Carcinogenicity and nephrotoxicity of 2-amino-, 1-amino- 2-methyl-, and 2-methyl-1-nitro-anthraquinone

2-Aminoanthraquinone (AA), l-amino-2-methylanthraquinone (l-Am-2-MeA), and 2-methyl-l-nitroanthraquinone (2-Me-1-Na) were tested for carcinogenicity in Fischer 344 rats and B6C3F₁ mice. In rats, all the 3 chemicals increased the incidence of hepatocellular neoplasms. Renal neoplasms were increased with 1-Am-2-MeA, and 2-Me-1-NA increased the incidence of subcutaneous fibromas in a dose-related manner. In mice, incidences of hepatocellular carcinomas were increased with feeding of AA, and 2-Me-l-NA increased the incidence of subcutaneous hemangiosarcomas. 1-Am-2-MeA did not appear to be carcinogenic in the mouse. Nephrotoxicity was associated with feeding of AA to female rats and 1-Am-2-MeA to mice.     

放射病预防药物的研究——Ⅱ.2-苯基和2-对氯苯基硫代吗啉及其取代胺类化合物的合成

本文介绍由α-溴代苯乙酸乙酯经五步反应合成了4-(N,N-取代氨基烷基)-2-苯基(或对氯苯基)-硫代吗咻Ⅲ,它与有较好辐射防护效果的药物氯丙嗪及对氯苯乙胺结构有相似之处。经药理试验结果,化合物Ⅲ_d。在Ⅹ-射线600伦照射后,对小白鼠的急性放射病有一定防护效果。     

Synthesis and antiradiation activity of 2-amino-4-oxo-5-amino-methyl(ethyl)thiazolines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 23, No. 7, pp. 832–834, July, 1989.     

S-2,omega-Diaminoalkyl dihydrogen phosphorothioates as antiradiation agents.

To enable further structure-activity comparisons among radioprotective phosphorothioates, S-2,omega-diaminoalkyl dihydrogen phosphorothioates were synthesized from L-2,4-diaminobutyric acid, L-ornithine, L-lysine, and DL-2,7-diaminoheptanoic acid as homologues of S-2,3-diaminopropyl dihydrogen phosphorothioate (4) and as isomeric analogues of S-2-[(omega-aminoalkyl)amino]ethyl dihydrogen phosphorothioates (e.g., 1). The preferred route that evolved from exploratory trials retained optical activity and involved the reduction of methyl 2,omega-bis(benzoylamino)alkanoates with lithium borohydride, debenzoylation-bromodehydroxylation, and reaction of the resulting 1-(bromomethyl)-1,omega-alkanediamine dihydrobromides with trisodium phosphorothioate. The products of an alternative route that involved the reduction of phthaloylated intermediates with sodium borohydride were racemic. Exploratory conversions of N-(omega-alkenyl)phthalimides failed to provide suitable precursors of the target compounds. In terms of a protective index, these homologues were significantly more radioprotective than the parent phosphorothioate 4 when administered intraperitoneally to mice prior to whole-body gamma irradiation. The homologues derived from L-lysine also showed good peroral activity. No apparent difference was observed in the protection afforded by optically active homologues and the corresponding racemates.     

2-Amino-2-oxazolines, V: Synthesis of some 5-dialkylaminomethyl-2-amino-2-oxazolines and evaluation of their diuretic activity.

A series of 5-dialkylaminomethyl-2-amino-2-oxazolines was prepared and screened for diuretic activity. These compounds were previously examined for their lipophilic behaviour using a reversed-phase HPLC technique. The capacity factors, expressed as log k'w, were correlated with the partition coefficient log P. A QSAR analysis of the diuretic activity in relation with the lipophilicity was attempted for these structurally related compounds.     

Potential anti-AIDS drugs. 2',3'-Dideoxycytidine analogues

5-Substituted 2',3'-dideoxycytidine analogues have been synthesized and evaluated in vitro for their capabilities to protect T4+ lymphocytes from the cytopathic effects of the HTLV-III/LAV (HIV) virus, the causative agent of acquired immunodeficiency syndrome (AIDS). These analogues were designed to be more lipophilic than 2',3'-dideoxycytidine (ddC) in order to enhance central nervous system penetration. Earlier reports had shown that ddC is a potent protective agent. When ddC is substituted at the 5-position with either methyl or bromo substituents, activity is completely abolished. However, when the substitution is fluoro (5-F-ddC), both activity and potency are retained. 2',3'-Dideoxy-5-azacytidine is also protective but more toxic than ddC or 5-F-ddC. In a different approach, an attempt was made to utilize ddCMP, ddTMP, and ddAMP as preformed nucleotides in order to circumvent the generally low level of phosphorylation achieved with dideoxynucleosides which function as relatively poor substrates for the cellular kinases. Only ddAMP is as active as its nucleoside precursor. Because ddAMP is not more active than ddA at low concentrations, it is possible that the active agent is ddA which is generated from ddAMP prior to cell entry.     

Umsetzung von 2-Amino-2-cycloalken-1-on-Derivaten mit p-Benzochinonen, 3. Mitteilung

Reaction of 2-Amino-2-cycloalken-1-one Derivatives with p-Benzoquinones, III Reaction of 1 with 2a yields the spirocyclic benzoxazine 3a , by-product is a 2,3-bisadduct 4 . Quinone 6 is isolated from the reaction of 1b , with 2b. 8 and 9a react to yield the benzofurane 11 , which is acetylated to the hydroquinone derivative 14 and transformed to 13 , respectively. Reaction of 8 with 9b yields 7a. 16a,b are obtained from 8 or 1 with 15. 16a is acetylated to 16c and split into 17a .