Amide derivatives of 9-oxo-13-trans-prostenoic acid

A racemic compound consisting of enantiomers of the formulae:

• ##STR24## wherein n is an integer from 1 to 2, inclusive;
• Z is a divalent radical selected from the group consisting of those of the formulae:
• ##STR25## wherein m is an integer from 1 to 8, inclusive, p is an integer from 2 to 4, inclusive, q is an integer from 3 to 6, inclusive, and R.sub.4 is an alkyl group having from 1 to 3 carbon atoms, and R.sub.5 is a lower alkyl group, phenyl or fluoro;
• R.sub.1 is selected from the group consisting of a straight chain alkyl group having from 3 to 10 carbon atoms, a straight chain alkyl group having from 3 to 6 carbon atoms and having one branched lower alkyl group, a straight chain alkenyl group having from 3 to 6 carbon atoms, a straight chain .omega.-haloalkyl group having from 3 to 6 carbon atoms, a straight chain .omega.-phenylalkyl group having from 1 to 4 carbon atoms in the chain, a straight chain .omega.-(cycloalkyl)alkyl group having from 1 to 4 carbon atoms in the chain and from 5 to 7 carbon atoms in cycloalkyl, and moieties of the formulae:
• --(CH.sub.2).sub.p --S--R.sub.4
• wherein p and R.sub.4 are as hereinabove defined;
• R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl lower alkyl, and .omega.-hydroxy lower alkyl;
• R.sub.3 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl, trifluoromethylphenyl, di(lower alkyl)aminophenyl, chlorophenyl, lower alkylphenyl, phenyl lower alkyl, .omega.-hydroxy lower alkyl, .omega.-lower alkoxy lower alkyl, .omega.-di(lower alkyl)amino lower alkyl amino and di(lower alkyl)amino;
• and the pharmaceutically acceptable anionic salts thereof when R.sub.3 contains a basic nitrogen atom.

A racemic compound consisting of enantiomers of the formulae:

• ##STR27## wherein n is an integer from 1 to 2, inclusive;
• Z is a divalent radical selected from the group consisting of those of the formulae:
• ##STR28## wherein m is an integer from 1 to 8 inclusive, p is an integer from 2 to 4, inclusive, q is an integer from 3 to 6, inclusive, R.sub.4 is an alkyl group having from 1 to 3 carbon atoms, and R.sub.5 is a lower alkyl group, phenyl or fluoro;
• R.sub.1 is selected from the group consisting of a straight chain alkyl group having from 3 to 10 carbon atoms, a straight chain alkyl group having from 3 to 6 carbon atoms and having one branched lower alkyl group, a straight chain alkenyl group having from 3 to 6 carbon atoms, a straight chain .omega.-haloalkyl group having from 3 to 6 carbon atoms, a straight chain .omega.-phenylalkyl group having from 1 to 4 carbon atoms in the chain, a straight chain .omega.-(cycloalkyl)alkyl group having from 1 to 4 carbon atoms in the chain and from 5 to 7 carbon atoms in cycloalkyl, and moieties of the formulae:
• --(CH.sub.2)p--S--R.sub.4
• wherein p and R.sub.4 are as hereinabove defined;
• R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl lower alkyl and .omega.-hydroxy lower alkyl;
• R.sub.3 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl, trifluoromethylphenyl, di(lower alkyl)aminophenyl, chlorophenyl, lower alkylphenyl, phenyl lower alkyl, .omega.-hydroxy lower alkyl, .omega.-lower alkoxy lower alkyl, .omega.-di(lower alkyl)amino lower alkyl, amino, and di(lower alkyl)-amino;
• and the pharmaceutically acceptable anionic salts thereof when R.sub.3 contains a basic nitrogen atom.

An enantiomer selected from the group consisting of those of the formulae:

• ##STR29## wherein n is an integer from 1 to 2, inclusive;
• Y is a divalent radical selected from the group consisting of those of the formulae:
• ##STR30## Z is a divalent radical selected from the group consisting of those of the formulae:
• ##STR31## wherein m is in integer from 1 to 8, inclusive, p is an integer from 2 to 4, inclusive, q is an integer from 3 to 6 inclusive, and R.sub.4 is an alkyl group having from 1 to 3 carbon atoms, and R.sub.5 is a lower alkyl group, phenyl or fluoro;
• R.sub.1 is selected from the group consisting of a straight chain alkyl group having from 3 to 10 carbon atoms, a straight chain alkyl group having from 3 to 6 carbon atoms and having one branched lower alkyl group, a straight chain alkenyl group having from 3 to 6 carbon atoms, a straight chain .omega.-haloalkyl group having from 3 to 6 carbon atoms, a straight chain .omega.-phenylalkyl group having from 1 to 4 carbon atoms in the chain, a straight chain .omega.-(cycloalkyl)alkyl group having from 1 to 4 carbon atoms in the chain and from 5 to 7 carbon atoms in cycloalkyl, and moieties of the formulae:
• --(CH.sub.2).sub.p --S--R.sub.4
• wherein p and R.sub.4 are as hereinabove defined;
• R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl lower alkyl, and .omega.-hydroxy lower alkyl;
• R.sub.3 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl, trifluoromethylphenyl, di(lower alkyl)aminophenyl, chlorophenyl, lower alkylphenyl, phenyl lower alkyl, .omega.-hydroxy lower alkyl, .omega.-lower alkoxy lower alkyl, .omega.-di(lower alkyl)amino lower alkyl, amino, and di(lower alkyl)amino;
• and the pharmaceutically acceptable anionic salts thereof when R.sub.3 contains a basic nitrogen atom.

An enantiomer selected from the group consisting of those of the formulae:

• ##STR32## wherein n is an integer from 1 to 2, inclusive;
• Z is a divalent radical selected from the group consisting of those of the formulae:
• ##STR33## wherein m is an integer from 1 to 8, inclusive, p is an integer from 2 to 4, inclusive, q is in integer from 3 to 6, inclusive, and R.sub.4 is an alkyl group having from 1 to 3 carbon atoms, and R.sub.5 is a lower alkyl group, phenyl or fluoro;
• R.sub.1 is selected from the group consisting of a straight chain alkyl group having from 3 to 10 carbon atoms, a straight chain alkyl group having from 3 to 6 carbon atoms and having one branched lower alkyl group, a staight chain alkenyl group having from 3 to 6 carbon atoms, a straight chain .omega.-haloalkyl group having from 3 to 6 carbon atoms, a straight chain .omega.-phenylaklyl group having from 1 to 4 carbon atoms in the chain, a straight chain .omega.-(cycloalkyl)alkyl group having from 1 to 4 carbon atoms in the chain and from 5 to 7 carbon atoms in cycloalkyl, and moieties of the formulae:
• --(CH.sub.2).sub.p --S--R.sub.4
• wherein p and R.sub.4 are as hereinabove defined;
• R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl lower alkyl, and .omega.-hydroxy lower alkyl;
• R.sub.3 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl, trifluoromethylphenyl, di(lower alkyl)aminophenyl, chlorophenyl, lower alkylphenyl, phenyl lower alkyl, .omega.-hydroxy lower alkyl, .omega.-lower alkoxy lower alkyl, .omega.-di(lower alkyl)amino lower alkyl, amino, and di(lower alkyl)amino;
• and the pharmaceutically acceptable anionic salts thereof when R.sub.3 contains a basic nitrogen atom.

An enantiomer selected from the group consisting of those of the formulae:

• ##STR34## wherein n is an integer from 1 to 2, inclusive;
• Z is a divalent radical selected from the group consisting of those of th formulae:
• ##STR35## wherein m is an integer from 1 to 8, inclusive, p is an integer from 2 to 4, inclusive, q is an integer from 3 to 6, inclusive, and R.sub.4 is an alkyl group having from 1 to 3 carbon atoms, and R.sub.5 is a lower alkyl group, phenyl or fluorine;
• R.sub.1 is selected from the group consisting of a straight chain alkyl group having from 3 to 10 carbon atoms, a straight chain alkyl group having from 3 to 6 carbon atoms and having one branched lower alkyl group, a straight chain alkenyl group having from 3 to 6 carbon atoms, a straight chain .omega.-haloalkyl roup having from 3 to 6 carbon atoms, a straight chain .omega.-phenylalkyl group having from 1 to 4 carbon atoms in the chain, a straight chain .omega.-(cycloalkyl)alkyl group having from 1 to 4 carbon atoms in the chain and from 5 to 7 carbon atoms in cycloalkyl, and moieties of the formulae:
• --(CH.sub.2).sub.p --S--R.sub.4
• wherein p and R.sub.4 are as hereinabove defined;
• R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl lower alkyl, and .omega.-hydroxy lower alkyl;
• R.sub.3 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclohexyl, phenyl, trifluoromethylphenyl, di(lower alkyl)aminophenyl, chlorophenyl, lower alkylphenyl, phenyl lower alkyl, .omega.-hydroxy lower alkyl, .omega.-lower alkoxy lower alkyl, .omega.-di(lower alkyl)amino lower alky, amino, and di(lower alkyl)amino;
• and the pharmaceutically acceptable anionic salts thereof when R.sub.3 contains a basic nitrogen atom.