Thienopyrimidine-based inhibitors of the SRC family

Abstract

Various thienopyrimidine-based analog compounds that selectively inhibit the Src family of tyrosine kinases. These compounds are thienopyrimidines and contain a hydrozone bridge created by heating a thienopyrimidine hydrazine with an aldehyde in ethanol at reflux. Such compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.

1. A compound of the formula: 
                 
 
       or a pharmaceutically acceptable salt or hydrate thereof, wherein
 R 1 =H,  alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor,  
 R 2 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor; and  
 R 3 =a hydrazone bridge attached to a H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor except that when R 3  is a hydrazone bridge attached to a phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH3-phenyl, then R 2  can not be phenyl if R 1  is H .  
 
     
     
       2. A compound of the formula: 
                 
 
       or a pharmaceutically acceptable salt or hydrate thereof, wherein
 R 4 =H,  alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor,  
 R 5 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor;  
 R 6 =H or alkyl;  
 R 7 =H or alkyl; and  
 R 8 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor except that when R 8  is phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH3-phenyl, then R 5  can not be phenyl if R 4  is H .  
 
     
     
       3. The compound of  claim 2 , wherein R 5 =phenyl. 
     
     
       4. The compound of  claim 2 , wherein R 4 =H,  R 5 =phenyl, R 6 =H, R 7 =H, and R 8 =3-pyridyl. 
     
     
       5. The compound of  claim 2 , wherein R 8 =3-pyridyl. 
     
     
       6. The compound of  claim 2 , wherein R 5 =H and R 8 =3-pyridyl. 
     
     
       7. The compound of  claim 2 , wherein the compound is selected from the group consisting of: 
       Benzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,4-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,5-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Chlorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,4-Dihydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       2-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       1H-Pyrrole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       2-Furancarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       1H-Imidazole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Hydroxy-3-nitrobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Ethoxy-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Hydroxy-4-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Fluorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Hydroxy-3-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Chloro-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Fluorobenzaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-y)hydrazone,  
       3-Pyridinecarboxaldehyde(thieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       5-Methyl-1H-imidazole-4-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       5-Methyl-2-thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       Cyclopropanecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone, and  
       3-Pyridinecarboxaldehyde(7-bromothieno[3,2-d]pyrimidin-4-yl)hydrazone and  
       3-Pyridinecarboxaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone .  
     
     
       8. A compound of the formula: 
                 
 
       or a pharmaceutically acceptable salt or hydrate thereof, wherein
 R 4 =H,  alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor;  
 R 5 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor  
 R 6 =H or alkyl;  
 R 7 =H or alkyl; and  
 R 8 =4-F-phenyl, 4-CF 3 -phenyl, 2,4-diOCH 3 -phenyl, 2,5-diOCH 3 -phenyl, 4-OCH 3 -phenyl, 4-N(CH 3 )2-phenyl, 4-pyridinyl, 3,4-di(OCH 3 )-phenyl, 3,5-di(OCH 3 )-phenyl, 3-Cl-phenyl, 4-NHCOCH 3 -phenyl, 2-Cl-5-NO 2 -phenyl, 2-Cl-6-NO 2 -phenyl, 3,4-diOH-phenyl, cyclohexyl, 2-pyridinyl, 3-pyridinyl, p-COOH-phenyl, 2-thienyl, 2-pyrrolyl, 3-OH-phenyl, 3-thienyl, 2-imidazolyl, 4-OBu-phenyl, 3-furanyl, 2-thiazolyl, 4-imidazolyl, 5-imidazolyl, 2,3-diOCH 3 -phenyl, 2-Cl-phenyl, 4-OEt-phenyl, 4-OH-3-NO 2 -phenyl, 3-OEt-4-OH-phenyl, 3-OH-4-OCH 3 -phenyl, 3-F-phenyl, 3-Cl-4-OH-phenyl, 4-Br-phenyl, 3-Br-phenyl, 5-CH 3 -4-imidazolyl, 1-CH 3 -2-imidazolyl, 3-CH 3 -2-thienyl, 5-CH 3 -2-thienyl, 4-CN-phenyl, 3-CN-phenyl, 4-Cl-3-NO 2 -phenyl, 4-OPr-phenyl, 3-OPr-phenyl, 3-OCH 3 -phenyl, 3-OEt-phenyl, 3-OBu-phenyl, 3-NO 2 -phenyl, 5-indolyl, methyl, 3-Cl-4-F-phenyl, 4-SCH 3 -phenyl, ethyl, propyl, butyl, (2-CH 3 )-propyl, cyclopropyl, 3-tetrahydrofuranyl, 3-cyclohexen-1-yl, 1-propenyl, benzyl, or (2-phenyl)ethyl, phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH 3 -phenyl except that when R 8  is phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH 3 -phenyl, then R 5  can not be phenyl if R 4  is H .  
 
     
     
       9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula: 
                 
 
       or a pharmaceutically acceptable salt or hydrate thereof, wherein
 R 1 =H,  alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor;  
 R 2 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor; and  
 R 3 =a hydrazone bridge attached to a H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor except that when R 3  is a hydrazone bridge attached to a phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH3-phenyl, then R 2  can not be phenyl if R 1  is H .  
 
     
     
       10. A method of synthesizing a compound of the formula: 
                 
 
       or a pharmaceutically acceptable salt or hydrate thereof, wherein
 R 1 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor,  
 R 2 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor; and  
 R 3 =a hydrazone bridge attached to a H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor except that when R 3  is a hydrazone bridge attached to a phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH3-phenyl, then R 2  can not be phenyl if R 1  is H; wherein a hydrazine is heated with an aldehyde in ethanol at reflux.  
 
     
     
       11. A method of inhibiting a protein tyrosine kinase, further defined as a member of the Src family of protein tyrosine kinases, by administering to a subject a compound of the formula: 
                 
 
       or a pharmaceutically acceptable salt or hydrate thereof, wherein
 R 1 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor;  
 R 2 =H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor;  
 R 3 =a hydrazone bridge attached to a H, alkyl, a halogen, a carbocyclic aromatic ring comprising six carbons, a carbocyclic non-aromatic ring of three to six carbons, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic non-aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members, a five or six member heterocyclic aromatic ring comprising carbon atoms and one or more nitrogen, oxygen and/or sulfur members fused to another aromatic ring, a hydrogen bond donor or a hydrogen bond acceptor except that when R 3  is a hydrazone bridge attached to a phenyl, 4-Cl-phenyl, 4-OH-phenyl, 4-NO 2 -phenyl, 2-furanyl, 2-OH-phenyl, or 4-OH-3-OCH3-phenyl, then R 2  cannot be phenyl if R 1  is H.  
 
     
     
       12. The method of  claim 11  comprising the step of the binding of the compound to said protein tyrosine kinase. 
     
     
       13. The method of  claim 11 , wherein the protein tyrosine kinase is Src. 
     
     
       14. The method of  claim 11 , wherein the protein tyrosine kinase is Fyn. 
     
     
       15. The method of  claim 11 , wherein the protein tyrosine kinase is Yes. 
     
     
       16. The method of  claim 11 , wherein the protein tyrosine kinase is Lyn. 
     
     
       17. The method of  claim 11 , wherein the protein tyrosine kinase is Lck. 
     
     
       18. The method of  claim 11 , wherein the protein tyrosine kinase is Blk. 
     
     
       19. The method of  claim 11 , wherein the protein tyrosine kinase is Hck. 
     
     
       20. The method of  claim 11 , wherein the protein tyrosine kinase is Fgr. 
     
     
       21. The method of  claim 11 , wherein the protein tyrosine kinase is Yrk. 
     
     
       22. The method of  claim 11 , wherein the subject is a mammal. 
     
     
       23. The method of  claim 11 , wherein the mammal is a human. 
     
     
       24. The method of  claim 11 , wherein the administering is parenteral. 
     
     
       25. The method of  claim 24 , wherein the parenteral administration is intravenous, intramuscular, subcutaneous, intraperitoneal, intraarterial, intrathecal or transdermal. 
     
     
       26. The method of  claim 11 , wherein the administering is alimentary. 
     
     
       27. The method of claim  25    26 , wherein the alimentary administration is oral, rectal, sublingual, or buccal. 
     
     
       28. The method of  claim 11 , wherein the administration is topical. 
     
     
       29. The method of  claim 11 , wherein the administration is by inhalation. 
     
     
       30. A compound or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound is selected from the group consisting of: 
       Benzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,4-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,5-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Chlorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,4-Dihydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       2-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       1H-Pyrrole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       2-Furancarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       1H-Imidazole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Hydroxy-3-nitrobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Ethoxy-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Hydroxy-4-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Fluorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Hydroxy-3-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Chloro-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Fluorobenzaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-y)hydrazone,  
       3-Pyridinecarboxaldehyde(thieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       5-Methyl-1H-imidazole-4-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       5-Methyl-2-thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       Cyclopropanecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone, and  
       3-Pyridinecarboxaldehyde(7-bromothieno[3,2-d]pyrimidin-4-yl)hydrazone, and  
       3-Pyridinecarboxaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone .  
     
     
       31. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as Benzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       32. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       33. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       34. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3,4-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       35. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3,5-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       36. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Chlorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       37. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3,4-Dihydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       38. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       39. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 2-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       40. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 1H-Pyrrole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       41. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 2-Furancarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       42. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       43. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       44. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 1H-imidazole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       45. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       46. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Hydroxy-3-nitrobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       47. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Ethoxy-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       48. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Hydroxy-4-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       49. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Fluorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       50. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Hydroxy-3-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       51. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Chloro-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       52. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Fluorobenzaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-y)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       53. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Pyridinecarboxaldehyde(thieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       54. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 5-Methyl-1H-imidazole-4-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       55. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 5-Methyl-2-thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       56. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 4-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       57. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       58. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       59. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       60. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as Cyclopropanecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       61. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       62. The compound, pharmaceutically acceptable salt, or hydrate of  claim 30 , further defined as 3-Pyridinecarboxaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       63. The compound of  claim 30 , further defined as comprised in a pharmaceutical composition. 
     
     
       64. The compound of  claim 1 , further defined as comprised in a pharmaceutical composition. 
     
     
       65. The compound of  claim 2 , further defined as comprised in a pharmaceutical composition. 
     
     
       66. The compound of  claim 8 , further defined as comprised in a pharmaceutical composition. 
     
     
       67. The method of  claim 11 , wherein the compound is selected from the group consisting of: 
       Benzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,4-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,5-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Chlorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3,4-Dihydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       2-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       1H-Pyrrole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       2-Furancarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       1H-Imidazole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Hydroxy-3-nitrobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Ethoxy-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Hydroxy-4-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Fluorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Hydroxy-3-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Chloro-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Fluorobenzaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-y)hydrazone,  
       3-Pyridinecarboxaldehyde(thieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       5-Methyl-1H-imidazole-4-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       5-Methyl-2-thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       4-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       Cyclopropanecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       3-Pyridinecarboxaldehyde(7-bromothieno[3,2-d]pyrimidin-4-yl)hydrazone and  
       3-Pyridinecarboxaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone,  
       or the pharmaceutically acceptable salts or hydrates of any of these compounds. 
     
     
       68. The method of  claim 11 , wherein the compound is further defined as Benzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       69. The method of  claim 11 , wherein the compound is further defined as 4-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       70. The method of  claim 11 , wherein the compound is further defined as 4-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       71. The method of  claim 11 , wherein the compound is further defined as 3,4-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       72. The method of  claim 11 , wherein the compound is further defined as 3,5-Dimethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       73. The method of  claim 11 , wherein the compound is further defined as 3-Chlorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       74. The method of  claim 11 , wherein the compound is further defined as 3,4-Dihydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       75. The method of  claim 11 , wherein the compound is further defined as 3-Pyridinecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       76. The method of  claim 11 , wherein the compound is further defined as 2-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       77. The method of  claim 11 , wherein the compound is further defined as 1H-Pyrrole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       78. The method of  claim 11 , wherein the compound is further defined as 2-Furancarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       79. The method of  claim 11 , wherein the compound is further defined as 3-Hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       80. The method of  claim 11 , wherein the compound is further defined as 3-Thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       81. The method of  claim 11 , wherein the compound is further defined as 1H-Imidazole-2-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       82. The method of  claim 11 , wherein the compound is further defined as 4-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       83. The method of  claim 11 , wherein the compound is further defined as 4-Hydroxy-3-nitrobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       84. The method of  claim 11 , wherein the compound is further defined as 3-Ethoxy-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       85. The method of  claim 11 , wherein the compound is further defined as 3-Hydroxy-4-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       86. The method of  claim 11 , wherein the compound is further defined as 3-Fluorobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       87. The method of  claim 11 , wherein the compound is further defined as 4-Hydroxy-3-methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       88. The method of  claim 11 , wherein the compound is further defined as 3-Chloro-4-hydroxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       89. The method of  claim 11 , wherein the compound is further defined as 4-Fluorobenzaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       90. The method of  claim 11 , wherein the compound is further defined as 3-Pyridinecarboxaldehyde(thieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       91. The method of claim wherein the compound is further defined as 5-Methyl-1H-imidazole-4-carboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       92. The method of  claim 11 , wherein the compound is further defined as 5-Methyl-2-thiophenecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       93. The method of  claim 11 , wherein the compound is further defined as 4-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       94. The method of  claim 11 , wherein the compound is further defined as 3-Cyanobenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       95. The method of  claim 11 , wherein the compound is further defined as 3-Methoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       96. The method of  claim 11 , wherein the compound is further defined as 3-Ethoxybenzaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       97. The method of  claim 11 , wherein the compound is further defined as Cyclopropanecarboxaldehyde(7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       98. The method of  claim 11 , wherein the compound is further defined as 3-Pyridinecarboxaldehyde(7-bromothieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof. 
     
     
       99. The method of  claim 11 , wherein the compound is further defined as 3-Pyridinecarboxaldehyde(6-phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone or a pharmaceutically acceptable salt or hydrate thereof.