New facile synthesis of 2-substituted aminobenzimidazoles.

In this investigation, the cyclodesulphurization of N-o-aminophenyl-N'-phenylthiourea to produce 2-phenylaminobenzimidazole under the influence of dimethylsulphate was thoroughly studied under different reaction conditions. The mechanism of such reaction was also suggested.     

The cyclodesulphurization of thio-compounds. Part 15: Synthesis of 6-substituted aminophenanthridines from some thiourea derivatives

Several N-alkyl, aryl, and aralkyl-N'-2-biphenylthiourea derivatives have been synthesized and cyclodesulphurized into the corresponding 6-substituted aminophenanthridines. The ring closure was brought about with mercuric chloride, phosphoryl chloride or polyphosphoric acid. Phosphoryl chloride was found to be the most efficient in inducing ring closure and producing the highest yield of cyclized products. The results of study on the cyclodesulphurization reaction mechanism suggested the formation of a carbodiimide intermediate and identified some of the organic mercurials involved in the various stages of the reaction.     

A new synthesis of imidazole derivatives. 1. Synthesis of 2-substituted imidazole-4-alcohols

A New Synthesis of Imidazole Derivatives The 2-substituted imidazole-4-alcohols (3) are obtained from alkyl- or aryl-iminoesters (1) and α-hydroxy-ketones (2) in liquid ammonia under pressure in good yields.     

N-azamonobactams. 1. The synthesis of some 3-substituted N-azamonobactam derivatives

Ring closure of the N-(tert-butyloxycarbonyl)-L-serine 2-(diphenylmethylene)hydrazide (10a) and the corresponding L-threonine derivative (10b) gave good yields of the beta-lactams 11a and 11b. Catalytic hydrogenation afforded the corresponding N-amino beta-lactams 12a and 12b. These compounds were then further transformed into 3-(S)-[[(2-amino-4-thiazolyl)-(Z)-(methoxyimino)acetyl]amino-2-oxo-1- azetidinyl]sulfamic acid analogs 18, 23, and 30a and 30b. None of these compounds exhibited any interesting biological activity.     

2-位取代苯并呋喃类化合物的生物活性及合成研究进展

苯并呋喃衍生物是当前研究杂环芳香族化合物的热点之一。据文献报道该类化合物具有抗肿瘤,抗氧化,钙内流阻滞,血管紧张素II受体拮抗,腺苷A1受体拮抗,抗真菌、抗菌活性和血小板聚集拮抗等药理作用。由于苯并呋喃具有广泛活性,因此吸引很多学者对其进行研究。为了更好地研究该类化合物的合成和生物活性,本文对近几年来文献报道的具有良好生物活性的2-位取代苯并呋喃衍生物进行综述,并对它们的合成方法进行概括,为开发新型2-取代苯并呋喃类化合物提供参考。     

Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity

The synthesis of potential "combined prodrugs" wherein phosphonoformate or phosphonoacetate was attached to the 5'-position of 2'-deoxyuridine, 2'-deoxythymidine, 5-iodo-2'-deoxyuridine (IDU), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), or 5-(2-bromovinyl)-2'-deoxyuridine (BVDU) or to the 3'-position of CEDU is described. The antiviral activities of these derivatives and of reference compounds were compared in Vero, HEp-2, and primary rabbit kidney cells against herpes simplex virus types 1 and 2 (HSV-1 and -2). The CEDU and BVDU analogues were also evaluated against systemic and intracutaneous HSV-1 infection in mice. The nature of the 5-substituent proved critical for antiviral activity, since only the 5-iodo-, 5-(2-bromovinyl)-, and 5-(2-chloroethyl)-substituted derivatives were inhibitory to the herpesviruses. Furthermore, the type specificity is determined by the nature of the 5-substituent: the IDU analogues were similarly inhibitory to HSV-1 and -2 whereas the CEDU and BVDU analogues inhibited HSV-2 replication only at considerably higher concentrations than HSV-1. In vivo, several derivatives were shown to possess significant antiviral activity; however, none surpassed its respective parent compound, CEDU or BVDU, in potency. It seems improbable, therefore, that a synergistic effect between PFA or PAA and the nucleoside analogue occurred. The extent of in vitro and in vivo activity of the CEDU and BVDU 5'-phosphonoformates and 5'-phosphonoacetates is most plausibly explained by the ease by which the "combined prodrugs" are hydrolyzed and the parent compound, CEDU and BVDU, respectively, is released.     

Synthesis of thiourea derivatives

Conclusions Substituted 1,4-thiazane thiocarbamyl derivatives were synthetized.Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 11, pp. 14–16, November, 1968.     

Pyridazinones. 2. Synthesis and antisecretory and antiulcer activities of thiourea and 2-cyanoguanidine derivatives

In an effort to develop new types of antiulcer agents, we synthesized a series of novel 2-[omega-(thioureido)alkyl]- and 2-[omega-(cyanoguanidino)alkyl]-3(2H)-pyridazinone derivatives. All target compounds were evaluated for gastric antisecretory activity in the pylorus-lygated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rats. Structure-activity relationships were established. Two series of the compounds had significant activity in antisecretory and/or antiulcer tests. The molecular features essential for the activities are a thiourea group or a 2-cyanoguanidine group, a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-carbon chain length between the 3(2H)-pyridazinone ring and the functional group, and a methyl group at the N-3 position of the functional group. Among them, the three thiourea derivatives (24, 26, and 38) and the six 2-cyanoguanidine derivatives (61, 62, 65, 75, 85, and 86) had the most potent antisecretory and/or antiulcer activities. These compounds are not histamine H2-receptor antagonists.     

Synthesis of 5-substituted uracil derivatives.

The synthesis of a series of 5-substituted uracil derivatives is described. 5-Bromoacetyluracil (2a) was converted to the glycolyl (2b), glycyl (2c), N,N-dimethylglycyl (2d), 4-imidazolyl (3), and 2-amino-4-thiazolyl (4) derivatives. 5-Formyluracil (5) was used in the preparation of the 2-imidazolyl (6), the 3-acrylic acid (7b), the ester (7a), and the 3-N,N-dimethylacrylamide (8) derivatives. A Mannich reaction converted 5-acetyluracil to the amino ketone 9 which was reduced to give the 3-dimethylamino-1-propanol derivative 10. Compounds 2b,d,3,4,6, and 7b failed to inhibit the growth of Escherichia coli B and Staphylococcus aureus.     

2-substituted 1H-pyrrolo [3,2-h] quinoline derivatives: synthesis and aspects of their biological activity.

Certain 2-substituted 1H-pyrrolo [3,2-h] quinolines have been prepared and their biological activity in mammalian cells and in some microorganisms have been studied. These compounds represent a simplified ellipticine heterocyclic moiety: in addition they have a different ring condensation, leading to an angular molecular structure instead of a linear one. In mammalian cells all compounds appeared to be able of inducing an antiproliferative effect and an extensive DNA fragmentation, similarly to ellipticine, even if to a reduced extent. The new derivatives behaved in a comparable way also on some microorganisms, such as T2 bacteriophage (which appears to be less sensitive than mammalian cells) and in mutagenesis tests carried out with E. coli WP2 TM9 and S. typhimurium TA 98, which are reverted by base substitution and frame-shift mutagens, respectively. Similarly to the reference compound, all ellipticine analogues appeared to be no mutagenic. The obtained results suggest that they induce the antiproliferative activity in mammalian cells mainly as topoisomerase inhibitors, similarly to ellipticine itself. Therefore, they represent an interesting model to design new potential anticancer drugs.     

Potentiation of glucose-induced insulin release by thiourea and thiourea derivatives

Summary The effect of thiourea and its derivatives, including methyl- and propylthiouracil as well as the imidazole derivative thiamazole on glucose-induced insulin secretion from incubated rat pancreatic islets was studied. Additionally, the effect of a single oral dose of propylthiouracil on plasma insulin and glucose tolerance was tested in anaesthetized rats.In the presence of 2.8 mM glucose, neither thiourea nor methylthiouracil, propylthiouracil or thiamazole stimulated the secretion of insulin from pancreatic islets. However, in the presence of 11.1 mM glucose all of the above compounds augmented the insulin-releasing properties of glucose in a concentration-related manner-propylthiouracil being the most potent drug. Propylthiouracil (100 and 200 mg/kg body weight) significantly augmented insulin secretion in vivo in response to i.v. glucose (0.5 g/kg). Accordingly, the rate constant of glucose elimination (K-value) was increased.The data suggest that thiourea-containing chemical compounds sensitize pancreatic islets to the insulin-triggering action of glucose.