bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life in patients with maxillectomy prostheses
Authors: Irish Jonathan , Sandhu Nimani , Simpson Colleen , Wood Robert , Gilbert Ralph , Gullane Patrick , Brown Dale , Goldstein David , Devins Gerald , Barker Emma
Published: March 2009

Background.

This cross‐sectional study sought to determine patient quality of life and function after prosthetic rehabilitation for maxillary and palate defects following cancer resection.

Methods.

Sixty‐nine patients were identified, 42 participated in the study (61%). The Obturator Functioning Scale (OFS) and 4 general quality of life measures (Mental Health Inventory [MHI], Impact of Events Scale [IES], Illness Intrusiveness Ratings Scale [IIRS], and Centre for Epidemiologic Studies Depression Scale [CES‐D]) were correlated with clinical parameters.

Results.

Leakage when swallowing foods was the most frequently reported problem with the obturator (29%). Positive correlation was noted between the OFS and both the IES subscales (p < .01) and CES‐D (p < .001). Difficulty with speech and eating was associated with increased avoidance of social situations. The surgical approach had a significant effect on the OFS, IES, and MHI subscales (p < .01).

Conclusion.

These results support the findings that good obturator function is associated with a better quality of life. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Cetuximab in hemodialysis: A case report
Authors: Aldoss Ibrahim T. , Plumb Troy , Zhen Weining (Ken) , Lydiatt Daniel D. , Ganti Apar Kishor
Published: March 2009

Background.

Concurrent chemoradiotherapy with cisplatin is the standard therapy for patients with unresectable locally advanced head and neck squamous cell carcinoma. However, cisplatin administration in patients on hemodialysis is complicated by the need to perform hemodialysis immediately after the infusion. Concurrent chemoradiation with cetuximab has been approved in definitive treatment of locally advanced head and neck cancer. Although cetuximab is not excreted via the kidneys, its use in patients on hemodialysis has not been reported.

Methods and Results.

We present the case of a 65‐year‐old man undergoing hemodialysis, with stage IVA squamous cell carcinoma of the hypopharynx. Given the logistics of performing hemodialysis immediately postcisplatin, he received concurrent chemoradiotherapy with cetuximab. He tolerated treatment well with minor side effects.

Conclusion.

Cetuximab can be safely used in patients with renal impairment. This is the first reported case of the use of cetuximab in a patient undergoing hemodialysis. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
COX‐2polymorphisms and the risk for head and neck cancer in white patients
Authors: Peters Wilbert H. M. , Lacko Martin , te Morsche Rene H. M. , Voogd Adri C. , Oude Ophuis Michael B. , Manni Johannes J.
Published: March 2009

Background.

Cyclooxygenase‐2 (COX‐2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether functional genetic polymorphisms inCOX‐2may have a risk‐modifying effect on head and neck carcinogenesis.

Methods.

Blood from 431 white patients with oral, pharyngeal, or laryngeal carcinoma and 438 white healthy controls was investigated for the presence of 2 functional promoter region polymorphisms (−1195A→Gand −765G→C) inCOX‐2.

Results.

Logistic regression analysis did not show differences inCOX‐2genotype distributions between patients and controls. Also no differences were found when stratified according to tumor localization, sex, or tobacco consumption.

Conclusion.

In contrast to earlier reports on the role of theseCOX‐2polymorphisms in mediating susceptibility to squamous esophageal carcinoma in a Chinese population, we could not demonstrate a risk‐modifying effect in head and neck carcinogenesis in whites. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Pseudogout mimicking an infratemporal fossa tumor
Authors: Kalish Larry H. , Ng Thomas , Kalnins Ian , Da Cruz Melville J.
Published: March 2009

Background.

The infratemporal fossa is a well‐concealed, complex anatomical space. Neoplasms arising in this area are heterogenous in nature and have an insidious onset and usually present late.

Methods and Results.

We present a case of a 71‐year‐old woman who presented with worsening facial pain, trismus, and a large mass in her infratemporal fossa with minimal associated temporomandibular joint destruction. She underwent a surgical excision of the mass, which revealed a pseudogout deposit.

Conclusion.

The clinical and radiological features of patients with tophaceous pseudogout frequently mimic those of a benign or malignant neoplasm of the infratemporal fossa, often resulting in more radical surgery. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Arteriovenous malformation in the parotid region presenting as pulsatile tinnitus: A case report
Authors: Chen Meng‐Chao , Chung Wen‐Yuh , Luo Chao‐Bao , Wu Hsiu‐Mei
Published: March 2009

Background.

Pulsatile tinnitus is a unique symptom in the general population and often leads patients to medical attention.

Methods and Results.

We report a patient who had an arteriovenous malformation of superficial temporal artery in the parotid region causing pulsatile tinnitus and insomnia. Magnetic resonance angiography and carotid angiography were useful tools for the detection of this vascular malformation. Successful treatment of this lesion was achieved by endovascular embolization.

Conclusion.

This case illustrates a thorough diagnostic work‐up with a high index of suspicion and a proper treatment option is rewarding when dealing with such a rare disease. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Rehabilitation of swallowing with polydimethylsiloxane injections in patients who underwent partial laryngectomy
Authors: Bergamini Giuseppe , Alicandri‐Ciufelli Matteo , Molteni Gabriele , De Siati Daniele Romolo , Luppi Maria Pia , Marchioni Daniele , Presutti Livio
Published: March 2009

Background.

We conducted this longitudinal prospective study to illustrate a surgical technique for swallowing rehabilitation of patients after partial laryngectomy.

Methods.

Nine patients with persistent swallowing impairment after partial laryngectomy were included in the study. Evaluation of swallowing was performed by fiberoptic endoscopic evaluation of swallowing (FEES), and was quantified using 2 scales: a dysphagia score and a modified penetration‐aspiration scale. The site of bolus inhalation was identified. Polydimethylsiloxane (PDMS) was injected into the neoglottis to fill these passages, and to obtain a certain continence of the organ.

Results.

Mean follow‐up was 25 months (range, 5–39). All patients showed an improvement both in the dysphagia score and in the modified penetration‐aspiration scale. Average improvement was 2.6 points in the dysphagia score (p = .0042) and 2.1 points in the modified penetration‐aspiration scale (p = .0043).

Conclusion.

PDMS injection can be considered as an option in surgical rehabilitation of swallowing in patients who underwent partial laryngectomy. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
The Dimensions of Learning Organization Questionnaire (DLOQ): A validation study in a Korean context
Authors: Song Ji Hoon , Joo Baek‐Kyoo (Brian) , Chermack Thomas J.
Published: March 2009

The purpose of this study is to assess the validity and reliability of the measurement scores of the learning organization culture, the Dimensions of Learning Organization Questionnaire (DLOQ), in a Korean context. A total of 1,529 cases from 11 firms in two major Korean conglomerates were analyzed. Rigorous translation procedures, including both forward and backward processes, have been applied to ensure the relevance of this instrumentation in different cultural contexts. As the results of confirma‐tory factor analysis, simple item‐internal consistency estimates, and item intercorrelation analysis show, the Korean version of the DLOQ has produced reliable measurement scores with a construct validity adequate to measure the learning organization culture in the Korean context.
Effects of trainer expressiveness, seductive details, and trainee goal orientation on training outcomes
Authors: Towler Annette
Published: March 2009

This study focuses on trainer expressiveness and trainee mastery orientation within the context of the seductive details effect. The seductive details effect refers to inclusion of “highly interesting and entertaining information that is only tangentially related to the topic” (Harp & Mayer, 1998, p. 1). One hundred thirty‐two participants listened to lectures that differed in seductive details and trainer expressiveness. Results indicated that participants had the highest problem‐solving score after an expressive, seductive‐details lecture. High‐mastery participants in the nonseductive/expressive condition did best on recall.
Approaches for defining thresholds and return periods for rainfall‐triggered shallow landslides
Authors: Frattini Paolo , Crosta Giovanni , Sosio Rosanna
Published: March 2009

Probabilistic thresholds for triggering shallow landslides by rainfall are developed using two approaches: a logistic regression model and Iverson's physically based model. Both approaches are applied to a 180 km2 area in northern Italy. For the physically based model a Monte Carlo approach is used to obtain probabilities of slope failure associated with differing combinations of rainfall intensity and duration as well as differing topographic settings. For the logistic regression model hourly and daily rainfall data and split‐sample testing are used to explore the effect of antecedent rainfall on triggering thresholds. It is demonstrated that both the statistical and physically based models provide stochastic thresholds that express the probability of landslide triggering. The resulting thresholds are comparable, even though the two approaches are conceptually different. The physically based model also provides an estimate of the percentage of potentially unstable areas in which failure can be triggered with a certain probability. The return period of rainfall responsible for landslide triggering is studied by using a Gumbel scaling model of rainfall intensity–duration–frequency curves. It is demonstrated that antecedent rainfall must be taken into account in landslide forecasting, and a method is proposed to correct the rainfall return period by filtering the rainfall maxima with a fixed threshold of antecedent rainfall. This correction produces an increase of the return periods, especially for rainstorms of short duration. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of temperature on permeation of low‐density lipoprotein particles through human carotid artery tissues
Authors: Ghosn Mohamad G. , Leba Michael , Vijayananda Astha , Rezaee Panteha , Morrisett Joel D. , Larin Kirill V.
Published: March 2009

Quantification of the diffusion of small molecules and large lipid transporting lipoproteins across arterial tissues could be useful in elucidating the mechanism(s) of atherosclerosis. Optical coherence tomography (OCT) was used to determine the effect of temperature on the rate of diffusion of glucose and low‐density lipoproteins (LDL) in human carotid endarterectomy tissue in vitro. The permeability rate for glucose was calculated to be (3.51 ± 0.27) × 10–5 cm/s (n = 13) at 20 °C, and (3.70 ± 0.44) × 10–5 cm/s (n = 5) at 37 °C; for LDL the rate was (2.42 ± 0.33) × 10–5 cm/s (n = 5) at 20 °C and (4.77 ± 0.48) × 10–5 cm/s (n = 7) at 37 °C, where n is the number of samples. These results demonstrate that temperature does not significantly influence the permeation of small molecules (e.g. glucose), however, raising the temperature does significantly increase the permeation of LDL. These results provide new information about the capacity of an atherogenic lipoprotein to traverse the intimal layer of the artery. These results also demonstrate the potential of OCT for elucidating the dynamics of lipoprotein perfusion across the arterial wall. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of the nanostructure and nanoporosity on bioactive nanohydroxyapatite/reconstituted collagen by electrodeposition
Authors: Ou Keng‐Liang , Wu Jeffery , Lai Wen‐Fu T. , Yang Charng‐Bin , Lo Wen‐Chang , Chiu Li‐Hsuan , Bowley John
Published: March 2009

Hydroxyapatite (HA)/collagen composites were reported to induce bony growth. Various methods for preparing HA‐based composites have been investigated as potential biomaterials for bone substitutes. However, no method can generate a thick nanoporous HA. A novel bone regenerative nanocomposite consisting of nano‐hydroxyapatite (HA), nano‐amorphous calcium phosphate (ACP) and reconstituted collagen by electrodeposition was designed in this research. Specimens with and without nanoporosity were evaluated using electrochemical measurements, material analyses, and cell‐material interactions. The results showed that reconstituted collagen/nano‐(HA and ACP) illustrated a multinanoporous structure and enhanced biocompatibility. Nanocomposite was comprised to nano‐(HA and ACP) and reconstituted collagen. The core cell structure was formed during electrodeposition. Nanoporosity and nanostructure were observed as formation of nanocomposite. The nano‐(HA and ACP) phases were essentially composed of a nanoporous and nanostructural biocomposite. Reconstituted collagen incorporation with the nanoporous and nanostructural biocomposite significantly facilitated the osteogenic differentiation of mesenchymal stem cells. Reconstituted collagen was covered with nano‐(HA and ACP), profoundly impacting the enhancement of biocompatibility on application of implant and tissue engineering. The bioactive nano‐HA/reconstituted collagen‐induced osteogenic differentiation of mesenchymal stem cells enables to enhance bone growth/repair and osseointegration. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Biodegradable β‐Tri‐Calciumphosphate/hydroxyethyl methacrylate enhanced three component bone adhesive demonstrates biocompatibility without evidence of systemic toxicity in a rabbit model
Authors: Bauer Natali B. , Brinke Nina , Heiss Christian , Skorupa Agnes B. , Peters Fabian , Kraus Ralf , Schnettler Reinhard , Moritz Andreas
Published: March 2009

Bone gluing is an attractive surgical technique; however, its use in patients is hampered by a variety of side effects. Therefore, it was the aim of this ethically approved study to evaluate a novel biodegradable β‐Tri‐Calciumphosphate (β‐TCP, Cerasorb®)‐enhanced bone adhesive regarding its toxicity and biocompatibility in a rabbit model. Fifty healthy New Zealand White rabbits were assigned in the study (n = 21) and sham‐operated control group (n = 29). In the study group, a cylindrical part (4.6 × 10.0 mm) of the proximal tibia and distal femur was removed, reimplanted, and bone adhesive was applied. Blinded physical examination and sampling for hematology, clinical chemistry, and acute phase proteins (haptoglobin, C‐reactive protein (CRP)) was performed before surgery and after 12, 24, 48, 72, 240, and 504 h. Significant findings of the physical examination included a slightly higher grading of warmth (p = 0.0019) and pain (p < 0.0001) of the wound 240 h after surgery in the study group. No significant differences between albumin, haptoglobin, CRP, and urea concentrations in both groups were evident, whereas the study group demonstrated significantly lower leukocyte count, total protein, and globulin concentrations (p < 0.0001). As expected, both groups showed a marked transient increase in muscle enzymes (Creatine Kinase and Aspartate Aminotransferase) following the surgery (p < 0.0001). Twelve to 24 h after surgery, a significant decrease in ionized calcium from 1.38 ± 0.12 mmol/L to 1.06 ± 0.13 mmol/L was noted in the study group (p < 0.0001). The results clearly indicated that the novel β‐TCP‐enhanced bone adhesive showed good biocompatibility without significant evidence of acute or subacute local or systemic toxicity. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Natural bone collagen scaffold combined with OP‐1 for bone formation induction in vivo
Authors: Qian Yu , Yao Guanfeng , Lin Zhen , Chen Jimin , Fan Ying , Davey Tamara , Xu Jiake , Zheng Minghao
Published: March 2009

The scaffold is a key element to osteogenic tissue engineering as it provides a microenvironment for bone formation. Natural bone collagen scaffold (NBCS) is a novel biomaterial scaffold acid‐extracted from organic human bone. The objective of this study was to characterize NBCS and evaluate the osteoconductivity of the scaffold, in combination with osteogenic protein‐1 (OP‐1), using a rabbit posteolateral lumbar fusion model. Thirty two rabbits were divided into 4 experimental groups, autograft, NBCS alone, OP‐1 alone or NBCS combined with OP‐1. Bone formation was evaluated by micro‐CT, quantitative histological analysis, immunohistochemistry and semi‐quantitative RT‐PCR at 6 weeks postoperatively. By scanning electronic microscope, we showed that NBCS maintains a porous, interconnecting microarchitecture. Micro‐CT analysis demonstrated that NBCS combined with OP‐1 significantly induced (p < 0.01) bone formation at the fusion site as compared to control groups. This was confirmed by quantitative histological analysis which demonstrated that the NBCS combined with OP‐1 significantly enhanced bone matrix area (17.7 mm2) (p < 0.05) and bone marrow cavity size (71.3 mm2) (p < 0.05) as compared to the controls. Immunohistochemical assessment and RT‐PCR also demonstrated that NBCS combined with OP‐1 enhanced type I collagen and osteonectin expression. Together, these results suggest that NBCS is an effective scaffold for osteogenesis, and combined with growth factors such as OP‐1, possesses both osteoconductive and osteoinductive properties that are sufficient for bone regeneration. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Nondestructive assessment of dentin demineralization using polarization‐sensitive optical coherence tomography after exposure to fluoride and laser irradiation
Authors: Manesh Saman K. , Darling Cynthia L. , Fried Daniel
Published: March 2009

Previous studies have demonstrated that polarization‐sensitive optical coherence tomography (PS‐OCT) can be used to image natural and artificial caries in dentin. The purpose of this study was to measure nondestructively the severity of artificial caries lesions in dentin and determine the efficacy of intervention with anticaries agents including fluoride and lasers. Although several studies have assessed the utility of PS‐OCT to image caries lesions in enamel and to quantify the lesion severity, only a few studies have focused on lesions in dentin. In this study, images of artificial dentin lesions on extracted human teeth were acquired with PS‐OCT. Before exposure to an artificial demineralizing solution, three incisions were made on the sample surfaces using either Er:YAG, Nd:YAG (λ = 355 nm), or TEA CO2 lasers and selected areas were treated with topical fluoride to create six unique treatment areas for each of the three laser conditions investigated. The integrated reflectivity and depth of demineralization were calculated for each of the six areas on each sample using the PS‐OCT images. Polarized light microscopy (PLM) and transverse microradiography (TMR) were used to measure lesion severity on histological thin sections for comparison. PS‐OCT successfully measured the inhibition of demineralization by topical fluoride. Laser irradiation was not particularly effective in increasing or decreasing the rate of dentin demineralization. PLM and TMR corroborated those results. This study demonstrates that PS‐OCT can be used to measure demineralization on dentin surfaces and determine the degree of inhibition of demineralization by anticaries agents. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
The effect of three chemical oxidants on subsequent biodegradation of 2,4‐dinitrotoluene (DNT) in batch slurry reactors
Authors: Cassidy Daniel , Northup Abraham , Hampton Duane
Published: March 2009

BACKGROUND: Recent studies indicate that chemical oxidation may be compatible with subsequent biodegradation in contaminated soils. To test this, soil contaminated with 2,4‐dinintrotoluene (2,4‐DNT) was treated in batch slurry reactors with (1) ozone, (2) modified Fenton chemistry (MFC), and (3) iron‐activated sodium persulfate (SPS). Chemical and subsequent biological oxidation were monitored, and compared with biodegradation alone. Release of nitrite and nitrate distinguished biological from chemical oxidation of 2,4‐DNT, respectively. DNT‐degrading microorganisms were enumerated. The disappearance of volatile fatty acids (VFAs) accumulated during chemical oxidation was also monitored.

RESULTS: In the biological reactor 66% of the 2,4‐DNT was degraded, but further biodegradation was inhibited by nitrite concentrations approaching 18 mmol L−1. At the doses tested, all oxidants achieved chemical oxidation followed by biodegradation, resulting in 98% DNT removal overall. Ozone achieved the greatest DNT removal (70%), but also caused the greatest reduction in DNT degraders and the longest rebound time (60 days) before biodegradation of the remaining DNT and VFAs. SPS resulted in the least DNT removal by chemical oxidation (37%), but showed no obvious rebound period for DNT degraders, and even signs of co‐existing chemical and biological oxidation. By releasing nitrate, which is less toxic than nitrite, the oxidants kept nitrite levels below 18 mmol L−1, enabling the follow‐on biodegradation step to attain lower concentrations of 2,4‐DNT than biodegradation alone.

CONCLUSIONS: All three chemical oxidants were compatible with biodegradation of residual 2,4‐DNT. Post‐oxidation bioremediation should be included in remedial designs. Copyright © 2009 Society of Chemical Industry
Automated thresholding method (ATM) for biomass fraction determination using FISH and confocal microscopy
Authors: Jubany Irene , Lafuente Javier , Carrera Julián , Baeza Juan A.
Published: March 2009

BACKGROUND: Fluorescence in situ hybridization (FISH) together with confocal laser scanning microscopy (CLSM) is widely used for the analysis and quantification of biomass fractions of activated sludge or biofilm systems in wastewater treatment research. Unlike the FISH technique, the CLSM image analysis and quantification is not generally unique and thus, several manual and automated methods exist that can lead to very different results.

RESULTS: A method based on the analysis of negative control images is reported in this paper. Histograms of negative control images were used in the segmentation of positive images (hybridized with FISH probes). The threshold (Ithr) was defined as the minimum intensity value that satisfies the following condition: the proportion of pixels with intensity I ≤ Ithr in the negative control images is greater than or equal to a value α. It was found that the optimal α–value was 99.90% for the specific case studied (nitrifying activated sludge samples) by comparing the automatic thresholding with manual thresholding by three expert operators.

CONCLUSION: The method developed was useful for following systematically the evolution of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) fractions in a nitrifying system under changing operating conditions. Copyright © 2009 Society of Chemical Industry
Crystal and molecular structure of 8,8‐dimethyl‐8‐azoniabicyclo [5.1.0] octane iodide
Authors: Trefonas L. M. , Towns Robert
Published: March 2009

The crystal and molecular structure of 8, 8‐dimethyl‐8‐azoniabicyclo[5.1. 0]octane iodide has been elucidated. The aziridine ring is bridged cis to the cycloheptane ring. The cycloheptane ring has been shown to have a distorted chair conformation. No close trans‐annular hydrogen distances have been observed. The compound crystallizes in the space group Pna21 with unit cell dimensions a = 17.31, b= 8.58 and c=7.56Å. The final value of R=Σ ‖ Fo| ‐ | Fc ‖/Σ| Fo| is 0.145 for the 734 observed reflections.
Aromaticity in heterocyclic systems. II. the application of N.M.R. in a study of the synthesis and structure of certain lmidazo[1,2‐c]pyrimidines and related pyrrolo[2,3‐d]pyrimidines
Authors: Noell C. Wayne , Robins Roland K.
Published: March 2009

Nuclear magnetic resonance spectra have been utilized in several instances to distinguish between ring closure to a derivative of imidazo[1, 2‐c]pyrimidine or pyrrolo[2, 3‐d]pyrimidine. N.m.r. studies have also been employed to select Vc as the most probable structure for 5‐methylthio‐2, 7‐imidazo[1, 2‐c]pyrimidinedione. Ultraviolet absorption spectra and n.m.r. studies in deuterium oxide support the conclusion that there is more aromaticity in the anion V g than in the neutral molecule. The present work describes several new synthetic routes to derivatives of imidazo[1,2‐c]pyrimidine and pyrrolo[2,3‐d]pyrimidine.
Acylations with the acid chlorides of 2,5‐diphenylfuran‐3,4‐dicarboxylic acid and 2,5‐dimethylfuran‐3,4‐dicarboxylic acid and related compounds. II
Authors: Nightingale Dorothy V. , Needles Howard L.
Published: March 2009

The Friedel‐Crafts acylation of six phenol ethers with 2, 5‐diphenylfuran‐3, 4‐dicarbonyl chloride and with 2, 5‐dimethylfuran‐3, 4‐dicarbonyl chloride yielded 2, 5‐di‐R‐3, 4‐diaroyl‐furans or cyclic diketones. 2,5‐Diphenylfuran‐3,4‐dicarboxylic acid anhydride reacted with these ethers to form keto acids.
Analogs of tetrahydrofolic acid. XIII. On the mode of binding of the anilino group of 2‐amino‐5‐(3‐anilinopropyl)‐6‐methyl‐4‐pyrimidinol to dihydrofolic reductase and thymidylate synthetase
Authors: Baker B. R. , Ho Beng‐Thong , Chheda Girish B.
Published: March 2009

Six analogs of 2‐amino‐5‐(3‐anilinopropyl)‐6‐methyl‐4‐pyrimidinol (II) with modifications in the anilino group have been synthesized in order to shed light on the mode of binding of the anilino group to dihydrofolic reductase and thymidylate synthetase. Replacement of the anilino group of II with n‐butylamino (XI) led to great decrease in binding, indicating that the anilino group did not bind to these enzymes in the protonated form. Replacement of the anilino group of II with benzyl gave a compound (XIIb) which was a 26‐fold and 1.5‐fold better inhibitor of dihydrofolic reductase and thymidylate synthetase, respectively; these results indicated that the NH portion of the anilino group contributed less to the enzyme binding than did the benzene ring, and that the latter probably was bound as an electron acceptor in a charge‐transfer complex to an electron‐rich locus on the enzyme. Further evidence was also obtained that the benzene ring was complexing as an electron acceptor by placement of electron‐donating or electron‐withdrawing groups on the p‐positions of anilino group, and by N‐acetylation of the anilino group.
Cinnoline chemistry. IX. 5‐, 6‐, 7‐ and 8‐halogen substituted 4‐mercaptocinnolines and related compounds
Authors: Castle Raymond N. , Shoup Regitze R. , Adachi Kikuo , Aldous Duane L.
Published: March 2009

A series of 4‐mercaptocinnolines (4) monosubstituted with halogen in the benzenoid ring was obtained when the corresponding 4‐hydroxycinnolines were treated with phosphorus pentasulfide in either pyridine or toluene. On prolonged heating in either or the two solvents, the halogen atom in 6‐chloro‐ and 6‐bromo‐4‐hydroxycinnoline was simultaneously substituted with a mercapto group, thus yielding 4,6‐dimercaptocinnoline. Nucleophilic substitution of the halogen atom was also observed in the reaction of 6‐fluoro‐ and 7‐fluoro‐4‐hydroxycinnoline, while 8‐halo‐4‐hydroxycinnoline gave exclusively 8‐halo‐4‐mercapto‐cinnoline. From the reaction of 5‐halo‐4‐hydroxycinnoline the only identified products were 5‐halo‐4‐mercaptocinnolines. Previously unknown 4‐hydroxycinnolines were synthesized. 4‐Alkylmercaptocinnolines and 4,6‐dialkylmercaptocinnolines of pharmacological interest were prepared from the parent mercaptocinnoline or from the corresponding chlorocinnoline.
Synthetic routes to β, β‐diaryl‐α‐amino acids via nitrogen hetercycles
Authors: Filler Robert , Rao Y. Shyamsunder
Published: March 2009

β, β‐Diphenylalanine and its ring‐substituted analogs are prepared from oxazolones, thiazolones, imidazolones, hydantoins, thiohydantoins, and piperazine 2,5‐diones by alkaline ring opening followed by acid cleavage of the N‐benzoyl group. The oxazolone approach, with its variations, offers the most advantageous route to these compounds. Several new amino acids are described.
1,3‐Dithioles and 1,3‐dithiole‐s‐oxides
Authors: Campaigne E. , Haaf F.
Published: March 2009

1,3‐Dithioles have been prepared by a new route from α‐haloketones and a gem‐dithiol. The reaction was carried out with aliphatic and aromatic α‐haloketones, which were condensed with 1,3‐diphenylpropane‐2,2‐dithiol to give 2,2‐dibenzyl‐4‐hydroxy‐1,3‐dithiolanes. These intermediates were dehydrated in the presence of acids to 2,2‐dibenzyl‐1, 3‐dithioles. Two of the 2,2‐dibenzyl‐1,3‐dithioles were oxidized with hydrogen peroxide to the corresponding S‐dioxides, S‐trioxides, and S‐tetroxides, which were separated by preparative thin layer chromatography. The condensation of 1,3‐diphenylpropane‐2, 2 ‐ dithiol with oxalyl chloride gave 2, 2‐dibenzyl‐1, 3‐dithiolane‐4, 5‐dione. Infrared and n.m.r. data of these compounds confirm the structural assignments.
Quinoxalinediones. I. Synthesis of 6‐methyl‐5,8‐quinoxalinediones
Authors: Levy Michèle R. W. , Joullié Madeleine M.
Published: March 2009

Various synthetic routes were investigated as potential methods of preparation of 6‐methyl‐5, 8‐quinoxalinediones which could be useful as antimetabolites of vitamin K. The preparation of 2,3‐dimethyl‐5,8‐quinoxalinedione (II) was achieved by the condensation of 2,3‐diamino‐1,4‐dimethoxybenzene with diacetyl. Demethylation was accomplished by the use of aluminum chloride in benzene and the resulting hydroquinone (I) was oxidized with dry silver oxide to the quinone (II). An analogous synthetic route could not be used to prepare 2, 3, 6‐trimethyl‐5, 8‐quinoxalinedione (VII). 6‐Methyl‐5, 8‐quinoxalinediones were prepared from 2,3‐dinitro‐4‐methoxy‐6‐methylacetanilide (III) which was reduced and condensed with appropriate carbonyl compounds. Acid hydrolysis yielded aminophenols which were oxidized to (VII) and (VIII) with chromic acid. The ultraviolet and infrared spectra of the compounds prepared are recorded.
Hydrazinopyrimidines
Authors: Wiley Richard H. , Lanet Jean , Hussung K. H.
Published: March 2009

A variety of hydrazino and dihydrazino‐5‐nitropyrimidines and their derivatives have been prepared by displacement reactions or reaction sequences from 2,4‐ or 4,6‐dichloro‐5‐nitropyrimidine. These include 2,4‐ and 4, 6‐dihydrazino, 2‐dimethylamino‐4‐hydrazino, 2‐hydrazino‐4‐dimethylamino, 2‐morpholino‐4‐hydrazino, and 2‐hydrazino‐4‐amino‐5‐nitropyrimidines. 2,4‐Dihydrazino‐5‐nitropyrimidine on condensation with selected aldehydes yielded a series of dihydrazones. Of these, p‐methoxybenzaldehyde (5‐nitropyrimidyl‐2, 4‐dihydrazone) showed a reproducible but slight activity in Sarcoma‐180 tests.
Diazepines. I. 3,8‐Dihalo‐11H‐dibenzo[c,f]‐[1,2] diazepines
Authors: Catala Adria , Popp Frank D.
Published: March 2009

The title compounds were prepared by lithium aluminum hydride reduction of the corresponding 2, 2′‐dinitro‐4, 4′‐dihalodiphenylmethanes. Peracetic acid oxidation of the title compounds led to the N‐oxides, chromic anhydride oxidation led to an 11‐ keto compound, and hydrazine ‐ Raney nickel reduction led to the dihydro compounds.
Imidazo[4,5‐d]pyridazines. III. The Synthesis of 2‐phenylimidazo [4,5‐d]‐pyridazines
Authors: Malm Miriam , Castle Raymond N.
Published: March 2009

Based upon an analogy with “Dyrenium”, (6‐phenyl‐2,4,7‐triaminopteridine) (I), 4,7‐diamino‐2‐phenylimidazo[4, 5‐d]pyridazine (II) has been prepared. This compound has been found to possess diuretic activity. In addition a number of other substituted 2‐phenylimidazo[4, 5‐d]pyridazines have been prepared.
The influence of alkyl substituents on the rates of hydrolysis of 2‐imidazolines
Authors: Harnsberger B. G. , Riebsomer J. L.
Published: March 2009

A number of 2‐imidazolines have been hydrolyzed in basic 95% ethanol, and the activation energies and half‐lives of these reactions have been determined. The reactions are base catalyzed and lead to the formation of amides through fission of the ring between positions one and two. The reaction rates are strongly influenced by various ring substituents.
The chemistry of pyrazine and its derivatives. X. The mono‐ and diacylation of tetramethylpyrazine
Authors: Chakrabartty Sujit K. , Levine Robert
Published: March 2009

By the use of sodium amide in liquid ammonia or phenyllithium in ether as the condensing agent it has been possible to synthesize a series of ketones containing the pyrazine ring with the structure, RCOCH2C4N2(CH3)3 where R is alkyl, aryl or heterocyclic. Also, under appropriate conditions, tetramethylpyrazine has been diacylated to give three diketones of the type (2‐RCOCH2)‐(6‐R' COCH2)C4N2(CH3)2‐3, 5.
The kinetics of the hydrolysis of some 2‐imidazolines
Authors: Harnsberger B. G. , Riebsomer J. L.
Published: March 2009

A 1,2‐disubstituted‐2‐imidazoline was hydrolyzed in aqueous solutions of varying PH. The rate of reaction approaches a maximum as the base concentration is increased. Salt effects and activation energies also seem to vary with PH.
Difluorodiazirine. II. Difluoromethane derivatives
Authors: Mitsch Ronald A.
Published: March 2009

The photolysis of difluorodiazirine is a convenient technique for the formation of difluorocarbene. Difluorocarbene, generated in this manner, has been shown to react with chlorine, iodine, dinitrogen tetroxide and nitryl chloride to yield the corresponding difluoromethane derivatives.
3‐Substituted thiophenes. XII. Bromination of β‐3‐thienylacrylic acid
Authors: Campaigne E. , Fedor L. , Johnson Roger E.
Published: March 2009

Bromination of β‐3‐thienylacrylic acid in glacial acetic acid gave β‐(2‐bromo‐3‐thienyl)‐acrylic acid with an equivalent of bromine, and β‐(2,5‐dibromo‐3‐thienyl)‐α,β‐dibromo‐propionic acid with excess bromine. In hot carbon tetrachloride, an excellent yield of the stable olefinic addition product, β‐3‐thienyl‐α,β‐dibromopropionic acid, was obtained, and its structure was confirmed by conversion to β‐bromo‐3‐thienylethylene in base. 3‐Thenaldehyde underwent a Darzen's Glycidic Ester condensation to produce ethyl β‐3‐thienyl‐α,β‐epoxypropionate, but treatment of this ester or the salt of its derived acid with hydrogen bromide led to the formation of unstable products. The structure of the bromo‐acids and derivatives were confirmed by unequivocal syntheses and/or by nuclear magnetic resonance spectra.
Analogs of tetrahydrofolic acid. XIX. On the mode of binding of the pyrimidyl moiety of n‐(2‐amino‐4‐hydroxy‐6‐methyl‐5‐pyrimidylpropionyl)‐P‐aminobenzoyl‐l‐glutamic acid to 5,10‐methylenetetrahydrofolate dehydrogenase
Authors: Baker B. R. , Almaula Prabodh I.
Published: March 2009

The synthesis of several analogs of the title compound (Ia) which had (a) replacement of the 4‐hydroxy group by thiol, (XXVIIIa), (b) replacement of the 6‐methyl group by 6‐phenyl (Ib), (c) replacement of the 2‐amino group by 2‐thiol (XXVI), or (d) replacement of both the 4‐hydroxyl and 6‐methyl groups by 4‐thiol and 6‐phenyl, respectively, have been described. The key intermediate was the appropriate 2,4,6‐trisubstituted5‐pyrimidyl‐propionic acids which were synthesized by suitable transformation of the 5‐pyrimidyl‐propionitriles (VIII and XII). Replacement (a) or (b) gave an improvement in inhibition of 5, 10 ‐ methylenetetrahydrofolate dehydrogenase, but the two changes in the same molecule (d) did not further increase inhibition. The 2‐amino group of the title compound (Ia) can be replaced by 2‐thiol without decreasing the inhibitory properties of Ia.
Amino Acids. I. DL‐β‐(diazaphenyl)alanines
Authors: Haggerty William J. , Springer Robert H. , Cheng C. C.
Published: March 2009

With the publication of this work, all six theoretically possible isomers of DL‐diaza‐phenylalanines have now been reported. 2‐Pyrazinyl‐ (VII), 3‐pyridazinyl‐ (VIII), 4‐pyridazinyl‐ (IX), 4‐pyrimidinyl‐ (X), and 2‐pyrimidinylalanine (XI) were synthesized by the catalytic (in the cases of VII‐X) or stannous chloride (in the case of XI) reduction of the corresponding (α‐oximino‐β‐(diazaphenyl)propionic acids. These compounds were in turn prepared by the Claisen condensation of appropriate methyldiazines with diethyl oxalate followed by treatment of the resulting pyruvic ester with hydroxylamine.

Condensation of 5‐bromomethylpyrimidine with diethyl N‐ carbobenzoxyaminomalonate yielded diethyl N‐carbobenzoxyarmno‐(5‐pyrimidinylmethyl)malonate. Hydrolysis and debenzylation of the condensation product readily gave the desired 5‐pyrhidinylalanine (XII).
Neighboring Group participation by the tetrahydrofuran ring
Authors: Kwiatkowski George T. , Kavarnos Spiro J. , Closson W. D.
Published: March 2009

Neighboring group participation in the solvolytic reactions of a series of ω‐(2‐tetx‐a‐hydrofuran)alkyl p ‐ bromobenzenesulfonate esters has been investigated. Anchimeric assistance to solvolysis is most pronounced in the case of 3‐(2‐tetrahydrofuran)propyl p‐bromobenzenesulfonate where a 1‐oxabicyclo[3.3.0]octane cation can form. A “special salt effect” and an “induced common ion effect” were observed in the acetolysis of this ester. It appears that the tetrahydrofuran ring is about twice as effective as the methoxyl group in neighboring group participation.
Analogs of tetrahydrofolic acid. XXI. Synthesis of 6‐bromomethyl‐5‐(p‐chlorophenyl)‐2,4‐diaminopyrimidine and its evaluation as a dihydrofolic reductase inhibitor
Authors: Baker B. R. , Jordaan Johannes H.
Published: March 2009

The title compound (IV) has been synthesized from p‐chlorophenylacetonitrile by Claisen condensation with ethyl ethoxyacetate, conversion to an enol ether, then reaction with guanidine to give the key intermediate 5‐(p‐chlorophenyl)‐2,4‐diamino‐6‐ethoxymethyl‐pyrimidine (V). Cleavage of the ethyl ether of V with hydrogen bromide in acetic acid gave IV. The bromomethylpyrimidine (IV) was a good reversible inhibitor of dihydrofolic reductase from pigeon liver, but IV was not an irreversible inhibitor of the enzyme.
Polyfunctional aliphatic compounds VI. The cyclization of dinitriles to benzazepines
Authors: Johnson Francis , Nasutavicus W. A.
Published: March 2009

The action of hydrogen bromide or iodide on aryl‐o‐diacetonitriles has been studied and found to give condensed azepine derivatives. This constitutes a new and interesting synthesis of seven‐membered ring nitrogen heterocycles. The structure of the parent substance has been shown by physical and chemical means to be 2‐amino‐4‐halo‐1H‐3‐benzazepine. Several related compounds have been prepared and assigned similar structures by analogy. A number of reactions of 2‐amino‐4‐bromo‐1H‐3‐benzazepine (III) have been examined. It is concluded that the reactivity of the bromo group is similar to that of 2‐bromopyridine. In its reactions, 2‐amino‐1H‐3‐benzazepine not only has some of the character of 2‐aminopyridine but resembles the simple amidines also.
The chemistry of heterocycles. III. 2H‐1,3‐benzoxazine‐2,4(3H)‐dione and Some 3‐substituted derivatives.
Authors: Crum J. D. , Franks J. A.
Published: March 2009

The preparation of 2H‐1,3‐benzoxazine‐2,4(3H)‐dione, the sodium salt, and the p‐anisoyl, benzoyl, m‐bromobenzoyl, benzyl, trans‐cinnamoyl, ethyl, myristoyl, p ‐nitro‐benzyl, phenyl and p‐phenylphenacyl derivatives substituted on 2H‐1,3‐benzoxazine‐2,4‐(3H)‐dione (I) at position 3 together with their infrared and ultraviolet spectra are described.
A synthesis of 7‐substituted benzo[b]thiophene derivatives
Authors: Macdowell D. W. H. , Greenwood Thomas D.
Published: March 2009

In order to develop a method for synthesizing 7‐substituted derivatives of benzo[b]‐thiophene, the benzo[b]thiophene analog of 1‐tetralone, 7‐oxo‐4, 5, 6, 7‐tetrahydrobenzo‐[b]thiophene has been synthesized using as starting material the readily accessible 3‐bromothiophene. The structure of this ketone has been verified by elemental analysis, spectra and conversion to derivatives of benzo[b]thiophene of known structure. Several hitherto unreported 7‐substituted derivatives of benzo[b]thiophene have been prepared from the cyclic ketone.
Analogs of tetrahydrofolic acid. XXIII. 1‐(ω‐phenylalkyl)‐4,6‐diamino‐1,2‐dihydro‐s‐triazines as inhibitors of dihydrofolic reductase
Authors: Baker B. R. , Ho Beng‐Thong
Published: March 2009

A series of 1‐(ω‐phenylalkyl)‐4,6‐diamino‐1, 2‐dihydro‐s‐triazines was synthesized by acid catalyzed condensation of 1‐(ω‐phenylalkyl)biguanides with acetone, aromatic aldehydes and ω‐phenylalkyl aldehydes; the intermediate biguanides were prepared by fusion of ω‐phenylalkylamines with cyanoguanidine at 150°. 4, 6‐Diamino‐1, 2‐dihydro‐2,2‐dimethyl‐1‐(4‐phenylbutyl)‐ and 1‐(3‐phenylpropyl)‐s‐triazines (Xe and Xd) were potent inhibitors of dihydrofolic reductase, being complexed with the enzyme about two hundred times better than the substrate, dihydrofolic acid; further Xd and Xe were about 15‐fold better inhibitors of dihydrofolic reductase than the earlier investigated 1‐(p‐chlorophenyl)‐4, 6‐diamino‐1,2‐dihydro‐2,2‐dimethyl‐s‐triazine, the antimalarial drug.

When the 2,2‐dimethyl group was replaced by p‐acetamidophenyl (IX) or phenyl (VIII), in inhibitors such as Xd and Xe, activity was reduced only 5‐30 fold; the corresponding change in 1‐(m‐chlorophenyl)‐4, 6‐diamino‐1,2‐dihydro‐2, 2‐dimethyl‐s‐triazine (V) gave a 19,000‐fold reduction in activity with the 2‐(p‐acetamidophenyl) analog (VII) and a 550‐fold decrease in activity with the 2‐phenyl analog. These decreases in activity are attributed to a combination of intramolecular steric effects, intermolecular (enzymeinhibitor) steric inhibition of binding, and inductive effects. By evaluation of suitable candidate compounds, these effects were partially separated for individual study.
Steroids. XIX. 3‐phenyl ‐ and 3‐ethyl‐4‐azacholestanes
Authors: Doorenbos Norman J. , Kerridge Kenneth A.
Published: March 2009

The hydrogenation of 4‐methyl‐4‐aza‐5‐cholesten‐3‐one (III) to yield the 5α‐ and 5β‐isomers under acid conditions is described. The reaction of III and 4‐methyl‐4‐aza‐5α‐cholestan‐3 ‐ one with phenylmagnesium bromide, ethylmagnesium iodide, phenyllithium and ethyllithium to yield 3‐substitutcd steroids is reported. Hydrogenation of these 3‐substituted steroids yielded 4‐methyl‐3ξ‐phenyl‐4‐aza‐5α‐cholestane and 3ξ‐ethyl‐4‐methyl‐4‐aza‐5α‐cholestane (XIII). XIII inhibits the biosynthesis of cholesterol.
An investigation of abnormal products in the reaction of benzyl and 2‐thenyl grignard reagents with 14C‐carbon dioxide
Authors: Campaigne E. , Collins Clair J.
Published: March 2009

An investigation of the abnormal products formed in the carbonation of benzyl and 2‐thenyl Grignard reagents has been carried out. Using the reverse isotope dilution technique, it has been shown that neither ortho‐ nor para‐toluic acids are formed in measurable amounts during the reaction of benzylmagnesium bromide with carbon dioxide. 2‐Thenylmagnesium chloride reacts to produce acids, about 64% of which is the normal product, 2‐thienylacetic acid, 30% the ortho ‐abnormal product, 2‐methyl‐3‐thenoic acid, and probably a small amount (1.0 – 1.5%) is the Para ‐abnormal product, 5‐methyl‐2‐thenoic acid.
Die kristall‐ und molekülstrutur des 1,4,6,9‐tetrachlorphenazins
Authors: Riganti Vincenzo , Locchi Stelio , Curti Renato , Bovio Bruna
Published: March 2009

Die Kristall‐ und Molekülstruktur des 1,4,6,9‐Tetrachlorphenazins C12H4N2Cl4 wurde röntgenographisch bestimmt. Die Kristalleo sind monoklin, Raumgruppe P21/n, und ergeben folgende Gitterkonstanten: a = 3.95 Å, b = 14.06 Å, c = 10.80 Å, β = 94°37′. Die intermolekularen Abstände stimmen mit denjenigen aus den van der Waals'schen Radien überein, mit Ausnahme eines C1….C1 Abstandes, der ein wenig kürzer als erwartet ist. Der intramolekdare CC1‐Abstand beträgt: 1.718 Å.
Mass spectrometry of benzo[a]‐ and benzo[c]acridines
Authors: Buu‐Hoi N. P. , Orley C. , Mangane M. , Jacquignon P.
Published: March 2009

The mass spectrograms of fourteen benzo[a]‐ and benzo[c]acridines, several of which are carcinogens, have been determined, and the following main features emerge: (a) presence of strong peaks corresponding to several stages of dehydrogenation; (b) very little fragmentation of the polycyclic frame, with, in ethylbenzacridines, a noteworthy splitting of methyl groups; and (c) importance of the double‐charged ions, some of which contribute more to the ionic current than do the corresponding single‐charged ones. The pattern of the spectrograms can vary considerably with the position of the substituents.
Morphanthridines II. 11‐aminoalkyl‐5,6‐dihydromorphanthridines
Authors: Drukker Alexander E. , Judd Claude I. , Spoerl Joan M. , Kaminski Frank E.
Published: March 2009

Butyl lithium converts 5‐substituted‐5,6‐dihydromorphanthridines to the 11‐position anion. Treatment of this lithium anion with aminoalkyl halides affords the 11‐aminoalkylated derivatives. Catalytic hydrogenation causes reductive cleavage of benzylamino bridge of the morphanthridine ring, a reaction which is used to structurally relate these compounds to the known 11‐aminoalkylidene‐5, 6‐dihydromorphanthridines
The synthesis of 5‐fluoro‐ and 7‐methyl‐indole and ‐tryptophane
Authors: Hoffmann Eliahu , Ikan Raphael , Galun Arjeh B.
Published: March 2009

5‐Fluoroindole was prepared in 4 steps in 46% overall yield from m‐fluorotoluene. 7‐Methylindole was prepared in 2 steps 2 from 6‐dimethylaniline. Both compounds were transformed to the corresponding tryptophanes in high yields. The final hydrolytic step was carried out in aqueous acidic medium.
Analogs of tetrahydrofolic acid. XXIX. Hydrophobic bonding to dihydrofolic reductase. II. On the mode of phenyl binding of 1‐aryl‐4,6‐diamino‐1,2‐dihydro‐2,2‐dimethyl‐s‐triazines
Authors: Baker B. R. , Ho Beng‐Thong
Published: March 2009

The inhibition of dihydrofolic reductase by twenty appropriately 1‐substituted‐4, 6‐diamino‐1, 2 ‐ dihydro‐2, 2‐dimethyl‐s‐triazines were compared in order to shed light on the mode of phenyl binding of 1‐aryl‐1,2‐dihydro‐s‐triazines. When the 1‐phenyl group was substituted by a cationic group at the 4‐position or an anionic group at either the 3‐ or 4‐position, a large loss in affinity by the enzyme for the resultant inhibitor was noted. This loss in affinity is best explained by the concept that the 1‐aryl group complexes with a hydrophobic region on the enzyme and that the hydrophobic region repels any aryl group bearing either a positively or negatively charged group. p‐Substituents coplanar with the 1‐aryl group caused a steric interaction with the enzyme resulting in considerable loss in binding to this enzyme isolated from pigeon liver; this steric effect was considerably less in the m‐position. Inductive effects of 1‐phenyl substituents on a possible charge‐transfer complex of the 1‐aryl group or on the binding ability of the 4,6‐diamino‐1,2‐dihydro‐s‐triazine ring system could not be correlated with the Hammett sigma‐values; therefore these effects were considered to be of minor importance.
Analogs of tetrahydrofolic acid. XXX. Inhibition of dihydrofolic reductase by some 6‐substituted 2,4‐diamino‐s‐triazines
Authors: Baker B. R. , Ho Beng‐Thong
Published: March 2009

Four different routes to 6‐alkyl‐, 6‐aryl‐, and 6‐aralkyl‐2,4‐diamino‐s‐triazines were investigated. The most convenient was reaction of an ester with biguanide in methanol at room temperature. Seven of these 6‐substituted 2,4‐diamino‐s‐triazines were investigated as inhibitors of dihydrofolic reductase. As a class they were weaker inhibitors than the corresponding 2,4‐diamino‐6‐substituted pyrimidines, this difference being attributed to the weaker basicity of the former class. Although hydrophobic bonding by 6‐alkyl and 6‐aralkyl groups on 2 the 4‐diamino‐s‐triazine system could be detected, the extent of hydrophobic bonding was much weaker than that previously seen with 2,4‐diaminopyrimidine containing a 5‐alkyl or 5‐aralkyl group or 1‐alkyl‐ and 1‐aralkyl‐2,4‐diamino‐1,2‐dihydro‐2,2‐dimethyl‐s‐triazines.