- Controlled oxygen release from pyridone endoperoxides promotes cell survival under anoxic conditions
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In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated pyridone-derived endoperoxides has led to the development of water-soluble molecules that undergo retro-Diels-Alder reactions in aqueous environment releasing oxygen in high yield and with half-lives of up to 13 h. These molecules in combination with vitamin C as singlet oxygen quencher significantly improved survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygen-depleted conditions.
- Benz, Sebastian,N?tzli, Sarah,Siegel, Jay S.,Eberli, Daniel,Jessen, Henning J.
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p. 10171 - 10182
(2014/01/17)
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- A new approach to the bicyclo[3.3.1]nonane framework of huperzine A-like molecules via palladium-catalyzed intramolecular γ-arylation
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In our synthetic studies toward huperzine A, a diastereoselective α′-alkylation of the α-amido-γ-methyl hexenone 4 was realized through a dianion intermediate which significantly enhanced the reactivity. Under the attempted Heck reaction conditions, an unexpected and unprecedented palladium-catalyzed intramolecular γ-arylation of 3 was observed, which generated 18 with bicyclo[3.3.1]nonane framework in satisfactory yield.
- Ding, Rui,Lu, Yunyu,Yao, Hequan,Sun, Bingfeng,Lin, Guoqiang
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scheme or table
p. 1097 - 1100
(2012/08/28)
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- Synthesis and structure-activity relationships of 8-(pyrid-3-yl)pyrazolo[1, 5-a]-1,3,5-triazines: Potent, orally bioavailable corticotropin releasing factor receptor-1 (CRF1) antagonists
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This report describes the syntheses and structure-activity relationships of 8-(substituted pyridyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. These CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research resulted in the discovery of compound 13-15, which is a potent, selective CRF1 antagonist (hCRF1 IC50 = 6.1 ± 0.6 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 13-15 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 13-15 has been advanced to clinical trials.
- Gilligan, Paul J.,Clarke, Todd,He, Liqi,Lelas, Snjezana,Li, Yu-Wen,Heman, Karen,Fitzgerald, Lawrence,Miller, Keith,Zhang, Ge,Marshall, Anne,Krause, Carol,McElroy, John F.,Ward, Kathyrn,Zeller, Kim,Wong, Harvey,Bai, Steven,Saye, Joanne,Grossman, Scott,Zaczek, Robert,Arneric, Stephen P.,Hartig, Paul,Robertson, David,Trainor, George
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experimental part
p. 3084 - 3092
(2010/02/28)
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- 1-(PIPERIDIN-4-YL)-1H-INDOLE DERIVATIVE
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The present invention provides a compound represented by the formula (1) or a pharmacologically acceptable salt thereof, or a hydrate thereof (provided that a compound in which all of R4a, R4b, and R4c are hydrogen atoms is excluded.): [wherein R1 represents a hydrogen atom, R2 represents a hydrogen atom, R3 represents the formula: wherein R4a, R4b, and R4c are the same as or different from each other and each represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group, etc.]
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Page/Page column 123-124
(2010/11/28)
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- PYRIDOAZEPINE DERIVATIVES
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The present invention relates to pyridoazepine derivatives that act as 5-HT ligands, e.g., 5-HT2C ligands. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
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Page/Page column 13
(2010/11/29)
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- NAPHTHYRIDINE COMPOUNDS
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Certain naphthyridine compounds are histamine H3 receptor and serotonin transporter modulators useful in the treatment of histamine H3 receptor- and serotonin-mediated diseases.
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Page/Page column 28
(2010/11/25)
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- LIGANDS FOR NICOTINIC ACETYLCHOLINE RECEPTORS, AND METHODS OF MAKING AND USING THEM
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One aspect of the present invention relates to heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. A second aspect of the invention relates to the use of a compound of the invention for modulation of a mammalian nicotinic acetylcholine receptor. The present invention also relates to the use of a compound of the invention for treating a mammal suffering from Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism or trichtillomania.
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- HETEROARYL- SUBSTITUTED PYRROLO` 2, 3- B! PYRIDINE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
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The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).
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Page/Page column 44
(2010/02/07)
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- 4 - (2-butylamino) - 2, 7-dimethyl-8- (2-methyl-6-methoxypyrid-3-yl) pyrazolo- [1,5-A] - 1,3,5-triazine, its enantiomers and pharmaceutically acceptable salts as corticotropin releasing factor receptor ligands
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Corticotropin releasing factor (CRF) antagonists of Formula (I): and its use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.
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- Synthesis, nicotinic acetylcholine receptor binding affinities, and molecular modeling of constrained epibatidine analogues
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Conformationally constrained epibatidine analogues 20a,b and 23a,b were synthesized using a radical cyclization as the key step. Radioligand displacement assays to six defined rat nicotinic acetylcholine receptor (nAChR) subtypes showed that 20a,b bind with moderate affinities, while 23a,b have low affinities. 20a exhibits higher affinity for the β2 containing subtype than for the β4 containing counterpart, while 20b possesses reversed selectivity. Modeling studies suggest that the spatial distribution of the ligand's atoms around the pharmacophore elements may control their nAChR subtype selectivity.
- Wei, Zhi-Liang,Petukhov, Pavel A.,Xiao, Yingxian,Tückmantel, Werner,George, Clifford,Kellar, Kenneth J.,Kozikowski, Alan P.
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p. 921 - 924
(2007/10/03)
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- Pyrazolopyrimidinone cGMP PDE5 inhibitors for the treatment of sexual dysfunction
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Compounds of the formulae (IA) and (IB): wherein R1is C1to C3alkyl optionally substituted with phenyl, Het or a N-linked heterocyclic group selected from piperidinyl and morpholinyl; wherein said phenyl group is optionally substituted by one or more substitutents selected from C1to C4alkoxy; halo; CN; CF3; OCF3or C1to C4alkyl wherein said C1to C4alkyl group is optionally substituted by C1to C4haloalkyl or haloalkoxy either of which is substituted by one or more halo atoms; R2is C1to C6alkyl and R13is OR3or NR5R6, or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity are potent and selective inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiesterase (cGMP PDE5) and have utility in the treatment of, inter alia, male erectile dysfunction (MED) and female sexual dysfunction (FSD).
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- A formal synthesis of (+)-Huperzine A
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A new formal stereoselective synthesis of (+)-Huperzine A (1) was achieved using as a key step a palladium mediated annulation between 2- methylene-1,3-propanediol diacetate and (1R,2S)-2-phenylcyclohexanol derived β-ketoester 2c. (C) 2000 Elsevier Science Ltd.
- Haudrechy, Arnaud,Chassaing, Christophe,Riche, Claude,Langlois, Yves
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p. 3181 - 3187
(2007/10/03)
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- Synthesis of novel chromeno[3,4-b]pyridinones
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A concise synthesis of two novel chromeno[3,4-b]pyridin-9-ones (as their ethylene ketals) has been achieved using, as a key step, the reaction between a mixed cuprate derived from 6-methoxy-2-methyl-3-lithiopyridine and 4-tert-butyldimethylsiloxycyclohex-2-enone.
- Caprio, Vittorio,Mann, John
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p. 3151 - 3155
(2007/10/03)
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- Aggregative activation in heterocyclic chemistry. Part 4. Metallation of 2-methoxypyridine: Unusual behaviour of the new unimetal superbase BuLi-Me2N(CH2)2OLi (BuLi-LiDMAE)
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A series of potential unimetal superbases BuLi-ROLi has been studied in order to increase the basicity/ nucleophilicity ratio ([B/N]R) of BuLi. The best [B/N]R ratio is found with BuLi-LiDMAE. This complex base apparently metallates 2-methoxypyridine at t
- Gros, Philippe,Fort, Yves,Caubere, Paul
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p. 3071 - 3080
(2007/10/03)
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- Electrophilic aromatic substitution on pyridine rings. Intramolecular cyclization using N-acyliminium ions
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The reaction of N-acyliminium ions with several activated pyridines resulted in an intramolecular cyclization to provide novel heterocycles. The reaction exhibited a regiochemical preference for cyclization para to the electron donating substitutent.
- Brodney, Michael A.,Padwa, Albert
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p. 6153 - 6156
(2007/10/03)
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- Functionalisation of 2-methoxy-6-methylpyridine
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Selective bromination of 2-methoxy-6-methylpyridine 2 afforded 5-bromo-2- methoxy-6-methylpyridine 8. Deprotonation of this pyridine derivative in benzylic position or lithium-bromine exchange allowed the regio-selective introduction of various electrophiles.
- Gray,Konopski,Langlois
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p. 1367 - 1379
(2007/10/02)
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- ALKOXY PYRIDINE COMPOUNDS
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The compounds are alkoxypyridine compounds which are histamine H 2-antagonists. Two specific compounds of the present invention are N-cyano-N'-methyl-N"-2-((3-methoxy-2-pyridyl)methylthio)ethyl!guanidine and 1-methylamino-1-2-(3-methoxy-2-pyridyl)methylthio)ethylamino!-2-nitroethylene. "
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