89781-82-8

Upstream product

• 85928-58-1 2-(1-imidazolyl)-3,4-dihydro-7-methoxy-1(2H)-naphthalenone 
• 288-32-4 1H-imidazole 
• 66125-08-4 3-bromo-6-methoxy-2,3-dihydro-4H-1-benzopyran-4-one 
• 89781-54-4 2-(1-imidazolyl)-1,2,3,4-tetrahydro-7-methoxy-1-naphthalenol 
• 85928-57-0 2-bromo-7-methoxy-3,4-dihydro-1(2H)-naphthalenone 
• 89781-56-6 1,2-dihydro-3-(1-imidazolyl)-6-methoxynaphthalene 

Relevant academic research and scientific papers

Synthesis and evaluation of azole-substituted tetrahydronaphthalenes as inhibitors of P450 arom, P450 17, and P450 TxA2

In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2-26). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 scc (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone (4) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin (12) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12, the 6-OCH3 derivative (compound 11) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone (13) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin (17) as well as 2-(imidazol-1-ylmethyl)-tetralin (16) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene (25) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests.

N-Imidazolyl derivatives of the naphthalene and chroman rings as thromboxane A2 synthase inhibitors

A series of N-imidazol-1-yl derivatives of 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthalene, 2H-1-benzopyran and some related compounds were synthesized and tested as inhibitors of thromboxane A2 synthase in ex vivo experiments with orally treated rats.Some compounds showed good activity which was confirmed in experiments in vitro in rabbit whole blood.Some structural requirements for significant TxA2 synthase inhibitory activity are discussed.The selected 5,6-dihydro-7-(1H-imidazol-1-yl)-2-naphthalene-carboxylic acid (compound 7) was conformationally analysed using the Sybyl molecular model system in comparison with dazoxiben.Compound 7 was further pharmacologically investigated and on the basis of its interesting activities in vitro, ex vivo and in vivo and its low toxicity was selected for clinical investigation.

N-Imidazolyl derivatives containing naphthalene or indene nucleus

Compounds of the formula (I) STR1 wherein the symbol represents a single or a double bond; Z completes a single bond or is a --CH2 -- group; each of R1, R2, R3 and R4, which may be the same or different is (a) hydrogen; hydroxy; halogen; cyano; C1 -C6 alkyl; C1 -C6 alkoxy; a C2 -C4 acyl or C2 -C4 acylamino group; --SR', --N(R') (R"), --CH2 OR', --COR or --CH2 COR, wherein R is OR' or --N(R') (R") and each of R' and R", being the same or different, is hydrogen or C1 -C6 alkyl; or (b) one of R1, R2, R3 and R4 is 5- tetrazolyl or a group selected from --COCH2 OR', --CH=C(R')-COR and --X-C(R') (R")-COR, wherein R, R' and R" are as defined above, and X is --O--, --S--, or --NH--, and the others are as defined above under (a); one of R5 and R6 is hydrogen and the other is hydrogen, C1 -C6 alkyl, C3 -C6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C1 -C4 alkoxy; or pharmaceutically acceptable salts thereof exhibit pharmaceutical activity as vasodilators or blood platelet aggregation inhibitors. Additionally, these compounds and their pharmaceutically acceptable salts are useful in the treatment of migraine, diabetic microangeopathy, rheumatoid arthritis, hypertension, peptic ulcers, osteoporosis, angina pectoris, atherosclerosis and dislipidaemies.