IP Library Granted Patent US 8,871,776
Granted Patent B2
US 8,871,776 · App. 13/648,494 · Granted Oct 28, 2014

Tricyclic compounds having cytostatic and/or cytotoxic activity and methods of use thereof

Inventor: Aleem Gangjee (Allison Park, PA)
Assignee: Duquesne University of the Holy Ghost
C07D487/04C07D239/70
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Quick Facts
Patent No.
US 8,871,776
App. No.
13/648,494
Granted
Oct 28, 2014
Kind
B2
Abstract

The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders.

Claims (11)

1. A compound of formula I:

wherein both B and C rings may be completely or partially saturated or unsaturated with respect to bond 4b-8a, 5-6 and 7-8; the C ring may have an N or substituted N depending on the saturation level of the C ring, and the substitution may be all of R 1 , R 2 and R 3 ;

X and Y=NH; P=NH;

R 1 =H; and R 2 =H;

Z=S;

wherein Z may be attached to the C ring at positions 5, 6, 7 or 8 and may be attached to more than one of said positions 5, 6, 7, or 8 on the ring;

wherein when the C-ring is saturated or partially saturated the Z or R 3 creates chirality, then all stereoisomers thereof both separately and as racemic and/or diastereoisomeric mixtures are included;

R 3 =aryl, alkylaryl, and substituted saturated or unsaturated alkylaryl wherein said substitution may be at either the alkyl or the aryl portion of the alkylaryl group and may be one or more substituents independently selected from (i) an alkoxy group, (ii) halogen atoms including chlorine, bromine, iodine, and fluorine, (iii) alkyl groups including straight or branched chains having from one to six carbon atoms, (iv) an aryl group, (v) a heteroaryl group having at least one atom in the aryl ring that is not carbon selected from oxygen, nitrogen or sulfur, and (vi) a carboxylic acid having up to seven carbon atoms.

2. The compound according to claim 1 , wherein Y=NH; R 2 =H; P=NR 4 ; R 4 =H; X=NH; R 1 =H; Z=S and R 3 ≡a phenyl.

3. The compound according to claim 1 , wherein Y=NH; R 2 =H; P=NR 4 ; R 4 =H; X=NH; R 1 =H; Z=S; and R 3 =a phenyl having a methyl substitution.

4. The compound according to claim 3 , wherein the substitution on the phenyl is at the 4 position of the phenyl ring.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2014
From: GANGJEE, ALEEM
To: DUQUESNE UNIVERSITY OF THE HOLY GHOST
Reel/Frame 033465/0526 →
Continuity (3)
Division 13098701 · May 2, 2011
Division 11845143 · Aug 27, 2007
Related Publication 20130102623A1 · Apr 25, 2013