US20050209253A1 - Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group - Google Patents

Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group Download PDF

Info

Publication number
US20050209253A1
US20050209253A1 US10/504,981 US50498105A US2005209253A1 US 20050209253 A1 US20050209253 A1 US 20050209253A1 US 50498105 A US50498105 A US 50498105A US 2005209253 A1 US2005209253 A1 US 2005209253A1
Authority
US
United States
Prior art keywords
phenyl
pyrrolo
dimethyl
alkyl
piperidin
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.)
Abandoned
Application number
US10/504,981
Other languages
English (en)
Inventor
Atsuro Nakazato
Taketoshi Okubo
Dai Nozawa
Mikato Yamaguchi
Tomoko Tamita
Ludo Kennis
Marcel De Bruyn
Jean-Pierre Bongartz
Frans Van Den Keybus
Yves Van Roosbroeck
Marcel Luyckx
Robert Hendrickx
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.)
Taisho Pharmaceutical Co Ltd
Original Assignee
Taisho Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Assigned to TAISHO PHARMACEUTICAL CO., LTD. reassignment TAISHO PHARMACEUTICAL CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HENDRICKX, ROBERT J.M., BONGARTZ, JEAN-PIERRE A.M., DE BRUYN, MARCEL F.L., KENNIS, LUDO E.J., LUYCKX, MARCEL G.M., VAN DEN KEYBUS, FRANS M.A., VAN ROOSBROECK, YVES E.M., NAKAZATO, ATSURO, NOZAWA, DAI, OKUBO, TAKATOSHI, TAMITA, TOMOKO, YAMAGUCHI, MIKAKO
Publication of US20050209253A1 publication Critical patent/US20050209253A1/en
Priority to US12/106,873 priority Critical patent/US7932259B2/en
Priority to US12/951,556 priority patent/US8455511B2/en
Abandoned legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Definitions

  • the present invention relates to a therapeutic agent for diseases in which corticotropin releasing factor (CRF) is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastral diseases, drug dependence, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation immunity-related diseases, alpecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc.
  • CCF corticotropin releasing factor
  • CRF is a hormone comprising 41 amino acids (Science, 213, 1394-1397, 1981; and J. Neurosci., 7, 88-100, 1987), and it is suggested that CRF plays a core role in biological reactions against stresses (Cell. Mol. Neurobiol., 14, 579-588, 1994; Endocrinol., 132, 723-728, 1994; and Neuroendocrinol. 61, 445-452, 1995).
  • CRF CRF Releasing Factor: Basic and Clinical Studies of a Neuropeptide, pp. 29-52, 1990.
  • Intraventricular administration of CRF to hypophysectomized rats and normal rats causes an anxiety-like symptom in both types of rats (Pharmacol. Rev., 43, 425-473, 1991; and Brain Res. Rev., 15, 71-100, 1990). That is, there are suggested the participation of CRF in hypothalamus-pituitary-adrenal system and the pathway by which CRF functions as a neurotransmitter in central nervous system.
  • WO02/002549 and WO0/053604 disclose pyrrolopyridine and pyrrolopyrimidine derivatives respectively as CRF receptor antagonists.
  • Bioorganic & Medicinal Chemistry 10 (2002) 175-183 also discloses pyrrolopyrimidine derivatives.
  • An object of the present invention is to provide an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastral diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alpecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc.
  • diseases in which CRF is considered to be involved such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastral diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alpecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc.
  • the present inventors earnestly investigated pyrrolopyrimidine and pyrrolopyridine derivatives substituted with a cyclic amino group that have a high affinity for CRF receptors, whereby the present invention has been accomplished.
  • the present invention is pyrrolopyrimidine and pyrrolopyridine derivatives substituted with a cyclic amino group explained below.
  • a 3- to 8-membered saturated cyclic amine means aziridine, azetidine, pyrrolidine, piperidine, azepane or azocane.
  • C 1-5 alkylene means a straight or branched chain alkylene of 1 to 5 carbon atoms, such as methylene, ethylene, propylene, trimethylene, tetramethylene, pentamethylene or the like.
  • a 3- to 8-membered saturated cyclic amine bridged with C 1-5 alkylene or C 1-4 alkylene-O—C 1-4 alkylene between any different two carbon atoms of the cyclic amine includes, for example, 8-azabicyclo[3.2.1]oct-8-yl, 9-azabicyclo[3.3.1]non-9-yl, 7-azabicyclo[2.2.1]hept-7-yl, 3-oxa-7-azabicyclo[3.3.1]non-7-yl and 3-oxa-9-azabicyclo[3.3.1]non-9-yl.
  • C 1-5 alkyl means a straight chain or branched chain alkyl group of 1 to 5 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, sec- butyl, pentyl, isopentyl or the like.
  • C 1-5 alkoxy means a straight chain or branched chain alkoxy group of 1 to 5 carbon atoms, such as methoxy, ethoxy, propoxy, isopropyloxy, butoxy, isobutyloxy, pentyloxy, isopentyloxy or the like.
  • C 1-5 alkoxy-C 1-5 alkyl means a substituted C 1-5 alkyl group having the above-mentioned C 1-5 alkoxy group as the substituent, such as methoxymethyl, 2-methoxyethyl, 2-ethoxyethyl or the like.
  • hydroxy-C 1-5 alkyl means a substituted C 1-5 alkyl group having hydroxy group, such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl or the like.
  • cyano-C 1-5 alkyl means a substituted C 1-5 alkyl group having cyano group, such as cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl or the like.
  • C 3-8 cycloalkyl means a cyclic alkyl group of 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or the like.
  • C 3-8 cycloalkyl-C 1-5 alkyl means a substituted C 1-5 alkyl group having the above-mentioned C 3-8 cycloalkyl as the substituent, such as cyclopropylmethyl, cyclopropylethyl, cyclopentylethyl or the like.
  • C 3-8 cycloalkyloxy means a cyclic alkoxy group of 3 to 8 carbon atoms, such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or the like.
  • halogen means fluorine, chlorine, bromine or iodine atom.
  • C 3-8 cycloalkyloxy-C 1-5 alkyl means a substituted C 1-5 alkyl group having the above mentioned C 3-8 cycloalkyloxy as the substituent, such as cyclopropyloxymethyl, 2-cyclopropyloxyethyl or the like.
  • C 1-5 alkylthio means a straight chain or branched chain alkylthio group of 1 to 5 carbon atoms, such as methylthio, ethylthio, propylthio or the like.
  • C 1-24 acyl means a straight chain or branched chain, and saturated or unsaturated acyl group of 1 to 24 carbon atoms, such as acetyl, propionyl, butyryl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, isobutyryl, 2,2-dimethylpropionyl, octadeca-9,12-dienoyl, eicosa-5,8,11,14-tetraenoyl, docosa-4,7,10,13,16,19-hexaenoyl, eicosa-5,8,11,14,17-pentaenoyl or the like.
  • C 1-10 alkoxycarbonyl means a straight chain or branched chain alkoxycarbonyl group of 2 to 11 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, heptyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, isopropoxycarbonyl, t-butoxycarbonyl or the like.
  • aryl means a monocyclic or bicyclic group of 6 to 12 ring carbon atoms having at least one aromatic ring, such as phenyl, naphthyl or the like.
  • aryl-C 1-5 alkyloxycarbonyl means a substituted C 1-5 alkyloxycarbonyl group having the above-mentioned aryl as the substituent, such as benzyloxycarbonyl, phenethyloxycarbonyl or the like.
  • arylcarbonyl means a substituted carbonyl group having the above- mentioned aryl as the substituent, such as benzoyl, naphthalene-1-carbonyl, naphthalene-2-carbonyl or the like.
  • heteroaryl means a monocyclic or bicyclic group of 5 to 12 ring atoms having at least one aromatic ring having in its ring 1 to 4 atoms which may be the same or different and are selected from nitrogen, oxygen and sulfur, such as pyridyl, pyrimidinyl, imidazolyl, quinolyl, indolyl, benzofuranyl, quinoxalinyl, benzo[1,2,5]thiadiazolyl, benzo[1,2,5]oxadiazolyl or the like.
  • heteroarylcarbonyl means a substituted carbonyl group having the above-mentioned heteroaryl as the substituent, such as pyridine-2-carbonyl, pyridine-3-carbonyl, pyridine-4-carbonyl, pyrimidine-2-carbonyl, pyrimidine-4-carbonyl, pyrimidine-5-carbonyl or the like.
  • C 2-5 alkenyl means a straight chain or branched chain alkenyl group of 2 to 5 carbon atoms, such as vinyl, isopropenyl, allyl or the like.
  • C 2-5 alkynyl means a straight chain or branched chain alkynyl group of 2 to 5 carbon atoms, such as ethynyl, prop-1-ynyl, prop-2-ynyl or the like.
  • C 1-5 alkysulfinyl means a straight chain or branched chain alkylsulfinyl group of 1 to 5 carbon atoms, such as methanesulfinyl, ethanesulfinyl or the like.
  • C 1-5 alkysulfonyl means a straight chain or branched chain alkylsulfonyl group of 1 to 5 carbon atoms, such as methanesulfonyl, ethanesulfonyl or the like.
  • hydroxy-C 2-5 alkylamino-C 2-5 alkoxy means a substituted C 2-5 alkoxy group having a hydroxy-C 2-5 alkylamino group as the substituent such as 2-(2-hydroxyethylamino)ethoxy or the like.
  • aryl-C 1-5 alkyl means a substituted C 1-5 alkyl group having the above-mentioned aryl as the substituent, such as benzyl, phenethyl, 3-phenylpropyl, naphthalen-1-ylmethyl, naphthalen-2-ylmethyl or the like.
  • heteroaryl-C 1-5 alkyl means a substituted C 1-5 alkyl group having the above-mentioned heteroaryl as the substituent, such as 1H-indol-3-ylmethyl, 1H- imidazol-4-ylmethyl or the like.
  • hydroxycarbonyl-C 1-5 alkyl means a substituted C 1-5 alkyl group having a hydroxycarbonyl group as the substituent, such as hydroxycarbonylmethyl, 2-hydroxycarbonylethyl, 3-hydroxycarbonylpropyl, 4-hydroxycarbonylbutyl or the like.
  • hydroxyphenyl-C 1-5 alkyl means a substituted C 1-5 alkyl group having a hydroxyphenyl group as the substituent, such as 4-hydroxybenzyl, 3-hydroxybenzyl 2-hydroxybenzyl, 2-(4-hydroxyphenyl)ethyl or the like.
  • amino-C 1-5 alkyl means a substituted C 1-5 alkyl group having a amino group as the substituent, such as aminomethyl, 1-aminoethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl or the like.
  • guanidino-C 1-5 alkyl means a substituted C 1-5 alkyl group having a guanidino group as the substituent, such as guanidinomethyl, 1-guanidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 5-guanidinopentyl or the like.
  • mercapto-C 1-5 alkyl means a substituted C 1-5 alkyl group having a mercapto group as the substituent, such as mercaptomethyl, 1-mercaptoethyl, 2-mercaptoethyl, 3-mercaptopropyl, 4-mercaptobutyl, 5-mercaptopentyl or the like.
  • C 1-5 alkylthio-C 1-5 akyl means a substituted C 1-5 alkyl group having the above-mentioned C 1-5 alkylthio group as the substituent, such as methylthiomethyl, 1-methylthioethyl, 2-methylthioethyl, 3-methylthiopropyl, 4-methylthiobutyl, 5-methylthiopentyl or the like.
  • aminocarbonyl-C 1-5 alkyl means a substituted C 1-5 alkyl group having an aminocarbonyl group as the substituent, such as aminocarbonylmethyl, 2-aminocarbonylethyl, 3-aminocarbonylpropyl, 4-aminocarbonylbutyl or the like.
  • aryl or heteroaryl which aryl or heteroaryl is unsubstituted or substituted with 1 or more substituents, which are the same or different, selected from the group consisting of halogen, C 1-5 alkyl, C 3-8 cycloalkyl, C 2-5 alkenyl, C 2-5 alkynyl, C 1-5 alkoxy, C 1-5 alkylthio, C 1-5 alkylsulfinyl, C 1-5 alkylsulfonyl, cyano, nitro, hydroxy, —CO 2 R 19a , —C( ⁇ O)R 19a , —CONR 11b R 12b , —OC( ⁇ O)R 19a , NR 11b CO 2 R 19a , —S(O) r NR 11b R 12b , hydroxy-C 2-5 alkylamino-C 2-5 alkoxy, trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy
  • the “pharmaceutically acceptable salts” in the present invention include, for example, salts with an inorganic acid such as sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid or the like; salts with an organic acid such as acetic acid, oxalic acid, lactic acid, tartaric acid, fumaric acid, maleic acid, citric acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, camphorsulfonic acid, ethanesulfonic acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, malic acid, malonic acid, mandelic acid, galactaric acid, naphthalene-2-sulfonic acid or the like; salts with one or more metal ions such as lithium ion, sodium ion, potassium ion, calcium ion, magnesium ion, zinc i
  • a compound of the present invention includes any isomers such as diastereomers, enantiomers, geometricisomers and tautomeric forms.
  • a compound represented by formula [I] if the cyclic amino group has one or more chiral carbons and/or if there is an axial chirality between Ar and pyrrolopyrimidine (or pyrrolopyridine) ring, several stereoisomers (diastereomers or enantiomers) can exist.
  • the compound of the present invention includes the individual isomers and the racemic and non-racemic mixtures of the isomers.
  • Y is CR 10
  • More preferable are compounds represented by the formula [III] in which Y is CR 10 ; n is 0; R 1 , R 2 , R 4 and R 5 are hydrogen; R 10 is hydrogen or halogen.
  • Y is CR 10
  • More preferable are compounds represented by the formula [V] in which Y is CR 10 ; m is an integer selected from 1, 2, 3, 4 and 5; n is 0; R 1 , R 2 , R 4 and R 5 are hydrogen; R 10 is hydrogen or halogen.
  • Y is CR 10 ; the cyclic amino group is a 4- to 7-membered saturated cyclic amine; m is an integer selected from 1, 2 and 3; n is 0; R 1 , R 2 and R 5 are hydrogen; R 4 is cyano; R 6 is methyl; R 7 and R 8 are the same or different, and independently are hydrogen or C 1-5 alkyl; R 10 is hydrogen or halogen; Ar is phenyl or pyridyl which phenyl or pyridyl is substituted with two or three substituents, which are the same or different, selected from the group consisting of halogen, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, trifluoromethyl, trifluoromethoxy and —N(R 20 )R 21 (wherein R 20 and R 21 are the same or different, and independently are hydrogen or C 1-3 alkyl), wherein a group represented by (CR
  • Especially preferable compounds of the present invention are: 2- ⁇ 1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl ⁇ -ethanol,
  • the compound represented by the formula [I] can be produced, for example, by the process shown in the following reaction scheme 1-4 [in the following reaction scheme, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , m, n, X, Y and Ar are as defined above; LG is chloro, bromo, iodo, methanesulfonyloxy, benzenesulfonyloxy, 4-toluenesulfonyloxy or trifluoromethanesulfonyloxy group; Z 1 and Z 2 are the same or different, and independently are chloride or bromide; R a and R b are the same or different, and independently are hydrogen, C 1-5 alkyl, C 3-8 cycloalkyl or C 3-8 cycloalkyl-C 1-5 alkyl; and X a is —(CHR 3 ) n —OH, —(CHR 3 ) n
  • Compound (3) a compound of the present invention, can be obtained by reacting Compound (1) with Compound (2) in an inert solvent in the presence or absence of a base.
  • the base includes, for example, amines such as triethylamine, N,N-diisopropylethylamine, pyridine and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide and the like; and Grignard reagents such as methylmagnesium bromide and the like.
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene, xylene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • the compound of the present invention can be converted to a salt in an inert solvent with an inorganic acid such as sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid or the like, with an organic acid such as acetic acid, oxalic acid, lactic acid, tartaric acid, fumaric acid, maleic acid, citric acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, camphorsulfonic acid, ethanesulfonic acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, malic acid, malonic acid, mandelic acid, galactaric acid, naphthalene-2-sulfonic acid or the like, with an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, zinc hydroxide, aluminum hydroxide or
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; esters such as ethyl acetate, ethyl formate and the like; ketones such as acetone, methylethylketone and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dichloromethane; chloroform; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • Step 2 is acetonitrile; dichloromethane;
  • Compound (4) can be converted to Compound (6) by reacting Compound (4) with Compound (5) in an inert solvent in the presence or absence of a base.
  • the base includes, for example, amines such as triethylamine, N,N-diisopropylethylamine, pyridine and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide and the like; and Grignard reagents such as methyl magnesium bromide and the like.
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene, xylene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • Compound (6) can be converted to Compound (7) by reacting Compound (6) with malononitrile in an inert solvent in the presence or absence of a base.
  • the base includes, for example, amines such as triethylamine, N,N-diisopropylethylamine, pyridine and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride, potassium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide, lithium hexamethyldisilazamide, sodium hexamethyldisilazamide, potassium hexamethyldisilazamide and the like; alkyl lithiums such as methyl lithium, n-butyl lithium, sec-butyl lithium
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • hydrocarbons such as benz
  • Compound (7) can be converted to Compound (8) by acylation of amino group in Compound (7) and followed by formation of pyrimidine ring.
  • the acylation and the formation of pyrimidine ring may occur continuously in one pot.
  • the acylation can be achieved by reacting Compound (7) with an acylating reagent in an inert solvent in the presence or absence of a base or an acid.
  • the following formation of pyrimidine ring can be carried out by heating the acylated compound in an inert solvent in the presence or absence of an acid.
  • the acylating reagent includes, for example, halogenated acyls such as acetyl chloride, acetyl bromide, propionyl chloride, propionyl bromide, butyryl chloride, cyclopropanecarbonyl chloride, benzoyl chloride and the like; acid anhydride such as acetic anhydride, propionic anhydride, butyric anhydride, benzoic anhydride and the like.
  • halogenated acyls such as acetyl chloride, acetyl bromide, propionyl chloride, propionyl bromide, butyryl chloride, cyclopropanecarbonyl chloride, benzoyl chloride and the like
  • acid anhydride such as acetic anhydride, propionic anhydride, butyric anhydride, benzoic anhydride and the like.
  • the base includes, for example, amines such as triethylamine, N,N-diisopropylethylamine, pyridine and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride, potassium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide, lithium hexamethyldisilazamide, sodium hexamethyldisilazamide, potassium hexamethyldisilazamide and the like; and Grignard reagents such as methyl magnesium bromide and the like.
  • amines such as triethylamine, N,N-diisopropylethylamine, pyridine and the like
  • inorganic bases such as sodium carbonate,
  • the acid includes, for example, organic acids such as formic acid, acetic acid, trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, trifluoromethanesulfonic acid and the like; inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, polyphosphoric acid, nitric acid or the like.
  • organic acids such as formic acid, acetic acid, trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, trifluoromethanesulfonic acid and the like
  • inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, polyphosphoric acid, nitric acid or the like.
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene, xylene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; acetic acid; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the
  • Compound (8) can be converted to Compound (9) by reacting (8) with a halogenating reagent or a sulfonating reagent in the presence or absence of a base in an inert solvent or without any solvent.
  • the halogenating reagent includes, for example, phosphoryl chloride, phosphoryl bromide, phosphorous pentachloride, phosphorous trichloride, phosphorous pentabromide, phosphorous tribromide, thionyl chloride, thionyl bromide, oxalyl chloride, oxalyl bromide and the like.
  • the sulfonating reagent includes, for example, p-toluenesulfonyl chloride, methanesulfonyl chloride, p-toluenesulfonic anhydride, methansulfonic anhydride, trifluoromethanesulfonic anhydride, N-phenylbis(trifluoromethanesulfonimide) and the like.
  • the base includes, for example, amines such as triethylamine, N,N-diisopropylethylamine, pyridine, N,N-dimethylaniline, N,N-diethylaniline and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide and the like; and Grignard reagents such as methyl magnesium bromide and the like.
  • amines such as triethylamine, N,N-diisopropylethylamine, pyridine, N,N-dimethylaniline, N,N-diethylaniline and the like
  • inorganic bases such as sodium carbonate, potassium carbon
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; dichloromethane; chloroform; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the
  • Compound (9) can be converted to Compound (11) by reacting Compound (9) with Compound (10) in the same method as step 1.
  • Compound (11) can be converted to Compound (12) by reduction of Compound (11) with a conventional reducing agent in an inert solvent. Or if necessary, treatment with an acid in the presence or absence of inert solvent after the reduction can provide Compound (12).
  • X a is —CO 2 —(C 1-5 alkyl)
  • the ester group can be converted to a hydroxymethyl group at the same time.
  • the reducing agent includes, for example, lithium borohydride, sodium borohydride, calcium borohydride, lithium triethylborohydride, lithium tri-sec-butylborohydride, potassium tri-sec-butylborohydride, zinc borohydride, borane, lithium trimethoxyborohydride, lithium triacetoxyborohydride, tetramethylammonium borohydride, lithium aluminum hydride, sodium aluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride, diisobutylaluminum hydride, trichlorosilane and the like.
  • the reduction can be also carried out by hydrogenation using a catalyst including palladium, platinum dioxide, Raney nickel or the like.
  • the acid includes, for example, organic acids such as acetic acid, trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid and the like; inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, polyphosphoric acid, nitric acid or the like.
  • organic acids such as acetic acid, trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid and the like
  • inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, polyphosphoric acid, nitric acid or the like.
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • hydrocarbons such as benz
  • Compoumd (7) can be converted to Compound (13) by reacting Compound (7) with ketones such as acetone and the like; vinyl ethers such as isopropenyl methyl ether and the like in an inert solvent in the presence or absence of an acid, and the following conversion from Compound (13) to Compound (14) can be carried out in the presence of base in an inert solvent.
  • the acid includes, for example, organic acids such as acetic acid, trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid and the like.
  • the base includes, for example, amines such as triethylamine, N,N-diisopropylethylamine, pyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide, lithium hexamethyldisilazamide, sodium hexamethyldisilazamide, potassium hexamethyldisilazamide and the like; alkyl lithiums such as n-butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium and the like; and Grignard reagents such as methyl magnesium bro
  • the inert solvent includes, for example, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; and mixtures of solvents selected from these inert solvents.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • hydrocarbons such as benzene, toluene and the like
  • amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like
  • Compound (14) can be converted to Compound (15) in the same manner as step 7.
  • Compound (15) can be converted into Compound (16) via the corresponding diazonium compound.
  • the conversion to the diazonium compound can be carried out using, for example, sodium nitrite, potassium nitrite, butylnitrite, tert-butylnitrite, iso-butylnitrite or the like in the presence or absence of an acid in an inert solvent.
  • the acid includes, for example, inorganic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, nitric acid or the like.
  • the inert solvent includes, for example, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • hydrocarbons such as benzene, toluene and the like
  • amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like
  • Compound (16) can be converted to Compound (17) in the same manner as step 5.
  • Compound (17) can be obtained from Compound (15) directly by formation of the diazonium compound in the presence of one or more metal salts in an inert solvent.
  • the formation of the diazonium compound can be carried out in the same manner as step 10.
  • the metal salts include, for example, potassium iodide, potassium bromide, sodium iodide, sodium bromide, sodium chloride, copper (I) chloride, copper (II) chloride, copper (I) bromide, copper (II) bromide, copper (I) iodide and the like.
  • the inert solvent includes, for example, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; water; and mixtures of solvents selected from these inert solvents.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like
  • hydrocarbons such as benzene, toluene and the like
  • amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like
  • Compound (17) can be converted to Compound (18) in the same manner as step 1.
  • Compound (20) can be converted to Compound (21) by a coupling of Compound (20) with the corresponding carboxylic acid using a conventional coupling reagent in the presence or absence of an additive or a base in an inert solvent or a coupling of Compound (20) with the corresponding acyl halide in the presence or absence of a base in an inert solvent.
  • R 9 has protective groups of an amino group, a hydroxy group, a mercapto goup, a carboxy group, a guanidine group or a phosphoric acid group, those protective groups can be removed by conventional methods for deprotection (ref. Theodora W Greene and Peter G. M.
  • the coupling reagent includes, for example, N,N′-dicyclohexylcarbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), 1,1′-carbonyldiimidazole (CDI), diphenylphosphorylazide (DPPA), diethyl cyanophosphate and the like.
  • the additive includes, for example, 1-hydroxybenzotriazole (HOBt), N-hydroxysuccinimide, 4-dimethylaminopyridine and the like.
  • the base includes amines such as triethylamine, N,N-diisopropylethylamine, pyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide, barium hydroxide, sodium hydride and the like; metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal amides such as sodium amide, lithium diisopropylamide, lithium hexamethyldisilazamide, sodium hexamethyldisilazamide, potassium hexamethyldisilazamide and the like; alkyl lithiums such as n-butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium and the like; and Grignard reagents such as methyl magnesium bromide and the
  • the inert solvent includes, for example, alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene and the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide; pyridine; chloroform; dichloromethane; water; and mixtures of solvents selected from these inert solvents.
  • alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycol and the like
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the
  • the compound of the present invention is useful as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved.
  • the compound of the present invention can be formulated into tablets, pills, capsules, granules, powders, solutions, emulsions, suspensions, injections and the like by a conventional preparation technique by adding conventional fillers, binders, disintegrators, pH-adjusting agents, solvents, etc.
  • the compound of the present invention can be administered to an adult patient in a dose of 0.1 to 500 mg per day in one portion or several portions orally or parenterally.
  • the dose can be properly increased or decreased depending on the kind of a disease and the age, body weight and symptom of a patient.
  • Table 1 and Table 2 list the compound obtained in Example 1 and compounds obtained by the similar procedure as in Example 1.
  • the low polar diastereoisomer was optically resolved by high performance liquid chromatography to give each enantiomer.
  • the high polar diastereoisomer was also optically resolved by high performance liquid chromatography to give each enantiomer.
  • CHIRAL PAK AD DICEL CHEMICAL INDUSTRIES, LTD
  • flow rate 5.0 mL/min.
  • Table 1 lists the compounds obtained in Example 2.
  • Lithium diisopropylamide in tetrahydrofuran solution (generated from 2.64M n-butyl lithium in hexane (127 mL), diisopropylamine (40.5 g) and tetrahydrofuran (300 mL)) was added dropwise over 30 minutes, and stirred at room temperature for 1 hour.
  • a saturated NH 4 Cl aqueous solution was added and separated.
  • the aqueous layer was extracted with CHCl 3 .
  • the organic layer was washed with water, dried over anhydrous sodium sulfate and filtered.
  • Table 3 lists the compound obtained in Example 5 and compounds obtained by the similar procedure as in Example 5.
  • Table 3 lists the compound obtained in Example 6 and compounds obtained by the similar procedure as in Example 6.
  • Table 3 lists the compound obtained in Example 7 and compounds obtained by the similar procedure as in Example 7.
  • R 6 R 7 R 8 Ar melting point (° C.) (solvent for crystallization) 1-001 1 CH 3 CH 3 CH 3 142-144 (hexane) 1-002 1 CH 3 CH 3 H 124-126 (hexane) 1-003 1 CH 3 CH 3 CH 3 amorphous 1-004 1 CH 3 CH 3 CH 3 146-148* 2 (EtOAc/EtOH) 1-005 1 CH 3 CH 3 H amorphous 1-006 1 CH 3 CH 3 CH 3 144-146 (hexane) 1-007 1 CH 3 CH 3 H 121-122 (hexane) 1-008 1 CH 3 CH 3 H 141-143* 2 (EtOAc/EtOH) 1-009 1 CH 3 CH 3 CH 3 134-136* 2 (EtOAc/EtOH) 1-010 1 CH 3 CH 3 H 157-159* 2 (EtOAc/EtOH) 1-011 1 CH 3 CH 3 CH 3 amorphous 1-012 1 CH 3 CH 3 H a
  • Monkey amygdala membranes were used as a receptor preparation.
  • 125 I-CRF was used as 125 I-labeled ligand.
  • Binding reaction using the 125 I -labeled ligand was carried out by the following method described in The Journal of Neuroscience, 7, 88 (1987).
  • Monkey amygdala was homogenized in 50 mM Tris-HCl buffer (pH 7.0) containing 10 mM MgCl 2 , 2 mM EDTA and centrifuged at 48,000 ⁇ g for 20 min, and the precipitate was washed once with Tris-HCl buffer. The washed precipitate was suspended in 50 mM Tris-HCl buffer (pH 7.0) containing 10 mM MgCl 2 , 2 mM EDTA, 0.1% bovine serum albumin and 100 kallikrein units/ml aprotinin, to obtain a membrane preparation.
  • the membrane preparation (0.3 mg protein/ml), 125 I-CRF (0.2 nM) and a test drug were reacted at 25° C. for 2 hours.
  • the reaction mixture was filtered by suction through a glass filter (GF/C) treated with 0.3% polyethylene imine, and the glass filter was washed three times with phosphate-buffered saline containing 0.01% Triton X-100. After the washing, the radioactivity of the filter paper was measured in a gamma counter.
  • the amount of 125 I-CRF bound when the reaction was carried out in the presence of 1 ⁇ M CRF was taken as the degree of nonspecific binding of 125 I -CRF, and the difference between the total degree of 125 I -CRF binding and the degree of nonspecific 125 I -CRF binding was taken as the degree of specific 125 I -CRF binding.
  • An inhibition curve was obtained by reacting a definite concentration (0.2 nM) of 125 I-CRF with various concentrations of each test drug under the conditions described above. A concentration of the test drug at which binding of 125 I -CRF is inhibited by 50% (IC 50 ) was determined from the inhibition curve.
  • compounds having a high affinity for CRF receptors have been provided. These compounds are effective against diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastric diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc.
  • diseases in which CRF is considered to be involved such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastric diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Dermatology (AREA)
  • Addiction (AREA)
  • Psychology (AREA)
  • Rheumatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Saccharide Compounds (AREA)
US10/504,981 2002-12-26 2003-12-24 Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group Abandoned US20050209253A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US12/106,873 US7932259B2 (en) 2002-12-26 2008-04-21 Pyrrolo[2,3-d]pyrimidine derivatives substituted with a cyclic amino group
US12/951,556 US8455511B2 (en) 2002-12-26 2010-11-22 Pyrrolopyridine derivatives substituted with cyclic amino group

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2002383667 2002-12-26
JP2002-383667 2002-12-26
PCT/JP2003/016598 WO2004058767A1 (en) 2002-12-26 2003-12-24 Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/106,873 Continuation US7932259B2 (en) 2002-12-26 2008-04-21 Pyrrolo[2,3-d]pyrimidine derivatives substituted with a cyclic amino group

Publications (1)

Publication Number Publication Date
US20050209253A1 true US20050209253A1 (en) 2005-09-22

Family

ID=32677471

Family Applications (3)

Application Number Title Priority Date Filing Date
US10/504,981 Abandoned US20050209253A1 (en) 2002-12-26 2003-12-24 Pyrrolopyrimidine and pyrrolopyridine derivatives substituted with cyclic amino group
US12/106,873 Expired - Fee Related US7932259B2 (en) 2002-12-26 2008-04-21 Pyrrolo[2,3-d]pyrimidine derivatives substituted with a cyclic amino group
US12/951,556 Expired - Fee Related US8455511B2 (en) 2002-12-26 2010-11-22 Pyrrolopyridine derivatives substituted with cyclic amino group

Family Applications After (2)

Application Number Title Priority Date Filing Date
US12/106,873 Expired - Fee Related US7932259B2 (en) 2002-12-26 2008-04-21 Pyrrolo[2,3-d]pyrimidine derivatives substituted with a cyclic amino group
US12/951,556 Expired - Fee Related US8455511B2 (en) 2002-12-26 2010-11-22 Pyrrolopyridine derivatives substituted with cyclic amino group

Country Status (23)

Country Link
US (3) US20050209253A1 (no)
EP (2) EP1787992B1 (no)
JP (1) JP4181126B2 (no)
KR (2) KR100688395B1 (no)
CN (1) CN1692115A (no)
AR (1) AR042667A1 (no)
AT (2) ATE430151T1 (no)
AU (1) AU2003292550B8 (no)
BR (1) BR0307587A (no)
CA (1) CA2485556C (no)
CL (1) CL2003002762A1 (no)
DE (2) DE60319951T2 (no)
EA (1) EA200401060A1 (no)
ES (2) ES2325596T3 (no)
HR (1) HRP20040724A2 (no)
MX (1) MXPA04008081A (no)
MY (1) MY141200A (no)
NO (1) NO20043508L (no)
PL (1) PL371810A1 (no)
TW (1) TWI270549B (no)
UA (1) UA77265C2 (no)
WO (1) WO2004058767A1 (no)
ZA (1) ZA200405982B (no)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070254898A1 (en) * 2004-01-06 2007-11-01 Atsuro Nakazato Thienopyrimidine and Thienopyridine Derivatives Substituted with Cyclic Amino Group
US20070270588A1 (en) * 2004-03-05 2007-11-22 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine Derivatives
US20070293670A1 (en) * 2004-06-25 2007-12-20 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and Pyrrolopyridine Derivatives Substituted with Tetrahydropyridine as Crf Antagonists
US7365078B2 (en) 2004-01-06 2008-04-29 Taisho Pharmaceutical Co., Ltd. Triaza-cyclopenta[cd]indene derivatives
US20080280928A1 (en) * 2004-06-25 2008-11-13 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and Pyrrolopyridine Derivatives Substituted with a Cyclic Amino Group As Crf Antagonists
US20110137031A1 (en) * 2004-01-06 2011-06-09 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and pyrrolotriazine derivatives
WO2011069038A2 (en) 2009-12-03 2011-06-09 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
WO2014151206A1 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders
EP2810951A2 (en) 2008-06-04 2014-12-10 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP2998314A1 (en) 2007-06-04 2016-03-23 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP3241839A1 (en) 2008-07-16 2017-11-08 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004042607A1 (de) * 2004-09-03 2006-03-09 Bayer Healthcare Ag Substituierte Phenylaminothiazole und ihre Verwendung
DE102006042143A1 (de) * 2006-09-08 2008-03-27 Bayer Healthcare Aktiengesellschaft Neue substituierte Bipyridin-Derivate und ihre Verwendung
DE102006056739A1 (de) * 2006-12-01 2008-06-05 Bayer Healthcare Ag Substituierte 4-Amino-3,5-dicyano-2-thiopyridine und ihre Verwendung
DE102006056740A1 (de) * 2006-12-01 2008-06-05 Bayer Healthcare Ag Cyclisch substituierte 3,5-Dicyano-2-thiopyridine und ihre Verwendung
DE102007035367A1 (de) 2007-07-27 2009-01-29 Bayer Healthcare Ag Substituierte Aryloxazole und ihre Verwendung
DE102007036076A1 (de) 2007-08-01 2009-02-05 Bayer Healthcare Aktiengesellschaft Dipeptoid-Produgs und ihre Verwendung
DE102007061764A1 (de) * 2007-12-20 2009-06-25 Bayer Healthcare Ag Anellierte Cyanopyridine und ihre Verwendung
DE102007061763A1 (de) 2007-12-20 2009-06-25 Bayer Healthcare Ag Substituierte azabicyclische Verbindungen und ihre Verwendung
DE102008013587A1 (de) * 2008-03-11 2009-09-17 Bayer Schering Pharma Aktiengesellschaft Heteroaryl-substituierte Dicyanopyridine und ihre Verwendung
CL2009001152A1 (es) 2008-05-13 2009-10-16 Array Biopharma Inc Compuestos derivados de n-(4-(cicloalquilo nitrogenado-1-il)-1h-pirrolo[2,3-b]piridin-3-il)amida, inhibidores de cinasa; proceso de preparacion; composicion farmaceutica; y su uso para el tratamiento de una enfermedad proliferativa.
EP2297104B1 (de) * 2008-05-29 2013-08-07 Bayer Intellectual Property GmbH 2-alkoxy-substituierte dicyanopyridine und ihre verwendung
DE102008062567A1 (de) 2008-12-16 2010-06-17 Bayer Schering Pharma Aktiengesellschaft Dipeptoid-Prodrugs und ihre Verwendung
DE102009006602A1 (de) * 2009-01-29 2010-08-05 Bayer Schering Pharma Aktiengesellschaft Alkylamino-substituierte Dicyanopyridine und deren Aminosäureester-Prodrugs
DE102010030688A1 (de) 2010-06-30 2012-01-05 Bayer Schering Pharma Aktiengesellschaft Substituierte Dicyanopyridine und ihre Verwendung
US20120058983A1 (en) 2010-09-02 2012-03-08 Bayer Pharma Aktiengesellschaft Adenosine A1 agonists for the treatment of glaucoma and ocular hypertension
KR20140059164A (ko) 2011-03-15 2014-05-15 트라이우스 테라퓨틱스, 아이엔씨. 트라이사이클릭 자이라제 억제제
BR112015019412A8 (pt) 2013-04-11 2019-11-12 Hoffmann La Roche inibidores de bace1, seus usos, e composição farmacêutica
SG11201509029PA (en) * 2013-05-02 2015-12-30 Hoffmann La Roche Pyrrolo[2,3-d]pyrimidine derivatives as cb2 receptor agonists
CN114829362A (zh) * 2019-12-10 2022-07-29 成都倍特药业股份有限公司 一种可用作shp2抑制剂的含氮杂原子的六元并五元芳环衍生物
CN114646700B (zh) * 2022-03-01 2023-10-20 浙江国邦药业有限公司 一种(s)-吡咯烷-2-甲腈盐酸盐的检测方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070060602A1 (en) * 2004-01-06 2007-03-15 Atsuro Nakazato Triaza-cyclopenta [cd] indene derivatives

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6765008B1 (en) 1992-12-17 2004-07-20 Pfizer Inc Pyrrolopyrimidines as CRF antagonists
US5646152A (en) 1994-06-15 1997-07-08 Pfizer Inc. Methods of administering CRF antagonists
PL181895B1 (pl) 1994-06-16 2001-10-31 Pfizer Nowe pirazolo-i pirolopirydyny _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ PL PL PL PL
ES2203937T3 (es) * 1997-03-26 2004-04-16 Taisho Pharmaceutical Co., Ltd Derivados de 4-tetrahidropiridilpirimidina.
AU756702B2 (en) * 1999-03-11 2003-01-23 Taisho Pharmaceutical Co., Ltd. Carbamoyl tetrahydropyridine derivatives
AR028782A1 (es) * 2000-07-05 2003-05-21 Taisho Pharmaceutical Co Ltd Derivados heterociclicos tetrahidropiridino o piperidino

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070060602A1 (en) * 2004-01-06 2007-03-15 Atsuro Nakazato Triaza-cyclopenta [cd] indene derivatives

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110137031A1 (en) * 2004-01-06 2011-06-09 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and pyrrolotriazine derivatives
US8106194B2 (en) 2004-01-06 2012-01-31 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and pyrrolotriazine derivatives
US7365078B2 (en) 2004-01-06 2008-04-29 Taisho Pharmaceutical Co., Ltd. Triaza-cyclopenta[cd]indene derivatives
US20070254898A1 (en) * 2004-01-06 2007-11-01 Atsuro Nakazato Thienopyrimidine and Thienopyridine Derivatives Substituted with Cyclic Amino Group
US20090111835A1 (en) * 2004-01-06 2009-04-30 Taisho Pharmaceutical Co., Ltd. Thienopyrimidine and thienopyridine derivatives substituted with cyclic amino group
US7557111B2 (en) 2004-01-06 2009-07-07 Taisho Pharmaceutical Co., Ltd. Substituted thieno[3,2-d]pyrimidines as CRF receptor antagonists
US20070270588A1 (en) * 2004-03-05 2007-11-22 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine Derivatives
US20080280928A1 (en) * 2004-06-25 2008-11-13 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and Pyrrolopyridine Derivatives Substituted with a Cyclic Amino Group As Crf Antagonists
US7951811B2 (en) 2004-06-25 2011-05-31 Taisho Pharmaceutical Co., Ltd. Pyrrolo[2,3-D]pyrimidine derivatives substituted with a cyclic amino group
US20070293670A1 (en) * 2004-06-25 2007-12-20 Taisho Pharmaceutical Co., Ltd. Pyrrolopyrimidine and Pyrrolopyridine Derivatives Substituted with Tetrahydropyridine as Crf Antagonists
EP2998314A1 (en) 2007-06-04 2016-03-23 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP2810951A2 (en) 2008-06-04 2014-12-10 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP3241839A1 (en) 2008-07-16 2017-11-08 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
WO2011069038A2 (en) 2009-12-03 2011-06-09 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
EP2923706A1 (en) 2009-12-03 2015-09-30 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia
WO2014151206A1 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders

Also Published As

Publication number Publication date
AU2003292550B8 (en) 2006-11-09
UA77265C2 (en) 2006-11-15
US8455511B2 (en) 2013-06-04
EP1787992B1 (en) 2009-04-29
AU2003292550B2 (en) 2006-09-21
DE60319951D1 (de) 2008-05-08
KR20060128063A (ko) 2006-12-13
ATE390426T1 (de) 2008-04-15
KR100688395B1 (ko) 2007-03-02
EA200401060A1 (ru) 2005-02-24
ES2325596T3 (es) 2009-09-09
JP4181126B2 (ja) 2008-11-12
TWI270549B (en) 2007-01-11
US7932259B2 (en) 2011-04-26
DE60319951T2 (de) 2009-05-20
ATE430151T1 (de) 2009-05-15
CA2485556C (en) 2006-01-10
JP2005539090A (ja) 2005-12-22
EP1467997A1 (en) 2004-10-20
EP1787992A1 (en) 2007-05-23
ZA200405982B (en) 2005-09-02
CA2485556A1 (en) 2004-07-15
MXPA04008081A (es) 2004-11-26
AU2003292550A1 (en) 2004-07-22
CL2003002762A1 (es) 2005-04-08
US20110130364A1 (en) 2011-06-02
HRP20040724A2 (en) 2004-10-31
KR100808756B1 (ko) 2008-02-29
US20080287397A1 (en) 2008-11-20
PL371810A1 (en) 2005-06-27
CN1692115A (zh) 2005-11-02
WO2004058767A1 (en) 2004-07-15
AR042667A1 (es) 2005-06-29
TW200505921A (en) 2005-02-16
BR0307587A (pt) 2005-02-01
EP1467997B8 (en) 2008-08-27
EP1467997B1 (en) 2008-03-26
MY141200A (en) 2010-03-31
NO20043508L (no) 2004-10-07
ES2302949T3 (es) 2008-08-01
KR20040111369A (ko) 2004-12-31
DE60327477D1 (de) 2009-06-10

Similar Documents

Publication Publication Date Title
US7932259B2 (en) Pyrrolo[2,3-d]pyrimidine derivatives substituted with a cyclic amino group
US7951811B2 (en) Pyrrolo[2,3-D]pyrimidine derivatives substituted with a cyclic amino group
AU2017315343A1 (en) Amino-pyrrolopyrimidinone compounds and methods of use thereof
US20070293670A1 (en) Pyrrolopyrimidine and Pyrrolopyridine Derivatives Substituted with Tetrahydropyridine as Crf Antagonists
AU2007215221A1 (en) Dihydrodiazepines useful as inhibitors of protein kinases
EP3166608A1 (en) Aminopyridazinone compounds as protein kinase inhibitors
US20090111835A1 (en) Thienopyrimidine and thienopyridine derivatives substituted with cyclic amino group
JP2006036762A (ja) 環状アミノ基で置換されているピロロピリミジン及びピロロピリジン誘導体

Legal Events

Date Code Title Description
AS Assignment

Owner name: TAISHO PHARMACEUTICAL CO., LTD., JAPAN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NAKAZATO, ATSURO;OKUBO, TAKATOSHI;NOZAWA, DAI;AND OTHERS;REEL/FRAME:016572/0206;SIGNING DATES FROM 20040712 TO 20040823

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION