- Discovery of Lu AA33810: A highly selective and potent NPY5 antagonist with in vivo efficacy in a model of mood disorder
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The structure-activity relationship of a series of tricyclic-sulfonamide compounds 11-32 culminating in the discovery of N-[trans-4-(4,5-dihydro-3,6- dithia-1-aza-benzo[e]azulen-2-ylamino)-cyclohexylmethyl]-methanesulfonamide (15, Lu AA33810) is reported. Compound 15 was identified as a selective and high affinity NPY5 antagonist with good oral bioavailability in mice (42%) and rats (92%). Dose dependent inhibition of feeding was observed after i.c.v. injection of the selective NPY5 agonist ([cPP1-7,NPY19-23,Ala 31,Aib32,Gln34]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress.
- Packiarajan, Mathivanan,Marzabadi, Mohammad R.,Desai, Mahesh,Lu, Yalei,Noble, Stewart A.,Wong, Wai C.,Jubian, Vrej,Chandrasena, Gamini,Wolinsky, Toni D.,Zhong, Hualing,Walker, Mary W.,Wiborg, Ove.,Andersen, Kim
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p. 5436 - 5441
(2011/10/12)
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- Nickel - promoted favorskii type rearrangement of cyclic α-bromoketones
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Favorskii type rearrangement of cyclic α-bromo ketones 2 is promoted by NiCl2 in refluxing methanol, giving the rearranged carboxylic acid ester 3 in excellent yields. The reaction of 4-bromo-2,3,4,5-tetrahydronaphth [2,1-b]oxepin-5-one (5) and its regioisomer 8 with NiCl2 in McOH resulted in Favorskii rearranged carboxylic acid esters 6 and 9 respectively.
- Tandon, Vishnu K.,Awasthi, Anoop K.,Singh, Kunwar A.,Maurya, Hardesh K.,Gautam, Sanjay K.
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experimental part
p. 593 - 600
(2010/04/27)
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- BENZOPYRAN AND BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
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Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 177
(2009/10/06)
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- Lewis Acid-Promoted Favorskii-Type Ring Contraction of Some Cyclic α-Bromo Ketones and Their Acetals
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The α-bromo cycloalkyl aryl ketones 2a-d on heating with zinc chloride in methanol furnished in moderate to good yields the ring-contracted products 3a-d having gem methyl carbomethoxy function.The acetals of the related α-bromo ketones 7a-c, lacking the methyl group on the halogen-bearing carbon atom, afforded in acceptable yields the ring-contracted esters 8a-c when heated in protic solvent.The limitation of the present ring-contraction procedure has been discussed.
- Maiti, Swaraj B.,Ray Chaudhuri, S. R.,Chatterjee, Amareshwar
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p. 806 - 809
(2007/10/02)
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