Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – 3,10-dihydroxy-2-naphthacene carboxamide or derivative doai
Patent
1996-07-22
1998-11-10
Lambkin, Deborah C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
3,10-dihydroxy-2-naphthacene carboxamide or derivative doai
514445, 552204, 552205, 549 65, A01N 3718, C07C23726
Patent
active
058344500
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/IB95/00026 filed Jan. 12, 1995.
This invention relates to novel doxycline analogs that exhibit antibiotic activity against a wide range of gram-positive and gram-negative organisms, including organisms that are resistant to tetracycline antiobiotics.
Doxycycline (.alpha.-6-deoxy-5-oxytetracycline) and other 6-deoxytetracyclines are referred to in articles by Stephens et al., J. Amer. Chem. Soc., 85, 2643-2652 (Sep. 5, 1963) and Petisi et al., J. Med. Pharm. Chem., 5 538 (1962). They are also referred to in U.S. Pat. No. 3,200,149, which issued on Aug. 10, 1965.
European Patent Application 536515A1, which was published on Apr. 14, 1993, refers to 7-substituted-9-(substituted amino)6-demethyl-6-deoxytetracycline compounds that exhibit activity against a wide spectrum of organisms including organisms that are resistant to tetracyclines. This application and the foregoing references are incorporated herein by reference in their entireties.
SUMMARY OF THE INVENTION
This invention relates to compounds of the formula ##STR2## wherein R.sup.1 is hydrogen or --CH.sub.2 NR.sup.5 R.sup.6 ;
R.sup.2 is hydrogen or R.sup.4 (CH.sub.2).sub.n CO--;
n is an integer from 0 to 4;
R.sup.3 is R.sup.8 (CH.sub.2).sub.m CO-- or R.sup.8 (CH.sub.2).sub.m SO.sub.2 --;
m is an integer from 0 to 4;
and when n is 0, then either:
(a) R.sup.4 is selected from hydrogen; amino; monosubstituted amino selected from straight or branched (C.sub.1 -C.sub.6)alkylamino, cyclopropylamino, cyclobutylamino, benzylamino and phenylamino; disubstituted amino selected from dimethylamino, diethylamino, ethyl(1-methylethyl)amino, monomethylbenzylamino, piperidinyl, morpholinyl, 1-imidazolyl, 1-pyrrolyl, 1-(1,2,3-triazolyl) and 4-(1,2,4-triazolyl); straight or branched (C.sub.1 -C.sub.4)alkyl selected from methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl and 1,1-dimethylethyl; (C.sub.3 -C.sub.6)cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; substituted (C.sub.3 -C.sub.6)cycloalkyl (substitution selected from (C.sub.1 -C.sub.3)alkyl, cyano, amino and (C.sub.1 -C.sub.3)acyl); (C.sub.6 -C.sub.10)aryl selected from phenyl, .alpha.-naphthyl and .beta.-naphthyl; substituted (C.sub.6 -C.sub.10)aryl (substitution selected from halo, (C.sub.1 -C.sub.4)alkoxy, trihalo(C.sub.1 -C.sub.3)alkyl, nitro, amino, cyano, (C.sub.1 -C.sub.4)alkoxycarbonyl, (C.sub.1 -C.sub.3)alkylamino and carboxy); (C.sub.7 -C.sub.9)aralkyl selected from benzyl, 1-phenylethyl, 2-phenylethyl and phenylpropyl; .alpha.-amino-(C.sub.1 -C.sub.4)alkyl selected from aminomethyl, .alpha.-aminoethyl, .alpha.-aminopropyl and .alpha.-aminobutyl; carboxy(C.sub.2 -C.sub.4)-alkylamino selected from aminoacetic acid, .alpha.-aminobutyric acid and .alpha.-aminopropionic acid and their optical isomers; (C.sub.7 -C.sub.9)aralkylamino (e.g., phenylglycyl); (C.sub.1 -C.sub.4)alkoxycarbonylamino substituted (C.sub.1 -C.sub.4)alkyl, substitution selected from phenyl and p-hydroxyphenyl; .alpha.-hydroxy(C.sub.1 -C.sub.3)alkyl selected from hydroxymethyl, .alpha.-hydroxyethyl, .alpha.-hydroxy-1-methylethyl and .alpha.-hydroxypropyl; .alpha.-mercaptopropyl; and halo-(C.sub.1 -C.sub.3)alkyl; or
(b) R.sup.4 is selected from Q.sup.1, Q.sup.2 and Q.sup.3, wherein Q.sup.1 is a five membered aromatic or saturated ring containing one N, O, S or Se heteroatom optionally having a benzo or pyrido ring fused thereto (e.g., ##STR3## wherein Z is N, O, S or Se);
Q.sup.2 is a five membered aromatic ring containing two heteroatoms independently selected from N, O, S and Se and optionally having a benzo or pyrido ring fused hereto (e.g., ##STR4## wherein Z and Z.sup.1 are independently selected from N, O, S and Se); and
Q.sup.3 is a five membered saturated ring containing one or two heteroatoms independently selected from N, O, S and Se and an adjacent appended O heteroatom (for example, ##STR5## wherein A is selected from hydrogen; straight or branched (C.sub.1 -C.sub.4)alkyl; C.sub.6 -aryl; substituted C.sub.6 -aryl (substitution select
REFERENCES:
patent: 5371076 (1994-12-01), Lee et al.
Appleman Jolene W.
Ginsburg P. H.
Lambkin Deborah C.
Pfizer Inc.
Richardson P. C.
LandOfFree
9- (substituted amino) -alpha-6-deoxy-5-oxy tetracycline derivat does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 9- (substituted amino) -alpha-6-deoxy-5-oxy tetracycline derivat, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 9- (substituted amino) -alpha-6-deoxy-5-oxy tetracycline derivat will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1516854