The invention provides compounds useful as PGI2 receptor agonist and pharmaceutical compositions, particularly pharmaceutical compositions containing as the active ingredient compounds represented by the general formula (1) or pharmaceutically acceptable salts thereof: (1) wherein R1 and R2 are each independently optionally substituted aryl; Y is N, CH, or the like; Z is N, CH, or the like; A is NH, NR5, O, S, ethylene, or the like; R5 is alkyl or the like; D is alkylene or alkenylene; E is phenylene or a single bond; G is O, S, CH2, or the like; R3 and R4 are each independently hydrogen or alkyl; and Q is carboxyl, alkoxycarbonyl, tetrazolyl, carbamoyl, N-(alkylsulfonyl)carbamoyl, or the like.

Heterocyclic compound derivatives and medicines

This review (Part II) is topically organized around the dienophile that is generated in a retro [4 + 2] reaction, and to the extent possible follows the principles adopted for Part I, which covers reactions in which both dienophile bonding centers are carbon atoms. The present chapter encompasses retro–Diels–Alder (rDA) reactions in which one or both of the dienophile reaction centers are heteroatoms.



Any of the other atoms in the starting material (cycloadduct) may be carbon or heteroatom. Substituents on all positions are encompassed, and any bond order available to any oxidation state of an element is included, as is bonding to non-nearest neighbor atoms (e.g., bicyclics).



The reader is directed to Part I (Vol. 52) for general discussion of the rDA reaction, the features that affect rates and outcome, and the use of acids, bases, other catalysts, and scavengers. Certain subclassifications (e.g., processes proposed under MS conditions, polymer applications) of rDA reactions have been omitted from both sections; these topics are listed in the Introduction to Part I. Citations to over 100 reviews on various aspects of the rDA reaction are collected at the beginning of the References to Part I. Those that are especially pertinent to Part II will be repeated here, in the context of the particular dienophile under discussion.



The decision to split the review of the rDA reaction into two parts was based on the volume of literature encountered, as outlined in the Introduction to Part I. Active literature searching was concluded for both Parts in April 1995, although occasional more recent references have been included.


Keywords:

nitriles;
retro Diels-Alder;
dienophiles;
oxazoles;
pyrimidines;
pyrazines;
triazines;
expelled;
imines;
isocyanates;
carbonyl compounds;
thiocarbonyl;
carbon dioxide;
alpha-pyrones;
mesionics;
dinitrogen;
aliphatic diazines;
pyridazines;
bis-heterodienophiles;
diimides;
nitrogen oxides;
oxygen;
phosphorus;
sulfur;
experimental conditions;
tabular survey

The Retro–Diels–Alder Reaction Part II. Dienophiles with One or More Heteroatom

Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are defined herein.

Triazine 11-beta hydroxysteroid dehydrogenase type 1 inhibitors

The invention discloses aryl heterocycle micromolecule compounds shown as a general structure formula I, derivatives or pharmaceutically acceptable salts and prodrugs thereof, and preparing methods and uses of the compounds, the derivatives, the pharmaceutically acceptable salts and the prodrugs of the compounds. The compounds have good physicochemical properties, and have antitumor activity. Research on mechanisms of action shows that: the compounds act on tubulin and are novel tubulin inhibitors. The general structure formula I is shown in the specification.

Aryl heterocycle micromolecule compounds, derivatives thereof, and preparing methods and uses of the compounds and the derivatives

Background. Literatures revealed that 1,4-pentadien-3-one and triazine derivatives exhibited a wide variety of biological activities. In order to develop highly bioactive molecules, in this study, a series of novel 1,4-pentadien-3-one derivatives containing triazine moieties were synthesized and their antibacterial and antiviral activities were investigated. Methods. A series of novel 1,4-pentadien-3-one derivatives containing triazinemoieties were synthesized and characterized in detail via 1H NMR, 13C NMR and HRMS spectra. The antibacterial activities against Xanthomonas axonopodispv. citri (Xac), Xanthomonas oryzaepv. oryzae (Xoo) and Ralstonia solanacearum (R.s) were evaluated at 100 and 50 μg/mL using a turbidimeter and N. tabacun L. leaves under the same age as that of test subjects. The curative, protective and inactivation activities against tobacco mosaic virus (TMV) at a concentration of 500 μg/mL were evaluated via the half-leaf blight spot method. Results. The bioassay results showed that some of the target compounds exhibited fine antibacterial activities against Xac and R.s. Particularly, half maximal effective concentration (EC50) values of some target compounds against R.s are visibly better than that of the positive control bismerthiazol (BT). Notably, compound 4a showed excellent inactivation activity against TMV with a EC50 value of 12.5 μg/mL, which was superior to that of ningnanmycin (NNM,13.5 μg/mL). Besides, molecular docking studies for 4awith tobacco mosaic virus coat protein (TMV-CP) showed that the compound was embedded well in the pocket between the two subunits of TMVCP. These findings indicate that 1,4-pentadien-3-one derivatives containing triazine moieties may be potential antiviral and antibacterial agents. Subjects Green Chemistry, Natural Products, Organic Chemistry (other), Organic Compounds, Synthetic Organic Chemistry

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Synthesis and biological activity of 1,4-pentadien-3-one derivatives containing triazine scaffolds

4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4-methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine.

Minako Kumazawa

Papers

Studies on as-Triazine Derivatives. XIX. Synthesis of 2,3-Diarylpyrazine and 2,3-Diarylpyridine Derivatives as Blood Platelet Aggregation Inhibitors