- Inhibition of carbonic anhydrase-II by sulfamate and sulfamide groups: An investigation involving direct thermodynamic binding measurements
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This paper examines the relative effectiveness of bioisosteric sulfamate and sulfamide derivatives for inhibition of human carbonic anhydrase-II (CA-II) by using a direct binding assay based on the ThermoFluor method (Matulis et al. Biochemistry 2005, 44, 5258). Compounds 1-10, which represent five cognate sulfamate/ sulfamide pairs, were studied by ThermoFluor to obtain binding affinities (Ka values). The corresponding dissociation constants, Kd, provide an independent measure of CA-II activity relative to commonly used Ki values from enzyme kinetics studies. There was a sizable difference in potency between the sulfamates and sulfamides, with the sulfamides being much less potent, by factors ranging from 25 (7/8) to 1200 (3/4), These results are consistent with our recent report that sulfamides tend to be much weaker inhibitors of CA-II than their corresponding sulfamates (Maryanoff et al. J. Med. Chem. 2005, 48, 1941). Additionally, for arylsulfamides 10-12 the Kd values determined by ThermoFluor and the Ki values determined from enzyme kinetics are consistent. It appears that the sulfamide group is less suitable than the sulfamate group for obtaining potent inhibition of CA-II.
- Klinger, Alexandra L.,McComsey, David F.,Smith-Swintosky, Virginia,Shank, Richard P.,Maryanoff, Bruce E.
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- Efficient synthesis of N-oxysulfonyl formamidines through thionyl chloride-promoted reaction of sulfamates with formamides
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N-Oxysulfonyl formamidine derivatives have been efficiently synthesized under mild conditions through direct condensation of various sulfamates and formamides in the presence of thionyl chloride. The scope of this reaction was investigated, and a plausible mechanism was proposed. The resulting N-oxysulfonyl formamidines can be converted to sulfamates through appropriate deprotection.
- Wusiman, Abudureheman,Hudabaierdi, Ruzeahong
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supporting information
p. 2015 - 2021
(2017/10/13)
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- N-Sulfonylcarboxamide as an Oxidizing Directing Group for Ruthenium-Catalyzed C–H Activation/Annulation
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N-Sulfonylcarboxamides can act as both a directing group for C–H activation and an internal oxidant in the Ru-catalyzed annulation reaction with alkynes to give isoquinolones. Of all of the N-sulfonylcarboxamides that were studied, the N-(2,6-difluorophenyl)sulfonamide derivatives were found to be the most efficient and led to the formation of an unstable sulfinate byproduct that decomposed into 1,3-difluorobenzene under the reaction conditions. The described isoquinolone synthesis provides an alternative to the currently known traceless annulations of hydroxamic acid and sulfoximine derivatives.
- Petrova, Elina,Rasina, Dace,Jirgensons, Aigars
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supporting information
p. 1773 - 1779
(2017/04/13)
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- Selective intermolecular amination of C-H bonds at tertiary carbon centers
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C-H insertion: A method for intermolecular amination of tertiary C-H bonds is described that uses limiting amounts of substrate and a convenient phenol-derived nitrogen source. Structure-selectivity and mechanistic studies suggest that steric interaction between the substrate and active oxidant is the principal determinant of product selectivity. Copyright
- Roizen, Jennifer L.,Zalatan, David N.,Du Bois
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supporting information
p. 11343 - 11346
(2013/11/06)
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- N-(tert -butoxycarbonyl)- N -[(triethylenediammonium)sulfonyl]azanide: A convenient sulfamoylation reagent for alcohols
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A convenient and efficient procedure is described for the sulfamoylation of alcohols using N-(tert-butoxycarbonyl)-N-[(triethylenediammonium)sulfonyl] azanide (1). The ambient temperature stable reagent 1 reacts with phenols as well as primary and secondary alcohols to give high to modest yields. The relative reaction rate of substrates was determined (primary > phenol > secondary ? tertiary). The reagent's utility as a selective sulfamoylation reagent with polyols is also demonstrated.
- Armitage, Ian,Berne, Alexander M.,Elliott, Eric L.,Fu, Mingkun,Hicks, Frederick,McCubbin, Quentin,Zhu, Lei
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supporting information; experimental part
p. 2626 - 2629
(2012/07/28)
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- Intermolecular amination of allyl alcohols with sulfamates: Effective utilization of mercuric catalyst
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Herein, we describe the intermolecular amination of allyl alcohols with sulfamates, which have been underutilized as nitrogen nucleophiles for allylic amination. Methyl sulfamate is a good nucleophile in the presence of mercuric triflate and efficiently generates monoallylation products in excellent yield at room temperature. Furthermore, the solid-supported mercuric catalyst silaphenyl mercuric triflate also showed remarkable catalytic activity for the allylic amination. Intermolecular amination of allyl alcohol with sulfamate as a modifiable nitrogen nucleophile is presented. Mercuric reagents act as highly efficient catalyst for the allylic amination, and the procedure was applied to the preparation of various amine derivatives. In many cases, the reaction can be carried out at room temperature and is applicable to a large range of allylic alcohols to give the monoallylated products in excellent yield. Copyright
- Yamamoto, Hirofumi,Ho, Elisabeth,Sasaki, Ikuo,Mitsutake, Mizuho,Takagi, Yuichi,Imagawa, Hiroshi,Nishizawa, Mugio
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supporting information; experimental part
p. 2417 - 2420
(2011/06/10)
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- A novel class of antihyperlipidemic agents with low density lipoprotein receptor up-regulation via the adaptor protein autosomal recessive hypercholesterolemia
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We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator,
- Asano, Shigehiro,Ban, Hitoshi,Tsuboya, Norie,Uno, Shinsaku,Kino, Kouichi,Ioriya, Katsuhisa,Kitano, Masafumi,Ueno, Yoshihide
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experimental part
p. 3284 - 3295
(2010/09/05)
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- Elimination mechanisms in the aminolysis of sulfamate esters of the type NH2SO2OC6H2X - Models of enzyme inhibitors
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The kinetics of the reaction of 4-nitrophenyl sulfamate NH 2SO2OC6H4NO2-4 (1a) in acetonitrile (ACN) with a series of pyridines (pKa range ca. 8 units) and alicyclic amines (pKa range ca. 3.6 units) has been studied in the presence of excess amine at various temperatures. The compounds 1a-1f are important as model substrates for the medicinally important sulfamate esters 667-coumate and emate and analogues. Pseudo-first-order rate constants (k obsd.) have been obtained mainly by the release of 4-nitrophenol/4-nitrophenoxide. Slopes of plots of kobsd. vs. [amine] gave second-order rate constants (k2), and Broensted plots were biphasic for the aminolysis (with alicyclic amines) with an initial slope β1 = 0.53 and a subsequent slope β2 = 0.19. The change in slope occurs near the first pKa of 1a (17.9) in ACN. Leaving-group effects were probed by using the same series of phenyl sulfamates, i.e. 1a-f and the alicyclic amines N-formylpiperazine and pyrrolidine. The reactions were considered to be dissociative in nature involving E2- and E1cB- type mechanisms with the phenyl sulfamate anion 2 being involved in pyridine and in the weaker alicyclic amines (β1 segment) and a phenyl sulfamate dianion 3 being involved with the stronger alicyclic bases (β2 segment). The calculation of Leffler indices (α) for bond-forming (base...H+) and bond-breaking (S-OAr) steps allows fuller interpretation of the mechanisms occurring, which are seen as having the N-sulfonylamines, HN=SO2 and -N=SO2 on the reaction pathways leading to products. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Spillane, William J.,O'Byrne, Andrew,McCaw, Cheryl J. A.
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experimental part
p. 4200 - 4205
(2009/04/11)
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- NOVEL SULFONAMIDE DERIVATIVE
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A compound of the formula (1): wherein m, n and p is independently an integer of 0 to 4 with the proviso that 3 a?| m + n a?| 8; X is the formula: NR4, etc.; R1, R3 and R4 are a substituted or unsubstituted aryl group, etc.; R2 is a hydrogen atom, etc.; a, b, c, d, e and f are a hydrogen atom or a substituted or unsubstituted alkyl group, etc.; Y is the formula: -SO2-, etc.; and Z is an oxygen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt of the same has an activity of potentiating an expression of a low density lipoprotein receptor and thus is useful as an agent for treating hyperlipidemia or arteriosclerosis.
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Page/Page column 45
(2010/11/25)
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- Ground state structures of sulfate monoesters and sulfamates reveal similar reaction coordinates for sulfuryl and sulfamyl transfer
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Structure/reactivity and structure/structure correlations of 5 sulfate monoesters and 11 sulfamate esters determined by low temperature X-ray crystallography reveal similar ground state deformations that suggest similar reaction coordinates for sulfuryl and sulfamyl group transfer. The Royal Society of Chemistry 2006.
- Denehy, Emma,White, Jonathan M.,Williams, Spencer J.
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p. 314 - 316
(2008/02/08)
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- Synthesis and evaluation of general mechanism-based inhibitors of sulfatases based on (difluoro)methyl phenyl sulfate and cyclic phenyl sulfamate motifs
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Several model mechanism-based inhibitors (MbIs) were designed and evaluated for their ability to inhibit sulfatases. The MbI motifs were based on simple aromatic sulfates, which are known to be commonly accepted substrates across this highly conserved enzyme class, so that they might be generally useful for sulfatase labeling studies. (Difluoro)methyl phenol sulfate analogs, constructed to release a reactive quinone methide trap, were not capable of irreversibly inactivating the sulfatase active site. On the other hand, the cyclic sulfamates (CySAs) demonstrated inhibition profiles consistent with an active site-directed mode of action. These molecules represent a novel scaffold for labeling sulfatases and for probing their catalytic mechanism.
- Hanson, Sarah R.,Whalen, Lisa J.,Wong, Chi-Huey
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p. 8386 - 8395
(2008/02/05)
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- HETEROCYCLIC COMPOUND DERIVATIVES AND MEDICINES
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The present invention provides a compound which is useful as a PGI2 receptor agonist, and a pharmaceutical composition. The present invention is directed to a pharmaceutical composition comprising a compound represented by the following formula [1]: (R1 and R2 are the same or different and each represents optionally substituted aryl, Y represents N or CH, Z represents N or CH, A represents NH, NR5, O, S, or ethylene, R5 represents alkyl, D represents alkylene or alkenylene, E represents phenylene or single bond, G represents O, S, or CH2, R3 and R4 are the same or different and each represents hydrogen or alkyl, Q represents carboxy, alkoxycarbonyl, tetrazolyl, carbamoyl, or N-(alkylsulfonyl)carbamoyl), or a pharmaceutically acceptable salt thereof as an active ingredient.
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- Carbonic anhydrase inhibitors. Inhibition of cytosolic isozymes I and II and transmembrane, tumor-associated isozyme IX with sulfamates including EMATE also acting as steroid sulfatase inhibitors
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A series of sulfamates or bis-sulfamates incorporating aliphatic, aromatic, polycyclic (steroidal), and sugar moieties in their molecules has been synthesized and assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more precisely of the cytosolic isozymes CA I and II, and the transmembrane, tumor-associated isozymes CA IX. Some of these compounds were previously reported to act as inhibitors of steroid sulfatases, among which estrone sulfatase (ES) and dehydroepiandrosterone sulfatase (DHEAS) are the key therapeutic targets for estrogen-dependent tumors. Very potent (nanomolar) inhibitors were detected against the three investigated CA isozymes. Best CA I inhibitors were phenylsulfamate and some of its 4-halogeno derivatives, as well as the aliphatic compound n-octyl sulfamate. Against CA II, low nanomolar inhibitors (1.1-5 nM) were phenylsulfamate and some of its 4-halogeno/nitro derivatives, n-octyl sulfamate, and estradiol 3,17β-disulfamate among others. All the investigated sulfamates showed efficient CA IX inhibitory properties, with inhibition constants in the range of 18-63 nM. The best CA IX inhibitor detected so far was 4-chlorophenylsulfamate. These data are critical for the design of novel antitumor properties, mainly for hypoxic tumors that overexpress CA IX, which are nonresponsive to radiation or chemotherapy. The antitumor properties of the ES/DHEAS inhibitors in clinical trials may on the other hand also be due to their potent inhibitory properties of CA isozymes involved in tumorigenicity, such as CA II and CA IX.
- Winum, Jean-Yves,Vullo, Daniela,Casini, Angela,Montero, Jean-Louis,Scozzafava, Andrea,Supuran, Claudiu T.
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p. 2197 - 2204
(2007/10/03)
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- Oxazole compounds as prostaglandin e2 agonists or antagonists
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Oxazole compounds of formula (I), wherein R1is aryl which may be substituted with halogen(s), R2is aryl which may be substituted with halogen(s), X is single bond, (a) or SO2, R3and R4are independentl
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- The mechanism of the irreversible inhibition of estrone sulfatase (ES) through the consideration of a range of methane- and amino-sulfonate-based compounds
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We report the results of our study into a series of simple phenyl and alkyl sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that the substituted phenyl sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were found to lack inhibitory activity; whilst the large alkyl chain containing methanesulfonate-based compounds were found to possess weak reversible inhibitory activity. Using the results of the inhibition study, we postulate the probable mechanism for ES and suggest that an attack by the gem-diol is a major requirement prior to the hydrolysis of the sulfamate group, following which, attack on the active site C=O occurs and which therefore leads to the production of an imine type functionality, resulting in irreversible inhibition.
- Ahmed, Sabbir,James, Karen,Owen, Caroline P.,Patel, Chirag K.,Sampson, Luther
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p. 1279 - 1282
(2007/10/03)
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- Acid dissociation constant, a potential physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES)
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We report the initial results of the synthesis and biochemical evaluation of a series of aminosulfonate based compounds of phenol and the determination of the pKa of the parent phenol in an attempt to investigate the role of this physicochemical factor in the irreversible inhibition of the enzyme estrone sulfatase (ES). The results of the study show that there is a strong correlation between the observed pKa and inhibitory activity. We postulate that the stability of the phenoxide ion, as indicated by the acid dissociation constant, is an important factor in the irreversible inhibition of this enzyme.
- Ahmed, Sabbir,Owen, Caroline P.,James, Karen,Patel, Chirag K.,Patel, Mijal
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p. 899 - 902
(2007/10/03)
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- Sulfamates as antiglaucoma agents
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Sulfamate esters of the formula where A is aryloxyalkyl, p is the number of unreacted hydroxy groups present on the alkyl moiety and may be zero, z is the number of --OS(O)2 NR1 R2 groups attached to carbons of the alkyl moiety and is always at least one; R1 and R2 are selected from hydrogen, loweralkyl, carboxy, and the like are useful in treating glaucoma.
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- Compounds having one or more aminosulfaonyloxy radicals useful as pharmaceuticals
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Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:(HO)p--A--[--OS(O) 2 NR 1 R 2 ] zwherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O) 2 NR 1 R 2 groups and is always at least one; R 1 and R 2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.
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- Aryl and aryloxyalkyl sulfamate esters useful as anticonvulsants
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Herein disclosed is a method of treating convulsions with a pharmaceutical composition containing a compound of the formula: where A is an aryl, arylalkyl, or aryloxyalkyl group and is substituted on 1 or more carbon atoms with a sulfamate group (--OSO2 NR1 R2) wherein R1 and R2, same or different, are hydrogen or loweralkyl wherein p is 0 or 1 and is the number of untreated hydroxyl groups and z is 1 or 2 and is the number of --OS(O2)NR1 R2 groups. Aryl is selected from phenyl, substituted phenyl, pyridinyl, naphthyl, quinolinyl, and the like. Phenyl substituents are selected from hydrogen, halo, hydroxy, phenyl, phenoxy, benzoyl, loweralkyl, loweralkoxy, carboxy, amino, loweralkylamino, diloweralkylamino, acetamido, cyano, nitro, loweralkoxycarboyl, aminosulfonyl, imidazolyl, triazolyl, and the like. Novel compounds not previously disclosed are also described.
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- LES SYSTEMES BIPHASIQUES. 7. SYNTHESE DE SULFAMATES SIMPLES ET N-SUBSTITUES DANS LES CONDITIONS DE TRANSFERT DE PHASE LIQUIDE-LIQUIDE
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We report the very facile and convenient syntheses of sulfamate esters of the general structures R-O-SO2-NH2 and R-O-SO2-NR1R2 respectively by reduction of aryloxysulfonyl azides and by reaction of amine N-sulfonyl chlorides with phe
- Hedayatullah, Mir,Hugueny, Jean Claude
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p. 371 - 376
(2007/10/02)
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- Versatile Synthesis of Sulphamate Esters by Phase-transfer Methods
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The syntheses of sulphamate esters of the general types R1R2NSO3R3, RNHSO3R3, and H2NSO3R3, where R3 may be aliphatic or aromatic, have been achieved in good yield by reaction of the appropriate sulphamoyl chlorides with alcohols and phenols under mild phase-transfer conditions.The present methods have led to generally higher yields, and to shorter reaction times and lower reaction temperatures than were hitherto found necessary.The prior preparation of the alkoxide has also been obviated.Some esters have been rearranged to the isomeric betaines.
- Spillane, William J.,Taheny, Anne P.,Kearns, M. Mary
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p. 677 - 680
(2007/10/02)
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