| 摘要 |
The present invention is concerned with novel antifungal 5,6-dihydro-4H-pyrrolo-[1,2-a][1,4]benzodiazepines and 6H-pyrrolo[1,2-a][1,4]benzodiazepines substituted with heterocyclic derivatives of Formula (I);
wherein R1, R2, R3, R4 and Het have the meaning defined in the claims. The compounds according to the present invention are active mainly against dermatophytes and systemic fungal infections. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament. |
| 主权项 |
1. A compound of formula (I) or a stereoisomeric form thereof, wherein, R1 is hydrogen, halo, C1-4alkyl or C1-4alkyloxy; R2 is hydrogen, halo, C1-4alkyl or C1-4alkyloxy; R3 and R4 are hydrogen; or R3 and R4 taken together form a bond; Het is a monocyclic or bicyclic heterocyclic radical selected from(d-1) and (d-2) are attached to the remainder of the molecule with a bond in position a, b or c;
(d-4), (d-6), (d-7), (d-10) and (d-12) are attached to the remainder of the molecule with a bond in position a or b; X1 is O, S or NH; X2 is O or S; X3, X4 and X5 each independently are CH or N; provided that exactly two of X3, X4 and X5 are N, the other being CH; X6, X7, X8 and X9 each independently are CH or N; provided that one or two of X6, X7, X8 and X9 are N, the other being CH; X10, X11, X12 and X13 each independently are CH or N; provided that maximum one of X10, X11, X12 and X13 is N, the other being CH; X14 is CH or N; X15 is O or S; X16 is CH or N; X17 is CH or N; X18 is NH, S or O; X19 is CH or N; X20 is NH or S; R5 and R6 taken together form a bivalent radical —R5-R6—, having formula:
—(CH2)m—O—(CH2)n-m— (a),—(CH2)n-m—O—(CH2)m— (b), or—(CH2)s— (c); wherein the bivalent radical —R5-R6— may, where possible, be substituted with one or more substituents selected from the group consisting of halo, C1-4alkyl, hydroxyl, C1-4alkyloxy and oxo; m represents 0, 1 or 2; n represents 2, 3 or 4; s represents 3, 4 or 5; wherein radicals (d-1)-(d-11) may be substituted with one or more substituents each independently selected from the group consisting of C1-4alkyloxy, halo, C1-4alkylcarbonyl, C1-4alkylthio, C1-4alkylsulphonyl, C1-4alkylsulphinyl, and C1-4alkyl optionally substituted with one or more halo substituents; provided that radicals (d-1)-(d-11) are not substituted in the α-positions to the carbon atom of attachment; or a pharmaceutically acceptable addition salt or a solvate thereof; provided that the compound is not 5,6-dihydro-4-(2-pyridinyl)-4H-pyrrolo[1,2-a][1,4]benzodiazepine or a salt thereof, or 5,6-dihydro-4-(3-pyridinyl)-4H-pyrrolo[1,2-a][1,4]benzodiazepine or a salt thereof. |
