 2018-06-12 Novartis Pharma Ag mTOR/JAK inhibitor combination therapy
US10039753B2 (en) 2015-09-14 2018-08-07 Pfizer Inc. Imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives as LRRK2 inhibitors
US10166191B2 (en) 2012-11-15 2019-01-01 Incyte Corporation Sustained-release dosage forms of ruxolitinib
WO2020198583A1 (en) 2019-03-27 2020-10-01 Insilico Medicine Ip Limited Bicyclic jak inhibitors and uses thereof
EP3877389A4 (en) * 2018-11-05 2022-07-13 Avista Pharma Solutions, Inc. Chemical compounds
WO2023055731A1 (en) * 2021-09-28 2023-04-06 Sanford Burnham Prebys Medical Discovery Institute Inhibitors of serine/threonine protein kinase stk3 or stk4 and uses thereof
RU2803741C2 (ru) * 2018-11-05 2023-09-19 Ависта Фарма Солюшнз, Инк. Химическое соединение
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
WO2024079345A1 (en) * 2022-10-13 2024-04-18 Norwegian University Of Science And Technology (Ntnu) Compound active as inhibitor of colony stimulation factor-1 receptor (csf-1 r)
WO2024079342A1 (en) * 2022-10-13 2024-04-18 Norwegian University Of Science And Technology (Ntnu) Compound active as inhibitor of colony stimulation factor-1 receptor (csf-1r)
US12116368B2 (en) 2018-10-22 2024-10-15 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto
US12202834B2 (en) 2019-01-29 2025-01-21 Vationpharma B.V. Solid state forms of oclacitinib maleate

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SK286640B6 (sk) * 1998-06-19 2009-03-05 Pfizer Products Inc. Pyrol [2,3-d] pyrimidínová zlúčenina, jej použitie na výrobu liečiva, farmaceutická kompozícia s jej obsahom, použitie jej kombinácie s ďalšími činidlami a súpravy s jej obsahom na výrobu liečiva
US20040102455A1 (en) * 2001-01-30 2004-05-27 Burns Christopher John Method of inhibiting kinases
CA2543116A1 (en) * 2003-10-27 2005-05-19 Genelabs Technologies, Inc. Methods for preparing 7-(2'-substituted-.szlig.-d-ribofuranosyl)-4-(nr2r3)-5-(substituted ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine derivatives
JP2008508358A (ja) 2004-08-02 2008-03-21 オーエスアイ・ファーマスーティカルズ・インコーポレーテッド アリール−アミノ置換ピロロピリミジンマルチキナーゼ阻害化合物
CA2705319C (en) * 2007-11-10 2019-01-15 Laurence Reid Systems and methods for workflow automation, adaptation and integration
EA019869B1 (ru) * 2007-11-28 2014-06-30 Дана Фарбер Кансер Инститьют, Инк. Низкомолекулярные миристатные ингибиторы тирозинкиназы bcr-abl и способы их применения
JP5368485B2 (ja) * 2008-02-25 2013-12-18 エフ．ホフマン−ラ ロシュ アーゲー ピロロピラジンキナーゼインヒビター
US20110201599A1 (en) * 2008-07-03 2011-08-18 Exelixis, Inc. CDK Modulators
JP2011529918A (ja) * 2008-08-01 2011-12-15 バイオクライスト ファーマシューティカルズ， インコーポレイテッド Ｊａｋ３阻害剤としてのピペリジン誘導体
US8385364B2 (en) * 2008-09-24 2013-02-26 Nec Laboratories America, Inc. Distributed message-passing based resource allocation in wireless systems
EP2360158A1 (en) * 2010-02-18 2011-08-24 Almirall, S.A. Pyrazole derivatives as jak inhibitors
CN103502249A (zh) * 2011-05-17 2014-01-08 普林斯匹亚生物制药公司 作为酪氨酸激酶抑制剂的氮杂吲哚衍生物
ES3018133T3 (en) 2011-11-30 2025-05-14 Univ Emory Jak inhibitors for use in the prevention or treatment of a viral disease caused by a coronaviridae
DK2875013T3 (en) * 2012-07-17 2018-01-22 Glaxosmithkline Intellectual Property (No 2) Ltd INDOLECAR CARBON NITRILS AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
CN108354938A (zh) * 2012-07-20 2018-08-03 硕腾服务有限责任公司 Janus激酶（jak）抑制剂的给药方案
CN102936251A (zh) * 2012-11-05 2013-02-20 上海毕得医药科技有限公司 一种吡咯并[2,3-d]嘧啶衍生物的制备方法
KR102081272B1 (ko) * 2015-05-29 2020-02-25 우시 포춘 파마슈티컬 컴퍼니 리미티드 Janus 키나아제 억제제
CN106831779B (zh) * 2015-11-28 2019-07-19 南昌弘益药业有限公司 一类jak激酶抑制剂的新化合物
JP7116063B2 (ja) 2016-12-14 2022-08-09 インターベット インターナショナル ベー． フェー． 選択的ヤヌスキナーゼ阻害剤としてのアミノピラゾール類
US11174263B2 (en) 2018-12-31 2021-11-16 Biomea Fusion, Inc. Inhibitors of menin-MLL interaction
SG11202106304RA (en) 2018-12-31 2021-07-29 Biomea Fusion Llc Irreversible inhibitors of menin-mll interaction
MX2023007150A (es) 2020-12-18 2023-09-04 Boehringer Ingelheim Animal Health Usa Inc Compuestos de pirazol que contienen boro, composiciones que los comprenden, métodos y usos de los mismos.
TW202320796A (zh) 2021-08-11 2023-06-01 美商拜歐米富士恩股份有限公司 用於糖尿病的menin-mll相互作用之共價抑制劑
US12018032B2 (en) 2021-08-20 2024-06-25 Biomea Fusion, Inc. Crystalline forms of N-[4-[4-(4-morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(r)-[(1-oxo-2-propen-1-yl)amino]-1-piperidinyl]methyl]-2-pyridinecarboxamide as an irreversible inhibitor of menin-MLL interaction
WO2023029943A1 (zh) * 2021-09-03 2023-03-09 星药科技(北京)有限公司 一种芳杂环化合物及其制备方法和用途
CN118541364A (zh) 2021-12-24 2024-08-23 英特维特国际股份有限公司 氨基吡唑化合物的用途
WO2024155710A1 (en) 2023-01-18 2024-07-25 Biomea Fusion, Inc. Crystalline forms of n-[4-[4-(4-morpholinyl)-7h-pyrrolo[2,3-d]pyrimidin-6- yl]phenyl]-4-[[3(r)-[(l-oxo-2-propen-l-yl)amino]-l-piperidinyl]methyl]-2-pyridinecarboxamide as a covalent inhibitor of menin-mll interaction

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0682027A1 (de) * 1994-05-03 1995-11-15 Ciba-Geigy Ag Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
WO1996040142A1 (en) * 1995-06-07 1996-12-19 Pfizer Inc. Heterocyclic ring-fused pyrimidine derivatives
WO1997002266A1 (en) * 1995-07-06 1997-01-23 Novartis Ag Pyrrolopyrimidines and processes for the preparation thereof
EP0795556A1 (en) * 1996-02-29 1997-09-17 PHARMACIA & UPJOHN S.p.A. 4-Substituted pyrrolopyrimidine compounds as tyrosin kinase inhibitors
WO1998007726A1 (en) * 1996-08-23 1998-02-26 Novartis Ag Substituted pyrrolopyrimidines and processes for their preparation
WO1998023613A1 (en) * 1996-11-27 1998-06-04 Pfizer Inc. Fused bicyclic pyrimidine derivatives

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3037980A (en) 1955-08-18 1962-06-05 Burroughs Wellcome Co Pyrrolopyrimidine vasodilators and method of making them
GB915303A (en) 1958-03-13 1963-01-09 Wellcome Found Pyrrolo[2,3-d]pyrimidine derivatives and the manufacture thereof
US6136595A (en) 1993-07-29 2000-10-24 St. Jude Children's Research Hospital Jak kinases and regulations of cytokine signal transduction
US5389509A (en) 1993-10-04 1995-02-14 Eastman Kodak Company Ultrathin high chloride tabular grain emulsions
IL112249A (en) 1994-01-25 2001-11-25 Warner Lambert Co Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds
JP4010563B2 (ja) 1995-07-05 2007-11-21 イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー 殺菌・殺カビ性のピリミジノン類
AR004010A1 (es) 1995-10-11 1998-09-30 Glaxo Group Ltd Compuestos heterociclicos
BR9607089A (pt) 1995-11-14 1997-11-11 Pharmacia & Upjohn Spa Compostos de pirimidina condensada biciclica composição farmacéutica utilização e produtos que contém os mesmos e processo para a preparação desses compostos
AU1441497A (en) 1996-01-23 1997-08-20 Novartis Ag Pyrrolopyrimidines and processes for their preparation
CH690773A5 (de) 1996-02-01 2001-01-15 Novartis Ag Pyrrolo(2,3-d)pyrimide und ihre Verwendung.
AU1794697A (en) 1996-03-06 1997-09-22 Novartis Ag 7-alkyl-pyrrolo{2,3-d}pyrimidines
AU3176297A (en) 1996-06-25 1998-01-14 Novartis Ag Substituted 7-amino-pyrrolo{3,2-d}pyrimidines and the use thereof
EA199900021A1 (ru) 1996-07-13 1999-08-26 Глаксо, Груп Лимитед Бициклические гетероароматические соединения в качестве ингибиторов протеинтирозинкиназы
HRP970371A2 (en) 1996-07-13 1998-08-31 Kathryn Jane Smith Heterocyclic compounds
WO1998033798A2 (en) 1997-02-05 1998-08-06 Warner Lambert Company Pyrido[2,3-d]pyrimidines and 4-amino-pyrimidines as inhibitors of cell proliferation
JP2001520748A (ja) 1997-03-24 2001-10-30 ファルマシア・アンド・アップジョン・カンパニー Ｊａｋ２／サイトカイン受容体結合の阻害剤を同定する方法
US6080847A (en) * 1997-12-04 2000-06-27 Incyte Pharmaceuticals, Inc. Proteins associated with cell proliferation
AU3378799A (en) 1998-04-02 1999-10-25 Neurogen Corporation Aminoalkyl substituted pyrrolo(2,3-b)pyridine and pyrrolo(2,3-d)pyrimidine derivatives: modulators of crf1 receptors
IL139641A0 (en) 1998-05-28 2002-02-10 Parker Hughes Inst Quinazolines for treating brain tumor
SK286640B6 (sk) * 1998-06-19 2009-03-05 Pfizer Products Inc. Pyrol [2,3-d] pyrimidínová zlúčenina, jej použitie na výrobu liečiva, farmaceutická kompozícia s jej obsahom, použitie jej kombinácie s ďalšími činidlami a súpravy s jej obsahom na výrobu liečiva
WO2000000202A1 (en) 1998-06-30 2000-01-06 Parker Hughes Institute Method for inhibiting c-jun expression using jak-3 inhibitors
KR20010089171A (ko) 1998-08-21 2001-09-29 추후제출 퀴나졸린 유도체
US6080747A (en) 1999-03-05 2000-06-27 Hughes Institute JAK-3 inhibitors for treating allergic disorders
DE60037345T2 (de) * 1999-12-10 2008-11-13 Pfizer Products Inc., Groton Pyrrolo(2,3-d)pyrimidin-Verbindungen
ATE423120T1 (de) * 2000-06-26 2009-03-15 Pfizer Prod Inc Pyrroloä2,3-düpyrimidin verbindungen als immunosuppressive wirkstoffe
AU2009100870A4 (en) 2008-10-01 2009-10-22 Rock Tone Enterprise Co., Ltd. Drive mechanism for dehydrator
TWM358618U (en) 2008-12-26 2009-06-11 Rock Tone Entpr Co Ltd Combination structure of mop holder and cleaning body

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0682027A1 (de) * 1994-05-03 1995-11-15 Ciba-Geigy Ag Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
WO1996040142A1 (en) * 1995-06-07 1996-12-19 Pfizer Inc. Heterocyclic ring-fused pyrimidine derivatives
WO1997002266A1 (en) * 1995-07-06 1997-01-23 Novartis Ag Pyrrolopyrimidines and processes for the preparation thereof
EP0795556A1 (en) * 1996-02-29 1997-09-17 PHARMACIA & UPJOHN S.p.A. 4-Substituted pyrrolopyrimidine compounds as tyrosin kinase inhibitors
WO1998007726A1 (en) * 1996-08-23 1998-02-26 Novartis Ag Substituted pyrrolopyrimidines and processes for their preparation
WO1998023613A1 (en) * 1996-11-27 1998-06-04 Pfizer Inc. Fused bicyclic pyrimidine derivatives

Cited By (224)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6635762B1 (en) 1998-06-19 2003-10-21 Pfizer Inc. Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use
US7569569B2 (en) 1998-06-19 2009-08-04 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US6627754B2 (en) 1999-12-10 2003-09-30 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
USRE41783E1 (en) 1999-12-10 2010-09-28 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
CZ303875B6 (cs) * 1999-12-10 2013-06-05 Pfizer Products Inc. Pyrrolo[2,3-d]pyrimidinová sloucenina a farmaceutická kompozice s jejím obsahem
WO2001042246A3 (en) * 1999-12-10 2001-11-22 Pfizer Prod Inc PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS
US7265221B2 (en) 1999-12-10 2007-09-04 Pfizer, Inc. Pyrrolo[2,3-d]pyrimidine compounds
US7091208B2 (en) 1999-12-10 2006-08-15 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
US7601727B2 (en) 1999-12-10 2009-10-13 Pfizer, Inc. Pyrrolo[2,3-d]pyrimidine compounds
US7842699B2 (en) 1999-12-10 2010-11-30 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
EP1686130A1 (en) * 2000-06-26 2006-08-02 Pfizer Products Incorporated Pyrrolo[2,3-d]pyrimidine compounds as immunosuppressive agents
US7192963B2 (en) 2000-06-26 2007-03-20 Pfizer Inc Pyrrolo[2,3-d]pyrimidine compounds
CN100351253C (zh) * 2000-06-26 2007-11-28 辉瑞产品公司 作为免疫抑制剂的吡咯并[2,3－d]嘧啶化合物
AP1911A (en) * 2000-06-26 2008-10-30 Pfizer Prod Inc Pyrrolo[2,3-d]pyrimidine compounds.
WO2002000661A1 (en) * 2000-06-26 2002-01-03 Pfizer Products Inc. PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS
US6696567B2 (en) 2000-06-26 2004-02-24 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US7547702B2 (en) 2000-09-20 2009-06-16 Ortho-Mcneil Pharmaceutical, Inc. 4-amino-quinazolines
DE10063294A1 (de) * 2000-12-19 2002-07-04 Aventis Pharma Gmbh Substituierte Heterocyclo-Norbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
US7449581B2 (en) 2001-02-12 2008-11-11 Poche Palo Alto Llc 6-Substituted pyrido-pyrimidines
US7169794B2 (en) 2001-02-12 2007-01-30 Roche Palo Alto Llc 6-substituted pyrido-pyrimidines
US7432370B2 (en) 2001-05-31 2008-10-07 Pfizer Inc. Chiral salt resolution
EP1609781A1 (en) * 2001-05-31 2005-12-28 Pfizer Products Incorporated Optical resolution of (1-benzyl-4-methylpiperidin-3-yl)-methylamine
CZ304366B6 (cs) * 2001-05-31 2014-04-02 Pfizer Products Inc. 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl)}-3-oxopropionitril, farmaceutický prostředek s jeho obsahem a použití
US7301023B2 (en) 2001-05-31 2007-11-27 Pfizer Inc. Chiral salt resolution
WO2002096909A1 (en) * 2001-05-31 2002-12-05 Pfizer Products Inc. Optical resolution of (1-benzyl-4-methylpiperidin-3-yl) -methylamine and the use thereof for the preparation of pyrrolo 2,3-pyrimidine derivatives as protein kinases inhibitors
EP1666481A3 (en) * 2001-05-31 2006-11-29 Pfizer Products Incorporated 3-((3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidinyl)-3-oxo-propionitrile as protein kinase inhibtor
HRP20030943B1 (hr) * 2001-05-31 2011-11-30 Pfizer Products Inc. Optičko razdvajanje (1-benzil-4-metilpiperidin-3-il)-metilamina i njegova upotreba u dobivanju pirolo 2,3-pirimidinskih derivata kao inhibitora protein kinaze
EA012666B1 (ru) * 2001-05-31 2009-12-30 Пфайзер Продактс Инк. Оптическое разделение (1-бензил-4-метилпиперидин-3-ил)метиламина и его применение для получения производных пирроло 2,3-пиримидина в качестве ингибиторов протеинкиназы
EA007415B1 (ru) * 2001-06-23 2006-10-27 Авентис Фармасьютикалз Инк. Пирролопиримидины как ингибиторы протеинкиназы
CN1294135C (zh) * 2001-06-23 2007-01-10 安万特药物公司 作为蛋白激酶抑制剂的吡咯并嘧啶
AU2002314325B8 (en) * 2001-06-23 2009-01-29 Aventis Pharmaceuticals Inc. Pyrrolopyrimidines as protein kinase inhibitors
WO2003000695A1 (en) * 2001-06-23 2003-01-03 Aventis Pharmaceuticals Inc Pyrrolopyrimidines as protein kinase inhibitors
AU2002314325B2 (en) * 2001-06-23 2009-01-08 Aventis Pharmaceuticals Inc. Pyrrolopyrimidines as protein kinase inhibitors
US7741335B2 (en) 2001-06-29 2010-06-22 Ab Science Use of tyrosine kinase inhibitors for treating inflammatory diseases
WO2003004007A3 (en) * 2001-06-29 2003-08-28 Ab Science Use of tyrosine kinase inhibitors for treating inflammatory bowel diseases (ibd)
US7727731B2 (en) 2001-06-29 2010-06-01 Ab Science Potent, selective and non toxic c-kit inhibitors
US7700610B2 (en) 2001-06-29 2010-04-20 Ab Science Use of tyrosine kinase inhibitors for treating allergic diseases
US7678805B2 (en) 2001-06-29 2010-03-16 Ab Science Use of tyrosine kinase inhibitors for treating inflammatory bowel diseases (IBD)
WO2003002109A3 (en) * 2001-06-29 2004-05-27 Ab Science Use of tyrosine kinase inhibitors for treating autoimmune diseases
US7323469B2 (en) 2001-08-07 2008-01-29 Novartis Ag 7H-pyrrolo[2,3-d]pyrimidine derivatives
US7390805B2 (en) 2001-08-07 2008-06-24 Novartis Ag 4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives
US7244729B2 (en) 2001-08-07 2007-07-17 Novartis Ag 4-amino-6-phenyl-pyrrolo[2,3-d]pyrimidine derivatives
US7829566B2 (en) 2001-09-17 2010-11-09 Werner Mederski 4-amino-quinazolines
US7803805B2 (en) 2001-12-06 2010-09-28 Pfizer Inc. Cristalline 3-{(3R,4R)-4 methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt
US6965027B2 (en) 2001-12-06 2005-11-15 Pfizer Inc. Crystalline 3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile citrate
JP2005523251A (ja) * 2002-01-10 2005-08-04 バイエル・ヘルスケア・アクチェンゲゼルシャフト Ｒｈｏ−キナーゼ阻害剤
US7648986B2 (en) 2002-01-10 2010-01-19 Bayer Healthcare Llc Substituted thieno[3,2-D]pyrimidines as Rho kinase inhibitors
EP1474126A4 (en) * 2002-01-18 2007-08-08 Massachusetts Inst Technology TREATMENTS FOR NEUROTOXICITY IN ALZHEIMER DISEASE
US6924290B2 (en) 2002-01-23 2005-08-02 Bayer Pharmaceuticals Corporation Rho-kinase inhibitors
US6943172B2 (en) 2002-01-23 2005-09-13 Bayer Pharmaceuticals Corporation Rho-kinase inhibitors
WO2003066632A1 (en) * 2002-02-05 2003-08-14 Glaxo Group Limited Sulphonyl compounds with 5 -ht6 receptor affinity
US8106050B2 (en) 2002-08-09 2012-01-31 Centre National De La Recherche Scientifique (C.N.R.S.) Derivatives of pyrrolo-pyrazines having a kinase inhibitory activity and their biological applications
EP1388541A1 (en) * 2002-08-09 2004-02-11 Centre National De La Recherche Scientifique (Cnrs) Pyrrolopyrazines as kinase inhibitors
WO2004016614A3 (en) * 2002-08-09 2004-05-06 Centre Nat Rech Scient Pyrrolopyrazines as kinase inhibitors
US7250420B2 (en) 2002-11-26 2007-07-31 Pfizer Inc. Method of treatment of transplant rejection
WO2005051393A1 (en) * 2003-11-25 2005-06-09 Pfizer Products Inc. Method of treatment of atherosclerosis
WO2005095357A3 (en) * 2004-03-30 2006-01-19 Taisho Pharmaceutical Co Ltd Pyrimidine derivatives and methods of treatment related to the use thereof
RU2373197C2 (ru) * 2004-03-30 2009-11-20 Тайсо Фармасьютикал Ко., Лтд. Пиримидиновые производные, обладающие активностью в отношении мсн
EP2583678A2 (en) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Small molecule immunopotentiators and assays for their detection
US7358250B2 (en) 2004-06-29 2008-04-15 Amgen Inc. Pyrrolo[2,3-d]pyrimidines that modulate ACK1 activity
WO2006004703A3 (en) * 2004-06-29 2006-03-09 Amgen Inc PYRROLO[2,3-d]PYRIMIDINES THAT MODULATE ACK1 AND LCK ACTIVITY
US8546407B2 (en) 2004-10-25 2013-10-01 Astex Therapeutics Limited Ortho-condensed pyridine and pyrimidine derivatives (e.g., purines) as protein kinases inhibitors
EP1828181A4 (en) * 2004-12-22 2010-08-25 Incyte Corp PYRROLO [2,3-B] PYRIDINE-4-YL-AMINE AND PYRROLO [2M3-B] PYRIMIDIN-4-YL-AMINE AS JANUSKINASEINHIBITORS
US8445488B2 (en) 2004-12-22 2013-05-21 Incyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as Janus kinase inhibitors
EP2671882A1 (en) * 2004-12-22 2013-12-11 Incyte Corporation pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2m3-b]pyrimidin-4-yl-amines as janus kinase inhibitors
US7335667B2 (en) 2004-12-22 2008-02-26 Incyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-4-yl-amines as Janus kinase inhibitors
US9879010B2 (en) 2004-12-22 2018-01-30 Incyte Holdings Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b] pyrimidin-5-yl-amines as Janus kinase inhibitors
US9090611B2 (en) 2004-12-22 2015-07-28 Incyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as janus kinase inhibitors
US9580419B2 (en) 2004-12-22 2017-02-28 Incyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as Janus kinase inhibitors
US8741895B2 (en) 2004-12-22 2014-06-03 Incyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as Janus kinase inhibitors
US8053433B2 (en) 2004-12-22 2011-11-08 Ineyte Corporation Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as janus kinase inhibitors
WO2006091450A1 (en) * 2005-02-18 2006-08-31 Lexicon Genetics Incorporated 4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine compounds
US8183248B2 (en) 2005-05-13 2012-05-22 Irm Llc Substituted pyrrolo[2,3-d]pyrimidines and compositions as protein kinase inhibitors
US8163767B2 (en) 2005-07-14 2012-04-24 Astellas Pharma Inc. Heterocyclic Janus Kinase 3 inhibitors
EP2251341A1 (en) 2005-07-14 2010-11-17 Astellas Pharma Inc. Heterocyclic Janus kinase 3 inhibitors
US8563541B2 (en) 2005-09-22 2013-10-22 Incyte Corporation Azepine inhibitors of Janus kinases
US8835423B2 (en) 2005-09-22 2014-09-16 Incyte Corporation Azepine inhibitors of janus kinases
US8580802B2 (en) 2005-09-30 2013-11-12 Vertex Pharmaceuticals Incorporated Pyrrolo[2,3-D]pyrimidines as inhibitors of Janus kinases
EP2532667A1 (en) * 2005-09-30 2012-12-12 Vertex Pharmaceuticals Incorporated Deazapurines useful as inhibitors of janus kinases
WO2007041130A3 (en) * 2005-09-30 2010-01-21 Vertex Pharmaceuticals Incorporated Deazapurines useful as inhibitors of janus kinases
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
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
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
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
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
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
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
US7598257B2 (en) 2005-12-13 2009-10-06 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
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
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
US7879844B2 (en) 2005-12-28 2011-02-01 Astellas Pharma Inc. Heterocyclic janus kinase 3 inhibitors
WO2007077949A1 (en) 2005-12-28 2007-07-12 Astellas Pharma Inc. Heterocyclic janus kinase 3 inhibitors
NO341555B1 (no) * 2005-12-28 2017-12-04 Astellas Pharma Inc Heterosykliske januskinase-3-inhibitorer
EP2007373A4 (en) * 2006-03-29 2012-12-19 Foldrx Pharmaceuticals Inc INHIBITION OF ALPHA SYNUCLEINE TOXICITY
US8796293B2 (en) 2006-04-25 2014-08-05 Astex Therapeutics Limited Purine and deazapurine derivatives as pharmaceutical compounds
US8513270B2 (en) 2006-12-22 2013-08-20 Incyte Corporation Substituted heterocycles as Janus kinase inhibitors
US8841318B2 (en) 2006-12-22 2014-09-23 Incyte Corporation Substituted heterocycles as janus kinase inhibitors
WO2008084861A1 (ja) 2007-01-12 2008-07-17 Astellas Pharma Inc. 縮合ピリジン化合物
WO2008119792A1 (en) * 2007-04-02 2008-10-09 Palau Pharma, S. A. Pyrrolopyrimidine derivatives as jak3 inhibitors
US8829013B1 (en) 2007-06-13 2014-09-09 Incyte Corporation Salts of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US8822481B1 (en) 2007-06-13 2014-09-02 Incyte Corporation Salts of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d] pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US10016429B2 (en) 2007-06-13 2018-07-10 Incyte Corporation Salts of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US7834022B2 (en) 2007-06-13 2010-11-16 Incyte Corporation Metabolites of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US10610530B2 (en) 2007-06-13 2020-04-07 Incyte Corporation Salts of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US8722693B2 (en) 2007-06-13 2014-05-13 Incyte Corporation Salts of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
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
US10463667B2 (en) 2007-06-13 2019-11-05 Incyte Incorporation Metabolites of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US9376439B2 (en) 2007-06-13 2016-06-28 Incyte Corporation Salts of the janus kinase inhibitor (R)-3(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US8889697B2 (en) 2007-06-13 2014-11-18 Incyte Corporation Metabolites of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
DE102007027800A1 (de) 2007-06-16 2008-12-18 Bayer Healthcare Ag Substituierte bicyclische Heteroaryl-Verbindungen und ihre Verwendung
US8420657B2 (en) 2008-02-06 2013-04-16 Novartis Ag Pyrrolo[2,3-D]pyrimidines and use thereof as tyrosine kinase inhibitors
US8158616B2 (en) 2008-03-11 2012-04-17 Incyte Corporation Azetidine and cyclobutane derivatives as JAK inhibitors
US8420629B2 (en) 2008-03-11 2013-04-16 Incyte Corporation Azetidine and cyclobutane derivatives as JAK inhibitors
WO2009115084A3 (de) * 2008-03-20 2010-04-08 Schebo Biotech Ag Pyrrolopyrimidin-derivate und deren verwendungen
US9271981B2 (en) 2008-08-20 2016-03-01 Zoetis Services Llc Pyrrolo[2,3-D]pyrimidine compounds
US9161939B2 (en) 2008-08-20 2015-10-20 Zoetis Services Llc Pyrrolo[2,3-d]pyrimidine compounds
US8133899B2 (en) 2008-08-20 2012-03-13 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
US8987283B2 (en) 2008-08-20 2015-03-24 Zoetis Llc Pyrrolo[2,3-D]pyrimidine compounds
US8299084B2 (en) 2009-04-20 2012-10-30 Auspex Pharmaceuticals, Inc. Piperidine inhibitors of Janus kinase 3
US9493469B2 (en) 2009-04-20 2016-11-15 Auspex Pharmaceuticals, Inc. Piperidine inhibitors of Janus kinase 3
US8962638B2 (en) 2009-04-20 2015-02-24 Auspex Pharmaceuticals, Inc. Piperidine inhibitors of janus kinase 3
US9856261B2 (en) 2009-04-20 2018-01-02 Auspex Pharmaceuticals, Inc. Piperidine inhibitors of Janus kinase 3
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
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
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
WO2011003418A1 (en) 2009-07-08 2011-01-13 Leo Pharma A/S Heterocyclic compounds as jak receptor and protein tyrosine kinase inhibitors
CN102574857B (zh) * 2009-07-08 2015-06-10 利奥制药有限公司 作为jak受体和蛋白酪氨酸激酶抑制剂的杂环化合物
CN102574857A (zh) * 2009-07-08 2012-07-11 利奥制药有限公司 作为jak受体和蛋白酪氨酸激酶抑制剂的杂环化合物
US9346809B2 (en) 2009-07-08 2016-05-24 Leo Pharma A/S Heterocyclic compounds as JAK receptor and protein tyrosine kinase inhibitors
US8609647B2 (en) 2009-07-31 2013-12-17 Japan Tobacco Inc. Nitrogen-containing spirocyclic compounds and pharmaceutical uses thereof
WO2011031554A3 (en) * 2009-08-27 2011-09-15 Biocryst Pharmaceuticals, Inc. Heterocyclic compounds as janus kinase 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
US9512161B2 (en) 2009-10-09 2016-12-06 Incyte Corporation Hydroxyl, keto, and glucuronide derivatives of 3-(4-(7H-pyrrolo[2,3-D]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
US8633206B2 (en) 2009-10-15 2014-01-21 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
WO2011045702A1 (en) 2009-10-15 2011-04-21 Pfizer Inc. Pyrrolo[2,3-d] pyrimidine compounds
US8372854B2 (en) 2009-12-18 2013-02-12 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine compounds
WO2011075334A1 (en) 2009-12-18 2011-06-23 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
WO2011097087A1 (en) 2010-02-05 2011-08-11 Pfizer Inc. Pyrrolo [ 2, 3 - d] pyrimidine urea compounds as jak inhibitors
US9999619B2 (en) 2010-03-10 2018-06-19 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
US9464088B2 (en) 2010-03-10 2016-10-11 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
CN102985425A (zh) * 2010-07-09 2013-03-20 利奥制药有限公司 作为蛋白酪氨酸激酶抑制剂的新的高哌嗪衍生物及其医药用途
US9034884B2 (en) 2010-11-19 2015-05-19 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors
US8933085B2 (en) 2010-11-19 2015-01-13 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US9233964B2 (en) 2011-01-07 2016-01-12 Leo Pharma A/S Sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use therof
WO2012093169A1 (en) 2011-01-07 2012-07-12 Leo Pharma A/S Novel sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use thereof
US9993480B2 (en) 2011-02-18 2018-06-12 Novartis Pharma Ag mTOR/JAK inhibitor combination therapy
WO2012127506A1 (en) 2011-03-22 2012-09-27 Advinus Therapeutics Limited Substituted fused tricyclic compounds, compositions and medicinal applications thereof
US9611269B2 (en) 2011-06-20 2017-04-04 Incyte Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
US9023840B2 (en) 2011-06-20 2015-05-05 Incyte 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
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
US9358229B2 (en) 2011-08-10 2016-06-07 Novartis Pharma Ag JAK PI3K/mTOR combination therapy
US9359358B2 (en) 2011-08-18 2016-06-07 Incyte Holdings Corporation Cyclohexyl azetidine derivatives as JAK inhibitors
US9487521B2 (en) 2011-09-07 2016-11-08 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US9718834B2 (en) 2011-09-07 2017-08-01 Incyte Corporation Processes and intermediates for making a JAK inhibitor
RU2618673C2 (ru) * 2011-12-21 2017-05-10 Цзянсу Хэнжуй Медсин Ко., Лтд. Производные пирролопиримидина, полезные в качестве ингибиторов jak-киназы
EP2796460A4 (en) * 2011-12-21 2015-05-20 Jiangsu Hengrui Medicine Co SULFUR PYRROL-HETEROARYL RING DERIVATIVE, METHOD OF MANUFACTURING THEREOF AND MEDICAL USES THEREOF
AU2012357296B2 (en) * 2011-12-21 2017-04-13 Jiangsu Hengrui Medicine Co., Ltd. Pyrrole six-membered heteroaryl ring derivative, preparation method therefor, and medicinal uses thereof
US9193733B2 (en) 2012-05-18 2015-11-24 Incyte Holdings Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors
US9296757B2 (en) 2012-05-21 2016-03-29 Bayer Pharma Aktiengesellschaft Substituted benzothienopyrimidines
AU2013282869B2 (en) * 2012-06-29 2015-12-24 Pfizer Inc. Novel 4-(substituted-amino)-7H-pyrrolo[2,3-d]pyrimidines as LRRK2 inhibitors
US9642855B2 (en) 2012-06-29 2017-05-09 Pfizer Inc. Substituted pyrrolo[2,3-d]pyrimidines as LRRK2 inhibitors
TWI482774B (zh) * 2012-06-29 2015-05-01 Pfizer 作爲ＬＲＲＫ２抑制劑之新穎４－（經取代胺基）－７Ｈ－吡咯并［２，３－ｄ］嘧啶類
US9156845B2 (en) 2012-06-29 2015-10-13 Pfizer Inc. 4-(substituted amino)-7H-pyrrolo[2,3-d] pyrimidines as LRRK2 inhibitors
EA025186B1 (ru) * 2012-06-29 2016-11-30 Пфайзер Инк. НОВЫЕ 4-(ЗАМЕЩЕННЫЙ АМИНО)-7Н-ПИРРОЛО[2,3-d]ПИРИМИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ LRRK2
WO2014001973A1 (en) * 2012-06-29 2014-01-03 Pfizer Inc. NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-d]PYRIMIDINES AS LRRK2 INHIBITORS
EP3255049A1 (en) * 2012-06-29 2017-12-13 Pfizer Inc Novel 4-(substituted-amino)-7h-pyrrolo[2,3-d]pyrimidines as lrrk2 inhibitors
WO2014044691A1 (en) * 2012-09-20 2014-03-27 Bayer Pharma Aktiengesellschaft Substituted pyrrolopyrimidinylamino-benzothiazolones as mknk kinase inhibitors
US9382255B2 (en) 2012-09-20 2016-07-05 Bayer Pharma Aktiengesellschaft Substituted pyrrolopyrimidinylamino-benzothiazolones as MKNK kinase inhibitors
US9593115B2 (en) 2012-09-21 2017-03-14 Advinus Therapeutics Ltd. Substituted fused tricyclic compounds, compositions, and medicinal applications thereof
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
US11576864B2 (en) 2012-11-15 2023-02-14 Incyte Corporation Sustained-release dosage forms of ruxolitinib
US11576865B2 (en) 2012-11-15 2023-02-14 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
US10874616B2 (en) 2012-11-15 2020-12-29 Incyte Corporation Sustained-release dosage forms of ruxolitinib
WO2014123332A1 (ko) * 2013-02-07 2014-08-14 한국과학기술연구원 ＪＡＫ-3 저해제로 유용한 ７Ｈ-피롤로[2,3-ｄ]피리미딘-4-싸이올 유도체
US9545405B2 (en) 2013-02-22 2017-01-17 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine derivatives
EP3290421A1 (en) 2013-02-22 2018-03-07 Pfizer Inc Combination of pyrrolo [2, 3 -d]pyrimidine derivatives with one or more additional agents as inhibitors of janus- related kinases (jak)
US9035074B2 (en) 2013-02-22 2015-05-19 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine derivatives
WO2014128591A1 (en) 2013-02-22 2014-08-28 Pfizer Inc. Pyrrolo [2, 3 -d]pyrimidine derivatives as inhibitors of janus- related kinases (jak)
US9549929B2 (en) 2013-02-22 2017-01-24 Pfizer Inc. Pyrrolo[2,3-D]pyrimidine derivatives
US9714233B2 (en) 2013-03-06 2017-07-25 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US9221845B2 (en) 2013-03-06 2015-12-29 Incyte Holdings Corporation Processes and intermediates for making a JAK inhibitor
US8987443B2 (en) 2013-03-06 2015-03-24 Incyte Corporation Processes and intermediates for making a JAK inhibitor
US9650375B2 (en) 2013-03-14 2017-05-16 Merck Sharp & Dohme Corp. Indole derivatives useful as anti-diabetic agents
WO2014139388A1 (en) * 2013-03-14 2014-09-18 Merck Sharp & Dohme Corp. Novel indole derivatives useful as anti-diabetic agents
US12151026B2 (en) 2013-08-07 2024-11-26 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
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
US10561616B2 (en) 2013-08-07 2020-02-18 Incyte Corporation Sustained release dosage forms for a JAK1 inhibitor
US12077533B2 (en) 2013-12-05 2024-09-03 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
WO2015083028A1 (en) 2013-12-05 2015-06-11 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
EP3318565A1 (en) 2013-12-05 2018-05-09 Pfizer Inc Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
US11111242B2 (en) 2013-12-05 2021-09-07 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
US9617258B2 (en) 2013-12-05 2017-04-11 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides
US9695171B2 (en) 2013-12-17 2017-07-04 Pfizer Inc. 3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazines as LRRK2 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
WO2016024185A1 (en) 2014-08-12 2016-02-18 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine derivatives useful for inhibiting janus kinase
US10966980B2 (en) 2014-08-12 2021-04-06 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine derivatives
WO2016178110A1 (en) 2015-05-01 2016-11-10 Pfizer Inc. Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof
US10703756B2 (en) 2015-05-01 2020-07-07 Pfizer Inc. Pyrrolo[2,3-D]pyrimidinyl, pyrrolo[2,3-B]pyrazinyl, pyrrolo[2,3-B]pyridinyl acrylamides and epoxides thereof
KR101771219B1 (ko) * 2015-08-21 2017-09-05 양지화학 주식회사 야누스 키나제 1 선택적 억제제 및 그 의약 용도
WO2017034245A1 (ko) * 2015-08-21 2017-03-02 양지화학 주식회사 야누스 키나제 1 선택적 억제제 및 그 의약 용도
US10407430B2 (en) 2015-08-21 2019-09-10 Yang Ji Chemical Co., Ltd. Janus kinase 1 selective inhibitor and pharmaceutical use thereof
US10039753B2 (en) 2015-09-14 2018-08-07 Pfizer Inc. Imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives as LRRK2 inhibitors
WO2017142740A1 (en) 2016-02-16 2017-08-24 Zoetis Services Llc Process for preparing 7h-pyrrolo [2, 3-d] pyrimidine compounds
EP3421473A4 (en) * 2016-02-23 2019-10-02 Cinkate Pharm Tech (Shanghai) Co., Ltd. PROCESS FOR THE PREPARATION OF PYRROLOPYRIMIDINE COMPOUND AND USE THEREOF
CN107098908A (zh) * 2016-02-23 2017-08-29 欣凯医药科技(上海)有限公司 一种吡咯并嘧啶类化合物的制备方法和应用
US12116368B2 (en) 2018-10-22 2024-10-15 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine tosylate salt, crystalline form thereof and manufacturing process and intermediates thereto
RU2803741C2 (ru) * 2018-11-05 2023-09-19 Ависта Фарма Солюшнз, Инк. Химическое соединение
EP3877389A4 (en) * 2018-11-05 2022-07-13 Avista Pharma Solutions, Inc. Chemical compounds
US12202834B2 (en) 2019-01-29 2025-01-21 Vationpharma B.V. Solid state forms of oclacitinib maleate
WO2020198583A1 (en) 2019-03-27 2020-10-01 Insilico Medicine Ip Limited Bicyclic jak inhibitors and uses thereof
US12286443B2 (en) 2019-03-27 2025-04-29 Insilico Medicine Ip Limited Bycyclic JAK inhibitors and uses thereof
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
WO2023055731A1 (en) * 2021-09-28 2023-04-06 Sanford Burnham Prebys Medical Discovery Institute Inhibitors of serine/threonine protein kinase stk3 or stk4 and uses thereof
WO2024079345A1 (en) * 2022-10-13 2024-04-18 Norwegian University Of Science And Technology (Ntnu) Compound active as inhibitor of colony stimulation factor-1 receptor (csf-1 r)
WO2024079342A1 (en) * 2022-10-13 2024-04-18 Norwegian University Of Science And Technology (Ntnu) Compound active as inhibitor of colony stimulation factor-1 receptor (csf-1r)

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