Lignan and neolignan derivatives from Magnolia denudata

A new tricyclo[4.2.0.0(2,8)]octane-type neolignan, 6-allyl-7-(3,4-dimethoxyphenyl)- 2,3-dimethoxy-8-methyl-tricyclo[4.2.0.0(2,8)]oct-3-en-5-one, together with 15 known lignan and neolignan derivatives have been isolated from the flower buds of Magnolia denudata DESR. and the structures of these compounds have been elucidated based on the 1H- and 13C-NMR spectra and two-dimensional NMR methods such as HMBC, HMQC, and NOESY.     

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitors IV. A series of new derivatives containing a spiro[5H-oxazolo[3,2-a]pyrazine-2(3H),4'-piperidin]-5-one skeleton

In the course of development of factor Xa (FXa) inhibitor in an investigation involving the synthesis of 1-arylsulfonyl-3-piperazinone derivatives, we found new compounds containing a unique spiro skeleton. Among such compounds, (-)-7-[(6-chloro-2-naphthalenyl)sulfonyl]tetrahydro-8a-(methoxymethyl)-1'-(4-pyridinyl)-spiro[5H-oxazolo[3,2-a]pyrazine-2(3H),4'-piperidin]-5-one (28, M55529) had activity more favorable than those of previously reported compounds. The inhibitory activity of M55529 for FXa is IC(50)=2 nM, with high selectivity for FXa over thrombin and trypsin.     

Novel A-seco-rearranged lanostane triterpenoids from Abies sachalinensis

From the needles of Abies sachalinensis, novel rearranged lanostane type triterpenes, 1-4, were isolated along with a known triterpene (5). The structures of the new compounds, 1-4, were elucidated to be 3,4-seco-8-(14-->13R)abeo-17,13-friedo-9beta-lanosta-4(28),7,14(30),22Z,24-pentaen-26,23-olide-3-oic acid, methyl 3,4-seco-8-(14-->13R)abeo-17,13-friedo-9beta-lanosta-4(28),7,14(30),22Z,24-penten-26,23-olide-3-oate, 3,4-seco-8(14-->13R)abeo-17,13-friedo-9beta-lanosta-4(28),7,14,22Z,24-pentaene-26,23-olide-3-oic acid and methyl 3,4-seco-8(14-->13R)abeo-17,13-friedo-9beta-lanosta-4(28),7,14,22Z,24-pentaene-26,23-olide-3-oate, respectively, by means of spectral experiments, especially two dimensional NMR spectroscopy, such as 1H-detected multiple quantum coherence (HMQC), 1H-detected heteronuclear multiple bond connectivity (HMBC) and 1H-1H-correlation spectroscopy (COSY) experiments. These new compounds have novel structures containing A-seco, rearranged spiro structure and a gamma-lactone conjugated with a diene. Some of these compounds showed potent antibacterial activity against gram positive bacteria.     

Facile synthesis of spiro[benzo[e]indole-2,2′-piperidine] derivatives and their transformation to novel fluorescent scaffolds

The reaction of azaheterocyclic enamines with acrylamide was employed for the preparation of novel fluorescent scaffolds possessing a benzo[e]indoline moiety. Reaction of 3-substituted 2-methylidene-1H-benzo[e]indole with acrylamide gave rise to spiro[benzo[e]indole-2,2′-piperidin]-6′-ones. Ring opening reactions of the latter spiro compounds were investigated. Benzo[e]indoline derivatives possessing 2-(3-carbamoylpropyl), 2-[3-(ethoxycarbonyl)propyl] and 2-(4-aminobutyl) side chains were synthesised. The optical properties of the benzo[e]indoline derivatives were studied by UV-vis and fluorescence spectroscopy.     

Synthesis of 1H-pyrazino[1,2-a]pyrido[2,3-e]pyrazine and 2H-Pyrano[2,3-b]pyrido[2,3-e]pyrazine Derivatives

With a continuing interest on heteropolycyclic structures which may show biological activities, we synthesized new tricyclic derivatives in which the pyridopyrazine skeleton is fused with pyrazine 7 and 8, B , n = 1. However, the initial design of obtaining also the cyclohomologous structure B (n = 2) produced instead a pyranopyridopyrazine derivative 11 . Thus during the attempt to prepare a pyridodiazepine intermediate, beside a very small amount of the desired product 10 , the pyridopyrazine 9 was obtained. The latter compound reacted with chloroacetyl chloride/chloroketene to give 4-carbethoxy-10-(chloroacetyl)-5,10-dihydro-5-methyl-2H-pyrano[2,3-b]pyrido[2,3-e]pyrazin-2-one ( 11 ). In studying the behavior of this derivative, compounds 12–14 were obtained. Compounds 4b,c, 5a,b, 7, 8, 9 and 14 have been submitted to preliminary pharmacological screening as CNS depressant agents.     

Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives embedded with benzimidazole moiety as potent antioxidants

Fourteen novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives bearing benzimidazole moiety ( 7a-n ) have been synthesized using the one-pot nitro reductive cyclization method. All the synthesized compounds were confirmed by ¹H nuclear magnetic resonance (¹H NMR), ¹³C NMR, fourier-transform infrared (FT-IR), mass spectrum, and elemental analyses. All the title compounds were subjected to in vitro antioxidant activity. The free radical scavenging activity of the compounds was examined using DPPH, nitric oxide, and superoxide radical scavenging methods. The results demonstrated that compound 3-(2-(3,4-dimethoxyphenyl)-1-propyl-1H-benzo[d]imidazol-5-yl)-6-4-tolyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine ( 7c ) was potent in scavenging both DPPH and nitric oxide radical with IC₅₀ values of 13.57 and 18.55 μg/ml when compared to the standard with IC₅₀ values of 23.75 and 23.14 μg/ml, respectively, which was due to the presence of electron-donating groups. The activity was found to decline when electron-donating groups were replaced by electron-withdrawing groups. Moderate scavenging activity was observed for the superoxide radical. Structure activity relationship and physiochemical properties were studied for all the derivatives.     

Synthesis and anti-tumor activities of novel [1,2,4]triazolo[1,5-a]pyrimidines

A series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives has been designed and synthesized in order to find novel anti-tumor compounds. The structures of all the compounds were confirmed by IR, 1H-NMR, MS and elemental analysis. Their anti-tumor activities against cancer cell lines (HT-1080 and Bel-7402) were tested by the MTT method in vitro. Among them, compound 19 displayed the best anti-tumor activity with IC50 values of 12.3 microM and 6.1 microM against Bel-7402 and HT-1080 cell lines respectively.     

Synthesis and analgesic activity of novel heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives

In order to develop analgesic compounds possessing a sulfur atom in the alicyclic ring, novel cis-fused heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives (II) were synthesized via a unique cyclization reaction starting from 4-(4-methoxyphenylthio)-2-butanone (1) or 6-methoxy-3,4-dihydro-2H-1-benzothiopyran-4-one (7). The analgesic effects of benzothiopyranopyrroles (16, 18) were measured by means of the writhing test. The phenolic derivative 18 completely inhibited the appearance of writhing at the dose of 50 mg/kg, but the methoxy derivative 16 had no analgesic effect.     

Ionic Liquid-Mediated Facile Synthesis and Antimicrobial Study of Thiazolo [2,3-b]Benzo[h]Quinazolines and Thiazino[2,3-b] Benzo-[h]Quinazolines

Abstract

8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one with thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H- benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro- benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with 1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl-6,7,9,10-tetrahydro-5 H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo [h][1,3]thiazino[2,3-b]quinazoline respectively. Arylidene derivatives have been obtained by two routes. The structures of the cyclized compounds have been established on the basis of elemental analysis and spectroscopic data. The synthesized compounds were screened for antimicrobial activity. Some of the compounds showed promising antimicrobial activities.     

Syntheses of 3-[5-Methyl-1-(4-Methylphenyl)-1,2,3-Triazol-4-yl]-6-Substituted-s-Triazolo[3,4-b]-1,3,4-Thiadiazoles

1,2,3-Triazole derivatives have been reported as inhibiting tumor proliferation, invasion, and metastasis^[1]. The fused l,3,4-triazolo[3,4-b]-1,3,4-thiadiazoles derivatives show various biological effects such as antifungal^[2], antibacterial, hypotensive and CNS depressant activities^[3]. We have reported several 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazoles in the previous paper^[4]. The novel 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[2,4-b]-1,3,4-thiadiazoles 6a-j have been synthesized by the condensation of 4-amino-5-mercapto-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazole 5 with various aromatic carboxylic acids in the presence of phosphorus oxychloride. The mercaptotriazole 5 was prepared from 4,the latter being prepared from 1 throng 2 and 3. The title compounds 6 were depicted in scheme 1. The structures of these compounds were established by elemental analysis, NMR, MS and IR techniques.     

Synthesis and bioactivity of novel triazolo [1,5‐a]pyrimidine derivatives[3]

In an attempt to discover novel compounds with high herbicidal activity and low toxicity, a series of novel 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives, α‐(5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐thio)acetamides 3 and α‐(5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐sul‐fonyl)acetamides 4 , have been designed and synthesized by a three‐step synthetic route. The structures of all compounds prepared were confirmed by elemental analyses and by ¹H NMR and mass spectroscopy. The results of preliminary bioassay indicate that the title compounds possess good herbicidal activity against rape (Brassica campestris L.) and barnyardgrass (Echinochloca crusgalli L.) © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:491–496, 2001     

Studies on Thiazolopyridines. Part 3: Reactivity of Thiazolo[3,2- a ]-3-aza[1,8]naphthyridine Towards Some Nucleophiles

A variety of new thiazolo[3,2- a ]pyridine derivatives 2a-h having 3-indolyl group were produced by refluxing 1a with different benzylidenemalononitrile derivatives. Reactivity of compound 4 toward some nitrogen nuclcophiles was investigated. Thus, the novel pyrazoles 6a , b were obtained when compound 4 was allowed to react with hydrazine and phenyl hydrazine in ethanol under reflux. On the other hand, pyrazolo[3',4':4,5]thiazolo[3,2- a ]-3-aza[1,8]naphthyridine 8 was formed by condensation of compound 4 with benzoyl hydrazine. Finally, condensed heterocyclic compounds containing pyran rings 9 and 10 were obtained by treatment compound 4 with active ethylene compounds.     

Novel rearranged acetophenone derivatives possessing diverse architectures from the leaves of Melicope ptelefolia

Melicolones C–K (1–9), nine acetophenone derivatives with three unprecedented architectures, were characterized from the leaves of Melicope ptelefolia. Among them, melicolone C (1) was a novel acetophenone analogue possessing a highly rearranged spiro skeleton. Melicolones D-F (2–4) were three novel acetophenone congeners bearing unusual octalactone ring. Melicolones G-K (5–9) were five new prenylated acetophenone derivatives featuring a 9-oxatricyclo [3.2.1.13, 8]nonane core. Their structures were established by extensive spectroscopic analysis and ECD spectra. These different structures were presumably derived from the same precursor via three major biosynthetic pathways. Compounds 5–9 exerted moderate effects to reverse multidrug-resistance in MCF-7/ADR cells with reversal fold values ranging from 6.2 to 13.3.     

Design, Synthesis, and Hypnotic Activity of Pyrazolo [1,5-a]pyrimidine Derivatives

On the basis of the Zaleplon structure, novel pyrazolo[1,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity. This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate. The structures of the derived target compounds were confirmed by their IR and ^1H-NMR spectroscopic data. The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, whilc derivative 1c was the most potent one.     

Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.     

Synthesis and spectroscopic studies of isosteviol-calix[4]arene and -calix[6]arene conjugates

Novel calix[4]arene derivatives functionalized with two or four isosteviol units at the upper rim and a new calix[6]arene having six isosteviol moieties at the lower rim have been synthesized. The structures of these compounds have been confirmed by NMR and mass spectrometry data. All ¹H and ¹³C NMR chemical shifts of isosteviol were fully assigned by extensive NMR spectroscopic methods, and used to clarify the structures and conformations of isosteviol-calixarene conjugates.     

Synthesis and electrophilic substitutions of novel pyrazolo[1,5-c]-1,2,4-triazolo[4,3-a]pyrimidines

5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1 were used as precursors for the preparation of a new series of 5-aryl-8-phenylpyrazolo[1,5-c]-1,2,4- triazolo[4,3-a]pyrimidines 2. The reactions of 2 with certain electrophilic reagents gave the respective 6-substituted derivatives 3-5 rather than the 7-isomeric products. Formylation of the key compounds 1 with ethyl formate yielded the formyl derivatives 6. Furthermore, boiling of compounds 1 with acetic acid afforded 7-acetylhydrazino-5-aryl-2-phenylpyrazolo[1,5-c]pyrimidines 7. Bromination of 7 yielded the dibromo- derivatives 8, while their iodination and nitration gave the monosubstituted derivatives 9 and 10, respectively. Also, treatment of 1 with boiling acetic anhydride yielded the triacetyl derivatives 11. The structure of synthesized products was confirmed by elemental analyses, IR, 1H NMR and MS spectra.     

7,8-亚甲二氧基-4-氧代-3,4-二氢嘧啶并[4,5-b]喹啉衍生物的合成

为了寻找具有药理活性的喹啉衍生物, 我们合成了五个新的喹啉衍生物和十一个7,8--亚甲二氧基-4-氧代-3,4-二氢嘧啶并[4,5-b]喹啉衍生物. 这些化合物的结构均经核磁共振光谱, 红外光谱和元素分析予以证实 .     

Synthesis and cytotoxic activity of benzo[a]pyrano[3,2-h] and [2,3-i]xanthone analogues of psorospermine, acronycine, and benzo[a]acronycine

Condensation of 2-hydroxy-1-naphthalenecarboxylic acid with phloroglucinol afforded 9,11-dihydroxy-12H-benzo[a]xanthen-12-one (6). Construction of an additional dimethylpyran ring onto this skeleton, by alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement, gave access to 6-hydroxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (12) and 5-hydroxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (13), which were methylated into 6-methoxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (14) and 5-methoxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (15), respectively. Osmium tetroxide oxidation of 14 and 15 gave the corresponding (+/-)-cis-diols 16 and 17, which afforded the corresponding esters 18-21 upon acylation. Similarly, condensation of 2-hydroxy-1-naphthalenecarboxylic acid with 3,5-dimethoxyaniline gave 11-amino-9-methoxy-12H-benzo[a]xanthen-12-one (23) which was converted into 11-amino-9-hydroxy-12H-benzo[a]xanthen-12-one (24) upon treatment with hydrogen bromide in acetic acid. Alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement afforded 6-amino-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (25) and 5-amino-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (26). The new benzopyranoxanthone derivatives only displayed marginal antiproliferative activity when tested against L1210 and KB-3-1 cell lines. The only compounds found significantly active against L1210 cell line, 16 and 20, belong to the benzo[a]pyrano[3,2-h]xanthen-7-one series, which possess a pyran ring fused angularly onto the xanthone basic core.     

Synthesis and antiestrogenic activity of the compounds related to the metabolites of (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]- 2-(4-isopropylphenyl)-1-butenyl]phenyl monophosphate (TAT-59) [corrected

The metabolites of (E) [corrected]-4-[1-[4-[2-dimethylamino)ethoxy]phenyl]- 2-(4-isopropylphenyl)-1-butenyl]phenyl monophosphate, TAT-59, (1), a potent antitumor agent for hormone-dependent tumors, and derivatives of TAT-59 were synthesized to confirm its proposed structure. The structure and the Z-configuration of the metabolites (2a-8a) were confirmed by comparison with synthesized authentic compounds. All of the metabolites and the derivatives of TAT-59 were tested for a binding affinity toward estrogenic receptors in vitro and antiuterotrophic activity in vivo. Most of the metabolites possessed remarkable binding affinity toward estrogenic receptors as well as fairly good antiuterotrophic activity.