- Discovery of small-molecule nonpeptide antagonists of nociceptin/orphanin FQ receptor: The studies of design, synthesis, and structure-Activity relationships for (4-Arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] derivatives
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Nociceptin/orphanin FQ (N/OFQ) and N/OFQ peptide (NOP) receptor are expressed and distributed in various regions such as central nervous system (CNS), peripheral nervous system, immune system, and peripheral tissues. N/OFQ and NOP receptor have important
- Hayashi, Shigeo,Ohashi, Katsuyo,Mihara, Sachiko,Nakata, Eriko,Emoto, Chie,Ohta, Atsuko
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p. 345 - 364
(2016/04/19)
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- Collection of traceable compounds and uses thereof
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The use of a collection of compounds of general formula (I), wherein: n is 0 or 1; p represents an integer between 1 and 6; r represents an integer between 1 and 12; R1 and R′1 represent in particular a hydrogen atom; R2 represents an amino acid side chain or an amino acid derivative; R3 represents a group derived from a carboxylic acid, bearing a basic entity; R4 represents in particular an alkyl group containing 1 to 10 carbon atoms; and A represents a hydrogen atom, a protecting group or a tracing group, in particular a fluorophor, a coloring agent or a quencher, for determining, through binding studies, ligands of receptors whose ligand is unknown or whose ligand useful for carrying out specific affinity binding assays is unknown.
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- New synthesis of tic-hydantoins sigma-1 ligands and pharmacological evaluation on cocaine-induced stimulant effects
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Activation of the newly identified σ1 chaperone protein is involved in several aspects of the psychostimulant and addictive effects of cocaine. The development of ligands that selectively target the σ1 protein may lead to putative potent anti-cocaine agen
- Toussaint,Debreu-Fontaine,Maurice,Melnyk
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experimental part
p. 355 - 373
(2011/09/13)
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- Muscarinic Receptor Antagonists
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This present invention generally relates to muscarinic receptor antagonists of Formula (I), which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic rece
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Page/Page column 10
(2008/12/04)
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- TETRAHYDROISOQUINOLINE COMPOUND AND MEDICINAL USE THEREOF
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The present invention provide a tetrahydroisoquinoline compound having a superior ACAT-inhibitory activity and/or anti-oxidation action, particularly, novel compound represented by the formula (I) (wherein each symbol is as described in the specification) and a pharmaceutically acceptable salt thereof.
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Page/Page column 26
(2010/11/28)
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- TETRAHYDROISOQUINOLINE OR ISOCHROMAN COMPOUNDS AS ORL-1 RECEPTOR LIGANDS FOR THE TREATMENT OF PAIN AND CNS DISORDERS
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This invention provides the compounds of formula (I), or its a pharmaceutically acceptable ester or amide of such compound, or a pharmaceutically acceptable salt thereof, wherein X1 is NH; R1, R2, R4 through Rs
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Page/Page column 40-41
(2010/02/10)
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- A versatile synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones
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A mild and general strategy for the synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. The seven-membered lactam is prepared by intramolecular amide bond formation from the intermediate amino acid, which is obtained e
- Van Rompaey, Karolien,Van Den Eynde, Isabelle,De Kimpe, Norbert,Tourwé, Dirk
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p. 4421 - 4432
(2007/10/03)
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- CCK2 receptor antagonists containing the conformationally constrained phenylalanine derivatives, including the new amino acid Xic
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The conformationally constrained analogues of phenylalanine, tetrahydroisoquinoline-3-carboxylic acid (Tic), Sic, Hic and Nic, and the new amino acid Xic have been incorporated into a potent and highly selective cholecystokinin-2 (CCK2) receptor antagonist (2) in place of the phenylalanine residue, producing compounds 15a-e. High selectivities for CCK2 over CCK1 were observed for compounds 15a-e. The in vitro profile of the analogue containing the Nic residue (15d) was identical to that of compound 2, whereas the alternative conformational constraints resulted in a significant loss of affinity. The apparent advantage of Nic in the context of these CCK2 ligands was subsequently demonstrated to be statistically significant.
- Gibson, Susan E,Guillo, Nathalie,Jones, Jerome O,Buck, Ildiko M,Kalindjian, S.Barret,Roberts, Sonia,Tozer, Matthew J
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p. 379 - 389
(2007/10/03)
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- Synthesis and structure-activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
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Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(α-methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the α-methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg-1, TD50 = 36.4 mg kg-1, PI = 6.3). Replacement of the piperidine ring of 1 by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man.
- Ho, Bin,Michael Crider,Stables, James P
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p. 265 - 286
(2007/10/03)
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- Boronic ester and acid compounds, synthesis and uses
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Disclosed herein are boronic ester and acid compounds, their synthesis and uses. More specifically, disclosed herein is a method for reducing the rate of degradation of proteins in an animal comprising contacting cells of the animal with certain boronic ester and acid compounds.
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- Intramolecular aziridination: Decomposition of diazoamides with tethered imino bonds
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(Matrix presented) Of three possible mechanistic pathways, tethered oximino ethers react intramolecularly with diazoamides to produce a diazabicyclo[5.1.0]-hexane aziridine containing skeleton. Several acyclic and cyclic templates were synthesized and reacted with rhodium catalysts to prepare their corresponding annulated aziridines. Anomalous behavior was discovered with the piperidine template, resulting in an aziridination occurring during the attempted diazo-transfer reaction, rather than the catalyzed carbenoid reaction.
- Wright, Dennis L.,McMills, Mark C.
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p. 667 - 670
(2008/02/14)
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- BORONIC ESTER AND ACID COMPOUNDS
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Disclosed herein is a method for reducing the rate of degradation of proteins in an animal comprising contacting cells of the animal with certain boronic ester and acid compounds. Also disclosed herein are novel boronic ester and acid compounds, their synthesis and uses.
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- Incorporation of conformationally constrained phenylalanine derivatives TIC, SIC, HIC and NIC into a cholecystokinin-B/gastrin receptor antagonist
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The preparation and biological properties of a conformationally constrained series of cholecystokinin-B/gastrin receptor ligands are described. The membered ring (Nic) derivative was found to be as active at these receptors as an unconstrained phenylalani
- Gibson, Susan E.,Guillo, Nathalie,Kalindjian, S. Barret,Tozer, Matthew J.
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p. 1289 - 1292
(2007/10/03)
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- Facile generation of aziridines from the reaction of α-diazoamides with tethered oximino-ethers
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In an attempt to prepare azomethine ylide intermediates for cycloaddition reactions with electron deficient olefins, oximino-ethers with tethered α-diazoamide moieties were reacted in the presence of metal catalyst. The reaction resulted in aziridine formation preferentially.
- McMills, Mark C.,Wright, Dennis L.,Zubkowski, Jeffrey D.,Valente, Edward J.
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p. 7205 - 7208
(2007/10/03)
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