- PROCESS FOR THE PREPARATION OF A CHIRAL PIPERAZINE-2-CARBOXYLIC ACID
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The invention relates to a novel process for the preparation of a chiral piperazine-2- carboxylic acid or of a salt thereof of the formula (I). The chiral piperazine-2-carboxylic acid derivatives of the formula (I) are key intermediates for the preparation of fused heteroaryl dihydro pyrimidines which are useful for the treatment and prophylaxis of hepatitis B virus infections.
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- RECEPTOR ANTAGONIST, PHARMACEUTICAL COMPOSITION COMPRISING SAME, AND USAGE THEREOF
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The present invention discloses a receptor inhibitor of formula (I), a composition comprising the same and the usage thereof.
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Paragraph 0221-0222; 0227-0228
(2021/01/14)
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- A traceless, solid-supported synthesis ofβ-turn mimetics based on the hexahydropyrazino[1,2-α ]pyrazine-1,2-dione scaffold
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The solid-supported synthesis of a library of-turn mimetics based on the three-component Petasis condensation and 2,5-diketopiperazine formation is reported. The eight-step sequence starts from optically pure (S)-piperazine-2-carboxylic acid dihydrochloride, which is first converted into an orthogonally protected, resin-bound amino derivative. The subsequent transformations lead to compounds having the common hexahydropyrazino[1,2-a] pyrazine-1,2-dione core and diverse side chains, which mimic the-turn structure. This synthetic route includes protection of the initial amino acid with two different protecting groups, followed by attachment to the Wang resin using the Mitsunobu reaction, deprotection of the-nitrogen atom, then Petasis reaction, amidation, deprotection of the-nitrogen atom, coupling with a Boc-protected-amino acid, cleavage of the Boc group, and the cyclizative cleavage from the resin, resulting in the requested bicyclic products obtained in good yields and having good to moderate purities. Six different boronic acids, four amines, and nine-amino acids were applied to this synthetic route, to explore the efficiency and limitations of the described method. Georg Thieme Verlag Stuttgart.
- Mieczkowski, Adam,Kozminski, Wiktor,Jurczak, Janusz
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experimental part
p. 221 - 232
(2010/04/02)
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- Disubstituted pyrimidines as Lck inhibitors
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We have developed a family of 4-benzimidazolyl-N-piperazinethyl-pyrimidin-2-amines that are subnanomolar inhibitors of Lck. A subset of these Lck inhibitors, with heterocyclic substituents at the benzimidazole C5, are also low-nanomolar inhibitors of cell
- Hunt, Julianne A.,Beresis, Richard T.,Goulet, Joung L.,Holmes, Mark A.,Hong, Xinfang J.,Kovacs, Ernest,Mills, Sander G.,Ruzek, Rowena D.,Wong, Frederick,Hermes, Jeffrey D.,Park, Young-Whan,Salowe, Scott P.,Sonatore, Lisa M.,Wu, Lin,Woods, Andrea,Zaller, Dennis M.,Sinclair, Peter J.
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supporting information; scheme or table
p. 5440 - 5443
(2010/04/26)
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- COMPOUNDS AND METHODS FOR TREATMENT OF HCV
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Aryl substituted pyrazole derivatives are provided, as well as processes for their preparation. The invention also provides compositions and methods for the treatment of HCV by administering a compound of the present invention, alone or in combination with additional antiviral agents, in a therapeutically effective amount.
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Page/Page column 73-74
(2008/12/05)
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- L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor
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A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with K(i) values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1(IIIb)-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.
- Dorsey,Levin,McDaniel,Vacca,Guare,Darke,Zugay,Emini,Schleif,Quintero,Lin,Chen -,Holloway,Fitzgerald,Axel,Ostovic,Anderson,Huff
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p. 3443 - 3451
(2007/10/02)
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