- Pseudosaccharin amines as potent and selective KV1.5 blockers
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Phenethyl aminoheterocycles like compound 1 were known to be potent IKur blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent KV1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.
- Lloyd, John,Finlay, Heather J.,Kover, Alexander,Johnson, James,Pi, Zulan,Jiang, Ji,Neels, James,Cavallaro, Cullen,Wexler, Ruth,Conder, Mary Lee,Shi, Hong,Li, Danshi,Sun, Huabin,Chimalakonda, Anjaneya,Huang, Christine,Salvati, Mark,Levesque, Paul
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p. 4983 - 4986
(2015/03/30)
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- Discovery of disubstituted piperidines and homopiperidines as potent dual NK1 receptor antagonists-serotonin reuptake transporter inhibitors for the treatment of depression
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This report describes the synthesis, structure-activity relationships and activity of piperidine, homopiperidine, and azocane derivatives combining NK1 receptor (NK1R) antagonism and serotonin reuptake transporter (SERT) inhibition. Our studies culminated in the discovery of piperidine 2 and homopiperidine 8 as potent dual NK1R antagonists-SERT inhibitors. Compound 2 demonstrated significant activity in the gerbil forced swimming test, suggesting that dual NK1R antagonists-SERT inhibitors may be useful in treating depression disorders.
- Wu, Yong-Jin,He, Huan,Bertekap, Robert,Westphal, Ryan,Lelas, Snjezana,Newton, Amy,Wallace, Tanya,Taber, Matthew,Davis, Carl,MacOr, John E.,Bronson, Joanne
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p. 2217 - 2228
(2013/05/08)
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- Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors
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The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.
- Sun, Daqing,Wang, Zhulun,Caille, Seb,Degraffenreid, Michael,Gonzalez-Lopez De Turiso, Felix,Hungate, Randall,Jaen, Juan C.,Jiang, Ben,Julian, Lisa D.,Kelly, Ron,McMinn, Dustin L.,Kaizerman, Jacob,Rew, Yosup,Sudom, Athena,Tu, Hua,Ursu, Stefania,Walker, Nigel,Willcockson, Maren,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
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scheme or table
p. 405 - 410
(2011/02/27)
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- SUBSTITUTED 4-AMINOCYCLOHEXANE DERIVATIVES
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The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.
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Page/Page column 51; 52
(2009/10/06)
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- Spirocyclic Azaindole Derivatives
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The invention relates to substituted azaindole derivatives, to methods for the production thereof, to medicaments containing said compounds and to the use of substituted azaindole derivatives for producing medicaments.
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Page/Page column 9
(2009/07/03)
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- Benzamide derivatives and uses related thereto
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Benzamide derivatives of formula I are described and have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorders: wherein R1, R2, R3, R4, R5, R6, R7, R8, and n are as defined herein.
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Page/Page column 44
(2008/06/13)
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- Fused heterocyclic compounds
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A compound of formula I wherein m, n, A, B, D, E, G, H, Y, R1, R2, R3, R4, R5, and R8, are described herein.
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Page/Page column 18
(2010/02/14)
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- Carbocyclic potassium channel inhibitors
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The present invention relates to a class of carbocyclic compounds of Formula I that are useful as potassium channel inhibitors to treat autoimmune disorders, cardiac arrhythmias, and the like.
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- 4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists I.
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A series of novel 4,4-disubstituted cyclohexylamine based NK(1) antagonists is described. The effect of changes to the C(1)-C(4) relative stereochemistry on the cyclohexane ring and replacements for the flexible linker are discussed, leading to the identification of compounds with high affinity and good in vivo duration of action.
- Elliott, Jason M,Castro, Jose L,Chicchi, Gary G,Cooper, Laura C,Dinnell, Kevin,Hollingworth, Gregory J,Ridgill, Mark P,Rycroft, Wayne,Kurtz, Marc M,Shaw, Duncan E,Swain, Christopher J,Tsao, Kwei-Lan,Yang, Lihu
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p. 1755 - 1758
(2007/10/03)
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- Benzamide potassium channel inhibitors
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This invention relates to benzamide potassium channel inhibitors of general structural Formula I. The compounds of this invention are useful in the treatment of autoimmune diseases, the prevention of rejection of foreign organ transplants and related affl
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- Synthesis and Reactivity of 4-Phenylisoquinuclidines
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Several approaches to the synthesis of the 2-alkyl-4-phenylisoquinuclidines 14 and 15, the 3,4-diphenylisoquinuclidines 22-24 and of 6-oxo-4-phenyl-3-isoquinuclidone (43) are described.The structure of the products of hydrolysis of 7-phenyl-1,4-dioxaspirodecanecarboxamide (36) were determined by spectroscopy and degradative reactions.
- Schneider, Woldemar,Krombholz, Gottfried
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p. 487 - 498
(2007/10/02)
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- 4-Amino-4-phenylcyclohexanone ketal compositions and process of use
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A class of new 4-amino-4-arylcyclohexanones, their ketals, and acid addition salts have been synthesized and found to be useful for relieving pain in animals. Their analgesic activity appears to be of high order, and in addition some exhibit narcotic antagonist activity that is useful in modifying the cardiovascular, respiratory, and behavioral depression caused by other analgesics. Several show mixed analgesic and narcotic antagonist activity. Preferred compounds of the class are 4-(m-hydroxyphenyl)-4-dimethylaminocyclohexanone ethylene ketal, and 4-(m-hydroxyphenyl)-4-(n-butylmethylamino)cyclohexanone ethylene ketal as free bases and as their hydrochloride salts. Processes for synthesis and intermediates are described. Unit dosage forms and therapeutic treatments are disclosed.
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- Benzospiran derivatives
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This invention relates to novel benzospiran derivatives embraced by the formula SPC1 Wherein the sum of A and B is at least the integer 2; A is selected from the group consisting of --(CH2)n -- wherein n is 1 through 5 and --(Cn H2n --2 XY)-- wherein X is selected from the group consisting of hydroxy, acetoxy, amino and acetamido and Y is hydrogen, and X when taken together with Y is selected from the group consisting of =O and =CR3 R4 wherein R3 and R4 are selected from the group consisting of hydrogen and lower alkyl of 1 through 3 carbon atoms; B is absent or --(CH2)n -- wherein n is 1 through 3; R1 is selected from the group consisting of hydrogen and lower alkyl of 1 through 3 carbon atoms; R2 is selected from the group consisting of hydrogen, lower alkyl of 1 through 3 carbon atoms, EQU1 WHEREIN N IS 2 THROUGH 5 AND Ar is phenyl having zero through three substituents selected from the group consisting of lower alkyl of 1 through 3 carbon atoms, lower alkoxy of 1 through 3 carbon atoms, bromine, chlorine and fluorine; R1 and R2 taken together with --N is a saturated heterocyclic amino radical selected from the group consisting of unsubstituted and substituted pyrrolidino, piperidino, and hexamethylenimino; Z is selected from the group consisting of hydrogen, lower alkyl of 1 through 3 carbon atoms, lower alkoxy of 1 through 3 carbon atoms, nitro, amino, monoalkylamino of 1 through 3 carbon atoms, acylamido of 1 through 4 carbon atoms, bromine, chlorine and fluorine; and a pharmacologically acceptable acid addition salt thereof. It also relates to intermediates and processes for the preparation of the aforesaid novel compounds (1) and novel derivatives thereof. The administration to humans and animals of the novel compounds (1) depresses their central nervous systems and lowers their blood pressures.
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