- NOVEL EP2 RECEPTOR AGONISTS
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The compounds of formula (1), in which R1, R4, A and X have the meanings as given in the description, are novel effective EP2 agonists.
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- COMPOUNDS FOR THE INHIBITION OF CELLULAR PROLIFERATION
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Compositions and methods for inhibiting translation are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, (4) disorders associated with viral infections, and/or (5) non-proliferative metabolic disorders such as type II diabetes where inhibition of translation initiation is beneficial using the compounds disclosed herein.
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- THIAZOLE DERIVATIVES AS SGLT2 INHIBITORS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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The present invention relates to a novel compound with thiazole ring having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney, and a pharmaceutical composition comprising the same as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly diabetes.
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Page/Page column 54
(2012/01/06)
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- RENIN INHIBITORS
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Renin inhibitors, which are spirocyclic piperidine amides, of structural formula (I) and pharmaceutical compositions thereof useful in the treatment of cardiovascular diseases and renal insufficiency, wherein n, for each instance in which it occurs, is independently 0, 1, or 2; R1 is hydrogen, C1-6 -alkyl or C3-6 -cycloalkyl, wherein said C1-6 -alkyl or C3-6 -cycloalkyl group can be independently substituted with 1-3 halogens; A is (i) a five- or six-membered saturated or unsaturated heterocyclic or carbocyclic monocyclic ring or (ii) a five- or six-membered saturated or unsaturated heterocyclic or carbocyclic ring which is fused to another five- or six-membered saturated or unsaturated heterocyclic or carbocyclic ring, V is a bond or -(C=O)-, -CH(OH)-, -CH2- or =CH-; U is a bond or -CH2-, or for the case when V is =CH-, U is -CH=; X is =CH-, =CF-, =C(OR3)-, or -C=O-; and Y is =CH-, =CF-, =N-, or for the case when X is -C=O-, Y is -N(R3)-.
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- NOVEL C-ARYL GLUCOSIDE SGLT2 INHIBITORS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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A novel C-aryl glucoside compound, or a pharmaceutically acceptable salt or a prodrug thereof having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney; and a pharmaceutical composition comprising the same as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly, diabetes, are provided.
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Page/Page column 113-114
(2010/12/31)
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- A rapid, large-scale synthesis of a potent cholecystokinin (CCK) 1R receptor agonist
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The development of a scalable synthesis of a potent cholecystokinin (CCK) IR receptor agonist is described. The focus on a rapid short-term delivery rather than longer-term development allowed for the preparation of multihundred gram quantities to support
- Kuethe, Jeffrey T.,Childers, Karla G.,Humphrey, Guy R.,Journet, Michel,Peng, Zhihui
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p. 1201 - 1208
(2013/01/03)
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- Synthesis, biological evaluation and molecular modelling studies of novel ACD- and ABD-ring steroidomimetics as inhibitors of CYP17
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Two novel classes of non-steroidal substrate mimetics were synthesised and examined for their potency as inhibitors of human CYP17. Selected compounds were tested for inhibition of hepatic CYP enzymes 3A4, 1A2, 2C9 and 2C19. The most promising compound 15
- Pinto-Bazurco Mendieta, Mariano A.E.,Negri, Matthias,Jagusch, Carsten,Hille, Ulrike E.,Mueller-Vieira, Ursula,Schmidt, Dirk,Hansen, Klaus,Hartmann, Rolf W.
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p. 267 - 273
(2008/09/17)
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- The mercury-mediated decarboxylation (Pesci reaction) of naphthoic anhydrides investigated by microwave synthesis
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The mercury-mediated decarboxylation (Pesci reaction) of several substituted naphthoic anhydrides has been investigated by microwave synthesis. A laboratory microwave reactor was found to be ideal for small-scale preparations of this slow reaction, reducing reaction times from typically four days to less than 1 h for the three-step process. The ionic reaction medium rapidly heated to high temperatures under microwave heating and could be efficiently maintained by low microwave power settings. Generation of stoichiometric CO2 was safely contained within the reaction tubes. A simplified reaction procedure has been developed. For substituted naphthoic anhydrides, 1H NMR analysis of the naphthoate ester derivatives indicated no change in the regioisomer ratio compared to previously reported thermal values.
- Moseley, Jonathan D.,Gilday, John P.
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p. 4690 - 4697
(2007/10/03)
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- A new approach to rapid parallel development of four neurokinin antagonists. Part 2. Synthesis of ZD6021 cyano acid
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The manufacture of ZD6021 cyano acid (1) using a new project approach is described. Research Department processes were scaled up to 100 L if process safety anal robustness were not compromised; other factors were treated according to the new approach. By using this strategy, we were able to manufacture a key intermediate on sufficient scale to support delivery of 1 kg quantities of bulk drug within 6 months of the start of lab work.
- Moseley, Jonathan D.,Moss, William O.,Welham, Matthew J.,Ancell, Claire L.,Banister, John,Bowden, Sharon A.,Norton, Glenn,Young, Maureen J.
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- Discovery of novel, orally active dual NK1/NK2 antagonists
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Exploration of the SAR around selective NK2 antagonists, SR48968 and ZD7944, led to the discovery that naphth-1-amide analogues provide potent dual NK1 and NK2 antagonists. ZD6021 inhibited binding of [3H]-NKA or [3H]-SP to human NK1 and NK2 receptors, with high-affinity (Ki=0.12 and 0.62 nM, respectively). In functional assays ZD6021 had, at 10-7 M, in human pulmonary artery pKB=8.9 and in human bronchus pKB=7.3, for NK1 and NK2, respectively. Oral administration of ZD6021 to guinea pigs dose-dependently attenuated ASMSP induced extravasation of plasma proteins, ED50=0.5 mg/kg, and NK2 mediated bronchoconstriction, ED50=13 mg/kg.
- Bernstein, Peter R.,Aharony, David,Albert, Jeffrey S.,Andisik, Donald,Barthlow, Herbert G.,Bialecki, Russell,Davenport, Timothy,Dedinas, Robert F.,Dembofsky, Bruce T.,Koether, Gerard,Kosmider, Benedict J.,Kirkland, Karin,Ohnmacht, Cyrus J.,Potts, William,Rumsey, William L.,Shen, Lihong,Shenvi, Ashok,Sherwood, Scott,Stollman, David,Russell, Keith
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p. 2769 - 2773
(2007/10/03)
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- Preparation of a series of substituted fluoromethylnaphthalenes
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A series of 22 3- and 4-substituted 1-fluoromethylnaphthalenes have been synthesized.Details of practical procedures for the preparation of all intermediates are described, and physical properties for all of the substituted naphthalenes synthesized, and spectral parameters for 51 previously unknown compounds, are given.
- Dixon, Elisabeth A.,Fischer, Alfred,Robinson, Frank P.
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p. 2629 - 2641
(2007/10/02)
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