Claims for Patent: 9,090,633

Summary for Patent: 9,090,633

Title:	Substituted 4-(arylamino) selenophenopyrimidine compounds and methods of use thereof
Abstract:	The invention discloses 4-(arylamino)selenophenopyrimidine derivatives of formula (I), hydrates, solvates, isomers, or pharmaceutically acceptable salts thereof; process for their preparation and methods of treating or inhibiting or controlling a cell proliferative disorders, particularly cancer using said compounds. Pharmaceutical compositions comprising 4-(arylamino)selenophenopyrimidine derivatives of formula (I) are useful for the treatment, inhibition, or control of cancer. ##STR00001##
Inventor(s):	Kasina; Sudhakar (Mercer Island, WA), Gokaraju; Ganga Raju (Vijayawada, IN), Somepalli; Venkateswarlu (Vijayawada, IN), Gokaraju; Rama Raju (Vijayawada, IN), Gokaraju; Venkata Kanaka Ranga Raju (Vijayawada, IN), Bhuphatiraju; Kiran (Vijayawada, IN), Golakoti; Trimurtulu (Vijayawada, IN), Sengupta; Krishanu (Vijayawada, IN), Alluri; Venkata Krishna Raju (Vijayawada, IN)
Assignee:	Kasina Laila Innova Pharmaceuticals Private Limited (Vijayawada, IN)
Application Number:	13/912,431
Patent Claims:	1. A selenophene compound of formula (I) ##STR00123## wherein X, Y, and Z are independently selected from the group consisting of selenium and carbon, with the proviso that one of X, Y, and Z is selenium; A is N or C--R.sup.4, wherein R.sup.4 is selected from the group consisting of hydrogen, halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiole, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.1-4alkylcarbonyl, C.sub.1-4alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6 alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, and C.sub.1-6 alkylsulfonyl; B is NR.sup.5; wherein R.sup.5 is selected from the group consisting of hydrogen, alkyl, alkoxy and haloalkyl; Ar is selected from the group consisting of an optionally substituted benzene ring, an optionally substituted napththalene ring; an optionally substituted 6-membered aromatic ring containing one, two or three nitrogen atoms; and an optionally substituted 5-membered aromatic ring containing at least one heteroatom selected from the group consisting of sulfur, oxygen, and nitrogen, with the proviso that said 5-membered aromatic ring contains no more than one oxygen or sulfur atom; p is 0, 1, 2, 3, 4, or 5; R and R.sup.3 are independently selected from the group consisting of hydrogen, halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkyl carbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, an optionally substituted aryl ring, an optionally substituted heteroaryl ring, and an optionally substituted heterocycloalkyl ring; R.sup.1 and R.sup.2 are: a) independently selected from the group consisting of hydrogen, halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkyl carbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7 cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, an optionally substituted aryl ring, an optionally substituted heteroaryl ring, an optionally substituted heterocycloalkyl ring, and a group having the formula: ##STR00124## wherein n is 0, 1, 2, 3, 4, or 5; * indicates the point of attachment to the selenophene ring in formula I; W is selected from the group consisting of CH.sub.2, O, S, or NH; R.sup.6 and R.sup.7 are independently selected from the group consisting of hydrogen, amino, trihalomethyl, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkylcarbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 [(C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl; or b) R.sup.1 and R.sup.2 are joined to form a group having the formula; ##STR00125## wherein m and o are independently 0, 1, 2, 3 or 4; * indicates the point of attachment to the selenophene ring in formula I; L is selected from CH.sub.2, O, S and NR.sup.8; and R.sup.8 is selected from the group consisting of hydrogen, amino, trihalomethyl, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkylcarbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, and a group of the formula: ##STR00126## wherein * indicates the point of attachment to N in NR.sup.8; D is selected from the group consisting of C.sub.1-6alkyl, C(O), S(O), and S(O).sub.2; and R.sup.9 and R.sup.10 are selected from the group consisting of hydrogen, halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6alkyl, C.sub.1-6secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkylcarbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6 alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6 alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, and C.sub.1-6 alkylsulfonyl; and R.sup.6 and R.sup.7 are joined, and taken together with the atom to which they are attached, form a 5- to 7-membered optionally substituted cycloalkyl or cycloheteroalkyl ring; or c) R.sup.1 and R.sup.2 are joined, and taken together with the atoms to which they are attached, form an optionally substituted aryl ring, an optionally substituted 6-membered aromatic ring containing one, two or three nitrogen atoms; or an optionally substituted 5-membered aromatic ring containing one or more heteroatoms selected from the group consisting of sulfur, oxygen, and nitrogen, with the proviso that no more than one oxygen or sulfur atom is present; wherein each optionally substituted ring is optionally substituted by halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-4alkylcarbonyl, C.sub.1-4 alkoxy-carbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6 alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7 cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, or C.sub.1-6 alkylsulfonyl. 2. The selenophene compound of formula (I) according to claim 1, wherein A is N. 3. The selenophene compound of formula (I) according to claim 1, wherein: X is selenium and both Y and Z are carbon; Y is selenium and both X and Z are carbon; or Z is selenium and both X and Y are carbon. 4. The selenophene compound of formula (I) according to claim 3, wherein X is selenium and both Y and Z are carbon. 5. The selenophene compound of formula (I) according to claim 3, wherein Y is selenium and both X and Z are carbon. 6. The selenophene compound of formula (I) according to claim 3, wherein Z is selenium and both X and Y are carbon. 7. A selenophene compound of formula (I) according to claim 1, wherein Ar is an optionally substituted benzene ring or an optionally substituted 6-membered aromatic ring containing one, two or three nitrogen atoms; wherein said selenophene compound is a compound of formula (VII) ##STR00127## wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 are independently selected from the group consisting of N and C--R.sup.11, wherein each R.sup.11 is independently selected from the group consisting of hydrogen, halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkyl carbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, optionally substituted phenyl ring, optionally substituted benzyl, and an optionally substituted five membered heteroaromatic ring containing one or more heteroatoms selected from sulfur, oxygen, nitrogen and selenium, with the proviso that no more than one oxygen or sulfur or selenium atom is present in said optionally substituted five membered heteroaromatic ring; wherein said phenyl ring, said benzyl, and said 5-membered heteroaromatic ring are optionally substituted by halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.1-4alkyl carbonyl, C.sub.1-4alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7 cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl. 8. A selenophene compound of formula (VII) according to claim 7, wherein each of Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 is C--R.sup.11. 9. A selenophene compound of formula (VII) according to claim 7, wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 are independently selected from the group consisting of N and C--R.sup.11, with the proviso that one of Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 is N. 10. A selenophene compound of formula (VII) according to claim 7, wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 are independently selected from the group consisting of N and C--R.sup.11, with the proviso that Z.sup.1 and Z.sup.2 are each N; or Z.sup.2 and Z.sup.3 are each N. 11. A selenophene compound of formula (VII) according to claim 7, wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 are independently selected from the group consisting of N and C--R.sup.11, with the proviso that Z.sup.1 and Z.sup.3 are each N; Z.sup.1 and Z.sup.5 are each N; or Z.sup.2 and Z.sup.4 are each N. 12. A selenophene compound of formula (VII) according to claim 7, wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 are independently selected from the group consisting of N and C--R.sup.11, with the proviso that Z.sup.1 and Z.sup.4 are each N. 13. A selenophene compound of formula (I) according to claim 1, wherein Ar is said optionally substituted 5-membered aromatic ring containing at least one heteroatom selected from the group consisting of sulfur, oxygen, and nitrogen, with the proviso that said 5-membered aromatic ring contains no more than one oxygen or sulfur atom; wherein said selenophene compound is a compound of formula (VIII) ##STR00128## wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of S, O, N, NH, and C--R.sup.11, with the proviso that at least one of Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 is not C--R.sup.11, and no more than one of Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 is O or S; wherein each R.sup.11 is independently selected from the group consisting of hydrogen, halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-4 alkyl carbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, optionally substituted phenyl ring, optionally substituted benzyl, and an optionally substituted five membered heteroaromatic ring containing one or more heteroatoms selected from sulfur, oxygen, nitrogen and selenium, with the proviso that no more than one oxygen or sulfur or selenium atom is present in said optionally substituted five membered heteroaromatic ring; wherein said phenyl ring, said benzyl, and said 5-membered heteroaromatic ring are optionally substituted by halogen, hydroxy, formyl, carboxylic acid, amino, nitro, cyano, sulfonic acid, thiol, trihalomethyl, sulfonamide, C.sub.1-6 alkyl, C.sub.1-6 secondary alkyl, C.sub.1-6 tertiary alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.1-4 alkyl carbonyl, C.sub.1-4 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6alkyl)aminocarbonyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 hydroxyalkoxy, C.sub.3-7cycloalkyl, C.sub.3-7 cycloalkoxy, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 aminoalkyl, C.sub.1-6 aminoalkoxy, C.sub.1-6 (C.sub.1-6 alkylamino)alkyl, C.sub.1-6 [di(C.sub.1-6alkyl)amino]alkyl, C.sub.1-6 alkylsulfinyl, or C.sub.1-6 alkylsulfonyl. 14. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of S and C--R.sup.11, with the proviso that one of Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 is S. 15. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of O and C--R.sup.11, with the proviso that one of Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 is O. 16. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of NH and C--R.sup.11, with the proviso that one of Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 is NH. 17. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of N, NH and C--R.sup.11, with the proviso that said optionally substituted 5-membered aromatic ring contains a N--NH bond. 18. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of N, NH, and C--R.sup.11, with the proviso that Z.sup.1 is N, and either Z.sup.3 or Z.sup.4 is NH. 19. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of N, O, and C--R.sup.11, with the proviso that either Z.sup.1 is N, and either Z.sup.3 or Z.sup.4 is O; or Z.sup.1 is O, and either Z.sup.3 or Z.sup.4 is N. 20. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of N, O, and C--R.sup.11, with the proviso that either Z.sup.1 is N and Z.sup.2 is O; Z.sup.1 is O and Z.sup.2 is N; or Z.sup.2 is N and Z.sup.3 is O. 21. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of N, S, and C--R.sup.11, with the proviso that either Z.sup.1 is N, and either Z.sup.3 or Z.sup.4 is S; or Z.sup.1 is S, and either Z.sup.3 or Z.sup.4 is N. 22. A selenophene compound of formula (VIII) according to claim 13, wherein Z.sup.1, Z.sup.2, Z.sup.3, and Z.sup.4 are independently selected from the group consisting of N, S, and C--R.sup.11, with the proviso that either Z is N and Z.sup.2 is S; or Z.sup.1 is S and Z.sup.2 is N; or Z.sup.2 is N and Z.sup.3 is S. 23. A selenophene compound selected from the group consisting of: (3-chloro-4-fluorophenyl)-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]- selenophen-4-ylamine; (5-bromo(3-pyridyl))-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selen- ophen-4-ylamine; (2,6-dichloropyridin-4-yl)-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d- ]selenophen-4-ylamine; (2,6-dichloropyrimidin-4-yl)-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6- -d]selenophen-4-ylamine; pyrazin-2-yl-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selenophen-4-- ylamine; (2,5-dibromo(3-thienyl)-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[- 5,6-d]selenophen-4-ylamine; (5-tert-butyl)-3-(5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selenoph- en-4-ylamino)thiophene-2-carboxamide; 5-(tert-butyl)-2-(5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selenoph- en-4-ylamino)furan-3-carbonitrile; 5-Phenyl-2-(5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selenophen-4-y- lamino)furan-3-carbonitrile; 2-Methylthio-4-(5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selenophen- -4-ylamino)-1,3-thiazole-5-carbonitrile; (2-Methylthio-5-nitro(1,3-thiazol-4-yl))-5,6,7,8-tetrahydrobenzo[1,2-b]py- rimidino[5,6-d]selenophen-4-ylamine; 4-(5,6,7,8-Tetrahydrobenzo[1,2-b]pyrimidino[5,6-d]selenophen-4-ylamino)be- nzene-sulfonamide; [5-(tert-Butyl)selenopheno[3,2-e]pyrimidin-4-yl](3-chloro-4-fluorophenyl)- amine; (3-Chloro-4-fluorophenyl)(5-phenylselenopheno[3,2-e]pyrimidin-4-yl]- amine; 4-[(3-Chloro-4-fluorophenyl)amino]-5-methylselenophnopheno[2,3-d]py- rimidine-6-carboxylic acid; [(3-Chloro-4-fluorophenyl)(6-methyl-5-phenylselenopheno[3,2-e]pyrimidin-4- -yl]amine; 4-[(3-Chloro-4-fluorophenyl)amino]-5-methylselenophnopheno[2,3-- d]pyrimidine-6-carboxamide; (3-Chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrimidino[5',6'-5,4]selenoph- eno[2,3-c]pyridine-4-ylamine; 4-[(3-Chloro-4-fluorophenyl)amino]-7-(methylsulfonyl)-5,6,7,8-tetrahydro-- pyrimidino[5',4'-5,4]selenopheno[2,3-c]pyridine; (3-Bromophenyl)-5,6,7,8-tetrahydropyrimidino[5',6'-5,4]selenopheno[2,3-c]- pyridine-4-ylamine; (3-Ethynylphenyl)-5,6,7,8-tetrahydropyrimidino[5',6'-5,4]selenopheno[2,3-- c]pyridine-4-ylamine; (3,4-Dichlorophenyl)-5,6,7,8-tetrahydropyrimidino[5',6'-5,4]selenopheno[2- ,3-c]pyridine-4-ylamine; Methyl 5-methyl-4-(5,6,7,8-tetrahydropyrimidino[5',6'-5,4]selenopheno[2,3-c]pyri- din-4-ylamino)thiophene-2-carboxylate; {4-[3-Chloro-4-fluorophenyl)amino]-5-methylselenopheno[2,3-d]pyrimidin-6-- yl}-N-(2-hydroxyethyl)carboxamide; N-(2-Chloroethyl) {4-[3-chloro-4-fluorophenyl)amino]-5-methylselenopheno[2,3-d]pyrimidin-6-- yl}carboxamide; 4-[(3-Chloro-4-fluorophenyl)amino]-5,6,8-trihydrobenzo[2,1-b]pyrimidino[5- ,4-d]selenophen-7-one; (3-Chloro-4-fluorophenyl)-6,7,8,9-tetrahydrobenzo[1,2-d]pyrimidino[5,6-b]- selenophen-4-ylamine; [6-(tert-butyl)selenopheno[2,3-e]pyrimidin-4-yl](3-chloro-4-fluorophenyl)- amine; (3-Chloro-4-fluorophenyl)(6-phenylselenopheno[2,3-e]pyrimidin-4-yl)- amine; Benzo[d]pyrimidino[5,6-b]selenophen-4-yl(3-chloro-4-fluorophenyl)am- ine; (3-Chloro-4-fluorophenyl)pyrimidino[4',5'-5,4]selenopheno[2,3-b]pyrid- in-4-ylamine; Ethyl 4-[(3-chloro-4-fluorophenyl)amino]-5-methylthioselenopheno[3,4-d]pyrimidi- ne-7-carboxylate; (4-Chlorophenyl)methyl-5,6,7,8-tetrahydropyrimidino[5',6'-5,4]selenopheno- [2,3-c]pyridine-4-ylamine; and (3-Chloro-4-fluorophenyl)(2-methyl-5,6,7,8-tetrahydrobenzo[1,2-b]pyrimidi- no[5,6-d]selenophen-4-yl)amine. 24. A process for the preparation of selenophene compound of formula (I) according to claim 1, wherein said process comprises a reaction selected from the group consisting of; [A] reacting a compound of formula II with formic acid and sulfuric acid to obtain a compound of formula III; reacting the compound of formula III with a chlorinating agent in the presence of DMF or a base to obtain a compound of formula IV; and reacting the compound of formula IV with an unsubstituted or substituted aromatic amino compound in the presence of a solvent and optionally in the presence of a base to obtain a compound of formula I; ##STR00129## [B] reacting a compound of formula II with dimethylformamide-dimethylacetal (DMF-DMA) in the presence of a solvent to obtain a compound of formula V; and reacting the compound of formula V with an unsubstituted or substituted aromatic amino compound to obtain a compound of formula I; or ##STR00130## [C] reacting a compound of formula II with a trialkyl orthoformate in the presence of a solvent to obtain a compound of formula VI, where R.sup.11 is alkyl; and reacting the compound of formula VI with an unsubstituted or substituted aromatic amino compound to obtain a compound of formula I wherein X, Y, Z, R.sup.1, R.sup.2, and R.sup.3 are as defined in claim 1. ##STR00131## 25. A pharmaceutical composition comprising at least one selenophene compound of formula (I) according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof, a hydrate thereof, or a stereoisomer thereof; and at least one additive selected from the group consisting of pharmaceutically acceptable excipients, pharmaceutically acceptable diluents, and pharmaceutically acceptable carriers. 26. A pharmaceutical composition according to claim 25, wherein said composition further comprises at least one anti-tumor agent selected from the group consisting of Alkylating agents, Anti-metabolites, Hormonal therapy agents, Anti-angiogenic compounds, Antibodies, VEGF inhibitors, EGFR (HER1) inhibitors, HER2 inhibitors, CDK inhibitors, Proteasome inhibitors, Serine/threonine kinase (Raf inhibitors), Tyrosine kinase inhibitors, Androgen receptor antagonists and Aromatase inhibitors. 27. A pharmaceutical composition according to claim 25, wherein additive is selected from the group consisting of glucose, fructose, sucrose, maltose, yellow dextrin, white dextrin, aerosol, microcrystalline cellulose, calcium stearate, magnesium stearate, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-alpha-tocopherol, glycerin, propylene glycol, glycerin fatty ester, poly glycerin fatty ester, sucrose fatty ester, sorbitan fatty ester, propylene glycol fatty ester, acacia, carrageenan, casein, gelatin, pectin, agar, vitamin B group, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives, distilled water, saline, aqueous glucose solution, alcohol, propylene glycol, polyethylene glycol, various animal and vegetable oils, white soft paraffin, paraffin and wax. 28. A pharmaceutical composition according to claim 26, wherein: the Alkylating agent is selected from the group consisting of nitrogen mustard N-oxide, cyclophosphamide, ifosfamide, thiotepa, ranimustine, nimustine, temozolomide, altretamine, apaziquone, brostallicin, bendamustine, carmustine, estramustine, fotemustine, glufosfamide, mafosfamide, bendamustin, mitolactol, cisplatin, carboplatin, eptaplatin, lobaplatin, nedaplatin, oxaliplatin, satraplatin, and mixtures thereof; the Anti-metabolite is selected from the group consisting of methotrexate, 6-mercaptopurineriboside, mercaptopurine, 5-fluorouracil, tegafur, doxifluridine, carmofur, cytarabine, cytarabine ocfosfate, enocitabine, gemcitabine, fludarabine, 5-azacitidine, capecitabine, cladribine, clofarabine, decitabine, eflornithine, ethynylcytidine, cytosine arabinoside, hydroxyurea, melphalan, nelarabine, nolatrexed, ocfosfate, disodium pemetrexed, pentostatin, pelitrexol, raltitrexed, triapine, trimetrexate, vidarabine, vincristine, vinorelbine, and mixtures thereof; the Hormonal therapy agent is selected from the group consisting of exemestane, Lupron, anastrozole, doxercalciferol, fadrozole, formestane, abiraterone acetate, finasteride, epristeride, tamoxifen citrate, fulvestrant, Trelstar, toremifene, raloxifene, lasofoxifene, letrozole, sagopilone, ixabepilone, epothilone B, vinblastine, vinflunine, docetaxel, paclitaxel, and mixtures thereof; the Anti-angiogenic compound is selected from the group consisting of acitretin, aflibercept, angiostatin, aplidine, asentar, axitinib, recentin, bevacizumab, brivanib alaninate, cilengitide, combretastatin, DAST, endostatin, fenretinide, halofuginone, pazopanib, ranibizumab, rebimastat, removab, revlimid, sorafenib, vatalanib, squalamine, sunitinib, telatinib, thalidomide, ukrain, vitaxin, and mixtures thereof; the Antibody is selected from the group consisting of trastuzumab, cetuximab, bevacizumab, rituximab, ticilimumab, ipilimumab, lumiliximab, catumaxomab, atacicept, oregovomab, alemtuzumab, and mixtures thereof; the VEGF inhibitor is selected from the group consisting of sorafenib, DAST, bevacizumab, sunitinib, recentin, axitinib, aflibercept, telatinib, brivanib alaninate, vatalanib, pazopanib, ranibizumab, and mixtures thereof; the EGFR (HER1) inhibitor is selected from the group consisting of cetuximab, panitumumab, vectibix, gefitinib, erlotinib, Zactima, and mixtures thereof; the HER2 inhibitor is selected from the group consisting of lapatinib, tratuzumab, pertuzumab, and mixtures thereof; the CDK inhibitor is selected from the group consisting of roscovitine, flavopiridol, and mixtures thereof; the Proteasome inhibitor is selected from the group consisting of bortezomib, carfilzomib, and mixtures thereof; Serine/threonine kinase (Raf) inhibitor is sorafenib; the Tyrosine kinase inhibitor is selected from the group consisting of dasatinib, nilotinib, DAST, bosutinib, sorafenib, bevacizumab, sunitinib, AZD2171, axitinib, aflibercept, telatinib, imatinib mesylate, brivanib alaninate, pazopanib, ranibizumab, vatalanib, cetuximab, panitumumab, vectibix, gefitinib, erlotinib, lapatinib, tratuzumab pertuzumab, and mixtures thereof; the Androgen receptor antagonist is selected from the group consisting of nandrolone decanoate, fluoxymesterone, Android, Prostaid, andromustine, bicalutamide, flutamide, apo-cyproterone, apoflutamide, chlormadinone acetate, Androcur, Tabi, cyproterone acetate, nilutamide, and mixtures thereof; and the Aromatase inhibitor is selected from the group consisting of anastrozole, letrozole, testolactone, exemestane, aminoglutethimide, formestane, and mixtures thereof. 29. A method for treating or inhibiting or controlling a cell proliferative disorder in a warm blooded animal in need thereof, wherein said method comprises administering to the said warm blooded animal a therapeutically effective amount of at least one selenophene compound of formula (I) according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof, a hydrate thereof, or a stereoisomer thereof, wherein said cell proliferative disorder is selected from the group consisting of cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, and parathyroid, lymphomas, sarcomas, and leukemias. 30. A method for treating, inhibiting, or controlling a cell proliferative disorder in a warm blooded animal in need thereof, wherein said method comprises administering to the said warm blooded animal a therapeutically effective amount of a pharmaceutical composition according to claim 25, wherein said cell proliferative disorder is selected from the group consisting of cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, and parathyroid, lymphomas, sarcomas and leukemias. 31. A method for treating, inhibiting, or controlling a cell proliferative disorder in a warm blooded animal in need thereof, wherein said method comprises administering to the said warm blooded animal a therapeutically effective amount of a pharmaceutical composition according to claim 26, wherein said cell proliferative disorder is selected from the group consisting of cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, and parathyroid, lymphomas, sarcomas and leukemias. 32. A method for treating or inhibiting, or controlling a cell proliferative disorder according to claim 29, wherein said administration comprises the routes selected from the group consisting of intraperitoneal (IP), intravenous (IV), oral (PO), intramuscular (IM), intracutaneous (IC), intradermal (ID), intrauterine, intratumoral and intrarectal.

Details for Patent 9,090,633

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2030-11-18
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2030-11-18
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2030-11-18
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2030-11-18
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2030-11-18