Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1989-07-25
1994-12-27
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514418, 514183, 540456, A61K 31395, A61K 31445, C07D49816
Patent
active
053766636
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel compounds, methods for their preparation, their use as medicaments, and compositions containing them.
European Patent Application 0184162 (to Fujisawa Pharmaceuticals Co. Ltd.) discloses a number of macrolides isolated from microorganisms belonging to the genus Streptomyces. The macrolides are numbered FR-900506, FR-900520, FR-900523 and FR-900525, and may be used as starting materials to produce the compounds of the present invention.
According to the invention, we provide compounds of formula I, ##STR2## wherein each vicinal pair of substituents [R.sup.1 and R.sup.2 ], [R.sup.3 and R.sup.4 ], [R.sup.5 and R.sup.6 ] independently attached;
in addition to its significance above, R.sup.2 may represent an alkyl group;
R.sup.7 represents H, OH or O-alkyl, or in conjunction with R.sup.1 it may represent .dbd.O,
R.sup.8 and R.sup.9 independently represent H or OH;
R.sup.10 represents H, alkyl, alkyl substituted by one or more hydroxyl groups, alkenyl, alkenyl substituted by one or more hydroxyl groups, or alkyl substituted by .dbd.O;
X represents O, (H,OH) (H,H) or --CH.sub.2 O--;
Y represents O, (H,OH), (H,H), N--NR.sup.11 R.sup.12 or N--OR.sup.13 ;
R.sup.11 and R.sup.12 independently represent H, alkyl, aryl or tosyl;
R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.22 and R.sup.23 independently represent H or alkyl;
R.sup.20 and R.sup.21 independently represent O, or they may independently represent (R.sup.20 a,H) and (R.sup.21 a,H) respectively; R.sup.20 a and R.sup.21 a independently represent OH, O-alkyl or OCH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3,
in addition, R.sup.20 a and R.sup.21 a may together represent an oxygen atom in an epoxide ring;
n is 1, 2 or 3;
in addition to their significances above, Y, R.sup.10 and R.sup.23, together with the carbon atoms to which they are attached, may represent a 5- or 6-membered N-, S- or O- containing heterocyclic ring, which may be saturated or unsaturated, and which may be substituted by one or more groups selected from alkyl, hydroxyl, alkyl substituted by one or more hydroxyl groups, O-alkyl, benzyl and --CH.sub.2 Se(C.sub.6 H.sub.5);
provided that when X and Y both represent O; R.sup.9 represents OH; R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.22 each represent methyl; R.sup.20 a represents OCH.sub.3 ; R.sup.8 and R.sup.23 each represent H; R.sup.21 a represents OH; [R.sup.3 and R.sup.4 ] and [R.sup.5 and R.sup.6 ] each represent a carbon-carbon bond, and represent hydrogen, then R.sup.10 does not represent an allyl group, hydrogen, then R.sup.10 does not represent methyl, ethyl, propyl or allyl, and represents a carbon-carbon bond, then R.sup.10 does not represent an allyl group;
and pharmaceutically acceptable salts thereof.
Pharmaceutically acceptable salts of the compounds of formula I include acid addition salts of any amine groups present.
Preferably when R.sup.2, R.sup.7, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.20 a, R.sup.21 a, R.sup.22 and R.sup.23 comprise carbon-containing groups, those groups contain up to 10 carbon atoms, more preferably from 1 to 6, e.g. methyl or methoxyl.
We prefer each of R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.22 to represent methyl.
Alkyl groups which R.sup.2, R.sup.7, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.20 a, R.sup.21 a, R.sup.22 and R.sup.23 may comprise include straight chain, branched and cyclic groups.
Alkyl groups substituted by .dbd.O which R.sup.10 may represent include ketone and aldehyde groups.
Preferably, R.sup.10 is allyl (i.e. prop-2-enyl), propyl, ethyl or methyl.
Preferably, n is 2.
We prefer R.sup.7 to be H or OH.
Preferably, R.sup.1 and R.sup.2 both represent H.
X is preferably O or (H,OH).
We prefer R.sup.20 a and R.sup.21 a to (independently) represent OH or OCH.sub.3.
When Y, R.sup.10 and R.sup.23 together represent a N-, S- or O- containing heterocyclic ring, we prefer tha
REFERENCES:
patent: 4668669 (1987-05-01), Barriere et al.
patent: 4894366 (1990-01-01), Okuhara et al.
patent: 4981792 (1991-01-01), Inamine et al.
Morrison and Boyd, Organic Chemistry (Boston, Allyn and Bacon, 1979) pp. 556 to 558.
Williams et al JACS 1981 103 7398-7399.
Casepio, et al JACS 1958 80 2584-2585.
Chang, et al JACS 1960 82 1401-5.
Morrison and Boyd, Organic Chemistry (Allyn and Bacon, 1979, Boston) pp. 639 to 640.
Cooper Martin E.
Donald David K.
Hardern David N.
Bond Robert T.
Fisons plc
LandOfFree
Macrocyclic compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Macrocyclic compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Macrocyclic compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-919955