US20170313665A1 - Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof - Google Patents

Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof Download PDF

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Publication number
US20170313665A1
US20170313665A1 US15/523,061 US201515523061A US2017313665A1 US 20170313665 A1 US20170313665 A1 US 20170313665A1 US 201515523061 A US201515523061 A US 201515523061A US 2017313665 A1 US2017313665 A1 US 2017313665A1
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United States
Prior art keywords
triazol
chlorophenyl
methyl
trifluoro
dihydro
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Abandoned
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US15/523,061
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English (en)
Inventor
Carsten Schmeck
Michael Gerisch
Nils Griebenow
Peter Kolkhof
Florian Kölling
Anna ENGELEN
Axel Kretschmer
Dieter Lang
Klemens Lustig
Thomas Mondritzki
Elisabeth Pook
Hartmut Beck
Frank Süssmeier
Sonja Vollmer
Pierre Wasnaire
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Bayer Pharma AG
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Bayer Pharma AG
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Assigned to BAYER PHARMA AKTIENGESELLSCHAFT reassignment BAYER PHARMA AKTIENGESELLSCHAFT ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LUSTIG, KLEMENS, DR., GRIEBENOW, NILS, DR., KOLKHOF, PETER, DR., KÖLLING, FLORIAN, DR., SÜSSMEIER, Frank, VOLLMER, SONJA, DR., BECK, HARTMUT, DR., ENGELEN, ANNA, DR., GERISCH, MICHAEL, DR., KRETSCHMER, AXEL, DR., LANG, DIETER, DR., MONDRITZKI, Thomas, POOK, ELISABETH, DR., SCHMECK, CARSTEN, DR., WASNAIRE, PIERRE, DR.
Publication of US20170313665A1 publication Critical patent/US20170313665A1/en
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the liquid content of the human body is subject to various physiological control mechanisms, the purpose of which is to keep it constant (volume homeostasis).
  • both the volume filling of the vascular system and also the osmolarity of the plasma are continuously recorded by appropriate sensors (baroreceptors and osmoreceptors).
  • the information which these sensors supply to the relevant centers in the brain regulates drinking behaviour and controls fluid excretion via the kidneys by means of humoral and neural signals.
  • the peptide hormone vasopressin is of central importance in this [Schrier R. W., Abraham W. T., New Engl. J. Med. 341, 577-585 (1999)].
  • Vasopressin exerts its action mainly via binding to three receptors, which are classified as V1a, V1b and V2 receptors and which belong to the family of G protein-coupled receptors.
  • V1a receptors are mainly located on the cells of the vascular smooth musculature. Their activation gives rise to vasoconstriction, as a result of which the peripheral resistance and blood pressure rise. Apart from this, V1a receptors are also detectable in the liver.
  • V1b receptors also named V3 receptors
  • vasopressin regulates the basal and stress-induced secretion of adrenocorticotropic hormone (ACTH) via the V1b receptor.
  • CSH corticotropin-releasing hormone
  • V2 receptors are located in the distal tubular epithelium and the epithelium of the collecting tubules in the kidney. Their activation renders these epithelia permeable to water. This phenomenon is due to the incorporation of aquaporins (special water channels) in the luminal membrane of the epithelial cells.
  • V2 receptor antagonists cause increased water excretion, without substantially increasing the excretion of electrolytes. This means that with V2 antagonist drugs, volume homeostasis can be restored without affecting electrolyte homeostasis.
  • drugs with V2 antagonistic activity appear particularly suitable for the treatment of all disease conditions which are associated with an overloading of the body with water, without the electrolytes being adequately increased in parallel.
  • hyponatremia sodium concentration ⁇ 135 mmol/L
  • hyponatremia sodium concentration ⁇ 135 mmol/L
  • comatose states and death are imminent.
  • hypovolemic euvolemic
  • hypervolemic hyponatremia The forms of hypervolemia with edema formation are clinically significant. Typical examples of these are the syndrome of inappropriate ADH/vasopressin secretion (SIADH) (e.g.
  • V1a and V2 vasopressin receptors
  • V1a and V2 vasopressin receptors
  • V1a and V2 vasopressin receptors
  • the provision of such combined vasopressin antagonists also appears to make sense inasmuch as a volume diminution mediated solely via V2 receptor blockade can entail the stimulation of osmoreceptors and, as a result, may lead to a further compensatory increase in vasopressin release.
  • vasopressin such as for example vasoconstriction and heart muscle hypertrophy
  • WO 2011/104322-A1 a particular group of bis-aryl-bonded 1,2,4-triazol-3-ones, including 5-phenyl-1,2,4-triazol-3-yl and 1-phenyl-1,2,3-triazol-4-yl derivatives thereof, has been disclosed as antagonists of vasopressin V1a and/or V2 receptors being useful for the treatment and/or prevention of cardiovascular diseases.
  • candidate compounds were frequently compromised by an unsatisfactory aquaretic potency when evaluated in vivo following peroral administration to conscious rats.
  • a robust aquaretic efficacy is a desirable prerequisite for the treatment of disease conditions that are associated with an overloading of the body with water, such as, for example, in congestive heart failure.
  • a significant increase in aquaretic potency would also help towards reducing the amount of substance which is going to be required to achieve and maintain the desired therapeutic effect, thus limiting the potential for unacceptable side effects and/or unwanted drug-drug interactions during the treatment of patients which might already be at high risk, such as, for example, in acute or chronic heart failure or renal failure.
  • the technical problem to be solved according to the present invention may therefore be seen in identifying and providing new compounds that act as potent antagonists of both vasopressin V1a and V2 receptors and, in addition, exhibit a substantial increase in aquaretic potency in vivo.
  • Compounds according to the invention are the compounds of the formula (I) and their salts, solvates and solvates of the salts, the compounds included in the formula (I) of the formulae mentioned in the following and their salts, solvates and solvates of the salts, and the compounds included in the formula (I) and mentioned in the following as process products and/or embodiment examples and their salts, solvates and solvates of the salts, where the compounds included in the formula (I) and mentioned in the following are not already salts, solvates and solvates of the salts.
  • Solvates in the context of the invention are designated as those forms of the compounds according to the invention which form a complex in the solid or liquid state by stoichiometric coordination with solvent molecules. Hydrates are a specific form of solvates, in which the coordination takes place with water. Hydrates are preferred solvates in the context of the present invention.
  • the compounds of this invention may, either by nature of asymmetric centers or by restricted rotation, be present in the form of isomers (enantiomers, diastereomers). Any isomer may be present in which the asymmetric center is in the (R)-, (S)-, or (R,S)-configuration.
  • isotopes for example of deuterium
  • isotopes can lead to particular therapeutic benefits as a consequence of greater metabolic stability of the compound, for example an extension of the half-life in the body or a reduction in the active dose required.
  • modifications of the compounds according to the invention may therefore in some cases also constitute a preferred embodiment of the present invention.
  • Isotopic variants of the compounds according to the invention can be prepared by processes known to those skilled in the art, for example by the methods described below and the methods described in the working examples, by using corresponding isotopic modifications of the particular reagents and/or starting compounds therein.
  • the present invention relates to compounds of formula (I), wherein
  • the present invention relates to compounds according to formula (I) selected from the group consisting of the following compounds
  • R 1 , R 2A and R 2B have the meanings described above, optionally followed, where appropriate, by (i) separating the compounds of formula (I) thus obtained into their respective diastereomers, preferably using chromatographic methods, and/or (ii) converting the compounds of formula (I) into their respective hydrates, solvates, salts and/or hydrates or solvates of the salts by treatment with the corresponding solvents and/or acids or bases.
  • the 1,2,4-triazole derivative of formula (V) produced by this reaction may also be present in other tautomeric forms, such as (V-A) or (V-B)
  • the compounds of the invention are suitable for treating urological diseases and diseases of the male and female urogenital system such as, for example, benign prostatic syndrome (BPS), benign prostatic hyperplasia (BPH), benign prostatic enlargement (BPE), bladder outlet obstruction (BOO), lower urinary tract syndromes (LUTS), neurogenic overactive bladder (OAB), interstitial cystitis (IC), urinary incontinence (UI), for example mixed, urge, stress and overflow incontinence (MUI, UUI, SUI, OUI), pelvic pains, erectile dysfunction and female sexual dysfunction.
  • BPS benign prostatic syndrome
  • BPH benign prostatic hyperplasia
  • BPE benign prostatic enlargement
  • BOO bladder outlet obstruction
  • LUTS lower urinary tract syndromes
  • OAB neurogenic overactive bladder
  • IC interstitial cystitis
  • UI urinary incontinence
  • MUI urinary incontinence
  • MUI UUI, SUI, OUI
  • reaction mixture was stirred at room temperature for 5 days, after which extra boronic acid (54.4 mg, 0.36 mmol, 0.5 eq.) was added due to incomplete conversion.
  • extra boronic acid 54.4 mg, 0.36 mmol, 0.5 eq.
  • the reaction mixture was diluted with MTBE and then quenched with aqueous hydrochloric acid (0.5 M). After phase separation, the aqueous phase was extracted twice with MTBE. The combined organic phases were dried over sodium sulfate, filtered, and concentrated in vacuo.
  • the crude product was purified by preparative HPLC [method 4], and the desired compound (73 mg, 0.14 mmol) was obtained (yield 22.4%, 98% purity).
US15/523,061 2014-11-03 2015-10-30 Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof Abandoned US20170313665A1 (en)

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EP14191491.1 2014-11-03
EP14191491 2014-11-03
PCT/EP2015/075200 WO2016071212A1 (en) 2014-11-03 2015-10-30 Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof

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WO2017191105A1 (en) 2016-05-03 2017-11-09 Bayer Pharma Aktiengesellschaft Amide-substituted aryltriazole derivatives and uses thereof
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EP4011874A1 (en) 2020-12-10 2022-06-15 Bayer Aktiengesellschaft Substituted pyrazolo piperidine carboxylic acids
WO2022214206A1 (en) 2021-04-08 2022-10-13 Bayer Aktiengesellschaft Combination of finerenone and pecavaptan for the treatment and/or prevention of cardiovascular and/or renal diseases
WO2023237577A1 (en) 2022-06-09 2023-12-14 Bayer Aktiengesellschaft Soluble guanylate cyclase activators for use in the treatment of heart failure with preserved ejection fraction in women

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3042466A1 (de) 1980-11-11 1982-06-16 A. Nattermann & Cie GmbH, 5000 Köln N-substituierte (omega) -(2-oxo-4-imidazolin-l-yl)-alkansaeure-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate
US5468448A (en) 1989-12-28 1995-11-21 Ciba-Geigy Corporation Peroxide disinfection method and devices therefor
DE4107857A1 (de) 1991-03-12 1992-09-17 Thomae Gmbh Dr K Cyclische harnstoffderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
WO1992020662A1 (en) 1991-05-10 1992-11-26 Merck & Co., Inc. Acidic aralkyl triazole derivatives active as angiotensin ii antagonists
WO1993017681A1 (en) 1992-03-02 1993-09-16 Abbott Laboratories Angiotensin ii receptor antagonists
SK94393A3 (en) 1992-09-11 1994-08-10 Thomae Gmbh Dr K Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those
GB9301192D0 (en) 1993-06-09 1993-06-09 Trott Francis W Flower shaped mechanised table
US6844005B2 (en) 2002-02-25 2005-01-18 Trutek Corp Electrostatically charged nasal application product with increased strength
FR2708608B1 (fr) 1993-07-30 1995-10-27 Sanofi Sa Dérivés de N-sulfonylbenzimidazolone, leur préparation, les compositions pharmaceutiques en contenant.
US5897858A (en) 1994-02-03 1999-04-27 Schering-Plough Healthcare Products, Inc. Nasal spray compositions exhibiting increased retention in the nasal cavity
US20010020100A1 (en) 1994-06-14 2001-09-06 G.D. Searle & Co. N-substituted-1, 2, 4-triazolone compounds for treatment of cardiovascular disorders
AU741769B2 (en) 1997-12-17 2001-12-06 Merck Sharp & Dohme Corp. Integrin receptor antagonists
DE19816882A1 (de) 1998-04-17 1999-10-21 Boehringer Ingelheim Pharma Triazolone mit neuroprotektiver Wirkung
JP2002521373A (ja) 1998-07-24 2002-07-16 バイエル アクチェンゲゼルシャフト 置換されたベンゾイルシクロヘキサンジオン類
DE19834047A1 (de) 1998-07-29 2000-02-03 Bayer Ag Substituierte Pyrazolderivate
DE19834044A1 (de) 1998-07-29 2000-02-03 Bayer Ag Neue substituierte Pyrazolderivate
DE19914140A1 (de) 1999-03-27 2000-09-28 Bayer Ag Substituierte Benzoylpyrazole
SK13532001A3 (sk) 1999-04-01 2003-02-04 Pfizer Products Inc. Aminopiridíny ako inhibítory sorbitoldehydrogenázy
DE19920791A1 (de) 1999-05-06 2000-11-09 Bayer Ag Substituierte Benzoylisoxazole
DE19921424A1 (de) 1999-05-08 2000-11-09 Bayer Ag Substituierte Benzoylketone
DE19929348A1 (de) 1999-06-26 2000-12-28 Bayer Ag Verfahren zur Herstellung von 2-Heterocyclylmethyl-benzoesäurederivaten
US6531142B1 (en) 1999-08-18 2003-03-11 The Procter & Gamble Company Stable, electrostatically sprayable topical compositions
DE19943635A1 (de) 1999-09-13 2001-03-15 Bayer Ag Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943634A1 (de) 1999-09-13 2001-04-12 Bayer Ag Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943636A1 (de) 1999-09-13 2001-03-15 Bayer Ag Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften
DE19943639A1 (de) 1999-09-13 2001-03-15 Bayer Ag Dicarbonsäurederivate mit neuartigen pharmazeutischen Eigenschaften
AR027575A1 (es) 2000-03-06 2003-04-02 Bayer Ag Benzoilciclohexenonas substituidas
US7080644B2 (en) 2000-06-28 2006-07-25 Microdose Technologies, Inc. Packaging and delivery of pharmaceuticals and drugs
AR031176A1 (es) 2000-11-22 2003-09-10 Bayer Ag Nuevos derivados de pirazolpiridina sustituidos con piridina
WO2002066447A1 (en) 2001-02-21 2002-08-29 Ono Pharmaceutical Co., Ltd. 4h-1,2,4-triazole-3(2h)-thione deratives as sphingomyelinase inhibitors
DE10110749A1 (de) 2001-03-07 2002-09-12 Bayer Ag Substituierte Aminodicarbonsäurederivate
DE10110750A1 (de) 2001-03-07 2002-09-12 Bayer Ag Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften
US20040071757A1 (en) 2001-11-20 2004-04-15 David Rolf Inhalation antiviral patch
DE10220570A1 (de) 2002-05-08 2003-11-20 Bayer Ag Carbamat-substituierte Pyrazolopyridine
JP4673295B2 (ja) 2003-03-14 2011-04-20 メルク・シャープ・エンド・ドーム・コーポレイション 単環式アニリドスピロヒダントインｃｇｒｐ受容体拮抗物質
EP1689252A2 (en) 2003-06-27 2006-08-16 Berglin Corporation of Washington Machine for precision low stress coring and slicing of apples and other soft-cored or pitted fruits
AU2004309164B2 (en) * 2003-12-22 2007-11-15 Pfizer Inc. Triazole derivatives as vasopressin antagonists
WO2005086836A2 (en) 2004-03-08 2005-09-22 Wyeth Ion channel modulators
CN1933832A (zh) 2004-03-08 2007-03-21 惠氏公司 离子通道调节剂
WO2005105779A1 (en) 2004-04-28 2005-11-10 Pfizer Limited 3-heterocyclyl-4-phenyl-triazole derivatives as inhibitors of the vasopressin v1a receptor
US7642275B2 (en) 2004-12-16 2010-01-05 Takeda San Diego, Inc. Histone deacetylase inhibitors
WO2006117657A1 (en) 2005-05-03 2006-11-09 Ranbaxy Laboratories Limited Triazolone derivatives as anti-inflammatory agents
DE102006024024A1 (de) 2006-05-23 2007-11-29 Bayer Healthcare Aktiengesellschaft Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung
EP2150534B1 (en) * 2007-04-26 2012-01-11 H. Lundbeck A/S Isoquinolinone derivatives as nk3 antagonists
DE102008060967A1 (de) 2008-12-06 2010-06-10 Bayer Schering Pharma Aktiengesellschaft Substituierte Phenylsulfonyltriazolone und ihre Verwendung
DE102010001064A1 (de) * 2009-03-18 2010-09-23 Bayer Schering Pharma Aktiengesellschaft Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung
DE102009013642A1 (de) 2009-03-18 2010-09-23 Bayer Schering Pharma Aktiengesellschaft Substituierte Phenylalaninderivate und deren Verwendung
DE102009028929A1 (de) 2009-08-27 2011-07-07 Bayer Schering Pharma Aktiengesellschaft, 13353 Heterocyclisch-substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung
PE20130683A1 (es) * 2010-02-27 2013-06-20 Bayer Ip Gmbh Ariltriazolonas ligadas a bisarilo y su uso
DE102010021637A1 (de) 2010-05-26 2011-12-01 Bayer Schering Pharma Aktiengesellschaft Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung
MX2013000198A (es) 2010-07-09 2013-01-28 Bayer Ip Gmbh Pirimidinadas y triazinas condensadas y su uso.
DE102010040187A1 (de) 2010-09-02 2012-03-08 Bayer Schering Pharma Aktiengesellschaft Substituierte N-Phenethyl-triazolonacetamide und ihre Verwendung
DE102010040233A1 (de) 2010-09-03 2012-03-08 Bayer Schering Pharma Aktiengesellschaft Bicyclische Aza-Heterocyclen und ihre Verwendung
DE102010043379A1 (de) 2010-11-04 2012-05-10 Bayer Schering Pharma Aktiengesellschaft Substituierte 6-Fluor-1H-Pyrazolo[4,3-b]pyridine und ihre Verwendung
US9604976B2 (en) 2012-03-22 2017-03-28 Spero Gyrase, Inc. Antibacterial compounds
AU2014334040A1 (en) * 2013-10-07 2016-04-28 Bayer Pharma Aktiengesellschaft Cyclic thienouracil-carboxamides and use thereof

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11091463B2 (en) 2016-05-03 2021-08-17 Bayer Pharma Aktiengesellschaft Amide-substituted pyridinyltriazole derivatives and uses thereof
US10927098B2 (en) 2016-10-20 2021-02-23 Bayer Pharma Aktiengesellschaft Hydroxyalkyl-substituted triazole derivatives and uses thereof
US11149023B2 (en) 2017-10-24 2021-10-19 Bayer Pharma Aktiengesellschaft Substituted triazole derivatives and uses thereof
US11173151B2 (en) 2017-10-24 2021-11-16 Bayer Aktiengesellschaft Substituted triazole derivatives and uses thereof
US11230540B2 (en) 2017-10-24 2022-01-25 Bayer Pharma Aktiengesellschaft Substituted triazole derivatives and uses thereof
US11298367B2 (en) 2017-10-24 2022-04-12 Bayer Aktiengesellschaft Prodrugs of substituted triazole derivatives and uses thereof
US11331314B2 (en) 2017-10-24 2022-05-17 Bayer Pharma Aktiengesellschaft Amine substituted triazole derivatives and uses thereof

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