Theophylline and 3-isobutyl-1 methylxanthine based N-7 substituted derivatives displaying inhibitory activities on PDE-5 phospodiesterase
View Patent ↗A variety of N-substituted derivatives are based upon the base chemicals of that provide for the induction of cavernosal relaxation in animals. R2 is a derivative based on a hetroaromatic group, an aromatic group or a cyclohexane.
1. A compound containing the theophylline moiety of formula II
wherein R 1 is —(CH 2 )cCH 3 ; R 2 is a member of the group selected from the group consisting of:
wherein
R 4 is a member selected from the group consisting of H, —(CH 2 ) n CH 3 , X, —NH 2 , and —NO 2 , wherein X
is selected from the group consisting of F, Cl, Br, and I,
c is an integer from 0 to 3;
n is an integer from 0 to 3;
R 5 is a member selected from H, and the group consisting of
wherein R 3 is a member selected from the group consisting of halogen, hydroxyl group, a saturated straight chain alkyl group of 1-3 carbon atoms and a hydrogen atom.
2. A process for the preparation of a compound of formula II according to claim 1 which comprises steps of (a) reacting of a compound of formula III
with 1,2-di-bromoethane to produce a monobromo compound of formula IV,
and (b) reacting said monobromo compound of formula IV with a N-substituted piperazine of formula piperazinyl-R2 to produce a compound of formula II.
3. A process for the preparation of a compound of formula II according to claim 1 which comprises steps of(a) reacting of a compound of formula III,
with 1,2-di-bromoethane to produce a monobromo compound of formula IV,
and (b) reacting said monobromo compound of formula IV with piperazine to produce a compound of formula V wherein the N is not substituted,
and (c) reacting said compound of formula V with a compound of formula R2-X to produce a compound of the following formula II:
wherein R 1 is —(CH 2 )cCH 3 ; R 2 is a member of the group selected from the group consisting of:
wherein
R 4 is a member selected from the group consisting of H, —(CH 2 ) n CH 3 , X, —NH 2 , and —NO 2 , wherein X
is selected from the group consisting of F, Cl, Br, and I,
c is an integer from 0 to 3;
n is an integer from 0 to 3;
R 5 is a member selected from H, and the group consisting of:
wherein R 3 is a member selected from the group consisting of halogen, hydroxyl group, a saturated straight chain alkyl group of 1-3 carbon atoms and a hydrogen atom.
4. The process of claim 2 wherein R 3 is H, and n is between 1 and 3.
5. A pharmaceutical composition which has corpus cavernosal relaxation activity containing a compound defined in claim 1 together with a carrier.
6. The compound of claim 1 wherein R 3 is H, and n is between 1 and 3.
7. The process of claim 3 wherein R 3 is H, and n is between 1 and 3.