Abstract
The bradykinin (BK) B1 receptor is an attractive target for the treatment of chronic pain and inflammation. Starting from a dual B1 and B2 antagonist, novel antagonists were designed that display low-nanomolar affinity for human B1 receptor and selectivity over B2. Initially, potent imidazoline derivatives were studied, but these compounds suffered from low bioavailability. This issue could be overcome by the use of less basic amino derivatives leading to orally active compounds.
MeSH terms
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Administration, Oral
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Analgesics / chemical synthesis*
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Analgesics / pharmacokinetics
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Analgesics / pharmacology
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Animals
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Binding, Competitive
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Biological Availability
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Bradykinin B1 Receptor Antagonists*
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Bradykinin B2 Receptor Antagonists*
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Cell Line
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Chlorocebus aethiops
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Cricetinae
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Cricetulus
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Humans
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Hyperalgesia / drug therapy
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Imidazolines / chemical synthesis
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Imidazolines / pharmacokinetics
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Imidazolines / pharmacology
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Male
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Mice
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Pain Measurement
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Piperazines / chemical synthesis*
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Piperazines / pharmacokinetics
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Piperazines / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / pharmacokinetics
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Piperidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / pharmacokinetics
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Sulfonamides / pharmacology
Substances
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Analgesics
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Bradykinin B1 Receptor Antagonists
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Bradykinin B2 Receptor Antagonists
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Imidazolines
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Piperazines
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Piperidines
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Sulfonamides