- Convenient synthesis of 2,3-dihydro-1,2,4-thiadiazoles, 4,5-dihydro-1,3-thiazoles, and 1,3-thiazoles through a [4+1]-type oxidative ring closure of 1,3-thiaza-1,3-butadienes
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1,3-Thiaza-1,3-butadienes bearing an N,N-dimethylamino group at the C-2 position were efficiently converted into 5H-1,2,4-oxathiazoles, 2,3-dihydro-1,2,4-thiadiazoles, 4,5-dihydro-1,3-thiazoles, and 1,3-thiazoles through an oxidative ring closure by treating with mCPBA, chloramine-T, metal carbenoids, or dichlorocarbene, respectively, via the ring closure of in situ generated heterocumulene-type reactive species involving thione S-oxides, thione S-imides, and thiocarbonyl ylides.
- Shimada, Kazuaki,Isogami, Megumi,Maeda, Kitami,Nishinomiya, Rei,Korenaga, Toshinobu
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p. 881 - 900
(2020/09/09)
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- Sultam thioureas: Synthesis and antiviral activity against west nile virus
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The syntheses of eleven sultam thioureas, including nine new compounds, are described. These compounds were synthesized from thioureas and include the first sultam thioureas in which the two thiourea nitrogen groups are not identical. In addition, the first X-ray crystal structures of sultam thioureas and the antiviral activity of these compounds against West Nile virus (WNV) are reported. Georg Thieme Verlag Stuttgart New York.
- Feeny, Rachel M.,Le, Diane N.,Parks, Joseph W.,Epstein, Mark G.,Pagano, Joseph V.,Abbene, Albert C.,Graham, Elaina B.,Farrell, Joanna R.,McGuire, Jason R.,Zoellner, Robert W.,Valente, Edward J.,Barklis, Eric,Wood, Warren J. L.
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supporting information; experimental part
p. 301 - 305
(2012/03/08)
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- Macrocyclic Inhibitors of Hepatitis C Virus
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Compounds of the formula (I): and N-oxides, salts and stereoisomers thereof wherein A is OR1, NHS(═O)pR2, NHR3, NRaRb, C(═O)NHR3 or C(═O)NRaRb wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl; R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl or NRaRb; R3 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl, —OC1-C6alkyl, —OC0-C3alkylenecarbocyclyl, —OC0-C3alkyleneheterocyclyl; wherein any alkyl, carbocyclyl or heterocycylyl in R1, R2 or R3 are optionally substituted p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; Rq is H or when L is CRz, Rq can also be C1-C6alkyl; Ry and Ry′ are independently C1-C6alkyl; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; W is —CH2—, —O—, —OC(═O)NH—, —OC(═O)—, —S—, —NH—, —NRa, —NHS(═O)2—, —NHC(=0)NH— or —NHC(═O)—, —NHC(═S)NH— or a bond; R8 is an optionally substituted ring system containing 1 or 2 saturated, partially saturated or unsaturated carbo or heterocyclic rings have utility in the inhibition of NS-3 serine proteases, such as flavivirus infections.
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Page/Page column 59
(2009/02/11)
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- Macrocylic Inhibitors of Hepatitis C Virus
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Compounds of the formula I: and N-oxides, salts, and stereoisomers thereof wherein A is OR1, NHS(═O)pR2; wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl;R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl;p is independently 1 or 2;n is 3, 4, 5 or 6; — denotes an optional double bond;L is N or CRz; Rz is H or forms a double bond with the asterisked carbon;Rq is H or when L is CRz, Rq can also be C1-C6alkyl;Rr is quinazolinyl, optionally substituted with one two or three substituents each independently selected from C1-C6 alkyl, C1-C6alkoxy, hydroxyl, halo, haloC1-C6alkyl, amino, mono- or dialkylamino, mono- or dialkylaminocarbonyl, C1-C6alkyl-carbonylamino, C0-C3alkylenecarbocyclyl and C0-C3 alkyleneheterocyclyl;R5 is hydrogen, C1-C6alkyl, C1-C6alkoxyC1-C6alkyl or C3-C7cycloalkyl;R6 is hydrogen, C1-C6alkyl, C1-C6alkoxy, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl, hydroxy, bromo, chloro or fluoro have utility in the treatment or prophylaxis of flaviviral infections such as HCV
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Page/Page column 51
(2009/05/28)
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- THIAZOLE AND OXAZOLE KINASE INHIBITORS
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The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
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Page/Page column 134
(2009/04/25)
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- THIAZOLE AND OXAZOLE KINASE INHIBITORS
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The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
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Page/Page column 147
(2009/07/17)
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- Synthesis and cytotoxicity studies of thiazole analogs of the anticancer marine alkaloid dendrodoine
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The synthesis and cytotoxicity evaluation of 2-N,N-dimethylamino-5-indol-3- oylthiazole as the first member of a new portfolio of the thiazole analogs of the cytotoxic marine alkaloid dendrodoine (3-N,N-dimethylamino-5-indol-3-oyl-1, 2,4-thiadiazole) is described. Exploiting the opportunity arising from the replacement of the thiadiazole ring of dendrodoine by a thiazole ring which allowed further substitution on the five-membered ring, 2-N,N-dimethylamino-5- indoI-3-oyl-4-phenylthiazole has also been synthesized. Structural diversity is further extended by synthesizing 5-fur-2-oyl- and 5-coumarin-3-oyl-2-N,N- dimethylaminothiazoles, as well as 5-fur-2-oyl, 5-thiophen-2-oyl, 5-(1-methylbenzimidazol-2-oyl) and 5-benzothiazol-2-oyl derivatives of 2-N,N-dimethylamino-4-phenylthiazoles. Among these new N,N- dimethylaminothiazoles, 2-N,N-dimethylamino-5-indol-3-oyl-4-phenylthiazole shows significant in vitro cytotoxicity against a panel of human cancer cell lines.
- Reji, T. F. Abbs Fen,Devi,Thomas,Sreejalekshmi,Manju,Francis,Philip,Bharathan,Rajasekharan
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p. 1145 - 1150
(2008/12/23)
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- HCV NS-3 serine protease inhibitors
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HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, having the formula I wherein A is
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- HCV NS-3 serine protease inhibitors
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HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, of formula: wherein A is
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- On the [2+2] cycloaddition of 2-aminothiazoles and dimethyl acetylenedicarboxylate. Experimental and computational evidence of a thermal disrotatory ring opening of fused cyclobutenes
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The reaction of 2-(phenylamino)- and 2-(dimethylamino)thiazoles with dimethyl acetylenedicarboxylate led unexpectedly to dimethyl 6-(phenylamino)- and 6-(dimethylamino)-3,4-pyridinedicarboxylates. Those compounds reasonably result from a sequence of reactions initiated by a [2 + 2] cycloaddition of the alkyne to the formal C=C of the thiazole ring. These pyridines were obtained in nearly all the cases assayed as the exclusive reaction products under rather mild conditions and in fair to good yields. In contrast, the regioisomeric 2-amino-3,4-pyridinedicarboxylates, which would result from a [4 + 2] cycloaddition followed by sulfur extrusion, were only obtained in one particular case. The two reaction paths leading alternatively to both regioisomers were investigated computationally. The respective [2 + 2] and [4 + 2] cycloadducts were found to be formed stepwise from a common dipolar intermediate. Notably, the step following the [2 + 2] cycloaddition (i.e., the ring opening of the fused cyclobutene intermediate to give an all-cis 1,3-thiazepine) was found to take place in a disrotatory mode. Although geometric constraints and electronic factors may reduce the energy for the disrotation, the implication of the fused five-membered ring in the electronic reorganization leading to the 1,3-thiazepine is determinant. In this sense, this step could be regarded also as a thermally allowed six-electron five-center disrotatory electrocyclic ring opening. The proposed mechanism was experimentally supported by the isolation of several intermediates and other experimental facts.
- Alajarin, Mateo,Cabrera, Jose,Pastor, Aurelia,Sanchez-Andrada, Pilar,Bautista, Delia
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p. 5328 - 5339
(2007/10/03)
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- CYSTEINE PROTEASE INHIBITORS
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A compound of the formula (II) wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(=O)2 ; where Ra is H, C1-C4 alkyl or CH3C(=O); R5 is independently selected from H or methyl; E is -C(=O)-, -S(=O)m-, -NR5S(=O)m-, -NR5C(=O)-, -OC(=O)-, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or hetorocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.
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Page/Page column 92
(2010/02/12)
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- Selenoureas and thioureas are effective superoxide radical scavengers in vitro
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Oxygen radicals, such as superoxide radicals, embellishing DNA, protein, lipids, etc., and carrying out the obstacle of the function of a cell is known. It depends for the oxidant level in the living body on the balance of a generation system and an elimination system of oxygen radicals, and research which controls an oxidant level in the living body is briskly done by taking in the substance which eliminates an oxygen radical. We investigated scavenging effects of superoxide radicals by selenoureas and thioureas using a highly sensitive and quantitative chemiluminescence method. At 330 nM, five selenoureas and five thioureas scavenged fractions of superoxide radicals (O 2-) ranging from 8.4% to 87.6%. Among five N,N-unsubstituted selenoureas and N,N-unsubstituted thioureas 1-selenocarbamoylpiperidine and 1-thiocarbamoylpyrrolidine were the most effective scavengers. A possibility that selenoureas could use it as a new superoxide anion-scavenging substance from the result of this research became clear.
- Takahashi, Hitoe,Nishina, Atsuyoshi,Fukumoto, Ryo-Hei,Kimura, Hirokazu,Koketsu, Mamoru,Ishihara, Hideharu
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p. 2185 - 2192
(2007/10/03)
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- Preparation of N,N-unsubstituted selenoureas and thioureas from cyanamides
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Reaction of cyanamides with LiAlHSeH and LiAlHSH in the presence of HCl in diethyl ether provided the corresponding N,N-unsubstituted selenoureas and thioureas in moderate to high yields, respectively.
- Koketsu, Mamoru,Fukuta, Yoshihisa,Ishihara, Hideharu
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p. 6333 - 6335
(2007/10/03)
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- PIPERIDINE DERIVATIVES, PROCESS FOR OBTAINING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Piperidine derivatives, process for obtaining them and pharmaceutical compositions containing them, of formula STR1 used as neurokinin receptor antagonists, which are, in particular, useful for the treatment of all substance P-and neurokinin-dependent pathologies.
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- Reaction of 1,4,2-Dithiazolium Salts with Amino Compounds
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Systematic studies on the behavior of 1,4,2-dithiazolium cations (1) toward various amino compounds (ammonia, aliphatic and aromatic amines, hydrazine, semicarbazide, thiosemicarbazide derivatives, etc.) were performed.The reaction pathway could be classified into three types depending on possibile three fission modes of the initially-formed adduct.The main products were 5-imino-1,4,2-dithiazole, thiourea, and 1,3,4-thiadiazole derivatives, through the three different pathways, respectively.In order to clarify the factors controlling the reaction courses, the reactions of 1 with p-substituted aniline derivatives were carried out under systematically varying conditions.The strength of bases and the polaritiy of solvents had clear influence on the reactivity.The reaction mechanism is also discussed.
- Yonemoto, Katsumi,Shibuya, Isao
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p. 4043 - 4050
(2007/10/02)
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- 2-(N,N-Disubstituted Amino)thiazoles with Electron-withdrawing Groups at Position 5: Prepaeation and Investigation on Structural Features
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A convenient procedure for preparing N-mono- and NN-di-substituted cyanamides from cyanogen bromide has been developed.N,N-Disubstituted thioureas, obtained from the cyanamides, were condensed with α-bromo-α-cyanoketones to give 5-cyano-2-(N,N-disubstituted amino)thiazoles and with α-bromo-ketones to give 2-(N,N-disubstituted amino)thiazoles.Substitution in the latter products afforded 5-trifluoroacetyl- and 5-nitro-2-(N,N-disubstituted amino)thiazoles; nitration is greatly facilitated by the presence of a 4-aryl group.The average values of the barriers of rotation of the barriers to rotation of the 2-NR2 groups (ΔG298) in the 5-substituted thiazoles were established by variable temperature 1H n.m.r. spectrometry to be 57.4 kJ mol -1 (5-NO2), 56.2 (5-COCF3), and 51.5 (5-CN).I.r. examination showed that the 5-trifluoroacetyl compounds adopt one rotational form preferentially; this is probably the carbonyl O,S-syn-conformation.
- Birkinshaw, Timothy N.,Gillon, David W.,Harkin, Shaun A.,Meakins, G. Denis,Tirel, Malkom D.
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p. 147 - 153
(2007/10/02)
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- N,N-Disubstituted 2-Aminothiazole-5-carbaldehydes: Preparation and Investigation of Structural Features
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Methods of preparing N,N-disubstituted 2-aminothiazoles have been investigated. 4-Substituted N,N-dimethyl-, N-benzyl-N-methyl-, and N-methyl-N-phenyl-amines were prepared and converted by Vilsmeier formylation into 2-amino-5-carbaldehydes which were examined by i.r. and 1H n.m.r. spectrometry.The aldehyde group adopts the carbonyl O,S-syn-conformation.With the N,N-dimethyl and N-benzyl-N-methyl compounds the barrier to rotation of the amine group (ΔG(excit.)) is 50-55 kJ mol-1 and is insensitive to the nature of the 4-substituent.The amine group of the N-methyl-N-phenyl compounds has a marked preference for one orientation.This was shown by a crystallographic study of 4-t-butyl-2-(N-methyl-N-phenylamino)thiazole-5-carbaldehyde to have the phenyl group directed towards the sulphur atom of the thiazole ring.
- Gillon, David W.,Forrest, Ian J.,Meakins, G. Denis,Tirel, Malcolm D.,Wallis, John D.
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p. 341 - 348
(2007/10/02)
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- Dithioallophanic Acids. Part-III: Interaction of Carbon Oxysulphide with 2-S-benzyl-1,1-Dimethyl/1-Phenyl Isothiocarbamides
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Interaction of carbon oxysulphide with 2-S-benyl-1,1-dimethtyl isothiocarbamide in benzene has been found to afford 1,1-dimethyl thiocarbamide thiocyanate, S-benzyl-N,N-dimethyl thiocarbamate, and S-benzyl-N,N-dimethyl dithiocarbamate. 2-S-Benzyl-1-phenyl isothiocarbamide also affords the corresponding thiocarbamate, dithiocarbamate and in addition phenyl thiocarbamide.Mechanism has been discussed in detail.
- Dravid, R. N.,Chande, M. S.
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p. 855 - 857
(2007/10/02)
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- Benzhydrylpiperozinyl thiazole derivatives and pharmaceutical composition comprising the same
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Benzhydrylpiperazinyl Thiazole compounds of the formula STR1 wherein R1 is hydrogen, amino, or mono- or di- substituted amino, in which the substituent is selected from lower alkyl, acyl and di(lower)alkylaminomethylene, R2 is hydrogen, halogen, lower alkyl or aryl, R3 is ar(lower)alkyl optionally substituted by halogen, A is lower alkylene optionally interrupted by a sulfur atom, and Y is C1 -C3 alkylene, having antiallergic activity.
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- Cephalosporin displacement reaction
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The present invention is directed to a process for the displacement of the acetoxy group of a cephalosporanic acid by a sulfur nucleophile, in an organic solvent and under essentially anhydrous conditions.
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- Pesticidal compositions containing phosphoric esters and divalent sulphur compounds
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Pesticidal composition comprising: a pesticidal, phosphoric ester the molecule of which has at least one alkyl group of 1 to 3 carbon atoms, 0.05 to 10% of an agent stabilizing the said ester against decomposition by protonisation, together with adjuvants characterized in that the stabilizing agent comprises at least one sulphur compound containing per molecule at least one divalent sulphur atom of which one valence is bonded to an atom chosen from sulphur, carbon, nitrogen, hydrogen, and metals capable of giving a salt, the other valence being bonded to an atom chosen from hydrogen, the carbon atom already noted, a second carbon atom, the nitrogen atom already noted, a second nitrogen atom, the metal atom already noted in the case of a metal of valence greater than one, a second atom of metal and oxygen when the first valence is not attached to an atom of hydrogen, the proportion of sulphur calculated with reference to the weight of the sulphur compound being between 5 and 99%. Process for stabilizing a phosphoric ester of which the molecule possesses at least one alkyl group containing 1 to 3 carbon atoms characterized in that there is added to the phosphoric ester or to a mixture which contains it, 0.05 to 10% calculated on the weight of the phosphoric acid ester of an agent capable of stabilizing the said phosphoric ester against protonisation and comprising at least one sulphur compound such as that defined thereupon.
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