Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-08-29
1996-02-06
Ford, John M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142278, 5142322, 5142362, 544198, 544113, 544 60, 544 83, A61K 3153, C07D40304, C07D40314, C07D41304
Patent
active
054895910
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to s-triazine derivatives represented by the formula (I) or pharmaceutically acceptable acid addition salts thereof and remedies for estrogen-dependent diseases containing the derivatives as effective components: ##STR1## wherein (1) when R.sub.1 and R.sub.2 are respectively independent and/or R.sub.3 and R.sub.4 are respectively independent, substituted with halogen atom, nitro or amino except for the case where all of R.sub.1. R.sub.2. R.sub.3 and R.sub.4 are methyl and coupled with neighboring nitrogen atom to form cyclic amino group, NR.sub.1 R.sub.2 represents 1-pyrrolidinyl; piperidino which may be substituted with phenyl; 1-piperazinyl which may be substituted with lower alkyl or phenyl; morpholino; or thiomorpholino, lower alkyl; 1-pyrrolidinyl which may be substituted with lower alkoxycarbonyl; piperidino which may be mono- or di-substituted with hydroxy, hydroxy lower alkyl, lower alkoxycarbonyl, lower alkyl, cyano, phenyl or ethylenedioxy; 1-piperazinyl which may be substituted with lower alkyl, benzyl, phenyl which in turn may be substituted with halogen atom, nitro or amino, pyridyl or pyrimidinyll morpholino which may be mono- or di-substituted with lower alkyl; 3-thiazolidinyl; thiomorpholino; 1-imidazolyl which may be mono- or di-substituted with lower alkyl; or 1,2,4-triazole-1-yl.
BACKGROUND ART
s-Triazine (1,3,5-triazine) derivatives have been researched in the fields of synthetic resins, synthetic fibers and agricultural chemicals and a number of such compounds have been synthesized. In the field of pharmaceuticals, researches have been made with respect to antitumor, anti-inflammatory, analgesic and antispasmodic activities. Especially, hexamethylmelamine (HMM) is well-known, which has been developed as analogue of antitumor agent triethylenemelamine (TEM) [B. L. Johnson et al. Cancer, 42:2157-2161 (1978)].
TEM is known as an alkylating agent and is an s-triazine derivative having cytotoxic antitumor activity. HMM has been marketed in Europe under the indications for the treatment of ovarian and small cell lung cancers, and its action on solid cancers has been attractive.
As to its antitumor spectrum and antitumor activity against solid cancers, however, there has been still room for improvement.
DISCLOSURE OF THE INVENTION
The inventors modified s-triazine for the purposes of expanding antitumor spectrum and enhancing antitumor activity of HMM to have surprisedly found out that the compounds represented by the formula (I) exhibit selective aromatase inhibitory activity which has never been reported with respect to conventional s-triazine derivatives, and in addition exhibit cytotoxic antitumor activities comparable to HMM, thus completing the present invention.
The aromatase inhibitory activity is an inhibition of enzymatic conversion from androgens to estrogens in the body. The compounds (I) of the present invention having such inhibitory activity are effective for the treatment of estrogen-dependent diseases such as endometriosis, multicystic ovarium, mastadenoma, endomatrioma and breast cancer.
The terms used for definition of letters in the formula (I) by which the compounds of the present invention are represented are defined and exemplified in the following.
The wording "lower" refers to a group having 1 to 6 carbon atoms unless otherwise indicated.
The "lower alkyl" refers to a straight- or branched-chain alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl or the like.
The "lower alkoxy" refers to a straight- or branched-chain alkoxy group such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy or the like.
The "halogen atom" may be fluorine, chlorine, bromine or iodine atom.
The compounds according to the present invention are for example as follows: ne e e e 5-triazine iazine azine azine azine ne ne 1,3,5-triazine azine iazine
The compounds of the present invention may have asymmetric carbon atoms in their structures. It is to be understood th
Fukuda Seiichi
Izumisawa Yasuhiro
Kato Masanobu
Kobayashi Hideshi
Komatsu Toshihiko
Ford John M.
Zenyaku Kogyo Kabushiki Kaisha
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