- TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS
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The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.
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Page/Page column 78
(2017/01/26)
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- D2 ANTAGONISTS, METHODS OF SYNTHESIS AND METHODS OF USE
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Provided are D2 or D3 antagonist compounds and pharmaceutical compositions of formula I and pharmaceutically acceptable salts thereof, or isomers thereof, wherein R1, R2 and R3 are as defined herein. The invention further comprises methods for making the compounds of the invention and methods for the treatment of conditions mediated by the dopamine D2 or D3 receptor from the compounds of the invention.
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Page/Page column 23
(2012/01/06)
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- TRICYCLIC SPIROCYCLE DERIVATIVES AND METHODS OF USE
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The present invention relates to novel Tricyclic Spirocycle Derivatives, pharmaceutical compositions comprising the Tricyclic Spirocycle Derivatives and the use of these compounds for treating or preventing allergy, an allergy-induced airway response, congestion, a cardiovascular disease, an inflammatory disease, a gastrointestinal disorder, a neurological disorder, a metabolic disorder, obesity or an obesity-related disorder, diabetes, a diabetic complication, impaired glucose tolerance or aired fasting glucose.
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Page/Page column 30
(2011/07/29)
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- Spiroimidazolidinone NPC1L1 inhibitors. Part 2: Structure-activity studies and in vivo efficacy
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Ezetimibe (Zetia), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-β-lactams can be effective CAIs.
- Howell, Kobporn L.,Devita, Robert J.,Garcia-Calvo, Margarita,Meurer, Roger D.,Lisnock, Jeanmarie,Bull, Herbert G.,McMasters, Daniel R.,McCann, Margaret E.,Mills, Sander G.
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scheme or table
p. 6929 - 6932
(2011/02/16)
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- Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626
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A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds share structural elements with the classical D 2-like dopamine rec
- Vangveravong, Suwanna,Taylor, Michelle,Xu, Jinbin,Cui, Jinquan,Calvin, Wesley,Babic, Sonja,Luedtke, Robert R.,MacH, Robert H.
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experimental part
p. 5291 - 5300
(2010/09/09)
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- Practical synthesis of p-aminophenethylspiperone (NAPS), a high-affinity, selective D2-dopamine receptor antagonist
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Because attempts to scale up the published synthetic preparation of p-aminophenethylspiperone (NAPS) by N-alkylation of spiperone with 4-nitrophenethyl bromide followed by reduction gave poor yields and difficulties during purification, an alternative synthetic approach has been developed. Use of 4-(N-tert-butyloxycarbonyl) aminophenethyl bromide to alkylate spiperone followed by the Boc group deprotection gave NAPS in 56% yield. This procedure provides an improved and efficient synthesis of the important high-affinity, selective D2-dopamine receptor antagonist NAPS. Copyright Taylor & Francis Group, LLC.
- Jin, Chunyang,Mayer, Louise D.,Lewin, Anita H.,Rehder, Kenneth S.,Brine, George A.
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p. 816 - 823
(2008/09/16)
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- PYRAZOLONE COMPOUNDS AS METABOTROPIC GLUTAMATE RECEPTOR AGONISTS FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, X, and n are as defined for Formula (I) in the description, processes for the preparation of the compounds and new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and the use of the compounds in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction.
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Page/Page column 238; 239
(2008/06/13)
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- SPIRO-SUBSTITUTED PYRROLOPYRIMIDINES
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The invention provides compounds of formula (I) or a pharmaceutically acceptable salt or ester thereof formula (I) wherein the symbols have the meaning as defined in the description. Said compounds are inhibitors of cathepsin K and/or cathepsin S and are useful for the treatment of diseases and medical conditions in which cathepsin K and/or cathepsin S is implicated, e.g. various disorders including neuropathic pain, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis, multiple sclerosis and tumours.
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- NOCICEPTIN ANALOGUES AND USES THEREOF
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The present invention relates to nociceptin analogues and uses thereof to modulate biological functions. In one aspect, the invention provides modified triazo-spiro compounds that include at least one specialized chemical group that is bound to the compou
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- 2-CYANOPYRROLOPYRIMIDINES AND PHARMACEUTICAL USES THEREOF
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The invention relates to pyrrolo pyrimidines of formula (I), wherein Y represents -(CH2)t-O- or -(CH2)r-S-, p is 1 or 2, r is 1, 2 or 3, t is 1, 2 or 3, or Y is -(CH2)j- or -CH=CH-, j is 1 or 2; p is 1 or 2, or Y is -(CH2)f-, f is 1 or 2, p is 1, and the further radicals and symbols have the meaning as defined herein; their preparation, their use as pharmaceuticals, pharmaceutical compositions containing them, the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment of neuropathic pain and to a method for the treatment of such a disease in animals, especially in humans.
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Page/Page column 39
(2010/02/08)
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- Phenoxyalkylamine derivatives useful as opioid receptor agonists
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A medicament useful for preventive and/or therapeutic treatment of nerve system diseases which comprises, as an active ingredient, a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof: wherein, X represents a group represented by the following general formula (II), (III), (IV), (V), or (VI), “A” represents a saturated or unsaturated 3- to 6-membered carbocyclic group and the like, “B” represents CH2 and the like, “n” represents 0 to 2, R1 represents a hydrogen atom, a halogen atom and the like, R2, R3, and R7 to R14 represent a hydrogen atom, a lower alkyl group which may be substituted and the like, R4 represents a hydrogen atom, a lower alkyl group which may be substituted and the like, R5 represents a hydrogen atom, a halogen atom and the like, R6 represents a saturated or unsaturated monocyclic or bicyclic carbocyclic group and the like, and R5 and R6, R7 and R8, R9 and R10, or R11 and R12 may bind to each other to form a cyclic structure.
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- Synthesis of [123I]-8-[4-[2-(5-iodothienyl)]-4-oxobutyl]-3-methyl-1- phenyl-1,3,8-triazaspiro[4.5]decan-4-one: A potential dopamine D2 receptor radioligand for SPECT
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[123I]-8-[4-[2-(5-Iodothienyl)]-4-oxobutyl]-3-methyl-1-phenyl-1,3,8- triazaspiro[4.5]-decan-4-one (1) has been synthesized as a potential ligand for dopamine D2 receptors. This new compound proved to be moderate in lipophilicity (log
- Waterhouse, Rikki N.,Gotsick, J. Timothy,Kabalka, George W.,Goodman, Mark M.,O'Brien
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p. 363 - 376
(2007/10/03)
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- Synthesis and characterization of pseudopeptide bradykinin B2 receptor antagonists containing the 1,3,8-triazaspiro[4.5]decan-4-one ring system
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A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro2-Pro3-Gly4-Phe5 section of the peptide bradykinin B2 receptor antagonist [Pro3, Phe5]HOE 140 (D-Arg0-Arg1- Pro2-Pro3-Gly4-Phe5-Ser6-D-Tic7-Oic8-Arg9) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.
- Mavunkel, Babu J.,Lu, Zhijian,Goehring, R. Richard,Lu, Songfeng,Chakravarty, Sarvajit,Perumattam, John,Novotny, Elizabeth A.,Connolly, Maureen,Valentine, Heather,Kyle, Donald J.
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p. 3169 - 3173
(2007/10/03)
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- Effect of N-alkylation on the affinities of analogues of spiperone for dopamine D2 and serotonin 5-HT2 receptors
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Two series of N-substituted spiperone analogues were prepared and evaluated in vitro to measure their affinities for dopamine D2 and serotonin 5-HT2 receptors. Substitution of the amide nitrogen with an alkyl group of five carbon uni
- Mach,Jackson,Luedtke,Ivins,Molinoff,Ehrenkaufer
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p. 423 - 430
(2007/10/02)
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