Fluorinated non-imidazole histamine H3 receptor antagonists

Isensee, Kathleen; Amon, Michael; Galaparti, A.; Ligneau, Xavier; Camelin, Jean-Claude; Capet, Marc; Stark, Holger

doi:10.1016/j.bmcl.2009.02.110

Cited by 29 publications

(23 citation statements)

References 17 publications

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“…Purification of the crude oil was achieved by means of distillation (20 mbar, 95°C). The oily product was crystallized as hydrochloride from 2-propanol (white solid, 54.6 g, 79% 1-(3-Chloropropyl)piperidine Hydrochloride (P2) 9,19,20) Alcohol P1 (13.4 g, 0.08 mol) was suspended in toluene (100 ml). Under inert atmosphere and at 0°C an excess of thionyl chloride (11.6 ml, 0.16 mol) was added dropwise.…”

Section: Methodsmentioning

confidence: 99%

“…3-(Piperidin-1-yl)propan-1-ol Hydrochloride (P1) 9,19,20) Piperidine (51.1 g, 0.6 mol), 3-chloropropan-1-ol (47.3 g, 0.5 mol), potassium carbonate (74.3 g, 0.75 mol) and potassium iodide (8.3 g, 0.05 mol) were refluxed in absolute acetone (300 ml) during 72 h. The mixture was allowed to cool to room temperature, inorganic components were removed by filtration and the filtrate was concentrated to dryness. Purification of the crude oil was achieved by means of distillation (20 mbar, 95°C).…”

Section: Methodsmentioning

confidence: 99%

“…A second basic moiety usually boosts H 3 R affinity as has been shown with many compounds of the class of diamine-based ligands. [7][8][9] Computational models support an additional ionic interaction with transmembrane domain 5. 10,11) However, due to the strong receptor binding and their lipophilicity diamine-based ligands tend to accumulate centrally, which as a result might induce severe side effects and/or phospholipidosis.…”

Section: Regular Articlementioning

confidence: 99%

“…9,19,20) Briefly, piperidine was alkylated with 3-chloropropan-1-ol under basic conditions (Chart 1). The resulting alcohol precursor P1 was chlorinated (P2) and subsequently transferred to phenol ether synthesis.…”

Section: Regular Articlementioning

confidence: 99%

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Kojic Acid Derivatives as Histamine H3 Receptor Ligands

et al. 2010

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The histamine H 3 receptor (H 3 R) is a promising target in the development of new compounds for the treatment of mainly centrally occurring diseases. However, emerging novel therapeutic concepts have been introduced and some indications in the H 3 R field, e.g. migraine, pain or allergic rhinitis, might take advantage of peripherally acting ligands. In this work, kojic acid-derived structural elements were inserted into a well established H 3 R antagonist/inverse agonist scaffold to investigate the bioisosteric potential of g-pyranones with respect to the different moieties of the H 3 R pharmacophore. The most affine compounds showed receptor binding in the low nanomolar concentration range. Evaluation and comparison of kojic acid-containing ligands and their corresponding phenyl analogues (3-7) revealed that the newly integrated scaffold greatly influences chemical properties (S Log P, topological polar surface area (tPSA)) and hence, potentially modifies the pharmacokinetic profile of the different derivatives. Benzyl-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)methanamine ligands 3 and 4 belong to the centrally acting diamine-based class of H 3 R antagonist/inverse agonist, whereas kojic acid analogues 6 and 7 might act peripherally. The latter compounds state promising lead structures in the development of H 3 R ligands with a modified profile of action.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Regular Articlementioning

confidence: 99%

Section: Regular Articlementioning

confidence: 99%

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Kojic Acid Derivatives as Histamine H3 Receptor Ligands

et al. 2010

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“…H 3 antagonists have been proposed for their potential usefulness in diseases characterized by impaired neurotransmission and they have demonstrated beneficial effects on learning and food intake in animal models [14,15]. These observations encouraged medicinal chemists to design new H 3 antagonists for treatment of various CNS diseases [8,16,17,18,19,20,6]. Thioperamide, clopenpropit, pyroxifan and perception (GT-2331) are selective H 3 antagonists with imidazole ring in their structures (Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2-[{4-(t-amino-1-yl) but-2-yn-1-yl }oxy]-1,3- benzothiazole derivatives as H3-antagonists

Rahmani¹,

kaissi²,

Arafat³

et al. 2014

iosrphr

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¹¹C‐labeled and ¹⁸F‐labeled PET ligands for subtype‐specific imaging of histamine receptors in the brain

Funke

Vugts

Janssen

et al. 2013

Labelled Comp Radiopharmac

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The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

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Fluorinated non-imidazole histamine H3 receptor antagonists

Cited by 29 publications

References 17 publications

Kojic Acid Derivatives as Histamine H3 Receptor Ligands

Kojic Acid Derivatives as Histamine H3 Receptor Ligands

Synthesis of 2-[{4-(t-amino-1-yl) but-2-yn-1-yl }oxy]-1,3- benzothiazole derivatives as H3-antagonists

¹¹C‐labeled and ¹⁸F‐labeled PET ligands for subtype‐specific imaging of histamine receptors in the brain

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Fluorinated non-imidazole histamine H3 receptor antagonists

Cited by 29 publications

References 17 publications

Kojic Acid Derivatives as Histamine H3 Receptor Ligands

Kojic Acid Derivatives as Histamine H3 Receptor Ligands

Synthesis of 2-[{4-(t-amino-1-yl) but-2-yn-1-yl }oxy]-1,3- benzothiazole derivatives as H3-antagonists

11C‐labeled and 18F‐labeled PET ligands for subtype‐specific imaging of histamine receptors in the brain

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¹¹C‐labeled and ¹⁸F‐labeled PET ligands for subtype‐specific imaging of histamine receptors in the brain