- 2-AMINO-N-(AMINO-OXO-ARYL-LAMBDA6-SULFANYLIDENE)ACETAMIDE COMPOUNDS AND THEIR THERAPEUTIC USE
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The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 2-amino-N-(amino-oxo-aryl-λ6- sulfanylidene)acetamide compounds (referred to herein as ANASIA compounds) that, inter alia, inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase; to treat disorders that are ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase; to treat bacterial infections; etc.
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Page/Page column 217
(2021/06/26)
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- Hetaryl Bromides Bearing the SO2F Group – Versatile Substrates for Palladium-Catalyzed C–C Coupling Reactions
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Synthesis of novel five- and six-membered heteroaromatic sulfonyl fluorides bearing bromine atom at various positions of the heterocyclic ring is described. The synthetic utility of these compounds is demonstrated by the Suzuki, Stille, and Negishi cross-
- Cherepakha, Artem Yu.,Stepannikova, Kateryna O.,Vashchenko, Bohdan V.,Gorichko, Marian V.,Tolmachev, Andrey A.,Grygorenko, Oleksandr O.
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p. 6682 - 6692
(2018/11/30)
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- New methods for the synthesis of 4H-dithieno[3,2-b:2′,3′-d]pyrrole
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Various alternative methods for the synthesis of 4H-dithieno[3,2-b:2′,3′-d]pyrrole (DTP) starting from commercially available bromothiophene precursors are presented. Crucial steps involve the Cadogan reaction, Ullmann-type C─N couplings, or Buchwald-Hartwig–type aminations to build up the central pyrrole ring of DTP, respectively. The use of ammonia surrogates afforded the fused target heteroacene in overall yields of 33% to 63%, and the corresponding methods are applicable on large scale.
- F?rtsch, Sebastian,Vogt, Astrid,B?uerle, Peter
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- Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design to Minimize Host Kinase Interactions
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Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (Ki ≈ 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 μM (1-2 μg/mL) against the H37Ra isolate of M. tuberculosis.
- Wang, Tiansheng,Bemis, Guy,Hanzelka, Brian,Zuccola, Harmon,Wynn, Michael,Moody, Cameron Stuver,Green, Jeremy,Locher, Christopher,Liu, Aixiang,Gao, Hongwu,Xu, Yuzhou,Wang, Shaohui,Wang, Jie,Bennani, Youssef L.,Thomson, John A.,Müh, Ute
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supporting information
p. 1224 - 1229
(2017/12/26)
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- Synthesis of Heteroaryl Sulfonamides from Organozinc Reagents and 2,4,6-Trichlorophenyl Chlorosulfate
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A method for the preparation of aryl and heteroaryl sulfonamides using 2,4,6-trichlorophenyl chlorosulfate (TCPC) is described. The reaction of 2-pyridylzinc reagents with TCPC resulted in 2,4,6-trichlorophenyl (TCP) pyridine-2-sulfonates, and the parent pyridine-2-sulfonate was shown to react with amines. Less electron-rich aryl- and heteroarylzinc reagents reacted with TCPC to afford sulfonyl chlorides that were converted in situ to sulfonamides.
- Colombe, James R.,Debergh, J. Robb,Buchwald, Stephen L.
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supporting information
p. 3170 - 3173
(2015/06/30)
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- Direct acyl substitution of carboxylic acids: A chemoselective o- to N-acyl migration in the traceless staudinger ligation
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A chlorophosphite-modified, Staudinger-like acylation of azides involving a highly chemoselective, direct nucleophilic acyl substitution of carboxylic acids is described. The reaction provides the corresponding amides with analytical purity in 32-97 % yield after a simple aqueous workup without the need for a pre-activation step. The use of chlorophosphites as dual carboxylic acid-azide activating agents enables the formation of acyl C-N bonds in the presence of a wide range of nucleophilic and electrophilic functional groups, including amines, alcohols, amides, aldehydes, and ketones. The coupling of carboxylic acids and azides for the formation of alkyl amides, sulfonyl amides, lactams, and dipeptides is described. Copyright
- Kosal, Andrew D.,Wilson, Erin E.,Ashfeld, Brandon L.
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p. 14444 - 14453,10
(2020/09/16)
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- Development of an acyl sulfonamide anti-proliferative agent, ly573636 ? na
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The synthesis of 5-bromo-thiophene-2-sulfonic acid 2,4-dichlo- robenzoylamide sodium salt on multikilogram scale is described. The initial clinical supplies were made using carbonyl diimidazole to converge the two fragments. A more efficient acid chloride process has been developed, which also provides better control of impurities and color throughout the synthesis.
- Yates, Matthew H.,Kallman, Neil J.,Ley, Christopher P.,Wei, Jeffrey N.
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scheme or table
p. 255 - 262
(2010/04/22)
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- Facile one-pot synthesis of aromatic and heteroaromatic sulfonamides
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A series of arene and heteroarene sulfonamides were prepared in one vessel from aryl and heteroaryl bromides via conversion into the corresponding Grignard reagents using either magnesium or isopropylmagnesium chloride and subsequent reaction with sulfur dioxide, sulfuryl chloride, and an amine.
- Pandya, Rina,Murashima, Takashi,Tedeschi, Livio,Barrett, Anthony G. M.
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p. 8274 - 8276
(2007/10/03)
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- Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
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Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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- N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
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Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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Page column 75
(2010/01/30)
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- THIENYL-, FURYL- AND PYRROLYL SULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN
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Thienyl-, furyl-and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl) furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
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- SULFONAMIDES AND DERIVATIVES THEREOF THAT MODULATE THE ACTIVITY OF ENDOTHELIN
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Sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided. The sulfonamides have formula I: STR1 in which Ar 1 is a 3-or 5-isoxazolyl and Ar. sup.2 is selected from among alkyl, including straight and branched chains, aromatic rings, fused aromatic rings and heterocyclic rings, including 5-membered heterocycles with one, two or more heteroatoms and fused ring analogs thereof and 6-membered rings with one, two or more heteroatoms and fused ring analogs thereof. Ar 2 is preferably thiophenyl, furyl, pyrrolyl, naphthyl, and phenyl. Compounds in which Ar. sup.1 is a 4-halo-substituted isoxazole are more active than the corresponding alkyl-substituted compound and compounds in which Ar 1 is substituted at this position with a higher alkyl tend to exhibit greater affinity for ET B receptors than the corresponding lower alkyl-substituted compound.
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- An Invastigation of Structure and Conformation of Thiophene-2-sulphonyl Radicals
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The e.s.r. spectra of a variety of photochemically generated thiophene-2-sulphonyl radicals are described.Their spin distribution is typical of ?-radicals; radicals without substituents at position 3 exhibit relatively rapid rotation about the C-S bond at all accessible temperatures while the 3-bromo-substituted ones demonstrate a marked conformational preference which has been interpreted in terms of a ?-type conjugated structure.These findings are substantiated also by the results of INDO calculations carried out for the unsubstituted thiophene-2-sulphonyl radical with different relative arrangements of the SO2 and heteroatomic moieties.
- Alberti, Angelo,Chatgilialoglu, Chryssostomos,Guerra, Maurizio
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p. 1179 - 1182
(2007/10/02)
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- The Use of N,N-Dimethylformamide-Sulfonyl Chloride Complex for the Preparation of Thiophenesulfonyl Chlorides
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A 1:1 N,N-dimethylformamide-SO2Cl2 complex was found to be a useful agent for the one-step preparation of thiophenesulfonyl chlorides.
- Sone, Tyo,Abe, Yukio,Sato, Norio,Ebina, Manabu
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p. 1063 - 1064
(2007/10/02)
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