bluuebunny/crossref_metadata_2025_split huggingface dataset:
The synthesis and chemistry of 2‐hydroxy‐4,6‐bis(trifluoromethyl)pyridine‐5‐carboxylates
Authors: Goure William F. 
Published: March 2009

AbstractThe facile two step, one pot synthesis of heretofore unknown 2‐hydroxy‐4,6‐bis(trifluoromethyl)‐pyridine‐5‐carboxylates by condensation of 3‐amino‐4,4,4‐trifluoro‐2‐butenoate with 4,4,4‐trifluoroacetoacetyl chloride and subsequent intramolecular cyclization of the resultant enamineamide is described. Methodology for the introduction of electrophiles at the 3‐position and elaboration of substituents at the 2‐ and 5‐positions is also discussed.
Synthesis and catalytic activity of a new class of cyclophosphazenic polypodands
Authors: Bullitta Maria Paola , Maccioni Elias , Corda Luciana , Podda Gianni 
Published: March 2009

AbstractA new class of solid‐liquid phase‐transfer catalysts (SL‐PTC) has been prepared by the reaction of octachlo‐rocyclotetraphosphazatetraene and polyethylene glycol monoalkyl ether. These polypodands are found to be powerful metal cation complexing agents and very efficient catalysts in anion promoted reactions (e.g. nucleophilic substitution and reduction reactions).
Synthesis of p‐aminobenzamides of several aminopyrazolidines: Potential antiarrhythmic agents related to procainamide
Authors: Kornet Milton J. , Abdul‐Nabi All K. , Steinberg Mitchell I. 
Published: March 2009

AbstractFour heterocyclic amines including 1,2‐diethyl‐3‐aminomethylpyrazolidine (3), 1‐(2‐aminoethyl)‐2‐methyl‐pyrazolidine (5), 1,2‐dimethyl‐4‐aminomethylpyrazolidine (7), and 1,2‐diethyl‐4‐aminopyrazolidine (9) have been synthesized. Each was acylated with p‐nitrobenzoyl chloride and afforded the corresponding p‐nitro‐benzamides 10, 12, 14, and 16. Catalytic reduction of these nitro intermediates gave the corresponding p‐aminobenzamides 11,13,15, and 17. The latter compounds are analogs of procainamide and two of them, 15 and 17, were evaluated in the isolated cardiac Purkinje fiber preparation by measuring their effects on the action potential upstroke velocity.
A study of 2‐aminofurans
Authors: Lythgoe David J. , Mcclenaghan Ian , Ramsden Christopher A. 
Published: March 2009

AbstractCatalytic reduction of 2‐nitrofurans 2 gives low yields of 2‐aminofurans 1 which are not isolated but are trapped using ethyl ethoxymethylenecyanoacetate (6) or ethoxymethylenemalononitrile (7). In these reactions 2‐aminofuran (1a) behaves like a dieneamine with substitution occurring at position 5 of the ring. When the 5‐position is substituted reaction takes place at position 3 and thermal cyclisation of the product gives furo‐[2,3‐b]pyridine derivatives 16. An AM1 calculation of the properties of 2‐aminofuran (1a) is reported and the results are consistent with observed properties.
β‐Ribo‐ and α‐arabinonucleosides containing the 1,2‐benzisoxazole and 1,2‐benzisothiazole rings
Authors: Yoshii Kiyotaka , Ohba Yoshihiro , Nishiwaki Tarozaemon 
Published: March 2009

AbstractThe reaction of the silylated base of 1,2‐benzisoxazol‐3(2H)‐one (1) and its 7‐methyl derivative5and 5‐methyl‐1,2‐benzisothiazol‐3(2H)‐one (9), respectively, with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose followed by basic deprotection gave the corresponding β‐D‐ribonucleosides, and the silylated base of1, when treated with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐α‐D‐arabinofuranose in the presence of stannic chloride, afforded the corresponding α‐arabinonucleoside. Structural proofs of these nucleosides are provided from elemental analyses and1H and13C nmr spectra.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline, benzo[f]phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline, and benzo[h]‐phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline
Authors: Camoutsis Charalampos , Castle Raymond N. 
Published: March 2009

AbstractThe synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline (13), benzo[h]‐phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline (14), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline (15).
First synthesis of the benzo[f]pyrido[2′,3′:3,4]‐pyrrolo[2,1‐a][2,7]naphthyridine ring system
Authors: Bracher Franz 
Published: March 2009

AbstractThe lithiated pyridine 7 on reaction with methyl 4‐methylquinoline‐3‐carboxylate (8) gave the ketone 9, which could be converted to the biaryl 11 via an effective two step anellation procedure. Treatment of 11 with dilute sulfuric acid resulted in an unexpected ring closure to give the title ring system.
Synthesis of 1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐sulfonamides
Authors: Shankar Ravi B. , Pews R. Garth 
Published: March 2009

AbstractThe 1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐sulfonamides are a new class of highly active herbicides. A novel cyclization method for the synthesis of these compounds is discussed.
The structure of the CT complex between 5,7,12,14‐tetramethoxydibenzo[b,i]thianthrene with TCNQ
Authors: Matsuoka Masaru , Iwamoto Akihiro , Ouchi Takeshi , Yoshioka Hiroshi , Nakatsu Kazumi 
Published: March 2009

AbstractThe structure of 1,4‐dithiines obtained from orthodihalogeno heterocycles with thiocarbonyl compounds was determined by X‐ray structure analysis of the intermolecular charge‐transfer complex between 5,7,12,14‐tetramethoxydibenzo[b,i]thianthrene and TCNQ. The formation of the thiazole ring has already been reported but the products were confirmed to be 1,4‐dithiines by X‐ray structure analysis and the previously reported results.
PolycyclicN‐heterocyclic compounds.XLI. Synthesis of 4‐substituted 6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepines, 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepines and their related compounds as a series of potential blood platelet aggregation inhibitors
Authors: Nagamatsu Tomohisa , Hantani Yoshiji , Yamada Minoru , Sasaki Kenji , Ohtomo Hiromi , Nakayama Taiji , Hirota Takashi 
Published: March 2009

AbstractAs a series of polyheterocyclic compounds for exploitation as anti‐platelet agents, tricyclic heterocyclic compounds, 4‐substituted 6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepines3–6, 9, 12–14, and16–26, having nitrogen, oxygen, or sulfur containing functional groups at the 4‐position, were prepared. In addition, tetra‐cyclic heterocyclic compounds, 3‐methyl‐1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzaze‐pinium chloride (7), 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepines10a‐e, 2,3,6,7‐tetrahydro‐1H5H‐pyrimido[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepine (11), and 1,2,5,6‐tetrahydro‐4H‐thiazolo‐[3′,2′:1,6]pyrimido[5,4‐d][1]benzazepinium chloride (15)viaring closure of 4‐(hydroxyalkylamino)‐6, 9a‐e, and3c, and 4‐(2‐hydroxyethylthio)‐6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepine (14) with phosphoryl chloride or thionyl chloride, respectively, were also prepared. Their inhibitory activities against collagen‐induced aggregation of rabbit blood plateletsin vitrowere investigated. Among them, compound5having a morpholino group at the 4‐position on the tricyclic nucleus, which enhanced the activity more than 14‐fold as compared with aspirin, was found to have the most satisfactory in inhibitory activity.
Synthesis and properties of 1,4,8,11,15,18,22,25‐octaalkoxy‐2,3,9,10,16,17,23,24‐octakis(phenylthio)phthalocyaninato copper(II)
Authors: Azuma Natsuhiro , Kitahara Kiyoshi , Motoi Takashi , Tokita Sumio , Nishi Hisao 
Published: March 2009

Abstract1,4,8,11,15,18,22,25‐Octaalkoxy‐2,3,9,10,16,17,23,24‐octakis(phenylthio)phthalocyaninato copper(II) was synthesized. They were easily soluble in organic solvents and their Q‐bands showed bathochromic shifts about 100 nm compared with unsubstituted phthalocyaninato copper(II). Their properties were examined.
PolycyclicN‐hetero compounds.XLIII.Syntheses and properties of 2‐substituted 1‐acetoxy‐6‐acetyl‐5,6‐dihydro‐4H‐imidazo[1′,2′:1,6]‐pyrimido[5,4‐d][1]benzazepinesviaN‐(6,7‐dihydro‐5H‐pyrimido[5,4‐d]‐[1]benzazepin‐4‐yl)amino acids and their analogous mesoionic compounds, and their related compounds as a series of potential blood platelet aggregation inhibitors
Authors: Nagamatsu Tomohisa , Hantani Yoshiji , Sasaki Kenji , Ohtomo Hiromi , Nakayama Taiji , Hirota Takashi 
Published: March 2009

AbstractA study of the cyclization method by heating ofN‐(6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepin‐4‐yl)amino acids3a‐h, 6, and9a,bwith excess acetic anhydride for the preparation of 2‐substituted 1‐acetoxy‐6‐acetyl‐5,6‐dihydro‐4H‐imidazo[1,2′:1,6]pyrirnido[5,4‐d][1]benzazepines4a‐hand tetra‐ and penta‐cyclic mesoionic compounds7and10a,bhas been made. In addition, a tetracyclic mesoionic compound having a sulfur atom on the skeleton, 5,6‐dihydro‐4H‐thiazolo[3′,2′:1,6]pyrimido[5,4‐d][1]benzazepiniurn‐1‐one (12) was similarly prepared by treatment of 2‐(6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepm‐4‐ylthio)acetic acid (11) with excess acetic anhydride. Their inhibitory activities against collagen‐induced aggregation of rabbit blood plateletsin vitrowere also investigated, and some heterocycles exhibited from a two‐ to a four‐fold more potent activity as compared with aspirin.
A convenient synthesis of tricyclic purine derivatives
Authors: Shimada Junichi , Kuroda Takeshi , Suzuki Fumio 
Published: March 2009

AbstractA convenient synthesis of new heterocycles such as 7,8‐dihydro‐1H‐imidazo[2,1‐i]purin‐5(4H)‐ones (2, n = 0) and 5,6‐dihydro‐1H‐imidazo[2,1‐b]purin‐9(8H)‐ones (3) was described. The syntheses of 2 and 3 were accomplished by treatment of 6‐methylthio‐7H‐purin‐2(3‐H)‐ones 7 or 2‐benzylthio‐1‐methyl‐9‐triphenylmethyl‐9H‐purin‐6(1H)‐one (15) with appropriate aminoalcohol followed by dehydrative cyclization using thionyl chloride. Compound 15 was efficiently prepared by benzylation of 6‐hydroxy‐2‐mercaptopurine (12) followed by tritylation and N‐methylation.
Convenient synthesis of 4‐amino‐7‐(dialkylamino)pyrido[2,3‐d]pyrimidines from polysubstituted pyridines
Authors: Cocco Maria Teresa , Congiu Cenzo , Maccioni Antonio , Onnis Valentina 
Published: March 2009

AbstractA convenient synthesis of 4‐amino‐7‐(dialkylamino)pyrido[2,3‐d]pyrimidines via cyclization of functionalized pyridines is reported. The preparation of the starting pyridines from 3‐amino‐3‐(dialkylaraino)propene‐nitriles and ethoxymethylenemalononitrile is described.
Synthesis of 4,6‐disubstituted 2‐methylpyridines and their 3‐carboxamides
Authors: Shibata Katsuyoshi , Katsuyama Isamu , Izoe Hideaki , Matsui Masaki , Muramatsu Hiroshige 
Published: March 2009

AbstractA new one‐pot synthesis of title compounds by the reactions of α,β‐unsaturated carbonyl compounds with β‐aminocrotononitrile in the presence of sodium hydroxide is described.
Synthesis of 6,7,8,9‐tetrahydro‐5H‐pyrimido‐[4,5‐b][1,4]diazepine‐6,8‐diones
Authors: Phillips Oludotun A. , Knaus Edward E. 
Published: March 2009

AbstractThe sodium ethoxide catalyzed condensation of 4,5‐diaminopyrimidine (3) with diethyl malonate afforded 6,7,8,9‐tetrahydro‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (4). Methylation of 6,7,8,9‐tetrahydro‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (4) using sodium hydride and two equivalents of iodomethane gave 5,9‐dimethyl‐6,7,8,9‐tetrahydro‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (5) which on further methylation using sodium hydride and one equivalent iodomethane yielded 6,7,8,9‐tetrahydro‐5,7,9‐trimethyl‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (6). Reaction of 6,7,8,9‐tetrahydro‐5H‐pyrirnido[4,5‐b][1,4]diazepine‐6,8‐dione (4) with 4.2 equivalents of sodium hydride and 4.1 equivalents of iodomethane afforded 6,7,8,9‐tetrahydro‐5,7,7, 9‐tetramethyl‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (7). 6,7,8,9‐Tetrahydro‐5,7,7,9‐tetramethyl‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (7) exhibited weak anticonvulsant activities in the subcutaneous pentylenetetrazole and maximal electroshock anticonvulsant screens indicating it is a partial bioisostere of the anticonvulsant drug clobazam (2).
The reaction of 2‐nitrosopyridine with nitrile oxides: First synthesis of 1,2,4‐triazolo[1,5‐a]pyridine 1,3‐Di‐N‐oxides
Authors: Gallos John K. , Lioumi Maria I. , Lekka Anastasia N. 
Published: March 2009

AbstractReactions of 2‐nitrosopyridine with nitrile oxides afford either the novel title compounds or the corresponding 1,2,4‐triazolo[1,5‐a]pyridine 3‐oxides.
A simple stereoselective one‐pot synthesis of C‐nucleosides by 1,3‐dipolar cycloaddition of chiral azomethine imines prepared in situ
Authors: Žličar Marko , Stanovnik Branko , Tišler Miha 
Published: March 2009

AbstractThe NH,NH‐dihydrocycloadduct 1 (6‐chloro‐9,9‐dimethyl‐7,8‐dihydro‐9H‐pyrazolo[4,3‐d]tetrazolo[1,5‐b]‐pyridazine) obtained by the cycloaddition of 2‐diazopropane to 6‐chlorotetrazolo[1,5‐b]pyridazine, is transformed with protected or unprotected carbohydrates 2, 5, 7,9, 11, 13 and 15 in the presence of methyl acrylate (3) into the corresponding C‐nucleosides 4,6,8,10,12,14 and 16. In this one‐pot synthesis two new chiral centers are formed stereoselectively, dependent on the chirality at C‐atom next to aldehydo group in the carbohydrate.
Synthesis and biological evaluation of nucleosides containing 8‐amino‐imidazo[1,2‐α]pyrazine as an isosteric replacement for adenine
Authors: Maccoss M. , Meurer L. C. , Hoogsteen K. , Springer J. P. , Koo G. , Peterson L. B. , Tolman R. L. , Emini E. 
Published: March 2009

AbstractA number of novelC‐nucleosides related to purine derivatives are described in which the purine moiety has been replaced by the isosteric heterocycle, 8‐aminoimidazo[1,2‐α]pyrazine. The nucleosides prepared include the ribo, 3′‐deoxy, 2′,3′‐dideoxy, and 2′,3′‐unsaturated derivatives. TheseC‐nucleosides represent derivatives containing acid stable glycosyl bonds and they can be considered as analogs of adenine‐ or 3‐deazaade‐nine‐containing nucleosides. Preparation of the parent ribonucleoside was accomplished by reaction of the C‐l functionalized sugar, (2ξ)‐1‐amino‐3,6‐anhydro‐l‐deoxy‐4,5‐O‐isopropylidene‐7‐O‐trityl‐D‐allo‐heptitol with 2,3‐dichloropyrazine, followed by ring closure to the 8‐chloroimidazo[1,2‐α]pyrazine nucleoside, conversion to the 8‐amino derivative and deblocking. A single crystal X‐ray structure of the parent 8‐amino‐3‐(β‐D‐ribofuranosyl)imidazo[1,2‐α]pyrazine is described and the conformation compared to that of formycin. The sugar‐modified analogs were prepared by subsequent functional group manipulations on the sugar moiety. Biological evaluation againstHIVinH9T‐lymphoid cell culture showed the nucleosides to be devoid of significant antiviral activity compared to DDA. The 3‐deazaadenosine analog also demonstrated weak suppression of mouse splenic NK activity toward YAC cells (mouse lymphoma cell targets). The imidazo[1,2‐α]pyrazine analog of 3‐deazaadenosine showed antiinflammatory activityin vivoin the rat pleurisy carrageenan model in the same range with 3‐deazaadenosine.
Heterocyclic amino acids as synthons. Reactions with dicarbonyl compounds
Authors: Kolar Patrik , Tišler Miha 
Published: March 2009

AbstractFrom some alkyl heteroarylglycinates and dicarbonyl compounds various heterocyclic systems are easily accessible. Transformations are described which lead to imidazo[1,5‐α]pyridines, heteroaryl‐substituted pyrroles, pyrido[1,2‐α]pyrazines, pyrido[1,2‐α]pyrimidines or quinolizin‐4‐ones.
β‐lithiations of carboxamides. Synthesis of β‐substituted‐α,β‐unsaturated amides
Authors: Katritzky Alan R. , Szajda Maria , Lam Jamshed N. 
Published: March 2009

AbstractN‐Methyl‐2‐methyl‐3‐(benzotriazol‐l‐yl)propanamide, on treatment with butyllithium forms a dianion which on treatment with alkyl and benzyl halides, aldehydes and ketones affords monosubstituted products; with ethylp‐toluate, a lactam is formed. The alkylated derivatives eliminate benzotriazole in the presence of base to afford trisubstituted α,β‐unsaturated amides.
Synthesis and reactions of tetrazolo[1,5‐α]pyrimidines
Authors: Kappe Thomas , Roschger Peter , Färber Gerald 
Published: March 2009

AbstractThe reaction of “magic malonates” (bis‐2,4,6‐trichlorophenyl malonates, 1) with 5‐aminotetrazole (2) in the presence of triethylamine yields the ammonium salts 3. Upon treatment of 3 with strong acids compounds 4a‐d were obtained as a mixture of isomeric tetrazolopyrimidines (A) and 2‐azidopyrimidines (B). Reaction of 4d with bromine or sulfuryl chloride leads by ring opening and decarboxylation to the halogenated tetrazole derivatives 5 or 7, respectively. The action of acetic anhydride in pyridine on 3d yields the zwitterionic tetra‐mic acid derivative 10.
Pyridine‐substituted hydroxythiophenes. II. Alkylation of o‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophenes: Regiospecific formation of o‐pyridyl‐3‐alkoxythiophenes
Authors: Zhang Yihua , Hörnfeldt Anna‐Britta , Gronowitz Salo 
Published: March 2009

AbstractThe alkylation of o‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophenes has been investigated. In the case of 4‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophene systems, the soft alkylating reagent, methyl iodide, using sodium hydride as the base and dimethylimidazolidinone as the solvent, gave rise to a mixture of O‐alkylated and O,C‐dialkylated products in the proportions of 4.6–6.5 to 1. However, in the case of 2‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophene systems, the same reaction conditions brought about exclusively O‐alkylated compounds in yields of 45–53%. In both cases, the hard alkylating reagent, methyl p‐toluenesulfonate, with the same base and solvent, only give O‐alkylated compounds in yields of 51–77%. These latter conditions resulted in a good preparative route for the regiospecific formation of o‐pyridyl‐3‐alkoxythiophenes by using ethyl 2‐bromopro‐pionate as well as methyl p‐toluenesulfonate as alkylating reagents. The hydrolysis of the esters, derived from alkylation with ethyl 2‐bromopropionate, has also been investigated.
Photoinduced β‐elimination of the triazole group in the 1‐(N,N‐bisacyl)amino‐1,2,3‐triazoles
Authors: Kalambokis E. A. , Maroulis A. J. , Alexandrou N. E. 
Published: March 2009

AbstractThe photoelimination of the 1,2,3‐triazole group from the title compounds proceeds, depending upon the reaction conditions, via an intra‐ or intermolecular hydrogen abstraction or electron‐transfer mechanism, followed by homolytic cleavage of the N,N bond. It can also proceed via π−‐assisted β‐cleavage of the same weak bond, when light of shorter wavelength is used. The composition of the products suggests that in all cases most probably a α‐type 1,2,3‐triazolyl radical 10 is eliminated which is further quenched by hydrogen or chlorine abstraction.
2′‐O,5‐dimethyluridine: A total synthesis and single crystal X‐ray diffraction study
Authors: Lewis Arthur F. , Revankar Ganapathi R. , Hogan Michael E. 
Published: March 2009

AbstractA new method for the synthesis of 2′‐O,5‐dimethyluridine (5) has provided the title compound in a higher yield. Application of a one‐pot ribosylation methodology resulted in an efficient, high yield synthesis of 5‐methyluridine (ribothymine, 3b). An X‐ray diffraction analysis of 5 disclosed the conformation of the sugar moiety of this nucleoside as anti, N(3′‐endo), g+.
On Triazoles. XXXII. The reaction of 5‐amino‐1 H‐1,2,4‐triazolylcarbothiohydrazides with β‐ and γ‐oxo‐esters
Authors: Reiter József , Barkóczy József , Pallagi István 
Published: March 2009

Abstract5‐Amino‐lH‐1,2,4‐triazolylcarbothiohydrazides gave β and γ‐oxo‐esters in boiling ethanol [1,2,4]triazolo‐ [1,5‐d][1,2,4,6]tetrazepine‐5‐thiones 3. Analogously ethyl 2‐oxocyclohexanecarboxylate provided a mixture of two diastereomeric spiro derivatives 5 and 6. At 130°, 2‐acetonyl‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazole‐5‐thione (8) was formed. Ring closure of 3e (R1 = CH3, R2 = CH2CH2COOEt, Q = morpholino) lead to the isomeric pyrrolo[2,1‐g][1,2,4]triazolo[1,5‐d][1,2,4,6]tetrazepin‐8(11H)‐one (12) and pyrrolo[1,2‐f][1,2,4]triazolo‐[1,5‐d][1,2,4,6]tetrazepin‐10(7H)‐one (13) derivatives representing two new ring systems.
Synthesis of certain N‐ and C‐alkyl purine analogs
Authors: Bhattacharya Birendra K. , Rao T. Sudhakar , Lewis Arthur F. , Revankar Ganapathi R. , Sanghvi Yogesh S. , Robins Roland K. 
Published: March 2009

AbstractA number of N‐ and C‐alkyl derivatives of selected guanine analogs have been synthesized as potential antiviral agents. n‐Pentyl, n‐hexyl and 6‐hydroxyhexyl derivatives in the imidazo[1,2‐α]‐s‐triazine, 9–11, imid‐azo[1,2‐α]pyrimidine, 13–17, and thiazolo[4,5‐d]pyrimidine, 19–21, ring system have been prepared by the direct alkylation of the sodium salt of the appropriate aglycon with the respective alkylbromides. Dehydra‐tive coupling of 3‐amino‐6‐hydrazino‐1,2,4‐triazin‐5(4H)‐one (22) with either hexanoic acid or heptanoic acid, and further ring closure of the reaction products 24a and 24b provided the n‐pentyl and n‐hexyl derivatives of 6‐amino‐1,2,4‐triazolo[3,4‐f][1,2,4]triazin‐8(7H)‐one 25a and 25b, respectively. A similar condensation of 3‐amino‐6‐aminomethyl‐1,2,4‐triazin‐5(4H)‐one (23) with heptanoic acid, followed by ring annulation, readily gave 2‐amino‐7‐n‐hexylimidazo[5,1‐f][1,2,4]triazin‐4(3H)‐one (25c). Bromination of 25c with N‐bromosuccini‐mide afforded the corresponding 5‐bromo derivative 26. Alkylation of the in situ generated sodium salt of 4‐methoxycarbonylmethyl‐5‐methoxycarbonyl‐2‐oxo‐1H,3H‐imidazole (27) with 1‐bromohexane gave the N‐1 alkylated product 31. Manipulation of the functional groups in 31 and further hydrazine mediated ring annulation furnished 5,6‐diamino‐1‐n‐hexyl‐3‐methylimidazo[4,5‐c]pyridine‐2,4‐dione (39). Catalytic hydrogena‐tion of 39 gave 7‐methyl‐8‐oxo‐9‐hexyl‐3‐deazaguanine (40), a congener of the immunostimulator 7‐methyl‐8‐oxoguanosine.
New azomycin acyclonucleoside. Synthesis and biodistribution of radiohalogenated analogues in tumor‐bearing mice
Authors: Hasan Ahmad , Knapp Furn F. , Kilbourn Michael R. , Buchsbaum Donald J. 
Published: March 2009

AbstractThe design, synthesis and biological activities of several acyclonucleoside analogues related to misoni‐dazole are described. The hydroxy‐5, bromo‐6, iodo‐7, and fluoro‐8 derivatives of ethoxymethylazomycin and iodopropenyloxymethylazomycin (12) have been prepared. Alkylation of silylated azomycin with haloethoxy‐methylene chloride gave the corresponding acyclonucleosides. Similarly, propargyloxymethylene chloride gave propargyloxymethylazomycin (10), which after hydrostannylation and subsequent iododestannylation yielded iodopropenyloxymethylazomycin (12). The radiolabeled [125I] or [18F] compounds were prepared from the corresponding substrates. Biodistribution results of the radiolabeled analogues in mice showed that compound 7 had good tumor uptake (2.0% injected dose/g at 1 hour). The high radioactive levels in blood and stomach, however, were perhaps due to in vivo deiodination or metabolism. Compound [125I]‐12 showed the highest tumor uptake (4.8 and 3.6% injected dose/g at 1 and 4 hours respectively) of all of the compounds tested. Relatively low thyroid uptake of radioactivity in mice dosed with compound [125I]‐12 indicates significantly reduced in vivo deiodination in comparison to compound [125I]‐7.
Aza‐analogues of cage compounds: Potential precursors to azacubanes and 1‐azahomocubanes
Authors: Gilardi Richard , George Clifford , Karle Jerome , Eaton Philip E. , Fisher Allison M. 
Published: March 2009

AbstractExploration of the reactions of the 9‐azahomocubane system led to derivatives of two small‐ring systems containing aza‐bridging atoms, 5‐azatetracyclo[4.2.0.03,8.04,7]octane and 9‐azatetracyclo[4.3.0.02,5.04,7]nonane. The structures were characterized by X‐ray diffraction analyses. There are no prior X‐ray structural reports on these systems.