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Continuous 6‐mercaptopurine (6‐MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose‐limiting hematopoietic toxicity. However, evidence‐based guidelines for gene‐based 6‐MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open‐label, active‐controlled clinical trial randomly assigned Chinese children with low‐ or intermediate‐risk ALL in a 1:1 ratio to receive TPMT–NUDT15 gene–based dosing of 6‐MP (N = 44, 10 to 50 mg/m2/day) or standard dosing (N = 44, 50 mg/m2/day) during maintenance therapy. The primary end point was the incidence of 6‐MP myelosuppression in both groups. Secondary end points included frequencies of 6‐MP hepatotoxicity, duration of myelosuppression and leukopenia, event‐free survival, and steady‐state concentrations of active metabolites (6‐thioguaninenucleotides and 6‐methylmercaptopurine nucleotides) in erythrocytes. A 2.2‐fold decrease in myelosuppression, the primary end point, was observed in the gene‐based–dose group using ~ 50% of the standard initial 6‐MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene‐based–dose group had a significantly lower risk of developing thiopurine‐induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady‐state concentrations of active metabolites in erythrocytes between the two groups. TPMT‐ and NUDT15‐based dosing of 6‐MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393. [ABSTRACT FROM AUTHOR]

BACKGROUND: Some traditional pesticide formulations are inefficient, leading to excessive use and abuse of pesticides, which in turn effects environment. Intelligent release pesticide formulations are ideal for improving pesticide utilization and persistence while reducing environmental pollution. RESULTS: We designed a benzil‐modified chitosan oligosaccharide (CO‐BZ) to encapsulate avermectin (Ave). Ave@CO‐BZ nanocapsules are prepared based on a simple interfacial method via cross‐linking of CO‐BZ with diphenylmethane diisocyanate (MDI). The Ave@CO‐BZ nanocapsules have an average particle size of 100 nm and exhibited a responsive release performance for ROS. The cumulative release rate of nanocapsules at 24 h with ROS increased by about 11.4% compared to that without ROS. The Ave@CO‐BZ nanocapsules displayed good photostability. Ave@CO‐BZ nanocapsules can penetrate root‐knot nematodes more easily and exhibited better nematicidal activity against root‐knot nematodes. The pot experiment showed that the control effect of Ave CS at low concentration was 53.31% at the initial stage of application (15 d), while Ave@CO‐BZ nanocapsules was 63.54%. Under the same conditions, the control effect of Ave@CO‐BZ nanocapsules on root‐knot nematodes was 60.00% after 45 days of application, while Ave EC was only 13.33%. The acute toxicity experiments of earthworms showed that the toxicity of nanocapsules was significantly lower than that of EC. CONCLUSION: The ROS‐responsive nanocapsules can improve the utilization of pesticides and non‐target biosafety. This modified chitosan oligosaccharide has great potential as a bio stimuli‐responsive material, and this simple and convenient method for preparing Ave@CO‐BZ nanocapsules provides a direction for the effective utilization of pesticides. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: To assess the effect and safety of probiotics for treating urticaria. Methods: Randomized controlled trial (RCT) papers on the probiotics treatment published before May 2019 were retrieved from various databases like PubMed, EMbase, MEDLINE (Ovid), SCI‐Hub, Springer, ClinicalKey, VIP, and CNKI. The treatment plan that we include are oral administration of single probiotic, multiple probiotics, and the combination of probiotics and antihistamines. Meta‐analysis of the data was performed by RevMan 5.3 software. Results: A total of nine RCT papers were included: four papers for oral administration of single probiotic, three papers for oral administration of multiple probiotics, and two papers for oral administration of a probiotic combined with antihistamines. The results of meta‐analysis showed that the therapeutic effect of the probiotic group was significantly higher than the control group (placebo or antihistamines) (RR = 1.09, 95% CI: 1.03–1.16, p = 0.006). And compared with the placebo group, the therapeutic effect of single probiotic group was significantly improved (RR = 1.11, 95% CI: 1.01–1.21, p = 0.03). Regarding therapeutic effect, there was no statistically significant difference between the multiple probiotics group and placebo group (RR = 1.00, 95% CI: 0.94 ~ 1.07, p = 0.91); the therapeutic effect of single probiotic combined antihistamine group was significantly higher than the antihistamine group (RR = 1.13, 95% CI: 1.07–1.19, p < 0.0001). Regarding the incidence of adverse reactions, there was no significant difference between the probiotic group and the control group (p = 0.46). Conclusion: The treatment plan of oral administration of probiotics has significant therapeutic effects on urticaria, but the therapeutic effects of the administration of multiple probiotics and the safety of probiotic therapy are still not yet obvious. Some large‐scale, multi‐centered RCT studies are needed in the future for clarification. [ABSTRACT FROM AUTHOR]

An operationally simple protocol for the synthesis of medium‐sized lactones and macrolactones via an intramolecular ring expansion of cyclic ketones has been developed. Using this method, a series of 10‐ and 12‐membered lactones was synthesized under mild conditions. Preliminary mechanistic studies showed that a radical pathway might be involved in this reaction. [ABSTRACT FROM AUTHOR]

In order to study the occurrence mechanism of rock burst in L-shaped zone during a fully mechanized mining period, the No. 705 working face which is located in Baojishan Colliery is taken as a typical engineering background. By means of in situ investigation, theoretical analysis, numerical simulation, in situ tests, and relevant monitoring methods, the occurrence mechanism of rock burst and corresponding prevention technology are studied. The results show that a coal pillar with some confining pressure in the L-shaped zone is established by FLAC3D numerical simulation software, and the numerical simulation results indicate that the change in static load has a greater effect than dynamic load on coal pillar unstable failure; the static load plays a role in storing energy, and dynamic load plays a role in inducing rock burst; the bolt-mesh-cable support and high-pressure water jet unloading combined technology is put forward to prevent rock burst in roadways, and the numerical simulation results show that stress distribution of surrounding rock meets the model of strong-soft-strong (3S) structure, and the moment distribution is reasonable. In the follow-up mining, a limit value of coal fines is used to determine that this measure is a reasonable method to prevent rock burst. The study conclusions provide theoretical foundation and new guidance for preventing rock burst by synergistic effect technology in roadways. [ABSTRACT FROM AUTHOR]

Background: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT.Methods: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model.Results: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728).Conclusions: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT. [ABSTRACT FROM AUTHOR]

Background: The affecting factors of mucocutaneous manifestations in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients remain unclear in China. Methods: A retrospective analysis was conducted among HIV/AIDS patients in Yunnan, China. The demographic data, mucocutaneous manifestations, CD4 cell counts, and antiretroviral therapy (ART) regimens were collected. The effects of CD4 cell count and ART on the spectrum of mucocutaneous manifestations were evaluated. Results: Among 508 HIV/AIDS patients, 86.0% of cases showed mucocutaneous manifestations. The average CD4 cell count (176 cells/μl) of the patients with manifestations was significantly lower than those without manifestations (328 cells/μl) (P < 0.001). Diseases such as herpes zoster, oral candidiasis, condyloma acuminatum, genital herpes, oral leukoplakia, talaromycosis, cryptococcosis, and HIV‐PPE (pruritic papular eruption) were represented quite frequently in patients with CD4 cell count <200 cells/μl (P < 0.05), but eczema was suffered by those with CD4 cell count ≥200 cells/μl (P < 0.05). ART could decline the incidence of herpes zoster, oral candidiasis, condyloma acuminatum, genital herpes, oral leukoplakia, talaromycosis, and cryptococcosis (P < 0.05). Conclusions: Mucocutaneous manifestations are closely related to the CD4 cell count and can be used as early predictors of HIV/AIDS and immune status in clinic. ART could reduce the incidence of certain mucocutaneous manifestations. [ABSTRACT FROM AUTHOR]

The 1918 Spanish flu virus has claimed more than 50 million lives. However, the mechanism of its high pathogenicity remains elusive; and the origin of the virus is controversial. The matrix (M) segment regulates the replication of influenza A virus, thereby affecting its virulence and pathogenicity. This study found that the M segment of the Spanish flu virus is a recombinant chimera originating from avian influenza virus and human influenza virus. The unique mosaic M segment might confer the virus high replication capacity, showing that the recombination might play an important role in inducing high pathogenicity of the virus. In addition, this study also suggested that the NA and NS segments of the virus were generated by reassortment between mammalian and avian viruses. Direct phylogenetic evidence was also provided for its avian origin. [ABSTRACT FROM AUTHOR]

Background. cIAP2 is involved in necroptosis as a key upstream regulation factor. We aimed to investigate the role of cIAP2 in ARDS/ALI induced by H7N9 virus through regulating the RIPK1/3 necroptosis pathway. Methods. Lung tissues of 11 patients who died from ARDS-complicated H7N9 infection between 2013 and 2016 were obtained as the H7N9-ARDS group. Lung tissues near benign lung nodules were acquired as the control group. Histological changes were evaluated by H&E staining. Protein levels of cIAP2, RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL in the lung tissues were detected by Western Blot. The mRNA levels of cIAP2, RIPK1, and RIPK3 were detected by real-time PCR. Results. H7N9 virus infection had a high mortality, with ARDS being the leading cause of death. The protein level of cIAP2 in the experimental group was lower than that in the control group (P<0.05). However, the experimental group showed higher RIPK1, RIPK3, and p-RIPK3 protein levels than the control group (P<0.05), as well as the expression level of MLKL and p-MLKL protein, which is a key downstream protein in necroptosis (P<0.05). Conclusion. In tissues from patients with fatal H7N9, downregulation of cIAP2 and induction of necroptosis was observed. We could speculate that necroptosis of the pulmonary epithelium is associated with severe H7N9 infection leading to ARDS. Thus, necroptosis inhibition may be a novel therapy for H7N9 influenza virus. [ABSTRACT FROM AUTHOR]

Objective. The Chronic Care Model, based on core elements of team-centered care in chronic diseases, has widely been accepted. This study was aimed at evaluating the effectiveness of the Chronic Care Model in type 2 diabetes management. Methods. A group randomized experimental study was conducted. Twelve communities of the Zhaohui Community Health Service Center in Hangzhou, China, were randomly assigned into an intervention group (n=6) receiving the Chronic Care Model-based intervention and a control group (n=6) receiving conventional care. A total of three hundred patients, twenty-five for each community, aged ≥18 years with type 2 diabetes for at least 1-year duration, were recruited. Data of health behaviors, clinical outcomes, and health-related quality of life (Short-Form 36-item questionnaire) were collected before and after a 9-month intervention and analyzed using descriptive statistics, t-test, chi-square test, binary logistic regression, and linear mixed regression. A total of 258 patients (134 in intervention and 124 in control) who completed the baseline and follow-up evaluations and the entire intervention were included in the final analyses. Results. Health behaviors such as drinking habit (OR=0.07, 95% CI: 0.01, 0.75), physical activity (OR=2.92, 95% CI: 1.18, 7.25), and diet habit (OR=4.30, 95% CI: 1.49, 12.43) were improved. The intervention group had a remarkable reduction in glycated hemoglobin (from 7.17% to 6.60%, P<0.001). The quality of life score changes of the role limitation due to physical problems (mean=9.97, 95% CI: 3.33, 16.60), social functioning (mean=6.50, 95% CI: 2.37, 10.64), role limitation due to emotional problems (mean=8.06, 95% CI: 2.15, 13.96), and physical component summary score (mean=3.31, 95% CI: 1.22, 5.39) were improved in the intervention group compared to the control group. Conclusion. The Chronic Care Model-based intervention helped improve some health behaviors, clinical outcomes, and quality of life of type 2 diabetes patients in China in a short term. [ABSTRACT FROM AUTHOR]

Objective: To examine potential associations between the presence of fibroids and obstetric outcomes in twin pregnancies.Methods: A prospective cohort study compared obstetric outcomes between individuals with twin pregnancies who did and did not have fibroids. Patients were considered for inclusion if they underwent first-trimester ultrasonography examination, and went on to deliver at the Beijing Obstetrics and Gynecology Hospital between September 1, 2012 and December 31, 2014. Participants were grouped based on the presence or absence of fibroids and baseline demographics, fibroid characteristics, and obstetric outcomes were recorded and compared between the two groups.Results: In total, 153 patients with twin pregnancies were recruited; 51 had fibroids and 102 did not. Patients in the fibroid group demonstrated a higher maternal age (P<0.001), higher pre-pregnancy body mass index (P=0.01), and higher rate of assisted reproductive technology use (P=0.04). The presence of fibroids was not associated with any change in obstetric outcomes, and obstetric outcomes were unaffected by the number, size, location, and type of fibroids (all P>0.05).Conclusion: Fibroids were not a risk factor for any adverse obstetric outcomes among patients with twin pregnancies. [ABSTRACT FROM AUTHOR]

Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward para-nitrophenyl phosphate, phospho-tyrosine-containing peptides, and the full-length phospho-ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N-terminal regulatory region and key residues in its active site. Specifically, both kinase interaction motif (KIM) and kinase-specific sequence of STEP were required for ERK interaction. In addition to the N-terminal kinase-specific sequence region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho-ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho-ERK peptide sequence through its active site, and the contact of STEP F311 with phospho-ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP-ERK recognition, which could serve as a potential therapy for neurological disorders. [ABSTRACT FROM AUTHOR]

Abstract: Cerebral amyloid angiopathy is a common feature in Alzheimer’s disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce Aβ42 under starvation. Starvation can increase the secretion of Aβ42 by altering the expression of β-secretases (BACE1) and γ-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of Aβ42 produced under starvation in HUVECs. These results suggest that starvation-induced Aβ42 secretion might contribute to the formation of CAA and hence vascular degeneration in AD. [Copyright &y& Elsevier]

Verticillium wilt is one of the most serious constraints to cotton production in almost all of the cotton-growing countries. In this study, “XinLuZao1” (XLZ1), a susceptible cultivar Gossypium hirsutum L. and “Hai7124” (H7124), a resistant line G. barbadense, and their F2:3 families were used to map and study the disease index induced by verticillium wilt. A total of 430 SSR loci were mapped into 41 linkage groups; the map spanned 3 745.9 cM and the average distance between adjacent loci was 8.71 cM. Four and five quantitative trait loci (QTLs) were detected based on the disease index investigated on July 22 and August 24 in 2004, respectively. These nine QTLs explained 10.63−28.83% of the phenotypic variance, six of them were located on the D sub-genome. Two QTLs located in the same marker intervals may partly explain the significant correlation of the two traits. QTLs explaining large phenotypic variation were identified in this study, which may be quite useful in cotton anti-disease breeding. [ABSTRACT FROM AUTHOR]

Abstract: Objective: p21WAF1/CIP1 is transcriptionally activated by p53 and is required for G1 to S phase progression. p21 plays a critical role in DNA repair after DNA damage. Thus, cells with defective p21 may result in an enhancement of radiation induced apoptosis and improved radiosensitivity. We tested the hypothesis that p21 antisense oligodeoxynucleotides (p21 AS ODNs) can be used to reduce p21 expression level and increase radiosensitivity in CNE-1-wtp53 nasopharyngeal carcinoma cell line with normal p53 function. Methods and materials: The p21 antisense oligodeoxynucleotides (p21 AS ODNs) and the random control oligodeoxynucleotides (p21 RD ODNs) were synthesized. p21 AS ODNs sequence: 5′-TGTCATGCTGGTCTGCCGCC-3′; p21 RD ODNs sequence: 5′-CCGGTGAACGAGCGAGCACA-3′. p21 AS ODNs and p21 RD ODNs were transfected into CNE-1-wtp53 nasopharyngeal carcinoma cell line. The protein expression levels of P21 were evaluated using Western blotting analysis. Cell cycle progression and apoptotic cells were assessed by flow cytometric analysis. The clonogenic survival assay was performed to determine the survival fraction. The parameters D 0, Dq, and N for the single-hit multitarget model and the parameters α, β, α/β, and SF2 for the linear-quadratic model were calculated. BALB/c nude mice were used to investigate the effect of p21 AS ODNs on the radiosensitivity of nasopharyngeal xenografts in vivo. Results: p21 AS ODNs were detected mainly in plasma with fluorescence microscopy investigation. P21 protein level dramatically decreased and the amount of apoptotic cells increased in p21 AS ODNs transfected cells than in p21 RD ODNs transfected cells after irradiation. The percentage of G1 arrest decreased in p21 AS ODNs transfected cells 24h after radiation, then G2 arrest decreased 48h after radiation. The values of D 0, Dq, SF2 decreased and α value increased in p21 AS ODNs transfected cells than in control cells. The inhibition rate in tumor xenografts exposed to X ray of 10Gy alone was 39.1%, while it was 51.4% in xenografts injected with p21 AS ODNs before exposure to radiation. Unfortunately, there was no significant difference between these two groups (P <0.05). Conclusion: p21 Antisense oligodeoxynucleotides led to inhibition of P21 protein expression, loss of G1 arrest, increase of apoptosis in CNE-1-wtp53 nasopharyngeal carcinoma cell line in vitro and inhibited tumor growth in vivo. Antisense oligodeoxynucleotides may become a promising strategy to enhance radiosensitivity in nasopharyngeal carcinoma cells with normal p53 function. [Copyright &y& Elsevier]

How to characterize short protein sequences to make an effective connection to their functions is an unsolved problem. Here we propose to map the physicochemical properties of each amino acid onto unit spheres so that each protein sequence can be represented quantitatively. We demonstrate the usefulness of this representation by applying it to the prediction of cell penetrating peptides. We show that its combination with traditional composition features yields the best performance across different datasets, among several methods compared. For the convenience of users, a web server has been established for automatic calculations of the proposed features at http://biophy.dzu.edu.cn/SNumD/. [ABSTRACT FROM AUTHOR]

The one-pot title reaction starts from aryl substituted Baylis-Hillman phosphonium salts, arylglyoxylates, alkyl cyanides, and primary alkyl amines and does not tolerate aryl amines. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "One-Pot Regioselective Synthesis of β-Lactams by a Tandem Ugi 4CC/SN Cyclization" by L. Wu and others, published in the journal "Tetrahedron" in 2014.

An abstract of the article "One-Pot Synthesis of 5-Oxopyrrolidine-2-carboxamides via a Tandem Ugi 4CC/SN Cyclization Starting from Baylis-Hillman Bromides" by Lei Wu and colleagues is presented.

In the title compound C20H21Cl2N2O2S, the thienopyrimidine ring system is essentially planar. The crystal packing is stabilized by van der Waals forces and by an inter­molecular C—H⋯O hydrogen-bonding inter­action, which links the mol­ecules into zigzag chains. [ABSTRACT FROM AUTHOR]

The title compound, C(18)H(22)N(4)O(2)S, contains a substituted pyrimidine ring fused to both a benzene ring and a substituted thioxopyrimidine ring. The pyrimidine and thioxopyrimidine rings adopt distorted chair conformations. In the crystal, adjacent mol-ecules are linked by pairs of N-H⋯S and N-H⋯O hydrogen bonds to generate centrosymmetric R(2) (2)(8) and R(2) (2)(16) loops, respectively. This combination leads to [100] chains of mol-ecules.

In the title compound, C(22)H(24)N(6)O(5), the triazole ring is essentially planar with a maximum deviation of 0.005 (2) Å and forms dihedral angles of 79.78 (11) and 86.22 (11)° with the phenyl and benzene rings, respectively. In the crystal, mol-ecules are linked by inter-molecular N-H⋯N, C-H⋯O and C-H⋯π inter-actions into a three-dimensional network.

In the title compound, C(18)H(23)N(5)O(2), the triazolopyrimidine ring system is essentially planar, with a maximum displacement of 0.032 (2) Å, and forms a dihedral angle of 87.59 (15)° with the phenyl ring. In the crystal, mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions into chains parallel to the c axis.

In the title compound, C(21)H(21)N(5)O(2), the triazolopyrimidine ring system is essentially planar [maximum displacement = 0.021 (4) Å] and forms dihedral angles of 41.17 (9) and 67.99 (8)° with the phenyl and benzene rings, respectively. The n-butyl side chains is disordered over two positions with an ccupancy ratio of 0.77:0.23. An intra-molecular C-H⋯O hydrogen-bonding inter-action stabilizes the mol-ecular conformation. In the crystal, mol-ecules are linked by inter-molecular C-H⋯O and C-H⋯N hydrogen bonds into a three-dimensional network. In addition, π-π stacking inter-actions involving the triazole and pyrimidine rings of adjacent mol-ecules are observed, with centroid-centroid distances of 3.545 (1) Å.

In the title compound, C(14)H(15)N(5)O(2), the whole mol-ecule apart from the terminal C atoms of the isopropyl group is located on a crystallographic mirror plane. An intra-molecular C-H⋯N hydrogen-bonding inter-action may stabilize the mol-ecular conformation. The crystal packing features weak slipped π-π inter-actions between the pyrimidine and the phenyl rings of symmetry-related mol-ecules [centroid-centroid distance = 3.746 (1)Å, slippage of 1.574 Å].

In the title compound, C(20)H(32)N(2)O(2)S(2), the cyclo-hexene ring is disordered over two half-boat conformations with occupancy factors of 0.71:0.29. One n-butyl chain is also disordered over two positions with occupancy factors of 0.83:0.17. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond.

The asymmetric unit of the title compound, C(21)H(21)N(5)O(3), consists of two geometrically similar mol-ecules. The fused rings of the triazolo[4,5-d]pyrimidine system are nearly coplanar, making dihedral angels of 1.48 (18) and 1.34 (16)°, and the phenyl rings are twisted by 12.3 (1) and 8.7 (1)° with respect to the triazolopyrimidine plane. The ethyl groups of the n-butyl side chains are disordered over two sites in each of the independent mol-ecules, the ratios of occupancies being 0.60:0.40 and 0.61:0.39.

In the title compound, C(20)H(19)N(5)O(2), all atoms of the 1,2,3-triazolo[4,5-d]pyrimidine ring system are essentially coplanar [maximum deviation = 0.015 (2) Å], indicating the existence of a conjugate system in which each carbon and nitrogen atom is sp(2) hybridized and ten π electrons (three from carbon atoms and seven from nitrogen atoms) constitute an aromatic heterocycle. The ring system forms dihedral angles of 68.37 (10) and 71.57 (9)° with the phenyl rings. The crystal packing is stabilized by van der Waals inter-actions and intermolecular C-H⋯π interactions.

The title compound, C(20)H(19)N(5)O(2), exhibits whole-mol-ecule disorder the refined ratios of the two components being 0.57 (2):0.43 (2). In the major component, the essentially planar [maximum deviation 0.033 (17) Å] fused pyrimidine and triazole ring system forms a dihedral angle of 10.5 (3)° with the phenyl ring, while in the minor component of disorder this angle is 27.5 (5)°. The crystal structure is stabilized by π-π stacking inter-actions between symmetry-related triazole and pyrimidine rings, with centroid-centroid distances of 3.594 (10) Å.

In the title compound, C(19)H(16)ClN(5)O(2), the triazolopyrimidine ring system is essentially planar, with a maximum displacement of 0.021 (4) Å, and forms dihedral angles of 1.09 (9) and 87.74 (9)° with the phenyl and benzene rings, respectively. Short intra-molecular C-H⋯O and C-H⋯N hydrogen-bonding inter-actions occur within the molecule. In the crystal structure, mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonds into chains parallel to the b axis. In addition, π-π stacking inter-actions involving the triazole and pyrimidine rings of adjacent mol-ecules are observed, with centroid-centroid distances of 3.600 (3) Å.

In the title compound, C(20)H(22)N(2)O(2)S, the central thieno-pyrimidine ring system is essentially planar, with a maximum displacement of 0.023 (2) Å. The attached cyclo-hexene ring is disordered over two possible conformations, with an occupancy ratio of 0.776 (12):0.224 (12). Neither inter-molecular hydrogen-bonding inter-actions nor π-π stacking inter-actions are present in the crystal structure. The mol-ecular conformation and crystal packing are stabilized by three intra-molecular C-H⋯O hydrogen bonds and two C-H⋯π inter-actions.

In the title compound, C(19)H(19)BrN(2)O(2)S, the central thieno-pyrim-idine ring system is essentially planar, with a maximum displacement of 0.068 (3) Å. The attached cyclo-hexene ring adopts a half-chair conformation. The molecular conformation and crystal packing are stabilized by three intra-molecular C-H⋯O hydrogen bonds and two C-H⋯π inter-actions.