- BACTERIAL EFFLUX PUMP INHIBITORS
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Disclosed herein are compounds of formula I: (formula I) and salts thereof. Also disclosed are compositions comprising compounds of formula I and methods using compounds of formula I.
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- ANTIMICROBIAL COMPOUNDS AND METHODS
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The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
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- BENZIMIDAZOLE-LINKED INDOLE COMPOUND ACTING AS NOVEL DIVALENT IAP ANTAGONIST
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The present invention discloses a benzimidazole-linked indole compound acting as novel divalent IAP antagonist, specifically disclosing the compound shown in fomulas (I) or a pharmaceutically acceptable salt thereof.
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- A pharmaceutical preparation of intermediate
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The invention discloses preparation methods of drug intermediates. The preparation method of a drug intermediate shown as formula 2-1 includes the following steps: reacting compound 2 with phenyl disulfide (PhSSPh) in a solvent under the action of an alka
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Paragraph 0066; 0068; 0071; 0073; 0076; 0079; 0088
(2018/11/03)
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- Design, synthesis and biological evaluation of small molecules as potent glucosidase inhibitors
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Abstract Herein we have reported design, synthesis and in vitro biological evaluation of a library of bicyclic lactams that led to the discovery of compounds 6 and 7 as a novel class of α-glucosidase inhibitors. They inhibited α-glucosidase (yeast origin)
- Hati, Santanu,Madurkar, Sanjay M.,Bathula, Chandramohan,Thulluri, Chiranjeevi,Agarwal, Rahul,Siddiqui, Faiza Amber,Dangi, Poonam,Adepally, Uma,Singh, Ashutosh,Singh, Shailja,Sen, Subhabrata
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p. 188 - 196
(2015/06/22)
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- Alternative route towards the convergent synthesis of a human purine nucleoside phosphorylase inhibitor-forodesine HCl
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Forodesine HCl is being investigated as a potential target for the control of T-cell proliferation. Herein we present an alternative route for the synthesis of the target molecule with addition of lactam to the lithiated deazahypoxanthine (generated in situ). The lactam was synthesized in five steps starting from l-pyroglutamic acid.
- Kamath, Vivekanand P.,Xue, Jie,Juarez-Brambila, Jesus J.,Morris Jr., Philip E.
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scheme or table
p. 5198 - 5200
(2009/12/06)
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- Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: A potential therapeutic agent for the treatment of hepatitis C infection
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Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or polyethylene glycol (PEG)-interferon-α alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.
- Venkatraman, Srikanth,Bogen, Stéphane L.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin,Jao, Edwin,Liu, Yi-Tsung,Lovey, Raymond,Hendrata, Siska,Huang, Yuhua,Pan, Weidong,Parekh, Tejal,Pinto, Patrick,Popov, Veljko,Pike, Russel,Ruan, Sumei,Santhanam, Bama,Vibulbhan, Bancha,Wu, Wanli,Yang, Weiying,Kong, Jianshe,Liang, Xiang,Wong, Jesse,Liu, Rong,Butkiewicz, Nancy,Chase, Robert,Hart, Andrea,Agrawal, Sony,Ingravallo, Paul,Pichardo, John,Kong, Rong,Baroudy, Bahige,Malcolm, Bruce,Guo, Zhuyan,Prongay, Andrew,Madison, Vincent,Broske, Lisa,Cui, Xiaoming,Cheng, Kuo-Chi,Hsieh, Yunsheng,Brisson, Jean-Marc,Prelusky, Danial,Korfmacher, Walter,White, Ronald,Bogdanowich-Knipp, Susan,Pavlovsky, Anastasia,Bradley, Prudence,Saksena, Anil K.,Ganguly, Ashit,Piwinski, John,Girijavallabhan, Viyyoor,Njoroge, F. George
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p. 6074 - 6086
(2007/10/03)
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- Stereoselective synthesis of protected (2S,3S)-N-methyl-5- hydroxyisoleucine, a component of halipeptins
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The stereocontrolled synthesis of the protected (2S,3S)-N-methyl-5- hydroxyisoleucine, a component of halipeptins A and B with potent anti-inflammatory activity, has been achieved. The key steps include (i) installation of a double bond to bicyclic lactam
- Hara, Sousuke,Makino, Kazuishi,Hamada, Yasumasa
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p. 8031 - 8035
(2007/10/03)
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- Total synthesis of (+)-calyculin A and (-)-calyculin B: Cyanotetraene construction, asymmetric synthesis of the C(26-37) oxazole, fragment assembly, and final elaboration
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A convergent total synthesis leading to (+)-calyculin A and (-)-calyculin B (1 and 2), antipodes of the potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, has been achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9-25) spiroketal dipropionate subunit (+)-BC; herein we describe construction of the C(1-8) cyanotetraene, an asymmetric synthesis of the C(26-37) oxazole, fragment assembly and final elaboration to (+)-1 and (-)-2. Highlights of the synthesis include: application of a one-pot three-component Suzuki reaction for the construction of phosphonate A, a bifunctional triene precursor of the light sensitive C(1-8) cyanotetraene subunit, an asymmetric synthesis of the C(26-32) oxazole (-)-D, exploiting the Silks-Odom 77Se NMR protocol to assess enantiomeric purity, construction of the C(33-37) subtarget (-)-E in a highly stereocontrolled fashion via an acyliminium ion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and (-)-calyculin B. The synthesis of (-)-2 also confirms the structure of calyculin B, previously based only on spectral comparison with calyculin A.
- Smith III, Amos B.,Friestad, Gregory K.,Barbosa, Joseph,Bertounesque, Emmanuel,Duan, James J.-W.,Hull, Kenneth G.,Iwashima, Makoto,Qiu, Yuping,Spoors, P. Grant,Salvatore, Brian A.
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p. 10478 - 10486
(2007/10/03)
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- Cyclopropanation reactions of pyroglutamic acid-derived synthons with akylidene transfer reagents
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The cyclopropanation of unsaturated lactams 1 and 3 derived from pyroglutamic acid with nucleophilic alkylidene transfer reagents is investigated. Good-to-modest yields of cyclopropanes were obtained with most sulfur ylides explored. Syn/anti selectivity was found to be dependent on the synthon as well as the sulfur ylide. This cyclopropanation methodology is used in the synthesis of arginine and glutamic acid analogues.
- Zhang, Rui,Mamai, Ahmed,Madalengoitia, Jose S.
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p. 547 - 555
(2007/10/03)
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- Synthesis of trans-epoxy-L-proline and cis-aziridino-L-proline from S-pyroglutamic acid. Regio- and diastereoselective ring opening of its derivatives
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The pyroglutamic acid derivative 4 was converted through several steps into 2S,3R,4S-epoxyproline 8. Key steps of the reaction sequence were the stereoselective epoxidation of 4 to 5 and the chemoselective reduction of the amide group of 5 with concomitan
- Herdeis, Claus,Aschenbrenner, Andrea,Kirfel, Armin,Schwabenlaender, Franz
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p. 2421 - 2432
(2007/10/03)
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- Functionalised pyrrolidinones derived from (S)-pyroglutamic acid by cycloaddition reactions
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The α,β-unsaturatcd bicyclic lactams 3a,c, prepared from (S)-pyroglutamic acid, are useful substrates for cycloaddition reactions, giving excellent regio- and diastereocontrol; however, lactam 3c has very superior reactivity with several dienes and dipoles under mild reaction conditions.
- Bailey, Jonathan H.,Cherry, David T.,Crapnell, Katherine M.,Moloney, Mark G.,Shim, Sung Bo,Bamford, Mark J.,Lamont, R. Brian
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p. 11731 - 11744
(2007/10/03)
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- A concise diastereoselective synthesis of the natural (2R, 3S)2-hydroxymethyl-3-hydroxy pyrrolidine
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(2R, 3S)-2-hydroxymethyl-3-hydroxy pyrrolidine 4, a constituent of CAstanospermum ausfrale, 1 was synthesized from (S)-pyroglutamic acid through diastereoselective epoxidation of α, β-unsaturated pyrrolidone 8.
- Griffart-Brunet, Dominique,Langlois, Nicole
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p. 119 - 122
(2007/10/02)
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- Chiral Pool Synthesis of trans-(2S,3S)-3-Hydroxyproline and Castanodiol from S-Pyroglutamic Acid.
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The Pyroglutamic acid derivative 1 was converted through several steps into Castanodiol 9 and 2S,3S-3-Hydroxyproline 11.Key steps of the reaction sequence were the stereoselective epoxidation of 1 to 2 and the regioselective ring opening of 2 to 3.BH3*S(CH3)2 reduction of the amide group of 3 and 4 resulted in a concomitant transformation of the acetal moiety into the N-benzyl protecting group.The air sensitive 5 and 6, were transformed to the stable N-Boc prolinol derivatives 7 and 8.Deprotection of 8 provided 9, while oxidation of 8 gave the protected proline derivative 10.Deprotection of 10 furnished enantiopure 2S,3S-3-Hydroxyproline 11.
- Herdeis, Claus,Hubmann, Hans Peter,Lotter, Hermann
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p. 119 - 128
(2007/10/02)
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- (L)-pyroglutamic acid as a chiral starting material for asymmetric synthesis
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Elaboration of lactam (1), readily available from (L)-pyroglutamic acid, provides access to a range of 2,4- and 2,3,4-substituted pyrrolidinones.
- Baldwin, Jack E.,Moloney, Mark G.,Shim, Sung Bo
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p. 1379 - 1380
(2007/10/02)
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