Design, synthesis, and fungicidal activities of novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties.

BACKGROUND: To study the effect of changing the piperidine ring of oxathiapiprolin on the fungicidal activity, we designed and synthesized novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties, and studied their fungicidal activities against Phytophthora capsici in vitro. RESULTS: These derivatives showed moderate to good fungicidal activities against Phytophthora capsici, two oxime ether derivatives showed higher fungicidal activity in vitro than dimethomorph (EC50  = 0.1331 µg mL-1 ) and comparable to oxathiapiprolin (EC50  = 0.0042 µg mL-1 ). Oxime ester derivatives showed significantly reduced activities compared with oxime ether derivatives. Most of these derivatives showed broad-spectrum fungicidal activity against the other eight kinds of fungi. Moreover, four derivatives exhibited good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. The hyphae morphology study showed that compound 10d might cause mycelial abnormalities of Phytophthora capsici. CONCLUSION: The activity of 10b against Phytophthora infestans was better than that of mandipropamid, and compound 10d exhibited higher fungicidal activities against Pseudoperonospora cubensis and Phytophthora infestans than mandipropamid. These two derivatives emerged as promising candidates for antifungal drugs. © 2023 Society of Chemical Industry.

Characteristics of Deep Venous Thrombosis in Isolated Lower Extremity Fractures and Unsolved Problems in Guidelines: A Review of Recent Literature.

Deep venous thrombosis (DVT) has been characterized by a disorder of venous return caused by abnormal blood clotting in deep veins. It often occurs in the lower limbs and is a common complication in orthopaedics. Therefore, relevant professional organizations domestic and overseas had formulated and constantly updated relevant guidelines to prevent the occurrence of DVT. According to the management strategy of the guidelines, the incidence of DVT can be significantly reduced. However, due to the variety of fractures types, the guidelines cannot expound precautions and characteristics of DVT for all fracture types at present, and there are other related unresolved problems. For example, there is still a lack of consistent optimal strategies for the management of DVT following isolated lower extremity fractures with a higher incidence. The best anticoagulant strategies for patients with upper limb fractures, pediatric fractures, and those combined with other injuries are rarely described in orthopaedic guidelines, but such fractures are common in clinical orthopaedics. The long-term complications after DVT, such as post-thrombotic syndrome, are not well-understood. In the absence of clear guidance, orthopaedic surgeons often resort to empiric anticoagulation or conservative treatment, so the prevention effects of DVT are inconsistent. The purpose of this review is to summarize the characteristics of DVT events after isolated lower extremity fractures and to discuss the unsolved issues in the guidelines by reviewing the previous literature and tracing the history of DVT discovery, to provide more scientific and comprehensive recommendations for the prediction and prevention of DVT.

Characteristics and Treatment Strategy of Isolated Calf Deep Venous Thrombosis after Fractures: A Review of Recent Literature.

Isolated calf deep venous thrombosis (ICDVT) includes thrombosis located at the far end of the popliteal vein, such as the anterior tibial vein, posterior tibial vein, fibular vein, and intramuscular vein of the soleus and gastrocnemius. This type of thrombosis has the highest incidence, accounting for approximately half of all deep vein thrombosis (DVT) cases; however, there is no consistent recommendation for ICDVT treatment across countries, and there is also no optimal management strategy. In recent years, increasing evidence has shown that ICDVT can develop into proximal DVT, even causing pulmonary embolism (PE). Therefore, some experts suggest anticoagulant therapy for this type of DVT, while others hold an opposing attitude. Therefore, the treatment strategy for this type of DVT has become a hot and difficult research topic. The purpose of this review is to summarize the characteristics of ICDVT and the effects of different treatment strategies by analyzing recent and important classical works in the literature in an attempt to provide recommendations for the treatment of this most common type of DVT in orthopaedic clinics.

Epidemiological Characteristics of Major Joints Fracture-Dislocations.

OBJECTIVE: To describe the epidemiological features of major joints fracture-dislocations between 2015 and 2019. METHODS: This retrospective study enrolled patients with majorintra-articular fracture-dislocations who were treated in the third hospital of Hebei Medical University from January 2015 to December 2019. A total of 582 patients (389 [66.84%] males and 193 [33.16%] females) were identified. The distribution characteristics of intra-articular fracture-dislocations involving shoulder, elbow, wrist, hip, knee, and ankle joints were included. The potential associations between fractures with concomitant dislocations and related factors, such as age, gender and sites were explored. RESULTS: There were 92 cases (15.81%) of shoulder joints, 67 cases (11.51%) of elbow joints, 45 cases (7.73%) of wrist joints, 181 cases (31.10%) of hip joints, 42 cases (7.22%) of knee joints, and 155 cases (26.63%) of ankle joints. The overall male-to-female ratio was 2.02:1.The highest proportion age group of the six types intra-articular fracture-dislocations included the ages 25-34 years. For males, the highest proportion age group was 25-34 years, for females, it was 45-54 years. For male patients, hip was the most common, accounted for 35.48%, but ankle fracture-dislocation was the most common for females, accounted for 30.57%. The highest proportion age group of shoulder fracture-dislocation included the ages 55-64 years(22.83%), with a male to female ratio of 1.24:1. While the age group with the highest risk of elbow, wrist, hip, knee and ankle fracture- dislocation was 25-34 years (28.36%) with a male to female ratio of 2.19:1, 25-34 years (31.11%) with a male to female ratio of 8:1, 45-54 years (27.07%) with a male to female ratio of 3.21:1, 15-24 years (45.24%) with a male to female ratio of 0.75:1, 25-44 years (43.87%) with a male to female ratio of 1.63:1, respectively. The most common site of joint fracture-dislocation in different age groups was corresponding as follows, 0-14 years(elbow), 15-24 years(knee), 25-34 years(hip), 35-44 years(hip), 45-54 years(hip), 55-64 years(ankle), 65-74 years(shoulder), ≥75 years(shoulder). CONCLUSION: Major joints fracture-dislocations were most common in the hip and the least common in the knee, and there were more men than women. Hip was the most common affected joint in men while ankle in women. Age and sex factors can significantly affect the location of intra articular fracture and dislocation. The current study could aid orthopaedic surgeons in a better understanding of this injury and help to implement targeted preventive measures.

Age- and Gender-Specific Epidemiologic Characteristics of Major Intra-Articular Fractures: Five-Year Data from a Level 1 Trauma Center.

OBJECTIVE: To investigate the epidemiological characteristics of major intra-articular fractures. METHODS: This retrospective study enrolled patients with major intra-articular fractures who were treated in the Third Hospital of Hebei Medical University from January 2015 to December 2019. A total of 11,084 patients (7,338 [66.20%] males and 3,746 [33.80%] females) meeting the inclusion and exclusion criteria were included. The distribution characteristics of intra-articular fractures involving shoulder, elbow, wrist, hip, knee, ankle, and subtalar joints were identified.The potential associations between fractures and various other factors, such as age, gender, sites, were explored. RESULTS: There were 74 cases (0.67%) of shoulder fractures, 1,941 cases (17.51%) of elbow fractures, 1,155 cases (10.42%) of wrist fractures, 520 cases (4.69%) of hip fractures, 3,118 cases (28.13%) of knee fractures, 2,156 cases (19.45%) of ankle fractures, and 2,120 cases (19.13%) of subtalar fractures. The overall male-to-female ratio was 1.96:1. The highest proportion age group of major intra-articular fractures included the ages 45-54 years. For males, the highest proportion age group was 45-54 years, for females, it was 55-64 years. The knee joint fracture was the most common type, accounting for 28.13%. For male and female patients, knee fractures accounted for 26.19% and 31.93%, respectively, with a male to female ratio of 1.13:1. The proportion of shoulder fractures was the smallest among this investigation, accounting for 0.67%. For male and female patients, shoulder fractures accounted for 0.44% and 1.12%, respectively, with a male to female ratio of 0.76:1. The age group with the highest proportion of shoulder joint fractures was ≥65 year olds (41.89%), with a male to female ratio of 0.76:1. The age group with the highest risk of elbow, wrist, hip, knee, ankle, and subtalar joint fracture was 5-14 year olds (33.59%) with a male to female ratio of 3.29:1, 5-14 year olds (23.98%) with a male to female ratio of 6.91:1, 45-54 year olds (26.92%) with a male to female ratio of 5.67:1, 45-54 year olds (24.60%) with a male to female ratio of 1.68:1, 25-34 year olds (20.36%) with a male to female ratio of 2.30:1, 45-54 year olds (27.41%) with a male to female ratio of 9.02:1, respectively. The most common site of intra-articular fractures in different age groups was corresponding as follows: 0-4 year olds (elbow), 5-14 year olds (elbow), 15-24 year olds (ankle), 25-34 year olds (subtalar joint), 35-44 year olds (subtalar joint), 45-54 year olds (knee), 55-64 year olds (knee), 65-74 year olds (knee), and ≥75 year olds (knee). CONCLUSION: The current study revealed the age- and gender-specific epidemiological characteristics of major intra-articular fractures, providing a basis for clinical evaluation and practices.

Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties.

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 µg/mL) which is higher than dimethomorph (EC50 = 0.1148 µg/mL) and diacetylenyl amide (EC50 = 0.040 µg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.

Design, synthesis and antifungal activity of threoninamide carbamate derivatives via pharmacophore model.

Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 µg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC50 values of 3.74-9.76 µg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.

Design, Synthesis, and Fungicidal Activities of Novel 5-Methyl-1H-1,2,3- trizole-4-carboxyl Amide Analogues.

Succinate dehydrogenase inhibitors (SDHIs) are fungicides with an amide bond widely used to control plant diseases caused by phytopathogenic fungi. Because of broad spectrum activity of new SDHIs, they have attracted wide attention from the research community. A series of structurally novel SDHIs with a bioactive 1,2,3-triazole moiety were designed and synthesized. Bioactivity screening showed that some of designed N-phenethyl-1,2,3-trizole-4-carboxyl amide analogues exhibited good fungicidal activities toward Sclerotinia sclerotiorum and Botrytis cinerea, while some of Nbenzyl- 1,2,3-trizole-4-carboxyl amide analogues exhibited good fungicidal activities toward Phytophthora capsici and Cercospora arachidicola. EC50 value of compound 5d against Cercospora arachidicola (6.6 µg/mL) was lower than that of chlorothalonil (12.3 µg/mL).

Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9µM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew.

Design, synthesis, and fungicidal evaluation of a series of novel 5-methyl-1H-1,2,3-trizole-4-carboxyl amide and ester analogues.

Succinate dehydrogenase inhibitors (SDHIs) are efficient fungicides that are widely used to control plant diseases caused by phytopathogenic fungi, although their effectiveness is undermined by the development of resistance across a range of different fungi. One of the most common structural features of SDHIs is their amide bond. The introduction of greater structural diversity to SDHIs is a promising strategy to delay the onset of resistance. A series of novel SDHIs containing a bioactive 1,2,3-triazole moiety have been designed and synthesized and their fungicidal and insecticidal activities evaluated. The results of these analyses show that most of the newly synthesized 1,2,3-trizole-4-carboxyl amide (ester) analogues exhibit good fungicidal activities, especially towards Sclerotinia sclerotiorum, and a structure-activity relationship study confirmed that the replacement of the amide group with an ester group had little effect on fungicidal activity, which could be provideous in terms of issues and metabolism. 1,6-Dimethyl phenyl was confirmed as the most efficient substituent of the current study when it was placed on both the amide and ester compounds. Interestingly, some of the newly synthesized compounds displayed good insecticidal activities against Culex pipiens pallens. The results of the current study show that these 1,2,3-triazole-4-carboxyl amide and ester analogues represent a new type of SDHI that could be used for the development of novel pesticides.

Design, synthesis, and fungicidal activity of novel carboxylic acid amides represented by N-benzhydryl valinamode carbamates.

Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 µg mL(-1).

Novel ultrasound-promoted parallel synthesis of trifluoroatrolactamide library via a one-pot Passerini/hydrolysis reaction sequence and their fungicidal activities.

An ultrasound-promoted one-pot Passerini/hydrolysis reaction sequence has been developed for the synthesis of trifluoroatrolactamide derivatives using a diverse range of trifluoroacetophenones and isonitriles in acetic acid. Parallel synthesis in a centrifuge tube using a noncontact ultrasonic cell crusher was used in this study as an efficient method for the rapid generation of combinatorial trifluoroatrolactamide libraries, and subsequent biochemical evaluation of the resulting compounds indicated that they possessed excellent broad-spectrum fungicidal activities. N-(4-chlorophenyl)-2-(4-ethylphenyl)-3,3,3-trifluoro-2-hydroxypropanamide and N-(4-chlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-(4-methoxyphenyl)propanamide, in particular, showed significant fungicidal activities against all of the fungal species tested in the current study.

Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity.

BACKGROUND: Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option. RESULTS: A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 µg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops. CONCLUSIONS: Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies.

Larvicidal activity and click synthesis of 2-alkoxyl-2-(1,2,3-triazole-1- yl)acetamide library.

Heterogeneous copper-in-charcoal-catalyzed click synthesis in 96-well polypropylene filter plates is an efficient method for the rapid generation of sufficient pure 2-alkoxyl-2-(1,2,3-triazole-1-yl) acetamide derivatives library by simple filtration, which directly assay the products for larvicidal activity against mosquitoes. In this procedure, copper nanoparticles on charcoal were arrayed into each well on a 96-well plate, reagents were delivered using a pipette gun, and a constant temperature shaker bath was used to complete the click reaction in 24-72 hours under temperature-controlled conditions. The results of bioassays indicated that the target compounds possessed excellent larvacidal activities against mosquitoes. In particular, the larvacidal activities against mosquitoes of compounds 8[2,3] and 8[7,1] at 2 µg.mL⁻¹ were 100% and 73% respectively.

Synthesis, crystal structure and larvicidal activity of novel diamide derivatives against Culex pipiens.

BACKGROUND: Culex is an important mosquito as vectors for the transmission of serious diseases, such as filariasis, West Nile virus, dengue, yellow fever, chikungunya and other encephalitides. Nearly one billion people in the developing countries are at risk. In order to discover new bioactive molecules and pesticides acting on mosquito, we designed active amide structure and synthesized a series of novel diamide derivatives. RESULTS: A series of novel diamide derivatives were designed and synthesized. Their structures were characterized by 1 H NMR, FTIR and HRMS. The single crystal structure of compound 6n was determined to further elucidate the structure. Biological activities of these compounds were tested. Most of them exhibited higher mosquito larvicidal activity. Especially compound 6r displayed relatively good activity to reach 70% at 2 µg/mL. CONCLUSION: A practical synthetic route to amide derivatives by the reaction of amide with another acid is presented. This study suggests that the diamide derivatives exhibited good effective against mosquito.

The structure-activity relationship in herbicidal monosubstituted sulfonylureas.

BACKGROUND: The herbicide sulfonylurea (SU) belongs to one of the most important class of herbicides worldwide. It is well known for its ecofriendly, extreme low toxicity towards mammals and ultralow dosage application. The original inventor, G Levitt, set out structure-activity relationship (SAR) guidelines for SU structural design to attain superhigh bioactivity. A new approach to SU molecular design has been developed. RESULTS: After the analysis of scores of SU products by X-ray diffraction methodology and after greenhouse herbicidal screening of 900 novel SU structures synthesised in the authors' laboratory, it was found that several SU structures containing a monosubstituted pyrimidine moiety retain excellent herbicidal characteristics, which has led to partial revision of the Levitt guidelines. CONCLUSIONS: Among the novel SU molecules, monosulfuron and monosulfuron-ester have been developed into two new herbicides that have been officially approved for field application and applied in millet and wheat fields in China. A systematic structural study of the new substrate-target complex and the relative mode of action in comparison with conventional SU has been carried out. A new mode of action has been postulated.

Synthesis and biological evaluation of isosteric analogs of mandipropamid for the control of oomycete pathogens.

A series of isosteric analogs of mandipropamid were designed and synthesized via 'click chemistry'. The amide bond of mandipropamid was substituted by a 1,2,3-triazole functional group. The bioassay results have indicated that some of the title compounds exhibited moderate fungicidal activity against Pseudoperonospora cubensis, and the activity has been systematically studied as a function of molecular structure. The low activity of the mandipropamid analog that contains a lipid chain is likely due to the presence of a weak hydrogen bond donor in the 1,2,3-triazole. Furthermore, we have performed the molecular modeling and found that N-methylamide could be more effective than amide as the surrogates to 1,2,3-triazole, which ultimately leads to a longer distance (1.1 Å longer) between the two substitutes in the 1,4-disubstituted 1,2,3-triazole compound.

Linkage of three polymorphisms on chromosome 20p12 to ossification of the posterior longitudinal ligament of spine and its severity in Han Chinese patients.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is characterized by the replacement of ligamentous tissue with new ectopic bone formation, and has a strong genetic background. Because of the abnormal bone metabolic features and the strong genetic component, osteoporosis is a related disorder with OPLL. Three polymorphisms on chromosome 20p12 were identified associated with the risk of osteoporosis and osteoporotic fracture. The rs996544 (C/T) "TT" and rs965291 (G/A) "AA" genotypes conferred higher risks for vertebral and hip fractures. The osteoporosis haplotype is defined by two polymorphisms, rs1116867 (A) and D35548 (T). However, it remains unknown whether these three polymorphisms predispose to an increased frequency and severity of OPLL in Han Chinese patients. METHODS: A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. Three single nucleotide polymorphisms (SNPs), rs996544 (C/T), rs965291 (G/A) and rs1116867 (A/G), were analyzed by direct sequencing. Associations between these SNPs with the occurrence and extent of OPLL were statistically evaluated. RESULTS: There was no significant association between the rs996544 (C/T) polymorphism and the prevalence of OPLL. The rs1116867 (A/G) polymorphism "AG" genotype was associated with the occurrence of OPLL. The rs1116867 (A/G) polymorphism "G" allele was associated with the occurrence of OPLL, but not with the extent of OPLL. The rs965291 (G/A) polymorphism in female patients was statistically different between cases and controls (P < 0.05). The rs965291 (G/A) polymorphism "A" allele was associated with the occurrence of OPLL in female patients. For the rs965291 (G/A) polymorphism, patients with the "A" allele (genotype, "AG" or "AA") showed a significantly greater number of ossified cervical vertebrae than those without the "A" allele (genotype, "GG", P < 0.05), particularly in female patients. CONCLUSIONS: The rs1116867 (A/G) and rs965291 (G/A) polymorphisms on chromosome 20p12 are associated with the occurrence and the extent of OPLL, at least in Han Chinese subjects. Our data should advance our understanding of the molecular etiology of OPLL and may guide approaches to prevent the onset of OPLL.

Synthesis and antiviral activity of new acrylamide derivatives containing 1,2,3-thiadiazole as inhibitors of hepatitis B virus replication.

A series of new acrylamide derivatives containing 1,2,3-thiadiazole were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities in vitro. The IC50 of compounds 9b (10.4 microg/mL), 9c (3.59 microg/mL) and 17a (9.00 microg/mL) of the inhibition on the replication of HBV DNA were higher than that of the positive control lamivudine (14.8 microg/mL). Compound 9d exhibited significant activity against secretion of HBeAg (IC50=12.26 microg/mL).

Synthesis and antiviral activity against tobacco mosaic virus and 3D-QSAR of alpha-substituted-1,2,3-thiadiazoleacetamides.

A series of alpha-substituted-1,2,3-thiadiazoleacetamides were prepared and tested in vitro against tobacco mosaic virus. The preliminary bioassays indicated that some of the new compounds are good as compared to the commercial pesticide Virus A at 500 mg/L, and the activity was influenced by the nature of the substituents. 3D-QSAR models were established based on the antiviral activity of the compounds. It has also been found that some of the new compounds also exhibit significant anti-HBV activity in human hepatoblastoma-derived liver Hep-G2 cells.