- Design, Synthesis, and Characterization of Cyclic Peptidomimetics of the Inducible Nitric Oxide Synthase Binding Epitope That Disrupt the Protein-Protein Interaction Involving SPRY Domain-Containing Suppressor of Cytokine Signaling Box Protein (SPSB) 2 and Inducible Nitric Oxide Synthase
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SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) 2-deficient macrophages have been found to exhibit prolonged expression of inducible nitric oxide synthase (iNOS) and enhanced killing of persistent pathogens, suggesting that inhibitors of the SPSB2-iNOS interaction have potential as novel anti-infectives. In this study, we describe the design, synthesis, and characterization of cyclic peptidomimetic inhibitors of the SPSB2-iNOS interaction constrained by organic linkers to improve stability and druggability. SPR, ITC, and 19F NMR analyses revealed that the most potent cyclic peptidomimetic bound to the iNOS binding site of SPSB2 with low nanomolar affinity (KD 29 nM), a 10-fold improvement over that of the linear peptide DINNN (KD 318 nM), and showed strong inhibition of SPSB2-iNOS interaction in macrophage cell lysates. This study exemplifies a novel approach to cyclize a Type II β-turn linear peptide and provides a foundation for future development of this group of inhibitors as new anti-infectives.
- Harjani, Jitendra R.,Yap, Beow Keat,Leung, Eleanor W. W.,Lucke, Andrew,Nicholson, Sandra E.,Scanlon, Martin J.,Chalmers, David K.,Thompson, Philip E.,Norton, Raymond S.,Baell, Jonathan B.
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Read Online
- 3-Cyano-3-aza-β-amino acid derivatives as inhibitors of human cysteine cathepsins
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Nitrile-type inhibitors are known to interact with cysteine proteases in a covalent-reversible manner. The chemotype of 3-cyano-3-aza-β-amino acid derivatives was designed in which the N-cyano group is centrally arranged in the molecule to allow for interactions with the nonprimed and primed binding regions of the target enzymes. These compounds were evaluated as inhibitors of the human cysteine cathepsins K, S, B, and L. They exhibited slow-binding behavior and were found to be exceptionally potent, in particular toward cathepsin K, with second-order rate constants up to 52 900 × 103M-1s-1.
- Schmitz, Janina,Beckmann, Anna-Madeleine,Dudic, Adela,Li, Tianwei,Sellier, Robert,Bartz, Ulrike,Gütschow, Michael
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Read Online
- WEE1 KINASE INHIBITORS AND METHODS OF TREATING CANCER USING THE SAME
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A compound, or a pharmaceutically acceptable salts or prodrugs thereof, having the chemical structure (I) and methods of using these compounds to inhibit WEE1 kinase and treat cancer in a subject.
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Page/Page column 39-40
(2019/09/18)
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- Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy
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WEE1 kinase regulates the G2/M cell-cycle checkpoint, a critical mechanism for DNA repair in cancer cells that can confer resistance to DNA-damaging agents. We previously reported a series of pyrazolopyrimidinones based on AZD1775, a known WEE1 inhibitor, as an initial investigation into the structural requirements for WEE1 inhibition. Our lead inhibitor demonstrated WEE1 inhibition in the same nanomolar range as AZD1775, and potentiated the effects of cisplatin in medulloblastoma cells, but had reduced single-agent cytotoxicity. These results prompted the development of a more comprehensive series of WEE1 inhibitors. Herein we report a series of pyrazolopyrimidinones and identify a more potent WEE1 inhibitor than AZD1775 and additional compounds that demonstrate that WEE1 inhibition can be achieved with reduced single-agent cytotoxicity. These studies support that WEE1 inhibition can be uncoupled from the potent cytotoxic effects observed with AZD1775, and this may have important ramifications in the clinical setting where WEE1 inhibitors are used as chemosensitizers for DNA-targeted chemotherapy.
- Matheson, Christopher J.,Casalvieri, Kimberly A.,Backos, Donald S.,Reigan, Philip
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supporting information
p. 1681 - 1694
(2018/08/01)
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- Synthetic method of Fmoc-Aza-beta 3-Ala
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The invention discloses a synthetic method of Fmoc-Aza-Beta 3-Ala. The method comprises the following steps: processing methylhydrazine by utilizing excessive di-tert-butyl dicarbonate ester to obtaina compound 1 as shown in formula B1, Fmoc-cl and NaHCO3 are added into the compound 1 shown in the formula B1 to have nucleophilic substitution to obtain a compound 2 as shown in formula B2, the compound 2 as shown in the formula B2 is obtained by virtue of the acidification of trifluoroacetic acid (TFA) or HCLG, so that a Boc protection group is broken to obtain a compound 3 as shown in formulaB3; the compound 3 as shown in the formula B3 is enable to have nucleophilic substitution with tert-butyl bromoacetate to obtain a compound 4 as shown in formula A4; and the compound 4 as shown in theformula A4 is enabled to have degreasing reaction with dichloromethane introduced with HCl gas to obtain a target product Fmoc-Aza-Beta 3-Ala as shown in formula B5. The preparation method provided by the invention is mild in reaction condition, the Fmoc protection group can be easily removed by utilizing a mild alkaline condition, the operation is simple, the acid instable group can be used forprotecting a side chain, and a route is simple and efficient.
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Paragraph 0033; 0034
(2018/07/07)
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- Preparation method of anamorelin intermediate
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The invention relates to the field of medicine synthesis, in particular to a preparation method of an anamorelin intermediate. On one hand, 1-boc-1-methylhydrazine is taken as a reaction material, anda key intermediate tert-butyl N,N',N'-trimethylhydrazinecarboxylate is prepared in one pot with a formaldehyde compound and palladium catalyst/hydrogen source alternative reaction method. The methodis simple to operate, and the used raw material is safe and easy to obtain; compared with the prior art, the method has the increased yield; on the other hand, in the method, tert-butyl N,N',N'-trimethylhydrazinecarboxylate and hydrochloric acid are subjected to a reaction in an organic solvent, and a high-yield and high-purity crystallized product of N,N',N'-trimethylhydrazine hydrochloride can be directly obtained, and the crystallized product is not required to be further purified and is low in moisture absorption, convenient to store and very suitable for industrial mass production.
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Paragraph 0102; 0104
(2018/07/06)
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- N -aminopyridinium salts as precursors for N-centered radicals - Direct amidation of arenes and heteroarenes
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Readily prepared N-aminopyridinium salts are valuable precursors for the generation of N-centered radicals. Reduction of these salts by single electron transfer allows for clean generation of amidyl radicals. It is shown that direct radical C-H amination of heteroarenes and arenes can be achieved with N-aminopyridinium salts under mild conditions by using photoredox catalysis.
- Greulich, Tobias W.,Daniliuc, Constantin G.,Studer, Armido
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supporting information
p. 254 - 257
(2015/03/05)
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- Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs
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Optimization of a new series of S-adenosyl-l-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 ± 3, 5.0 ± 2.0, and 8.5 ± 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD+ and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.
- Nakao, Akira,Suzuki, Hiroko,Ueno, Hiroaki,Iwasaki, Hiroshi,Setsuta, Tomofumi,Kashima, Akiko,Sunada, Shinji
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p. 4952 - 4969
(2015/08/03)
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- Design and synthesis of 5-[(2-chloro-6-fluorophenyl)acetylamino]-3-(4- fluorophenyl)-4-(4-pyrimidinyl)isoxazole (AKP-001), a novel inhibitor of p38 MAP kinase with reduced side effects based on the antedrug concept
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Inhibitors of p38 mitogen-activated protein (MAP) kinase, which are closely involved in the production of inflammatory cytokines, are considered promising curative drugs for chronic inflammatory disorders. However, there is also a growing concern regarding its systemic side effects. To reduce the occurrence of side effects, we have identified a novel p38 MAP kinase inhibitor that shows properties of an antedrug, which imparts its effect solely on the inflammatory site and is metabolically inactivated right after. We have designed isoxazole derivatives through the addition of a fresh interacting fourth site to the structure of the prototypical p38 MAP kinase inhibitor that harbors three point interactive sites. The derivative 26d (AKP-001) shows excellent p38 MAP kinase inhibitory activity and a high selectivity for various kinases. Its rapid metabolism has been confirmed in rats. Moreover, 26d has been shown to be effective in animal models of inflammatory bowel disease.
- Hasumi, Koichi,Sato, Shuichiro,Saito, Takahisa,Kato, Jun-Ya,Shirota, Kazuhiko,Sato, Jun,Suzuki, Hiroyuki,Ohta, Shuji
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p. 4162 - 4176
(2014/08/18)
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- Stereodynamics of nitrogen chiral centers in aza-β3- cyclodipeptides
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The present work is devoted to the synthesis, conformational analysis, and stereodynamic study of aza-β3-cyclodipeptides. This pseudopeptidic ring shows E/Z hydrazide bond isomerism, eight-membered ring conformation, and chirotopic nitrogen atoms, all of which are elements that are prone to modulate the ring shape. The (E,E) twist boat conformation observed in the solid state by X-ray diffraction is also the ground conformation in solution, and emerges as the lowest in energy when using quantum chemical calculations. The relative configuration associated with ring chirality and with the two nitrogen chiral centers is governed by steric crowding and adopts the (P)SNSN/(M)RNRN combination which projects side chains in equatorial position. The nitrogen pyramidal inversion (NPI) at the two chiral centers is correlated with the ring reversal. The process is significantly hindered as was shown by VT-NMR experiments run in C2D2Cl4, which did not make it possible to determine the barrier to inversion. Finally, these findings make it conceivable to resolve enantiomers of aza-β3-cyclodipeptides by modulating the backbone decoration appropriately.
- Le Grel, Philippe,Asprogenidi, Aikaterini,Huez, Philippe,Le Grel, Barbara,Salauen, Arnaud,Roisnel, Thierry,Potel, Michel,Rasti, Elham,Hocquet, Alexandre
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p. 341 - 349
(2013/07/27)
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- E-64c-hydrazide: A lead structure for the development of irreversible cathepsinc inhibitors
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CathepsinC is a papain-like cysteine protease with dipeptidyl aminopeptidase activity that is thought to activate various granule-associated serine proteases. Its exopeptidase activity is structurally explained by the so-called exclusion domain, which blocks the active-site cleft beyond the S2 site and, with its Asp1 residue, provides an anchoring point for the Nterminus of peptide and protein substrates. Here, the hydrazide of (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane (E-64c) (k2/Ki=140±5M-1s-1) is demonstrated to be a lead structure for the development of irreversible cathepsinC inhibitors. The distal amino group of the hydrazide moiety addresses the acidic Asp1 residue at the entrance of the S2 pocket by hydrogen bonding while also occupying the flat hydrophobic S1′-S2′ area with its leucine-isoamylamide moiety. Furthermore, structure-activity relationship studies revealed that functionalization of this distal amino group with alkyl residues can be used to occupy the conserved hydrophobic S2 pocket. In particular, the n-butyl derivative was identified as the most potent inhibitor of the series (k2/Ki=56000±1700M-1s-1).
- Radzey, Hanna,Rethmeier, Markus,Klimpel, Dennis,Grundhuber, Maresa,Sommerhoff, Christian P.,Schaschke, Norbert
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p. 1314 - 1321
(2013/08/23)
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- Induction of chirality: Experimental evidence of atropisomerism in azapeptides
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Methylation of the peptide bond in model azadipeptides leads to the E configuration and hence to atropisomerism due to a restricted rotation around the N-N axis. This journal is
- Ottersbach, Philipp A.,Schnakenburg, Gregor,Guetschow, Michael
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supporting information; experimental part
p. 5772 - 5774
(2012/08/28)
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- THERAPEUTIC AGENT FOR CEREBRAL INFARCTION
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The invention provides a therapeutic drug for ischemic stroke. The therapeutic drug has the formula (I) wherein each symbol is as defined herein, or a pharmacologically acceptable salt thereof, or a solvate thereof, as an active ingredient.
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- Aza-β3-amino acid containing peptidomimetics as cAMP-dependent protein kinase substrates
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Peptidomimetic analogs of the peptide RRASVA, known as the "minimal substrate" of the catalytic subunit of the cAMP-dependent protein kinase (PKA), were synthesized by consecutive replacement of natural amino acids by their aza-β3 analogs. The peptidomimetics were tested as PKA substrates and the kinetic parameters of the phosphorylation reaction were determined. It was found that the interaction of these peptidomimetics with the enzyme active center was sensitive to the location of the backbone modification, while the maximal rate of the reaction was practically not affected by the structure of substrates. The pattern of molecular recognition of peptidomimetics was in agreement with the results of structure modeling and also with the results of computational docking study of peptide and peptidomimetic substrates with the active center of PKA. It was concluded that the specificity determining factors which govern substrate recognition by the enzyme should be grouped along the phosphorylatable substrate, and such clustering might open new perspectives for pharmacophore design of peptides and peptide-like ligands.
- Kisseljova, Ksenija,Kuznetsov, Aleksei,Baudy-Floc'H, Michle,Jaerv, Jaak
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supporting information; experimental part
p. 229 - 233
(2010/10/01)
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- Orthogonal regioselective synthesis of N-alkyl-3-substituted tetrahydroindazolones
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A divergent strategy for the regioselective and orthogonal synthesis of complementary regioisomers of N-alkyl-3-substituted-tetrahydroindazolones 3 and 4 was achieved from. Boc-protected alkylhydrazmes 1. The robustness and sub-strate generality of this method were validated by synthesizing 3 and. 4 through the intra- and intermolecular condensation of 1 with various 2-acylcyclohexane-l,3-diones 2 and aldehydes, respectively.
- Kim, Jonghoon,Song, Heebum,Park, Seung Bum
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supporting information; experimental part
p. 3815 - 3822
(2010/09/10)
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- NG-aminoguanidines from primary amines and the preparation of nitric oxide synthase inhibitors
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A concise, general, and high-yielding method for the preparation of N G-aminoguanidines from primary amines is reported. Using available and readily prepared materials, primary amines are converted to protected N G-aminoguanidines in a one-pot procedure. The method has been successfully applied to a number of examples including the syntheses of four nitric oxide synthase (NOS) inhibitors. The inhibitors prepared were investigated as competitive inhibitors and as mechanistic inactivators of the inducible isoform of NOS (iNOS). In addition, one of the four inhibitors prepared, NG-amino-NG-2,2,2-trifluoroethyl-L-arginine 19, displays the unique ability to both inhibit NO formation and prevent NADPH consumption by iNOS without irreversible inactivation of the enzyme.
- Martin, Nathaniel I.,Beeson, William T.,Woodward, Joshua J.,Marletta, Michael A.
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p. 924 - 931
(2008/09/20)
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- Pyrazolones as inhibitors of 11B-hydroxysteroid dehydrogenase
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
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Page/Page column 11
(2008/06/13)
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- COMPOSITION FOR INDUCTION OR INHIBITION OF STEM CELL DIFFERENTIATION
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The present invention relates to composition and methods for inducing or inhibiting differentiation of stem cells. The invention also relates to applications in the treatment of medical conditions, e.g., osteoporosis, bone fracture, bone injuries, myocardiac infarction, cardiomyopathy, degenerative muscle diseases, myopathy, and urinary incontinence.
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Page/Page column 49
(2008/06/13)
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- Synthesis of the pyrazolo[4,3-e][1,2,4]triazine family of natural products: Nostocine A, fluviol A, and pseudoiodinine
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The first syntheses of any members of the naturally occurring pyrazolo[4,3-e][1,2,4]triazine family are reported, verifying the structures of nostocine A and fluviol A, and leading to the revision of the structure of pseudoiodinine. The revised structure of pseudoiodinine was also established by total synthesis. Copyright
- Kelly, T. Ross,Elliott, Eric L.,Lebedev, Rimma,Pagalday, Jaione
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p. 5646 - 5647
(2007/10/03)
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- New substituted thiophene carboxamides, process for their preparation and their use as medicaments
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The present invention relates to new substituted thiophene-2-carboxylic acid amides of general formula wherein A, and R1 to R8c are defined as in claim 1, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.
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Page/Page column 53
(2010/02/14)
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- Solid-phase synthesis of "mixed" peptidomimetics using Fmoc-protected aza-β3-amino acids and α-amino acids
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A solid-phase fluorenylmethyloxycarbonyl (Fmoc)-based synthesis strategy is described for "mixed" aza-β3-peptides as well as a convenient general approach for their required building blocks, the aza-β3-amino acid residues (aza-β3-aa). These monomers allow the synthesis of relatively large quantities of pure mixed aza-β3-peptides. The required Fmoc-substituted aza-β3-amino acids are accessible by convenient synthesis, and a number of monomers including those containing side chains with functional groups have been synthesized. The method was applied toward the solid-phase ynthesis of aza-β3-peptide mimetics of a biologically active histone H4 sequence.
- Busnel, Olivier,Bi, Lanrong,Dali, Hayet,Cheguillaume, Arnaud,Chevance, Soizic,Bondon, Arnaud,Muller, Sylviane,Baudy-Floc'h, Michele
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p. 10701 - 10708
(2007/10/03)
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- TETRAHYDROBENZAZEPINE DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS (ANTIPSYCHOTIC AGENTS)
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The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, e.g. as agents to treat various aspects drug dependency or as antipsychotic agents.
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Page/Page column 26
(2010/02/14)
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- 7-PYRAZOLYLBENZAZEPINES HAVING AFFINITY FOR D3 RECEPTOR
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Compounds of formula (I) or a salt thereof are disclosed (I): wherein R1 is pyrazolyl substituted by two or three substituents independently selected from halogen, C1-4alkyl and haloC1-4alkyl; R2 is hydrogen or methyl; and R3 is quinolinyl, oxazolyl or phenyl, each of which is optionally substituted by one or two halogen, C1-4alkyl or haloC1-4alkyl. Processes for preparation and uses of the compounds in medicine, for example for the treatment of schizophrenia or drug dependency, are also disclosed.
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Page/Page column 16; 18
(2008/06/13)
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- N- and C-terminal modifications of negamycin
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Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. An orthogonally protected β-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support. This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies. The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity. The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC50=2.3 μM), has antibacterial activity (Escherichia coli, MIC=16 μg/mL), and is efficacious in an E. coli murine septicemia model (ED50=16.3 mg/kg).
- Raju,Mortell, Kathleen,Anandan, Sampathkumar,O'Dowd, Hardwin,Gao, Hongwu,Gomez, Marcela,Hackbarth, Corinne,Wu, Charlotte,Wang, Wen,Yuan, Zhengyu,White, Richard,Trias, Joaquim,Patel, Dinesh V.
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p. 2413 - 2418
(2007/10/03)
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- The synthesis of azapeptidomimetic beta-lactam molecules as potential protease inhibitors.
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Synthetic methods for the construction of a novel peptidomimetic structure are reported. The structure incorporates a beta-lactam and an azapeptide in a peptide backbone with the intention of generating rationally designed substrate-based protease inhibitors. The beta-lactam is formed by subjecting serine or threonine-azapeptides to Mitsunobu reaction conditions. Importantly, the azapeptidomimetic beta-lactam structure permits extended binding inhibition and the synthetic methods to create tetrapeptidomimetic structures are described.
- Malachowski, William P,Tie, Chenyang,Wang, Katherine,Broadrup, Robert L
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p. 8962 - 8969
(2007/10/03)
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- 3-(substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds
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3-(Substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds are useful as insecticides and acaricides. New synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds are also provided.
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- 3-substituted indole antiproliferative angiogenesis inhibitors
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3-Substituted indole carbohydrazides having the formula are useful for inhibiting angiogenesis and cell proliferation. Also disclosed are compositions which inhibit angiogenesis and cell proliferation and methods of inhibiting angiogenesis and cancer in a mammal.
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- N-tert-butoxycarbonylaminophthalimide, a versatile reagent for the conversion of alcohols into alkylated tert-butylcarbazates or hydrazines via the Mitsunobu protocol
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An efficient two-step method has been developed for the conversion of alcohols to substituted hydrazines. The use of N-tert- butoxycarbonylaminophthalimide as an acid partner in Mitsunobu reactions with a variety of alcohols permits the synthesis of the corresponding monoalkylated tert-butylcarbazates and hydrazines.
- Brosse, Nicolas,Pinto, Maria-Fatima,Jamart-Grégoire, Brigitte
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p. 205 - 207
(2007/10/03)
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- New Synthesis of 1,1-Substituted Hydrazines by Alkylation of N-Acyl- or N-alkyloxycarbonylaminophthalimide Using the Mitsunobu Protocol
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N-acyl- and N-alkoxycarbonylaminophthalimides are prepared using a convenient reaction and are efficiently used as acid partners in Mitsunobu reaction. This reaction allows them to be alkylated by primary, secondary or benzyl groups. Comparison of the reactivities and pKa values of these N-substituted aminophthalimides suggest that the success of the Mitsunobu reaction in this case seems to be governed more by steric than by electronic effects. A final dephthaloylation step results in an efficient method for the preparation of 1,1-substituted hydrazines.
- Brosse, Nicolas,Pinto, Maria-Fatima,Jamart-Gregoire, Brigitte
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p. 4370 - 4374
(2007/10/03)
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- N-tert-butoxycarbonyl-N-substituted hydrazines in S(N)Ar displacements. Synthetic pathways to N-1-substituted anthrapyrazoles, aza-anthrapyrazoles and aza-benzothiopyranoindazoles
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The synthesis of several N-tert-butoxycarbonyl(Boc)-protected-N- substituted hydrazines has been accomplished. The use of these protected hydrazines in S(N)Ar substitutions leads to products in which the most nucleophilic nitrogen displaces the leaving group. Treatment of these compounds with trifluoroacetic acid readily removes the Boc-protecting group and the intermediates readily undergo cyclizations to yield N-1-substituted aza-benzothiopyranoindazoles, anthrapyrazoles and aza-anthrapyrazoles. Side chain buildup was employed in the synthesis of several aza-anthrapyrazoles.
- Oliva, Ambrogio,Ellis, Michael,Fiocchi,Menta, Ernesto,Krapcho, A. Paul
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- 3-(substituted phenyl)-5-(thienyl or furyl)-1, 2, 4-triazole compounds
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3-(Substituted phenyl)-5-(thienyl or furyl)-1,2,4-triazole compounds are useful as insecticides and acaricides. New synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds are also provided.
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- Cephalosporin derivatives
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7 α-formamido cephalosporin derivatives having a 3[N-(optionally substituted)aminothiopyridinium thiomethyl] substituent have anti-bacterial activity and are of use in anti-bacterial therapy. Processes for the preparation thereof and intermediates for use in these processes are also disclosed.
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- Synthesis and biological activity of 3-(N-substituted pyridinium-4-thiomethyl)-7α-formamido cephalosporins
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The synthesis and antibacterial activity of a series of 3-(1-substituted pyridinium-4-thiomethyl)-7α-formamido cephalosporins is described. All the derivatives showed good potency and stability to bacterial β-lactamases. The antibacterial efficacy seen with the N-alkyl pyridinium substituents was enhanced by the introduction of a catecholic side chain at C-7 and by preparation of N-(substituted amino)pyridinium derivatives.
- Guest,Adams,Basker,Brain,Branch,Harrington,Neale,Pearson,Zomaya
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p. 1279 - 1288
(2007/10/02)
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- Monobactam hydrazide derivatives
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Compounds having the formula I and pharmaceutically acceptable salts thereof which possess antibacterial activity. Rs is a substituted hydroxy pyridone of the formulae: II and III wherein Y1 is CH2X; COOR6; CONR7R8; OH; OCH2R9; CHF2; CHO; CH=N-OR10; CH=CH-R11; CN; CH=N-NHR12, and Y2 is hydrogen; COOH; CONH2; CN; CSNH2; COO lower alkyl; CONR7/R8
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- MONOBACTAM HYDRAZIDES CONTAINING CATECHOL SULFONIC ACID GROUPS
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Antibacterial activity is exhibited by novel compounds having the formula or a pharmaceutically acceptable salt thereof. R3 and R4 are the same or different and each is hydrogen or alkyl or R3 and R4 taken together with the nitrogen atoms to which they are attached form a 1,2-diazacyclobutane, 1,2-diazacyclopentane, 1,2-diazacyclohexane, or 1,2-diazacycloheptane ring. Y1 and Y2 are either hydrogen or OR11 but are not the same. R11 is hydrogen, alkanoyl of from one to ten carbon atoms, substituted alkanoyl of from two to ten carbon atoms, phenylcarbonyl, (substituted phenyl) carbonyl, heteroarylcarbonyl, phenylalkanoyl, (substituted phenyl) alkanoyl, or heteroarylalkanoyl
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- Heteroaroylhydrazide derivatives of monocyclic beta-lactam antibiotics
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Compounds having the formula STR1 and pharmaceutically acceptable salts thereof and possessing antibacterial activity, and intermediates to compounds of formula I having the formula
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- Synthesis of 1,2,4-Triazines, IX. Synthesis of Cyclopenta-1,2,4-triazines
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Derivatives 12a - f and 23a - c of hitherto unknown cyclopenta-1,2,4-triazine system 1 were prepared from cyclopentadienedicarboxylates 9a,b and amidrazones 10a - d or 14a - c, respectively.
- Metz, Hans-Joachim,Neunhoeffer, Hans
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p. 2807 - 2818
(2007/10/02)
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