- Inhibitors of hepatitis C virus NS3·4A protease 2. Warhead SAR and optimization
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The α-ketoamide warhead (e.g., 15) was found to be a practical replacement for aliphatic aldehydes in a series of HCV NS3·4A protease inhibitors. Structure-activity relationships and prime side optimization are discussed.
- Perni, Robert B.,Pitlik, Janos,Britt, Shawn D.,Court, John J.,Courtney, Lawrence F.,Deininger, David D.,Farmer, Luc J.,Gates, Cynthia A.,Harbeson, Scott L.,Levin, Rhonda B.,Lin, Chao,Lin, Kai,Moon, Young-Choon,Luong, Yu-Ping,O'Malley, Ethan T.,Rao, B. Govinda,Thomson, John A.,Tung, Roger D.,Van Drie, John H.,Wei, Yunyi
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Read Online
- AZALACTAM COMPOUNDS AS HPK1 INHIBITORS
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This invention relates to compounds of general Formula (I) and pharmaceutically acceptable salts thereof, in which R1, R2, R3a, R3b, and R4 are as defined herein, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.
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- The synthesis of α,α-disubstituted α-amino acids via ichikawa rearrangement
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An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X7-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis.
- Szczes?niak, Piotr,Pieczykolan, Micha?,Stecko, Sebastian
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p. 1057 - 1074
(2016/02/19)
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- NOVEL PYRROLIDINE DERIVATIVES
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The invention relates to a compound of formula (I) wherein A and R1 to R7 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
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Paragraph 0178
(2013/06/05)
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- Synthesis of proline analogues as potent and selective cathepsin S inhibitors
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Cathepsin S is a potential target of autoimmune disease. A series of proline derived compounds were synthesized and evaluated as cathepsin S inhibitors. We discovered potent cathepsin S inhibitors through structure-activity relationship studies of proline analogues. In particular, compound 19-(S) showed promising in vitro/vivo pharmacological activities and properties as a selective cathepsin S inhibitor.
- Kim, Mira,Jeon, Jiyoung,Song, Jiyeon,Suh, Kwee Hyun,Kim, Young Hoon,Min, Kyung Hoon,Lee, Kwang-Ok
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p. 3140 - 3144
(2013/06/26)
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- NOVEL PYRROLIDINE DERIVATIVES AS INHIBITORS OF CATHEPSIN
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The invention relates to a compound of formula (I), wherein A and R1 to R7 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
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Page/Page column 24
(2013/06/06)
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- CATHEPSIN C INHIBITORS
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Disclosed are 4-amino-2-butenamides of Formula (I) having pharmacological activity, pharmaceutical compositions containing them, and methods for the treatment of diseases mediated by the cathepsin C enzyme such as chronic obstructive pulmonary disease.
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- Cyclic amine compounds
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The present invention relates to pharmaceutical agents which are agents for the prophylaxis or treatment of hypogonadism, male climacteric disorder, frailty, cachexia or osteoporosis; the pharmaceutical agents frailty suppressants, muscle strength enhance
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Page/Page column 48
(2009/03/07)
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- Synthesis and dipeptidyl peptidase inhibition of N-(4-substituted-2,4-diaminobutanoyl)piperidines
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In this paper, we report the synthesis of diastereomerically pure N-(4-substituted-2,4-diaminobutanoyl)piperidines. These compounds were prepared to investigate the influence of the 4-substitution on the dipeptidyl peptidase II (DPP II) activity and selectivity of the parent N-(2,4-diaminobutanoyl)piperidine. The (4S)-methyl compound showed subnanomolar inhibition, comparable with the parent compound. The (4R)-methyl group or bigger substituents decreased the activity.
- Soroka, Anna,der Veken, Pieter Van,Meester, Ingrid De,Lambeir, Anne-Marie,Maes, Marie-Berthe,Scharpe, Simon,Haemers, Achiel,Augustyns, Koen
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p. 4777 - 4779
(2007/10/03)
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- COMPOUNDS AND COMPOSITIONS AS CATHEPSIN S INHIBITORS
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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of Cathepsin S.
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Page/Page column 36-37
(2010/02/14)
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- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The application is directed to haloalkyl-substituted compounds of Formula (I), wherein R1, R1a, R2, R3, R4’ and E are as defined in the claims. The compounds are inhibitors of cysteine proteases, in p
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Page/Page column 57
(2010/02/11)
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- AMIDINO COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 25
(2010/02/12)
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- SILINANE COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them. The present invention is also directed to the use of these inhibitors in combination with a therapy that causes a deleterious immune response in patients receiving the therapy.
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Page/Page column 55
(2008/06/13)
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- Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
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The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.
- Catalano, John G,Deaton, David N,Furfine, Eric S,Hassell, Annie M,McFadyen, Robert B,Miller, Aaron B,Miller, Larry R,Shewchuk, Lisa M,Willard Jr., Derril H,Wright, Lois L
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p. 275 - 278
(2007/10/03)
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- AMIDINO COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceu
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Page/Page column 55
(2010/02/09)
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- Enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)butane]platinum(II) complexes: Synthesis and antitumor activity against MCF-7 and MDA-MB 231 breast cancer and LnCaP/FGC prostate cancer cell lines
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Enantiomerically pure 1,2-diamino-1-(4-fluorophenyl)butanes were synthesized by stereoselective procedures. The enantiomeric purity was determined by 1H NMR spectroscopy after derivatization with (1R)-myrtenal. For the coordination to platinum,
- Dullin, Anja,Dufrasne, Francois,Gelbcke, Michael,Gust, Ronald
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p. 654 - 667
(2007/10/03)
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- Process for preparing heteroaryl and unsaturated heterocycloalkylmagnesium reagents and uses thereof
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The present invention is directed to a novel process for preparing heteroaryl and unsaturated heterocycloalkylmagnesium reagents that are useful in the synthesis of a variety of pharmaceuticals, in particular certain cysteine protease inhibitors.
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- CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine protease, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceut
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Page/Page column 53-54
(2010/02/07)
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- PEPTIDIC COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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- Short synthesis of protease inhibitors via modified Passerini condensation of N-Boc-α-aminoaldehydes
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Extension of the previously reported modification of Passerini multicomponent reaction (involving condensation with N-Boc-α-aminoaldehydes followed by a deprotection-transacylation step) to α-aminoacid derived carboxylic or isocyanide components, allowed the highly convergent and short synthesis of complex peptidomimetic structures, including known potent inhibitors of serine proteases.
- Banfi, Luca,Guanti, Giuseppe,Riva, Renata,Basso, Andrea,Calcagno, Emiliano
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p. 4067 - 4069
(2007/10/03)
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- Stereospecific Synthesis of Peptidyl α-Keto Amides as Inhibitors of Calpain
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Peptidyl α-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain.A stereospecific synthesis was devised in which Cbz-dipeptidyl-α-hydroxy amides were oxidized with TEMPO/hypochlorite to the corresponding α-keto amides
- Harbeson, Scott L.,Abelleira, Susan M.,Akiyama, Alan,Barrett, Robert,Carroll, Renee M.,et al.
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p. 2918 - 2929
(2007/10/02)
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