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WO2003035653A1 - Compose pyridothienopyrimidine et son sel - Google Patents

Compose pyridothienopyrimidine et son sel Download PDF

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Publication number
WO2003035653A1
WO2003035653A1 PCT/JP2002/011028 JP0211028W WO03035653A1 WO 2003035653 A1 WO2003035653 A1 WO 2003035653A1 JP 0211028 W JP0211028 W JP 0211028W WO 03035653 A1 WO03035653 A1 WO 03035653A1
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WO
WIPO (PCT)
Prior art keywords
group
chloro
benzylamino
methoxy
pyrimidine
Prior art date
Application number
PCT/JP2002/011028
Other languages
English (en)
Japanese (ja)
Inventor
Hirokazu Yamada
Seiichi Uchida
Nobuhiro Umeda
Mitsumasa Takata
Seiichi Ikeyama
Yasuyuki Shiinoki
Original Assignee
Nippon Soda 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 Nippon Soda Co.,Ltd. filed Critical Nippon Soda Co.,Ltd.
Priority to JP2003538168A priority Critical patent/JPWO2003035653A1/ja
Publication of WO2003035653A1 publication Critical patent/WO2003035653A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to pyridothienopyrimidine compounds and salts thereof useful as cGMP-specific phosphodiesterase (cGMP-PDE) inhibitors, and methods for producing them.
  • Background technology cGMP-specific phosphodiesterase (cGMP-PDE) inhibitors, and methods for producing them.
  • c GMP is a substance that plays an important role as a second messenger in the signal transduction pathway in the living body, and its degrading enzyme, c GMP-PDE inhibitor, increases the intracellular c GMP concentration.
  • c GMP-PDE inhibitor increases the intracellular c GMP concentration.
  • X is a cycloalkyl group, a phenyl group or a heterocyclic group which may have a substituent.
  • X represents alkylene, cycloalkyl, or the like, substituted with a carboxylic acid, a carboxylic acid amide, or the like.
  • WO 00/59912 also discloses pyridothienopyrimidine compounds similar to the compounds of the present invention. Are described, but the compound of the present invention is not described!
  • the present invention provides novel thienopyridine compounds that are useful as pharmaceuticals, particularly as cGMP-PDE inhibitors.
  • the present invention provides:
  • A represents a pyridyl group which may be substituted with a hydroxyl group or a halogen atom, or a pyrazolyl group;
  • B is amidino group, di C - 6 alkyl force Rubamoiru group, di-C 6 alkylsulfamoyl group, or a group of the formula: - represents a Y- group represented by G.
  • B is, amidino group, dimethylcarbamoyl group, dimethylsulfamoyl group, one C OGx, -YG 2 or is an Y- G 3, compound and pharmaceutically acceptable salts thereof.
  • G 2 represents any of the groups shown below,
  • R 2 represents a hydrogen atom, a methyl, a formyl group, an acetyl group or a tert-butoxycarbonyl group.
  • G 3 represents a pyridyl group optionally substituted with a hydroxyl group or a halogen atom, or a pyrazolyl group optionally mono- or di-substituted with a methyl group.
  • A represents a pyridyl group or a pyrazolyl group which may be substituted with a hydroxyl group or a halogen atom, and more specifically, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-chloro-5- Pyridyl, 2-hydroxy-5-pyridyl, 3-birazolyl and the like.
  • B is an amidino group; a di-C i-6 alkyl sulfamoyl group such as dimethylcarbamoyl and getylcarbamoyl; a diCi-6 alkylsulfamoyl group such as dimethylsulfamoyl and getylsulfamoyl; formula: —Y — G (where Y represents a carbonyl group or a sulfonyl group, and G is a 5- or 6-membered saturated group containing 13 nitrogen, oxygen or sulfur atoms, which may be substituted with R. Alternatively, it represents an unsaturated heterocyclic group.
  • heterocyclic group examples include pyridyl, pyrazolyl, pyrrolyl, piberidinyl, piperazinyl, pyrrolidinyl, morpholino, tetrahydrofuranyl, tetrahydrothenyl, tetrahydrothiaviranyl, tetrahydroviranyl, and the like.
  • Halogen atoms such as black and bromo; hydroxyyl groups; oxo; methyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl and t-butyl groups _ 4 alkyl group; formyl group; Asechiru group, C 4 alkylcarbonyl group or main butoxycarbonyl group such as propionyl group, ethoxycarbonyl group, optionally substituted with C i _ 4 alkoxycarbonyl group such as a tert- butoxycarbonyl group Is also good.
  • hetero ring When the hetero ring has two or more substituents, they may be the same or different.
  • Examples of the pharmaceutically acceptable salts include salts of compounds represented by the general formula (1) with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid; acetic acid, propionic acid, lactic acid, succinic acid, tartaric acid; Queen Examples include salts of organic acids such as acids, benzoic acid, salicylic acid, nicotinic acid, and heptagluconic acid.
  • inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid
  • acetic acid, propionic acid lactic acid, succinic acid, tartaric acid
  • Queen Examples include salts of organic acids such as acids, benzoic acid, salicylic acid, nicotinic acid, and heptagluconic acid.
  • the starting compound and the compound (1) of the present invention have optical isomers, and not only the racemic form but also the optically active form are included in the compound of the present invention.
  • the compound of the present invention has a c-GMP-specific phosphodiesterase inhibitory action.
  • the following compounds show excellent PDE selectivity and antianginal action and are promising as pharmaceuticals. That is, a compound in which B is an amidino group, a dimethylcarbamoyl group, a dimethylsulfamoyl group, one COG ⁇ —Y—G 2 or one Y—G 3 .
  • R 3 is a hydrogen atom, a methyl group, a formyl group, were or Asechiru group Represents a tert-butoxycarbonyl group.
  • G 2 represents any of the groups shown below.
  • R 2 represents a hydrogen atom, a methyl, a formyl group, an acetyl group or a tert-butoxycarbonyl group.
  • G 3 represents a pyridyl group optionally substituted with a hydroxyl group or a halogen atom, or a pyrazolyl group optionally mono- or di-substituted with a methyl group.
  • condensing agent examples include 1,3-dicyclohexylcarpoimide, 11- (3-dimethylaminopropyl) -13-ethylcarpoimide, and 2-ethoxy-11-ethoxycarbonyl. 1,2-dihydroquinoline and the like can be used.
  • Compound (lb) can also be produced by condensing compound (2) with compound G "—Y—C1 by a conventional method.
  • the condensation reaction is not particularly limited as long as it is a commonly performed method, but the reaction can proceed more quickly by coexisting a base.
  • a base inorganic bases such as sodium hydrogen carbonate and potassium carbonate, and amines such as triethylamine and pyridine can be used.
  • the desired product after completion of the reaction, the desired product can be obtained by performing ordinary post-treatment.
  • PDE 5 c GMP-specific phosphodiesterase
  • PDE 5 was obtained from human platelets according to the method of Thampson et al. (Thompson WJ, eta ⁇ ., Advancesin Cyclic Nucleotide Research 10, 69-92, 1979). — Cellulose column chromatography (Whatman, DE-52, 3.2 x 13 cm), 70-: LOO OmM Sodium acetate was separated and purified by concentration gradient elution.
  • Photoreceptorc GMP-specific phosphodiesterase (hereinafter PDE 6) was prepared from rod outer segments of the retina. The PDE activity was measured by partially modifying the method of Thamps0n et al.
  • Control drug s i 1 de n a f i 1 Pharmacological test example 2 Antianginal effect
  • a certain metacholine (A-2251, Sigma) was used for coronary artery administration.
  • a blood pressure measurement force neuron was inserted through the right femoral artery and placed, and the other end was connected to a pressure transducer.
  • a forcenula PE-50, Clay Adams
  • saline was placed in the right femoral vein for administration of the test drug.
  • a second electrocardiogram was derived with a bioelectric amplifier through electrodes attached to the limbs, and the heart rate was measured from the R wave.
  • the ST change of the electrocardiogram was recorded on a thermal recorder at a high speed of 5 Omm / mV with high sensitivity (S OmmZ seconds) or recorded on a data recording and analysis system (PowerLab, Bioresearch Center) and analyzed.
  • the electrocardiogram, heart rate and blood pressure waveform were drawn on a thermographic recorder via a polygraph (Nihon Kohden).
  • methacholine 2-6 g is administered several times, The force neuron was fixed at the position where the ST elevation of the fixed ECG was obtained. Approximately 10 minutes before administration of the test substance (100 zg / kg) and 2, 10, and 30 minutes after administration, methacholine was injected into the coronary artery and compared with the electrocardiogram before administration of methacholine. The difference between the S-wave magnitude from the baseline immediately before the administration of methacholine and the S-wave magnitude at the time when the increase of the S-wave after the administration of methacholine was the maximum was defined as the increase in the S-wave. Small ST gain (approximately when ST gain is less than 0.2 mV) Individuals were not subjected to the experiment. The evaluation of the antianginal effect was the change rate of ST increase calculated by the following formula. Table 4 shows the results.
  • test substance was intravenously administered at 100 g / kg.
  • the compound of the present invention has a strong PDE 5 inhibitory activity and a high PDE 5 selectivity c GMP-specific PDE (PDE 5) inhibitory action, an antianginal action, such as hypertension, heart failure, Prevention of myocardial infarction, angina, arteriosclerosis, restenosis after PTCA, cardiac edema, pulmonary hypertension, renal failure, renal edema, hepatic edema, asthma, bronchitis, dementia, immunodeficiency, glaucoma or impotence Or useful for treatment.
  • PDE 5 PDE 5 inhibitory activity
  • PDE 5 selectivity c GMP-specific PDE (PDE 5) inhibitory action an antianginal action, such as hypertension, heart failure, Prevention of myocardial infarction, angina, arteriosclerosis, restenosis after PTCA, cardiac edema, pulmonary hypertension, renal failure, renal edema, hepatic edema, asthma, bronchitis, dementia

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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Psychiatry (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

L'invention concerne un composé thiénopyrimidine de formule (1), utile en tant que médicament, notamment comme inhibiteur de cGMP-PDE : (1), dans laquelle A représente pyridyle éventuellement substitué ou pyrazolyle éventuellement substitué, B signifie amidino, carbamoyle di(C1-6 alkyle), sulfamoyle di(C1-6 alkyle) ou un groupe de formule Y G (où Y représente carbonyle ou sulfonyle et G signifie un groupe hétérocyclique (in)saturé, à 5 ou 6 chaînons, éventuellement substitué, ce groupe contenant un à trois atomes d'azote, d'oxygène ou de soufre).
PCT/JP2002/011028 2001-10-26 2002-10-24 Compose pyridothienopyrimidine et son sel WO2003035653A1 (fr)

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JP2003538168A JPWO2003035653A1 (ja) 2001-10-26 2002-10-24 ピリドチエノピリミジン化合物およびその塩

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JP2001/329605 2001-10-26
JP2001329605 2001-10-26

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005047292A1 (fr) * 2003-11-04 2005-05-26 Merck Patent Gmbh Utilisation de thienopyrimidines
JP2006525347A (ja) * 2003-04-29 2006-11-09 オシエント ファーマシューティカルズ 抗生テトラヒドロ−β−カルボリン誘導体
US20100298297A1 (en) * 2006-03-20 2010-11-25 Bayer Healthcare Ag Tetrahydropyridothienopyrimidine Compounds and Methods of Use Thereof
US8524722B2 (en) 2007-09-14 2013-09-03 Bayer Intellectual Property Gmbh Substituted tricyclic compounds and methods of use thereof
US10588894B2 (en) 2017-06-21 2020-03-17 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US10870657B2 (en) 2015-12-22 2020-12-22 SHY Therapeutics LLC Compounds for the treatment of cancer and inflammatory disease
US12391705B2 (en) 2018-12-19 2025-08-19 Shy Therapeutics, Llc Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998006722A1 (fr) * 1996-08-12 1998-02-19 Merck Patent Gmbh Thienopyrimidines
WO1998017668A1 (fr) * 1996-10-24 1998-04-30 Merck Patent Gmbh Thienopyrimidines a effet inhibiteur de la phosphodiesterase v
WO1999028325A1 (fr) * 1997-11-28 1999-06-10 Merck Patent Gmbh Thienopyrimidines
WO1999055708A1 (fr) * 1998-04-29 1999-11-04 Merck Patent Gmbh Thienopyrimidines condensees a effet inhibiteur de la phosphodiesterase v
WO2000059912A1 (fr) * 1999-03-30 2000-10-12 Nippon Soda Co., Ltd. Composes de thienopyrimidine et leurs sels, et procede de preparation desdits composes et sels
WO2000078767A1 (fr) * 1999-06-19 2000-12-28 Merck Patent Gmbh Thienopyrimidines utilisees comme inhibiteurs de phosphodiesterase
WO2001021620A2 (fr) * 1999-09-17 2001-03-29 Merck Patent Gmbh Derives d'amine
WO2001064192A2 (fr) * 2000-03-03 2001-09-07 Merck Patent Gmbh Utilisation d'inhibiteurs de pde v
JP2002105082A (ja) * 2000-09-29 2002-04-10 Nippon Soda Co Ltd 縮合チエノピリミジン化合物、その塩及び製造法

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998006722A1 (fr) * 1996-08-12 1998-02-19 Merck Patent Gmbh Thienopyrimidines
WO1998017668A1 (fr) * 1996-10-24 1998-04-30 Merck Patent Gmbh Thienopyrimidines a effet inhibiteur de la phosphodiesterase v
WO1999028325A1 (fr) * 1997-11-28 1999-06-10 Merck Patent Gmbh Thienopyrimidines
WO1999055708A1 (fr) * 1998-04-29 1999-11-04 Merck Patent Gmbh Thienopyrimidines condensees a effet inhibiteur de la phosphodiesterase v
WO2000059912A1 (fr) * 1999-03-30 2000-10-12 Nippon Soda Co., Ltd. Composes de thienopyrimidine et leurs sels, et procede de preparation desdits composes et sels
WO2000078767A1 (fr) * 1999-06-19 2000-12-28 Merck Patent Gmbh Thienopyrimidines utilisees comme inhibiteurs de phosphodiesterase
WO2001021620A2 (fr) * 1999-09-17 2001-03-29 Merck Patent Gmbh Derives d'amine
WO2001064192A2 (fr) * 2000-03-03 2001-09-07 Merck Patent Gmbh Utilisation d'inhibiteurs de pde v
JP2002105082A (ja) * 2000-09-29 2002-04-10 Nippon Soda Co Ltd 縮合チエノピリミジン化合物、その塩及び製造法

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006525347A (ja) * 2003-04-29 2006-11-09 オシエント ファーマシューティカルズ 抗生テトラヒドロ−β−カルボリン誘導体
WO2005047292A1 (fr) * 2003-11-04 2005-05-26 Merck Patent Gmbh Utilisation de thienopyrimidines
US20100298297A1 (en) * 2006-03-20 2010-11-25 Bayer Healthcare Ag Tetrahydropyridothienopyrimidine Compounds and Methods of Use Thereof
US8501755B2 (en) * 2006-03-20 2013-08-06 Bayer Intellectual Property Gmbh Tetrahydropyridothienopyrimidine compounds and methods of use thereof
US8524722B2 (en) 2007-09-14 2013-09-03 Bayer Intellectual Property Gmbh Substituted tricyclic compounds and methods of use thereof
US12168668B2 (en) 2015-12-22 2024-12-17 SHY Therapeutics LLC Compounds for the treatment of cancer and inflammatory disease
US10870657B2 (en) 2015-12-22 2020-12-22 SHY Therapeutics LLC Compounds for the treatment of cancer and inflammatory disease
US11560390B2 (en) 2015-12-22 2023-01-24 SHY Therapeutics LLC Compounds for the treatment of cancer and inflammatory disease
US10940139B2 (en) 2017-06-21 2021-03-09 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US11000515B2 (en) 2017-06-21 2021-05-11 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US11026930B1 (en) 2017-06-21 2021-06-08 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US11213515B1 (en) 2017-06-21 2022-01-04 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US11541041B1 (en) 2017-06-21 2023-01-03 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, Rasopathies, and fibrotic disease
US10933054B2 (en) 2017-06-21 2021-03-02 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US10588894B2 (en) 2017-06-21 2020-03-17 SHY Therapeutics LLC Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
US12391705B2 (en) 2018-12-19 2025-08-19 Shy Therapeutics, Llc Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease

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