- HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS
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Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein HET, R1, R2, R3, R4, R5, L, L1, X1, X2, X3 and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.
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Page/Page column 112; 169
(2020/06/05)
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- Catalytic Ring Expansions of Cyclic Alcohols Enabled by Proton-Coupled Electron Transfer
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We report here a catalytic method for the modular ring expansion of cyclic aliphatic alcohols. In this work, proton-coupled electron transfer activation of an allylic alcohol substrate affords an alkoxy radical intermediate that undergoes subsequent C-C bond cleavage to furnish an enone and a tethered alkyl radical. Recombination of this alkyl radical with the revealed olefin acceptor in turn produces a ring-expanded ketone product. The regioselectivity of this C-C bond-forming event can be reliably controlled via substituents on the olefin substrate, providing a means to convert a simple N-membered ring substrate to either n+1 or n+2 ring adducts in a selective fashion.
- Zhao, Kuo,Yamashita, Kenji,Carpenter, Joseph E.,Sherwood, Trevor C.,Ewing, William R.,Cheng, Peter T. W.,Knowles, Robert R.
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supporting information
p. 8752 - 8757
(2019/06/13)
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- Synthesis and biological evaluation of pyrimidine derivatives with diverse azabicyclic ether/amine as novel GPR119 agonist
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A class of novel pyrimidine derivatives bearing diverse conformationally restricted azabicyclic ether/amine were designed, synthesized and evaluated for their GPR119 agonist activities against type 2 diabetes. Most compounds exhibited superior hEC50
- Yang, Zunhua,Fang, Yuanying,Park, Haeil
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p. 2515 - 2519
(2017/05/10)
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- SUBSTITUTED 2-AZABICYCLES AND THEIR USE AS OREXIN RECEPTOR MODULATORS
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The present invention is directed to compounds of Formula I: wherein X is N or CR1; Y is N or CR2; R1 is H, alkoxy, halo, triazolyl, pyrimidinyl, oxazolyl, isoxazole, oxadiazolyl, or pyrazolyl; R2 is H, alkyl, alkoxy, or halo; Z is NH or O; R3 is H, alkyl, alkoxy, halo, or triazolyl; R4 is H or alkyl; or R3 and R4, together with the atoms to which they are attached, form a 6-membered aryl ring or a 5- or 6-membered heteroaryl ring; R5 is pyridyl, pyrazinyl, or pyrimidinyl, wherein the pyridyl, pyrazinyl, or pyrimidinyl is optionally substituted with halo or alkyl; and n is 1 or 2. Methods of making the compounds of Formula I are also described. The invention also relates to pharmaceutical compositions comprising compounds of Formula I. Methods of using the compounds of the invention are also within the scope of the invention.
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- Synthesis of novel azanorbornylpurine derivatives
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Azanorbornylpurine derivatives were prepared by Mitsunobu reaction of appropriate hydroxyazanorbornane derivative with 6-chloropurine or construction of purine base at azanorbornylamines. The prepared target compounds were evaluated for antiviral activity and effect on neuronal and muscle nicotinic acetylcholine receptors.
- H?ebabecky, Hubert,Dejmek, Milan,Dra?ínsky, Martin,?ála, Michal,Leyssen, Pieter,Neyts, Johan,Kaniaková, Martina,Kr?ek, Jan,Nencka, Radim
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experimental part
p. 1286 - 1298
(2012/02/15)
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- Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes
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The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development.
- Xia, Yan,Chackalamannil, Samuel,Greenlee, William J.,Jayne, Charles,Neustadt, Bernard,Stamford, Andrew,Vaccaro, Henry,Xu, Xiaoying,Baker, Hana,O'Neill, Kim,Woods, Morgan,Hawes, Brian,Kowalski, Tim
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p. 3290 - 3296
(2011/06/24)
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- Improved synthesis of monoprotected 5- and 6-amino-2-azanorbornanes
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(Chemical Equation Presented) An improved synthesis of Boc-monoprotected 5- and 6-amino-2-azanorbornanes is reported. The synthetic scheme consists of five steps and allows multigram quantities of the title compounds to be obtained. The regio- and stereochemistries of the products are established by two-dimensional NMR experiments. Copyright Taylor & Francis Group, LLC.
- Dacenko, Oleksandr P.,Manoylenko, Olga V.,Grygorenko, Oleksandr O.,Mykhailiuk, Pavel K.,Volochnyuk, Dmitriy M.,Shishkin, Oleg V.,Tolmachev, Andrey A.
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p. 981 - 992
(2011/04/25)
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- BRIDGED BICYCLIC RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
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The present invention is directed to synthetic bridged bicyclic compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptab
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Page/Page column 51
(2011/06/26)
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- PIPERAZINO DERIVATIVES AS NEUROKININ ANTAGONISTS
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The invention relates to compounds of formula (I) wherein Z, Rc, y, m, u, Ar2, n, X, Rc', l and Ar2 are as described herein. These compounds are neurokinin antagonists. These compounds are useful in the treatment of chronic airway diseases such as asthma.
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Page/Page column 38
(2010/11/08)
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- Heterocyclic compounds
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The present invention provides heterocyclic 2-aza-bicyclo[2.2.1]heptane compounds which are useful for modulating a muscarinic ptor.
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