Beta-lactamylalkanoic acids for treating premenstrual disorders

1. A method for treating the emotional symptoms of a premenstrual disorder selected from the group consisting of premenstrual dysphoric disorder, premenstrual syndrome, and a combination thereof, the method comprising the step of administering an effective amount of a compound to a patient in need of relief from the disorder, where the compound is of the formula

2(S)-[4-(2-phenylethyl)piperazinyl-carbonylethyl]-2-[3 (S)-(4(S)-phenyloxazolidin-2-on-3-yl)-4(R)-(2-styryl)azetidin-2-on-1-yl]acetic acid N-(3-trifluoromethylbenzyl)amide;

2(R)-[[4-(Piperidinyl)piperidinyl]carbonylmethyl]-2-[3(S)-(4(S)-phenyloxazolidin-2-on-3-yl)-4(R)-(2-styryl)azetidin-2-on-1-yl]acetic acid N-(2-fluoro-3-trifluoromethylbenzyl)carboxamide;

2(R)-[[4-(Piperidinyl)piperidinyl]carbonylmethyl]-2-[3(S)-(4(S)-phenyloxazolidin-2-on-3-yl)-4(R)-(2-styryl)azetidin-2-on-1-yl]acetic acid N—[(R)-α-methylbenzyl]amide;

2(R)-[[4-(Piperidinyl)piperidinyl]carbonylmethyl]-2-[3(S)-(4(S)-phenyloxazolidin-2-on-3-yl)-4(R)-(2-styryl)azetidin-2-on-1-yl]acetic acid N-methyl-N-(3-trifluoromethylbenzyl)amide;

(2S)-[(4-cyclohexylpiperazinyl)carbonylethyl]-2-[3(S)-(4(S)-phenyloxazolidin-2-on-3-yl)-4(R)-(2-phenyleth-1-yl)azetidin-2-on-1-yl]acetic acid N-(3-trifluoromethylbenzyl)amide;

(2S)-(Benzylthiomethyl)-2-[3(S)-(4(S)-phenyloxazolidin-2-on-3-yl)-4(R)-(2styryl)azetidin-2-on-1-yl]acetic acid N-[4-[2-(piperid-1-yl)ethyl]piperidin-1-yl]amide;

where A′ is 4-[2-(piperidinyl)ethyl]piperidinyl;

where A′ is 1-benzylpiperidin-4-ylamino;

where A′ is 4-benzylpiperazinyl, 4-butylpiperazinyl, 4-isopropylpiperazinyl, 4-cyclohexylpiperazinyl, 4-(2-cyclohexylethyl)piperazinyl, 4-[2-(morpholin-4-yl)ethyl]piperazinyl, or 4-(cyclohexylmethyl)piperazinyl;

where A is (3,5-dichlorobenzyl)amino, (2,3-dichlorobenzyl)amino, (2-fluoro-5-trifluoromethylbenzyl)amino, (3-fluoro-5-trifluoromethylbenzyl)amino, (2-fluoro-3-trifluoromethylbenzyl)amino, (2-trifluoromethylbenzyl)amino, (3,5-difluorobenzyl)amino, (3-chlorobenzyl)amino, (3-nitrobenzyl)amino, (3-bromobenzyl)amino, (3-methylbenzyl)amino, N-methyl-N-(3-trifluoromethylbenzyl)amino, [(S)-α-methylbenzyl]amino, [(5-methylfur-2-yl)methyl]amino, (thien-2-ylmethyl)amino, [(S)-1,2,3,4-tetrahydro-1-naphth-1-yl]amino, [(R)-1,2,3,4-tetrahydro-1-naphth-1-yl]amino, (indan-1-yl)amino, (2,5-dimethoxybenzyl)amino, N-methyl-2,3-Cl-benzylamide, (R)-1-(3-trifluorophenyl)ethylamide, 1-phenyl-cyclohexylamide, or indan-2-ylamino;

where A′ is 4-cyclohexylpiperazinyl or 4-n-butylpiperazinyl; or

where A′ is 4-(piperidinyl)piperidinyl, 4-(piperidinylmethyl)piperidinyl, or 4-[2-(piperidinyl)ethyl]piperidinyl;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 wherein the premenstrual disorder is accompanied by primary dysmenorrhea.

4. The method of claim 1 wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

5. The method of claim 2 wherein the premenstrual disorder is premenstrual syndrome.

6. The method of claim 2 wherein the premenstrual disorder is premenstrual dysphoric disorder.

7. The method of claim 4 wherein the premenstrual disorder is premenstrual syndrome.

8. The method of claim 4 wherein the premenstrual disorder is premenstrual dysphoric disorder.