Synthesis and Anticancer Evaluation of Novel Derivatives of Isoxazolo[4,5-e][1,2,4]triazepine Derivatives and Potential Inhibitors of Protein Kinase C.

In the present study, using Thorpe's reaction with Gewald's modification, 4-acetylamino-5-acetyl or 5-benzoyl 3-carboxamide compounds 3 or 4 were obtained. From these compounds, two series of compounds (5, 7, and 9 and 6, 8, and 10) were obtained with 98% hydrazine. Compounds 6, 7, 8, and 9 were then reacted with the appropriate aldehydes to afford a series of new isoxazole derivatives (11-18, 27-36, and 37-41) and the main compounds, 19-26 and 42-45, were isoxazolo[4,5-e][1,2,4]triazepine derivatives. The anticarcinogenic activities of selected compounds were tested on six lines of cancer cells, and their activities were compared with the relevant concentrations of the anticarcinogenic drugs cisplatin and doxorubicin in IITD PAN. Several compounds were tested on 60 lines of cancer cells by the NCI (Bethesda, MD, USA). The cyclization of compound 12 into derivative 46 was also carried out. Compound 21 showed extremely high antitumor activity.

Synthesis and anticancer evaluation of novel 3,5-diaryl-thiazolo[4,5-d]pyrimidin-2-one derivatives.

The 2-oxo analogs of thiazolo[4,5-d]pyrimidine-2-thiones were prepared to study their cytotoxic activity. Five of the newly synthesized compounds were selected by the National Cancer Institute (Bethesda, MD, USA) for a primary in vitro antitumor assay. 7-Chloro-3,5-diphenyl-thiazolo[4,5-d]pyrimidin-2-one (5a) proved to be the most active one among the screened derivatives and was further evaluated in the full panel of 60 cell lines at five different concentrations. The structures of compounds were determined by IR, 1H-NMR, 13C-NMR, X-ray, and elemental analysis.

Synthesis and antitumor screening of novel 3-phenylthiazolo [4,5-d]pyrimidin-2-thione derivatives.

A series of new derivatives of 3-phenylthiazolo[4,5-d]pyrimidine-2-thiones were synthesized by the cyclization of 4-amino-5-alkyl(aryl) carboxamido-2,3-dihydrothiazolo-2-thione with aromatic aldehydes. Amine moieties were substituted in position 7 of the obtained bicyclic compounds. The synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, and 13C-NMR spectral data. Some of the newly synthesized compounds were selected by the U.S. National Cancer Institute for in vitro antitumor screening. The two compounds 3d 7-chloro-5-(4-fluorophenyl)-3-phenyl-4,5-dihydro-3H-thiazolo[4,5-d]pyrinimidine-2-thione and 4i 5-(2-chlorophenyl)-7-(4-fluorobenzylaxnlno)-3-phenyl-4,5-dihydro-3H-thiazolo[4,5-dipyrhflldlfle-2thione proved to be the most active in the present study and their antitumor activities against 60 human tumor cell lines were described.

Beyond "objective" and "projective": a logical system for classifying psychological tests: comment on Meyer and Kurtz (2006).

I present a formal system that accounts for the misleading distinction between tests formerly termed objective and projective, duly noted by Meyer and Kurtz (2006). Three principles of Response Rightness, Response Latitude and Stimulus Ambiguity are shown to govern, in combination, the formal operating characteristics of tests, producing inevitable overlap between "objective" and "projective" tests and creating at least three "types" of tests historically regarded as being projective in nature. The system resolves many past issues regarding test classification and can be generalized to include all psychological tests.

Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine.

A number of derivatives of isoxazolo[4,5-d]pyrimidine were prepared with structures similar to that of purine. Condensation of the hydrazide of 4-amino-5-benzoylisoxazolo-3-carboxylic acid 2 with ethyloxalyl chloride followed by cyclization gave 3-oxdiazolo-[1,3,4]-4-amino-5-benzoylisoxazole 7 which, upon cyclization with acetonitrile followed by reactions with different amines, gave derivatives of isoxazolo[4,5-d]pyrimidine 9 and 10d-g. Compounds 8g and 10f were tested for their effects on the immune response in the mouse model. Both compounds significantly inhibited the humoral immune response in vivo to sheep erythrocytes at a dose of 100 microg, whereas in the delayed type hypersensitivity assay a suppressive activity was shown only by compound 10f. In addition, compound 8g inhibited and compound 10f stimulated the proliferative response of mouse splenocytes to concanavalin A. The results indicated that compound 10f was a universal inhibitor of the immune response, while compound 8g selectively suppressed the humoral immune response.

Synthesis and pharmacological assessment of derivatives of isoxazolo[4,5-d]pyrimidine.

A series of new 5-alkyl and 5-arylisoxazolo[4,5-d]pyrimidinones (5a-g, 6-8) were prepared from 4-amino-3-oxo-isoxazolidine-5-carboxylic acid amide. Some of the aryl derivatives of isoxazolo[4,5-d]pyrimidine were tested pharmacologically in comparison with Diazepam. Compounds 5b-d and 7 demonstrated interesting anxiolytic activity.

Using broad measures of maladjustment to assess psychological states of outpatients with schizophrenia.

Two broad indexes of maladjustment derived from two projective tests and administered at two separate points to the same 50 outpatients with schizophrenia showed substantial convergent validity at both testings (r=.52, p<.001; r=.58, p<.001). Conversely, test-retest reliabilities for both indexes were nonsignificant. These findings suggest that broad measures of maladjustment may be more suitable for reflecting current states of adjustment for subjects known to be diagnosed with certain symptoms, the manifestations of which fluctuate over time.

Defining projective techniques: finding common ground for discourse.

In 2000 Lilienfeld, Wood, and Garb defined projective tests in a traditional yet loose manner. When a more precise and exclusive definition is furnished, two classes of responses indicative of deviancy can be logically derived. It is suggested that a focused review of the literature yields consistent relations between psychopathology and two response types, falsifications and misrepresentations. This provides common ground for recognizing a circumscribed core of valid predictors across projective techniques.

Differences on the projective hand test among chronic pain patients reporting three different pain experiences.

This study examined personality differences among individuals experiencing 3 different types of pain. The projective Hand Test was administered to 90 individuals who were seeking treatment at a pain clinic in an urban area of the southeast United States. These people were seeking treatment for either arthritis (n = 31), fibromyalgia (n = 29), or migraine headaches (n = 30). A 2 (gender) x 3 (pain group) x Age Group multivariate analysis of variance was conducted using the quantitative Hand Test scoring variables as dependent measures. Results indicated that individuals who were seeking treatment for migraine headaches had a higher production rate of responses involving exhibitionistic displays (EXH) than individuals in the other 2 groups. Individuals who were seeking treatment for fibromyalgia had a higher production rate of responses indicating fear and phobic concerns (FEAR) than individuals in the other 2 groups. Individuals who were seeking treatment for arthritis had a higher production rate of Active (ACT) responses than individuals in the other 2 groups. Possible causes and consequences of these effects are discussed.