- Abolishing Dopamine D2long/D3Receptor Affinity of Subtype-Selective Carbamoylguanidine-Type Histamine H2Receptor Agonists
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3-(2-Amino-4-methylthiazol-5-yl)propyl-substituted carbamoylguanidines are potent, subtype-selective histamine H2receptor (H2R) agonists, but their applicability as pharmacological tools to elucidate the largely unknown H2R functions in the central nervous system (CNS) is compromised by their concomitant high affinity toward dopamine D2-like receptors (especially to the D3R). To improve the selectivity, a series of novel carbamoylguanidine-type ligands containing various heterocycles, spacers, and side residues were rationally designed, synthesized, and tested in binding and/or functional assays at H1-4and D2long/3receptors. This study revealed a couple of selective candidates (among others31and47), and the most promising ones were screened at several off-target receptors, showing good selectivities. Docking studies suggest that the amino acid residues (3.28, 3.32, E2.49, E2.51, 5.42, and 7.35) are responsible for the different affinities at the H2- and D2long/3-receptors. These results provide a solid base for the exploration of the H2R functions in the brain in further studies.
- Tropmann, Katharina,Bresinsky, Merlin,Forster, Lisa,M?nnich, Denise,Buschauer, Armin,Wittmann, Hans-Joachim,Hübner, Harald,Gmeiner, Peter,Pockes, Steffen,Strasser, Andrea
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p. 8684 - 8709
(2021/06/30)
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- PYRIDINYL PYRAZOLES AS MODULATORS OF RORyT
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The present invention comprises compounds of Formula I. wherein: R1, R3, R4, R5, R6, and Q are defined in the specification. The invention also comprises a method of treating or ameliorating a ROR-γ-t mediated syndrome, disorder or disease, including wherein the syndrome, disorder or disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, and psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.
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Paragraph 0261
(2020/01/08)
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- PHENYL AND PYRIDINYL SUBSTITUTED IMIDAZOLES AS MODULATORS OF RORyT
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The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, Ra, Rb, Q1, and Q2 are defined in the specification. The invention also comprises a method of treating or ameliorating a ROR-γ-t mediated syndrome, disorder or disease, including wherein the syndrome, disorder or disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, and psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.
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Paragraph 0312-0313
(2020/01/08)
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- PHENYL SUBSTITUTED PYRAZOLES AS MODULATORS OF RORgT
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The present invention comprises compounds of Formula I. wherein: R1, R3, R4, R5, R6, R7, R8, and Q are defined in the specification. The invention also comprises a method of treating or ameliorating a ROR-γ-t mediated syndrome, disorder or disease, including wherein the syndrome, disorder or disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, and psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.
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Paragraph 0377-0378
(2020/01/09)
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- Synthesis of some unsymmetrical bridged terpyridines
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Novel unsymmetrical terpyridines 1 and 2 are synthesized using intra- and intermolecular Michael additions as the key reactions, followed by the construction of the central pyridine ring. Terpyridine 1 represents a heretofore unknown hexacyclic ring system.
- Kelly, T. Ross,Lebedev, Rimma L.
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p. 2197 - 2205
(2007/10/03)
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