- HETEROARYL SUBSTITUTED HETEROCYCLYL SULFONES
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The invention relates to aryl substituted heterocyclyl sulfones as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 133
(2015/11/09)
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- 2-Cyanophenyl fused heterocyclic compounds, and compositions and uses thereof
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Fused heterocyclic compounds are provided according to formula 1: where R1, R2, R3, and m are as defined herein. Provided compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, cognitive disorders, anxiety, depression, and others.
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Page/Page column 29; 30
(2008/12/08)
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- Practical asymmetric synthesis of a non-peptidic αvβ 3 antagonist
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(Chemical Equation Presented) The development of a practical and highly convergent synthesis of an αvβ3 antagonist is described. The two key fragments present in this compound, a tetrahydropyrido[2,3-b]azepine ring system and a chiral 3-aryl-5-oxopentanoic acid, were constructed independently and then coupled at a late stage using a Wittig reaction. The pyridoazepine moiety was prepared from N-Boc 6-chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in situ cyclization. A Suzuki reaction was then used to attach the propionaldehyde side-chain required for Wittig coupling. The coupling partner was prepared from asymmetric methanolysis of a 3-substituted glutaric anhydride followed by elaboration of the acid moiety to the requisite β-keto phosphorane. Using this route, kilogram quantities of the desired drug candidate were prepared.
- Keen, Stephen P.,Cowden, Cameron J.,Bishop, Brian C.,Brands, Karel M. J.,Davies, Antony J.,Dolling, Ulf H.,Lieberman, David R.,Stewart, Gavin W.
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p. 1771 - 1779
(2007/10/03)
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- Nonpeptide alphavbeta3 antagonists. Part 11: discovery and preclinical evaluation of potent alphavbeta3 antagonists for the prevention and treatment of osteoporosis.
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3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC(50) = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.
- Coleman, Paul J,Brashear, Karen M,Askew, Ben C,Hutchinson, John H,McVean, Carol A,Duong,Feuston, Bradley P,Fernandez-Metzler, Carmen,Gentile, Michael A,Hartman, George D,Kimmel, Donald B,Leu, Chih-Tai,Lipfert, Lorraine,Merkle, Kara,Pennypacker, Brenda,Prueksaritanont, Thomayant,Rodan, Gideon A,Wesolowski, Gregg A,Rodan, Sevgi B,Duggan, Mark E
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p. 4829 - 4837
(2007/10/03)
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- Shock sensitivity of a vinamidinium bis-perchlorate reagent and demonstration of a lower energy alternative
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'Vinamidinium' bis-perchlorate salt 1 (2-dimethylaminomethylene-1,3-bis(dimethylimmonio)-propane bis-perchlorate) was found to possess remarkably high thermal energy as well as significant shock sensitivity. A reported method for preparation of 2,5-disubstituted pyrimidines with 1 was of interest, and we found that the corresponding bis-tetrafluoroborate salt 2 was equally effective in this transformation, while possessing significantly lower thermal energy.
- Ragan,McDermott,Jones,Am Ende,Clifford,McHardy,Heck,Liras,Segelstein
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p. 1172 - 1174
(2007/10/03)
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- An Alternative Preparation of the 2-Dimethylaminomethylene-1,3-bis(dimethylimminio)propane Salt from Phosphonoacetic Acids and Some Applications in Heterocyclic Synthesis
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An alternative preparation of a 2-iminovinamidinium salt from phosphonoacetic acids is described along with its application to the synthesis of 5-formylpyrimidines and masked 4-formylpyrazoles.
- Gupton, John T.,Gall, John E.,Riesinger, Steve W.,Smith, Stanton Q.,Bevirt, Kathy M.,et al.
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p. 1281 - 1285
(2007/10/02)
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