Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Patent
1995-03-06
1997-11-04
Bernhardt, Emily
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
544232, 544235, 544238, 544239, C07D23704, C07D40904, C07D23726
Patent
active
056841515
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The invention relates to novel 1-phenylsulphonyl, phenylcarbonyl and 1-phenylphosphenyl-3-phenyl-1,4,5,6-tetrahydropyridazine compounds, and to novel methods for preparing the compounds. The novel compounds are useful as contraceptives and in the treatment of osteoporosis. The invention further relates to pharmaceutical compositions in which a compound of the present invention is the active ingredient.
BACKGROUND OF THE INVENTION
The unacylated 3-phenyl-1,4,5,6-tetrahydropyridazine, A, is described by J.-L. Aubagnac et al., Bull. Chem. Soc. France, 7, 2868, (1972). A number of 1-acylated derivatives of 1 are also disclosed. ##STR2##
W. Jones et al., J. Het. Chem., 21, 889 (1984) disclose that the thiocarbamoylation of A with methyl isothiocyanate produces the corresponding thiocarbamide derivative, B. No biological activity is disclosed. ##STR3##
S. J. Clarke et al., J. Chem. Research, (S) 310 (1985) disclose carbamate, carbamide and para-toulene sulfonamide derivatives of A. (sulfonamide derivative is C), which are prepared via cycloaddition reactions. Again, no biological activity is disclosed.
______________________________________ ##STR4##
R.sup.1 R.sup.3
R.sup.4 R.sup.5
R.sup.6
______________________________________
H H H OEt H
H H Me OEt H
H Me H OEt H
H H H OMe Me
NO.sub.2 H H OEt H
NO.sub.2 H H OMe Me
Br H H OEt H
Br H Me OEt H
Br Me H OEt H
Br H H OMe Me
______________________________________
R. Faragher et al., in J. Chem. Soc. Perkin Trans, I, 249 (1979), disclose para-toulene sulfonamide and carbamate derivatives of A, (sulfonamide derivative is 4) which compounds are also prepared by cycloaddition reactions. As above, no biological activity is disclosed. ##STR5##
Kalyanam et al., Synthetic Communications, 18 (16 & 17), (1988) disclose compounds of the formula: ##STR6## wherein n is 1 or 2, as being antiamoebics.
SUMMARY OF THE INVENTION
Briefly, according to the present invention, there are provided preferred progestin agonists of the general formula: ##STR7## W is absent or --CH.dbd.CH--; R.sup.1 are independently selected from the group consisting of halogen, --CF.sub.3, and NO.sub.2, or both R.sup.1 may be joined to form a bi-radical which is --CH.dbd.CHCH.dbd.CH--; C.sub.1-6 branched or linear alkyl, halogen and --CF.sub.3, with the proviso that R.sup.3 at the 3-position must be H where R.sup.3 at the 4-position is H, or both R.sup.3 may be joined to form a bi-radical selected from the group consisting of --CH.dbd.CHCH.dbd.CH--, --C(NC.sub.1-4 alkyl.sub.2)=CHCH.dbd.CH-- and --(CH.sub.2).sub.4 --; bi-radical; and the stereoisomers.
Also provided by the present invention are preferred progestin antagonists of the general formula: ##STR8## W is absent or --CH.dbd.CH--; R.sup.1 is selected from the group consisting of halogen, --CF.sub.3 and --NO.sub.2, or both R.sup.1 may be joined to form a bi-radical which is --CH.dbd.CHCH.dbd.CH--; alkoxy, carboxy C.sub.1-4 alkyl and C.sub.1-4 alkoxy carbonyl C.sub.1-4 alkoxy with the proviso that R.sup.3 at the 2-position is not hydrogen, or R.sup.3 may be joined to form a bi-radical which is --CH.dbd.CHCH.dbd.CH-- attached at the 2- and 3-positions; proviso that each may be halogen where R.sup.3 is selected only from halogen; alternatively, R.sup.5 may be joined with the 6-position hydrogen to form a bi-radical which is (5)-CH.sub.2 CH.dbd.CH-(6); fused bi-radical; and the steroisomers and pharmaceutically acceptable salts and esters thereof.
Also provided by the present invention are preferred compounds useful to promote bone cell gowth, said compounds having the general formula: ##STR9## Y is O or S; R.sup.3 is hydrogen or halogen with the proviso that at least two R.sup.3 are halogen;
4. DETAILED DESCRIPTION OF THE INVENTION
The compounds of the present invention may be manufactured in what is basically a two step process. In the first step and as demonstrated in schemes 1 and 2, a 3-phenyl-1,4,5,6-tetrahydropyridazine intermediate is formed. In the second step and as demonstrated in s
REFERENCES:
Clark et al, Chemical Abstracts, vol. 104, No. 109560 (1986).
Faragher et al, J. Chem. Soc. Perkin Trans. 1, p. 249 (1979).
Hishmat et al, Arzheim.-Forsch/Drug Res. 35, pp. 784-786 (1985).
Shabarov et al, Chemical Abstracts, vol. 54, No. 14260b (1960).
Bernhardt Emily
Ortho Pharmaceutical Corporation
LandOfFree
1-arylsulphonyl, arylcarbonyl and 1-arylphosphonyl-3-phenyl-1,4, does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 1-arylsulphonyl, arylcarbonyl and 1-arylphosphonyl-3-phenyl-1,4,, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 1-arylsulphonyl, arylcarbonyl and 1-arylphosphonyl-3-phenyl-1,4, will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1834175