Patent Publication Number: US-2006004002-A1

Title: Small molecule thienopyrimidine-based protein tyrosine kinase inhibitors

Description:
BACKGROUND  
      1. Technical Field  
      Novel compounds useful for the treatment of diseases related to the Src family of tyrosine kinases are disclosed along with methods of synthesis of these compounds and methods of treatment employing these compounds. The novel compounds are one or more disclosed thienopyrimidine-based compounds capable of inhibiting the Src family of protein tyrosine kinases.  
      2. Background of the Related Art  
      Sequencing of the human genome has indicated that there are 90 protein tyrosine kinases (PTKs). Most of these PTKs belong to the receptor class (Robinson et al., 2000). Over the last two decades there have been great efforts to determine which PTKs are therapeutic targets (Sridhar et al., 2000). The first PTK inhibitors to be approved by the FDA are directed against the mutant Abl protein kinase (Abl PTK) (Schindler et al., 2000). Inhibitors for many protein kinases in addition to tyrosine kinase are in clinical development (Dancey &amp; Sausville, 2003).  
      Src is a protein tyrosine kinase (PTK) associated with cellular membranes and is involved in signal transduction and growth regulation pathways (Frame, 2002). It transmits cellular signals by transferring the gamma phosphate of ATP to the side chain of tyrosine residues on substrate proteins. To this date, eight members of the Src protein tyrosine kinase family have been discovered. The members are Src, Yes, Fyn, Fgr, Blk, Lck, Lyn, and Hck. The family members, Fgr, Blk, Lck, Lyn, and Hck, are expressed and are active primarily in hematopoietic cells (Bjorge et al., 1999).  
      Alterations in the phosphorylation of Src substrates are key events in cellular signaling. Most normal cells have very low levels of Src and low activities of Src (Barnekow, 1989). Further, the Src enzyme is not required for the establishment or maintenance of cell viability (Soriano et al., 1991).  
      In contrast, Src activity is greatly increased in many human cancers including: breast cancer (Partanen, 1994); stomach cancer (Takeshima et al., 1991); colon cancer (Termuhlen et al., 1993); hairy cell leukemia and a subgroup of B-cell lymphomas (Lynch et al., 1993); low grade human bladder carcinoma (Fanning et al., 1992); neuroblastoma (Bjelfman et al., 1990); ovarian cancer (Wiener et al., 1999); and non-small cell lung carcinoma (Budde et al., 1994). In the case of colon cancer, Src is activated more frequently than Ras or p53 (Jessup and Gallick, 1993), and Src undergoes two distinct activations corresponding with malignant transformation of colonocytes (Cartwright et al., 1990) and tumor progression (Termuhlen et al., 1993).  
      Antisense to Src inhibits growth of human monoblastoid leukemia cells (Waki et al., 1994), K562 human leukemia cells (Kitanaka et al., 1994) and HT-29 human colon cancer cells (Staley et al., 1997). Src activity was reduced in a human ovarian cancer cell line (SKOv-3) by antisense technology. The reduced Src activity in SKOv-3 was associated with altered cellular morphology, reduced anchorage-independent growth, diminished tumor growth and reduced vascular endothelial growth factor mRNA expression in vitro (Wiener et al., 1999). Thus, Src is a drug target in oncology (Irby &amp; Yeatman, 2000) and tyrosine kinase inhibitors are being studied for the treatment of hematologic and solid-tumors.  
      Changes in Src activity are associated with changes in the cell cycle (Chackalaparampil &amp; Shalloway, 1988) and alterations in the regulation of Src activity have been associated with neoplasia (Sabe et al., 1992). More recent studies have also indicated that Src contributes to the metastatic spread of cancer (Boyer et al., 2002; Nam et al., 2002). Inhibitors of Src would have the effect of interrupting the signal transduction pathways in which it participates and would thereby reduce the rate of growth of cancer cells.  
      Tyrosine kinase inhibitors are currently being studied for use in treatment of inflammatory diseases and autoimmune diseases (Sinha and Corey, 1999). Treatments which alter the levels of Fyn in appropriate tissues have been proposed to be effective treatments in alcoholism and autoimmune disease (Resh, 1998). Lck and Fyn play an important role in T cell activation through their association with CD4 and CD3, respectively. Autoimmune diseases could by treated by inhibition of T cell activation through Lck and/or Fyn (Sinha and Corey, 1999). In allergic/immunological diseases, development of inhibitors of Lyn, Hck, Lck, Fgr, and Blk are proposed to be useful in treatment of autoimmunity and transplantation rejection (Bolen and Brugge, 1997).  
      Some members of the Src family are targets for treatment or prevention of allergic responses. For example, Lyn is indispensable for mast cell-mediated allergic responses (Hibbs and Dunn, 1997). Lyn plays a role in B cell receptor and IgE receptor signal transduction. Inhibition of Lyn may provide a treatment for anaphylaxis or allergy. Lyn-deficient mice are unable to experience anaphylaxis (Sinha and Corey, 1999). While Lyn is primarily located in normal hematopoetic cells, it has also been show to be a drug-target for prostate cancer (Goldenberg-Furmanov et al., 2004).  
      The levels of Fyn, a Src family tyrosine kinase, are increased in Alzheimer&#39;s Disease. The phosphorylation by Fyn of the microtubule-associated protein, tau, affects the ability of tau to bind to microtubules. Abnormally phosphorylated tau is found in the neurofibrillary tangles associated with Alzheimer&#39;s Disease. It is also thought that the Aβ peptide in senile plaques activates tyrosine kinases (Lee et al., 1998). Src has been demonstrated to regulate the NMDA receptor (Yu and Salter, 1999). Therefore, the neuronal Src family members may be prime targets for treating CNS disorders including, but not limited to, Alzheimer&#39;s Disease, various forms of senility, Parkinson&#39;s Disease and chronic pain (Wijetunge et al., 2000).  
      Neuronal Src kinase activity is increased in hippocampal slices treated with a potassium channel blocker in Mg 2+ -free medium to induce epileptiform discharges. The frequency of the epileptiform discharges is decreased by the addition of an inhibitor of the Src family of tyrosine kinases. Therefore, the Src family may provide a key target for treating epilepsy and other disorders related to NMDA receptor function (Sanna et al., 2000).  
      Herpesviridae, papovaviridae, and retroviridae have been shown to interact with non-receptor tyrosine kinases and use them as signaling intermediates. The HIV-1 Nef protein interacts with members of the Src family of tyrosine kinases. Nef mediates downregulation of CD4 membrane expression, modification of T-cell activation pathways, and increases virus infectivity (Collette et al., 1997). The HBx protein of the hepatitis B virus is essential for infection by hepadnaviruses and activates Ras by activating the Src family of tyrosine kinases. The activation of Ras is necessary for the ability of the HBx protein to stimulate transcription and release growth arrest in quiescent cells (Klein and Schneider, 1997). Activity of the Src family of tyrosine kinases is altered by association with viral proteins such as mouse and hamster polyomavirus middle-T antigens, Epstein-Barr virus LMP2A, and herpesvirus saimiri Tip (Dunant and Ballmer-Hofer, 1997).  
      Src inhibitors also may provide a potential for treatment for osteoporosis, a condition in which bone resorption is increased resulting in weakening of bone. It was shown that mice depleted of the Src gene developed osteoporosis (Soriano et al., 1991) and that Src is involved with bone resorption (Susa et al., 2000).  
      Potential sites for targeting inhibitors of Src family PTKs are the SH2 and SH3 domains (e.g. Park et al., 2003), the phosphoryl transfer site (SH1 domain), or other unknown sites on the enzyme. Compounds (and preferably small compounds) binding to SH2 and SH3 domains would block the protein-protein interactions and the recruitment of other signal transduction proteins mediated by these domains.  
      Despite the wide range of possible applications, there are few potent small-molecule inhibitors of the Src family of tyrosine kinases that possess suitable pharmacokinetics, affinity, or specificity to serve as effective treatments for human disease (Zhu et al., 1999; Sun et al., 2000; Missbach et al., 2000; Sawyer et al., 2001). Many previously identified small-molecule inhibitors show low specificity for individual PTKs. While recent advances in identifying inhibitors of the Src family include anilinoquinazolines (Ple et al., 2004), quinolines (Berger et al., 2002, Boschelli et al., 2003), bisphosphonates to target the bone (Wang et al., 2003), isoquinolin-9-ones (Goldberg et al., 2003), thiazoles (Wityak et al., 2003), pyrrolo-pyrimidines (Calderwood et al., 2002), and pyrazolo-pyrimidines (Burchart et al., 2002), improved small molecule inhibitors are still urgently needed.  
      Initially, most “small molecule” inhibitors of PTKs were isolated from natural products. However, many of these inhibitors show low specificity for individual PTKs. While inhibitors of the Abl protein tyrosine kinases has found utility in the clinic, few small-molecule inhibitors of the Src family possess suitable pharmacokinetics, affinity, or specificity to serve as effective treatments for human disease. Therefore, there is still an urgent need for small-molecule inhibitors of the Src family of PTKs.  
     SUMMARY OF THE DISCLOSURE  
      In satisfaction of the aforenoted needs, disclosed herein are a number of small-molecule thienopyrimidine-based inhibitors of the Src family that are suitable to act as pharmaceuticals. The inhibitors disclosed herein are targeted to the phosphoryl transfer site (SH1 domain), i.e., the active site. Active-site directed inhibitors can be targeted to the ATP binding site, the protein substrate binding site, or both (bisubstrate analogues).  
      The disclosed compounds have the following general formula:  
                 
          or pharmaceutically acceptable salts or hydrates thereof, wherein:     R 1 =methyl, ethyl, vinyl, hydroxy, hydroxymethyl, ethoxymethyl, morpholin-4-yl-ethoxy, cyano, or 4,5-dihydroxy-2-oxylpentyl;     R 2 =2-ethoxyphenyl, 2-aminomethylphenyl, 3-aminomethylphenyl, 4-aminomethylphenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, morpholin-4-yl, 3-[(morpholin-4-yl)-methyl]-phenyl, phenylaminomethyl, 3-aminocarbonylphenyl, 4-aminocarbonylphenyl, 2-cyanophenyl, 3-cyanophenyl, 3-benzamidine, 4-fluorophenyl, 4-hydroxyphenyl, 4-nitrophenyl, 4-N,N-dimethylaminophenyl, 4-N-acetylaminophenyl, N-hydroxy-benzamidin-3-yl, N-hydroxy-benzamidin-4-yl, 4-[(morpholin-4-yl)methyl]-phenyl, 4-N-ethylaminophenyl, 2-ethoxy-4-fluorophenyl, 4-hydroxyphenyl, 2-allyloxyphenyl, 2-benzyloxyphenyl, or 2-propoxyphenyl, 2-hydroxyphenyl; and     R3=methyl-4-formylbenzoate, 4-carboxybenzaldehyde, 3-pyridinecarboxaldehyde, 2-thiophenecarboxaldehyde, 3-hydroxy-4-methoxybenzaldehyde, 4-methyl-5-imidazolecarboxaldehyde, 3-(2-morpholin-4-yl-ethoxy)-4-methoxy-benzaldehyde, 3,4-dimethoxybenzaldehyde, 3-methoxy-4-(2-morpholin-4-yl-ethoxy)-benzaldehyde, 3-methoxy-4-hydroxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, 3-hydroxy-4,5-dimethoxybenzaldehyde, 3,5-dimethoxy-4-hydroxybenzaldehyde, 2,3-dihydro-benzo[1,4]dioxine-6-carbaldehyde, 2-chlorobenzaldehyde, 2-fluorobenzaldehyde, 2,4-dimethoxybenzaldehyde, 3-methoxy-4-hydroxy-5-bromobenzaldehyde, 3-chloro-4-hydroxybenzaldehyde, 3-thiophenecarboxaldehyde, 2-imidazolecarboxaldehyde, 3,4-dimethoxy-5-hydroxybenzaldehyde, 1-imidazolecarboxaldehyde, 4-(1H-imidazol-1-yl)benzaldehyde, 4-pyridinecarboxaldehyde, 2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbaldehyde, 2-furancarboxaldehyde, 3-methyl-2-thiophenecarboxaldehyde, 3-chloro-4-fluorobenzaldehyde, 5-methyl-2-thiophenecarboxaldehyde, 3-furancarboxaldehyde, 4-acetamidobenzaldehyde, 4-N,N-dimethylaminobenzaldehyde, 5-methyl-2-furancarboxaldehyde, 4-fluorobenzaldehyde, 1-methyl-2-imidazolecarboxaldehyde, 3-cyanobenzaldehyde, 4-cyanobenzaldehyde, 4-bromobenzaldehyde, 2-pyridinecarboxaldehyde, 3-tetrahydrofurancarboxaldehyde, 3-methoxybenzaldehyde, 4-methoxybenzaldehyde, 3-(2-diethylamino-ethoxy)-4-methoxy-benzaldehyde, 3,5-dimethoxy-4-(2-diethylamino-ethoxy)-benzaldehyde, 2-fluorobenzaldehyde, 3-[bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde, or 3-dimethylamino-4-(morpholin-4-yl)-benzaldehyde.        

      In a further embodiment, the at least one small-molecule Src inhibiting compound is selected from the group consisting of: 
      Methyl 4-formylbenzoate (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(4-aminomethyl)phenyl-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(4-aminomethyl)phenyl-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(4-aminomethyl)phenyl-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4methoxybenzaldehyde (6-(4-aminomethyl)phenyl-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(3-aminomethyl)phenyl-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-aminomethyl)phenyl-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(4-aminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(4-aminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-aminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(3-aminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(3-aminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-aminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-methyl-6-(morpholin-4-yl)methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (7-methyl-6-(morpholin-4-yl)methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methyl-5-imidazolecarboxaldehyde (7-methyl-6-(morpholin-4-yl)methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-methyl-6-(3-(morpholin-4-yl)methyl)phenylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-methyl-6-(phenylamino)methylthieno[3,2-d]pyrimidin-4-yl)hydrazone);     3-Hydroxy-4-methoxybenzaldehyde (6-(3-aminocarbonylphenyl)-7-methylthieno[3,2-d pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(3-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(3-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(3-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(4-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(4-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(4-aminocarbonylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(3-cyanophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(3-cyanophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(3-cyanophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(3-cyanophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-cyanophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(benzamidin-3-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl)-hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-hydroxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-nitrophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-N,N-dimethylaminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-N-acetylaminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(benzamidin-3-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl] hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-(morpholin-4-yl)methylphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-N-ethylaminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-N-ethylaminophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(N-hydroxy-benzamidin-3-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(N-hydroxy-benzamidin-4-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(N-hydroxy-benzamidin-4-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxy-3-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4-Dimethoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxy-4-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4,5-Trimethoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4-Dimethoxy-5-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2,3-Dihydro-benzo[1,4]dioxine-6-carbaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(4-hydroxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl]hydrazone;     4-Carboxybenzaldehyde (6-(4-hydroxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl]hydrazone;     2-Chlorobenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2,4-Dimethoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-allyloxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-benzyloxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(2-benzyloxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-methyl-6-(2-propoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-hydroxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxy-3-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-ethoxymethyl)-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-((±)-4,5-dihydroxy-2-oxopentyl)-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-aminophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Hydroxy-3-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromo-4-hydroxy-5-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Chloro-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Thiophenecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Imidazolecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4-Dimethoxy-5-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(1H-imidazol-1-yl)benzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Pyridinecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2,4-Dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Carboxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methyl-5-imidazolecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     Methyl 4-formyl benzoate (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Furancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methyl-2-thiophenecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Chloro-4-fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     5-Methyl-2-thiophenecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Furancarboxaldehyde(6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Acetamidobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-N,N-Dimethylaminobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     5-Methyl-2-furancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     1-Methyl-2-imidazolecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Cyanobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Cyanobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Bromobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Pyridinecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Tetrahydrofurancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methoxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-(2-(morpholin-4-yl)-ethoxy)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl) thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(4-aminophenyl)-7-cyanolthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (7-cyano-6-(2-ethoxy-4-fluorophenyl) thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Pyridinecarboxyaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Hydroxy-3-methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromo-4-hydroxy-5-methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Chloro-4-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Thiophenecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Imidazolecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4-Dimethoxy-5-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(1H-Imidazol-1-yl)benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (7-cyano-6-(2-ethoxy-4-fluorophenyl) thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Pyridinecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2,4-Dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Carboxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methyl-5-imidazolecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     Methyl 4-formyl benzoate (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Furancarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methyl-2-thiophenecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Chloro-4-fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d)pyrimidin-4-yl)hydrazone;     5-Methyl-2-thiophenecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Furancarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Acetamidobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-N,N-Dimethylaminobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     5-Methyl-2-furancarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     1-Methyl-2-imidazolecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Cyanobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Cyanobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Bromobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Pyridinecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Tetrahydrofurancarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-[Bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Dimethylamino-4-(morpholin-4-yl)-benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-vinylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl) 7-ethylthieno[3,2-d]pyrimidin-4-yl)hydrazone; and mixtures thereof.    

      More preferably, the small molecule Src inhibiting compound is selected from the group consisting of: 
      4-Methoxy-3-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxy-3-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(1H-Imidazol-1-yl)benzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Acetamidobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-N,N-Dimethylaminobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     5-Methyl-2-furancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     1-Methyl-2-imidazolecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Cyanobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Cyanobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Bromobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Pyridinecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Tetrahydrofurancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromo-4-hydroxy-5-methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Thiophenecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4-Dimethoxy-5-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     1-Methyl-2-imidazolecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Cyanobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Bromobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Pyridinecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Tetrahydrofurancarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3;2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-[Bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Dimethylamino-4-(morpholin-4-yl)-benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone; and mixtures thereof.    

      A further embodiment is a pharmaceutical composition for the treatment of human and mammal diseases including but not limited to hyperproliferative diseases, hematologic diseases such as osteoporosis, neurological diseases such as Alzheimer&#39;s Disease, epilepsy or senility, autoimmune diseases, allergic/immunological diseases such as anaphylaxis, or viral infections which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one compound disclosed herein or a pharmaceutically acceptable salt or hydrate thereof. The use of the disclose Src inhibiting compounds is not limited to the diseases listed herein.  
      Another embodiment is a method of synthesizing one or more of the compounds disclosed herein or a pharmaceutically acceptable salt or hydrate thereof. Synthesis procedures are explained in detail below.  
      Another embodiment is a method of inhibiting a member of the Src family of protein tyrosine kinases by administering to a subject one or more compounds disclosed herein or a pharmaceutically acceptable salt or hydrate thereof.  
      In a further embodiment, the step of the binding at least one of the disclosed compounds to protein tyrosine kinases may be included. In a further embodiment, the cell may be contacted with one or more of the disclosed compounds in order to alter cell morphology, migration, adhesion, cell cycle progression, secretion, differentiation, proliferation, anchorage-independent growth, vascular endothelial growth factor expression, microtubule binding by tau, viral infectivity, or bone reabsorption. In further embodiments, the protein tyrosine kinase may be Src, Fyn, Yes, Lyn, Lck, Blk, Hck, or Fgr.  
      Another embodiment is a method of treating a Src family of tyrosine kinase-related disease in a subject comprising the step of administering to the subject a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the disclosed compounds.  
      In further embodiments, the administering may parenteral. In still further embodiments, the parenteral administration may be intravenous, intramuscular, subcutaneous, intraperitoneal, intraarterial, intrathecal or transdermal. In a further embodiment, the administering may be alimentary. In a further embodiment, the alimentary administration may be oral, rectal, sublingual, or buccal. In a further embodiment, the administration may be topical. In a further embodiment, the administration may be by inhalation. In a further embodiment, the administering may be combined with a second method of treatment.  
      Another embodiment is a method of preventing replication of a virus in an organism by administering to the organism infected with the virus one or more of the compounds disclosed herein. In a further embodiment, the virus may be a herpesvirus, papovavirus, hepadnavirus or retrovirus.  
      More preferably, the small molecule Src inhibiting compound is selected from the group consisting of: 
      4-Methoxy-3-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxy-3-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde (6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Carboxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(1H-imidazol-1-yl)benzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Acetamidobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-N,N-Dimethylaminobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     5-Methyl-2-furancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     1-Methyl-2-imidazolecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Cyanobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Cyanobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Bromobenzaldehyde (6-(2-ethoxyphenyl]-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Pyridinecarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Tetrahydrofurancarboxaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (6-(2-ethoxyphenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromo-4-hydroxy-5-methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Thiophenecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,5-Dimethoxy-4-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3,4-Dimethoxy-5-hydroxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     1-Methyl-2-imidazolecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Cyanobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Bromobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Bromobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Pyridinecarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Tetrahydrofurancarboxaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     4-Methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Methoxybenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     2-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-[Bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     3-Dimethylamino-4-(morpholin-4-yl)-benzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone; and mixtures thereof.    

      As used herein the specification, “a” or “an” may mean one or more. As used herein in the claim(s), when used in conjunction with the word “comprising,” the words “a” or “an” may mean one or more than one. As used herein “another” may mean at least a second or more.  
      Other features and advantages of the disclosed compounds, synthesis methods and treatment methods will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating certain preferred embodiments, are given by way of illustration only, since various changes and modifications that fall within the spirit and scope of this disclosure will become apparent to those skilled in the art from this summary and the following detailed description.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The following drawings form part of the present disclosure and are included to further demonstrate certain aspects of the disclosed compounds and methods, wherein:  
       FIG. 1  illustrates the general structure of the disclosed thienopyrimidine-based compounds, wherein the R 1 , R 2  and R 3  groups are defined as herein;  
       FIG. 2  is a schematic flow chart illustrating the synthesis of 4-(2-diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 160; Example 1);  
       FIG. 3  is a schematic flow chart illustrating the synthesis of 2-thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 107; Example 2);  
       FIG. 4  is a schematic flow chart illustrating the synthesis of 4-(2-diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 159; Example 3);  
       FIG. 5  is a schematic flow chart illustrating the synthesis of 3-hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methoxythieno[3,2-d]pyrimidin-yl)hydrazone (Compound 40; Example 4);  
       FIG. 6  is a schematic flow chart illustrating the synthesis of 3-fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 139; Example 5); and  
       FIG. 7  is a schematic flow chart illustrating the synthesis of 3-hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-vinylthieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 34; Example 6). 
    
    
     DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS  
      The Src family of PTKs catalyzes the transfer of the gamma phosphate of ATP to protein substrates within the cell. The thienopyrimidine-based inhibitors act by blocking this transfer of the phosphate thereby inhibiting the catalytic activity of the Src family. These compounds are reversible inhibitors that exhibit a “competitive” type of inhibition against ATP. By blocking the catalytic activity of the Src family, the signal-transduction pathway regulating the growth of tumor cells can be stopped or significantly impeded. The disclosed thienopyrimidine-based inhibitors show specificity for Src over the two other kinases tested, Csk and FGFr.  
      Definitions  
      Hematologic Disease As used herein, “hematologic disease” refers to a disease in which there is abnormal generation of blood cells.  
      Neurologic Disease As used herein, “neurologic disease” refers to a disease caused by abnormalities within the nervous system.  
      Proliferative Disease As used herein, “proliferative disease” refers to a disease that occurs due to abnormal growth or extension by the multiplication of cells (Cambridge Dictionary of Biology, 1990).  
      Autoimmune Disease As used herein, “autoimmune disease” refers to a disease caused by the presence and activation of T or B lymphocytes capable of recognizing “self” constituents with the release of auto-antibodies or damage caused to cells by cell-mediated immunity (Cambridge Dictionary of Biology, 1990).  
      Allergic/Immunological Disease As used herein, “allergic/immunological disease” refers to disease caused by one or more aspects of the immune system. Examples of included types of diseases are immunodeficiency, characterized by increased susceptibility to infections due to the deficiency of a component of the immune system (B cells, T cells, phagocytic cells, and complement); hypersensitivity disorders, which result from immunologically specific interactions between antigens (exogenous or endogenous) and humoral antibodies or sensitized lymphocytes; and reactions to transplantations, in which allografts are rejected through either a cell-mediated or a humoral immune reaction of the recipient against antigens present on the membranes of the donor&#39;s cells (The Merck Manual, 1999).  
      Viral Infection As used herein, “viral infection” refers to a disease caused by the invasion of body tissue by a micro-organism that requires a cell in which to multiply (Cambridge Dictionary of Biology, 1990).  
      Src family of protein tyrosine kinases As used herein, “Src family of protein tyrosine kinases” refers to a group of intracellular non-receptor tyrosine kinases that share similar structural features and regulation such as a N terminal sequence for lipid attachment, a unique domain, SH3, SH2, and kinase domains, followed by a C-terminal negative regulatory tail (Smithgall, 1998). Any reference to the Src family or its individual members includes all alternatively spliced forms of these proteins. Examples include alternatively spliced neuronal Src and alternatively spliced forms of Fyn and Lyn. Alternatively spliced forms of Src are referred to as N x , where x indicates the size of the N-loop within the SH3 domain where alternative splicing occurs. Therefore, Src is also referred to as N 6 . Examples of alternatively spliced forms of Src include N 12  and N 23 .  
      Src family of tyrosine kinase-related disease As used herein, “Src family of tyrosine kinase-related disease” refers to any disease in which the disorder occurs due to an alteration in the activity of the Src family of tyrosine kinases, or in which it is advantageous to block the signaling pathway of a Src family member.  
      Binding As used herein, “binding” refers to the non-covalent or covalent interaction of two chemical compounds.  
      Inhibiting As used herein, “inhibiting” refers to the ability of a substance to reduce the velocity of an enzyme-catalyzed reaction (Biochemical Calculations, 1976). A substance is a better inhibitor than another if it is able to cause the same amount of reduction in velocity at a lower concentration than another substance.  
      Functional equivalent As used herein, “functional equivalent” refers to a chemical structure, other than a hydrazone bridge, that when inserted in place of the hydrazone bridge, is capable of providing inhibition of a Src tyrosine kinase. The present invention encompasses functional equivalents of a hydrazone bridge oriented with either end of the bridge attached to the thienopyrimidine structure at R 3 .  
      Halogen As used herein, “halogen” refers to fluoro, chloro, bromo, or iodo.  
      Alkyl As used herein, “alkyl” refers to a group of carbon and hydrogen atoms derived from an alkane molecule by removing one hydrogen atom. “Alkyl” may include saturated monovalent hydrocarbon radicals having straight, cyclic or branched moieties. Said “alkyl” group may include an optional carbon-carbon double or triple bond where said alkyl group comprises at least two carbon atoms. It is understood that for cyclic moieties at least three carbon atoms are required in said alkyl group.  
      Aryl As used herein, “aryl” refers to an organic radical derived from an aromatic hydrocarbon by removal of one hydrogen.  
      Hydrazone As used herein, “hydrazone” refers to any of a class of compounds containing the group RC═NNHR′. The thienopyrimidine structure may be represented by either R or R′. Therefore, either end of the bridge may be attached to the thienopyrimidine structure at R 3 .  
      Alkoxy As used herein, “alkoxy” refers to O-alkyl groups wherein “alkyl” is as defined above.  
      Hydrogen bond As used herein, “hydrogen bond” refers to the primarily electrostatic bond formed by interaction of a hydrogen atom covalently bound to a highly electronegative element (e.g., oxygen, nitrogen, or fluorine) and a second electronegative atom (e.g., oxygen, nitrogen, or fluorine). The bonding partners are called “hydrogen bond donor atom,” that is the atom to which hydrogen is covalently bound, and “hydrogen bond acceptor atom.” 
      Salt bridge As used herein, “salt bridge” refers to the attractive force, described by Coulomb&#39;s law, between either a cation and an anion or between a cationic and an anionic group of atoms; the cationic and anionic groups may be on the same molecule or on different molecules.  
      Heterocyclic As used herein, heterocyclic, refers to a cyclic compound in which one or more of the atoms in the ring are elements other than carbon. The atoms that are not carbon may be any possible substituent. Heterocyclic compounds may or may not be aromatic.  
      Orientation of Compounds  
      Certain disclosed compounds may exist in different enantiomeric forms. This disclosure relates to the use of all optical isomers and stereoisomers of the disclosed compounds that possess the desired activity. One of skill in the art would be aware that if a given isomer does not possess the desired activity, that isomer should not be used for treatment.  
      Pharmaceutical Compositions  
      Pharmaceutically Acceptable Carriers  
      The disclosed compositions comprise an effective amount of one or more disclosed thienopyrimidine-based compounds or pharmaceutically acceptable salts thereof, dissolved and/or dispersed in a pharmaceutically acceptable carrier.  
      The phrases “pharmaceutically and/or pharmacologically acceptable” refer to molecular entities and/or compositions that do not produce an adverse, allergic and/or other unacceptable reaction when administered to an animal.  
      As used herein, “pharmaceutically acceptable carrier” includes any and/or all solvents, dispersion media, coatings, antibacterial and/or antifungal agents, isotonic and/or absorption delaying agents and/or the like. The use of such media and/or agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media and/or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. For human administration, preparations should meet sterility, pyrogenicity, general safety and/or purity standards as required by FDA Office of Biologics standards. Various pharmaceutical preparations and administration methods are discussed in U.S. Pat. No. 6,503,914 and the references cited therein.  
      Lipid Formulations and/or Nanocapsules  
      In certain embodiments, the use of lipid formulations and/or nanocapsules is contemplated for the introduction of with the disclosed thienopyrimidine-based compounds or pharmaceutically acceptable salts thereof into host cells as disclosed in U.S. Pat. No. 6,503,914.  
      Kits  
      Disclosed therapeutic kits comprise the disclosed thienopyrimidine-based compounds or pharmaceutically acceptable salts thereof. Such kits will generally contain, in suitable container means, a pharmaceutically acceptable formulation of with the disclosed thienopyrimidine-based compounds in a pharmaceutically acceptable formulation as disclosed in U.S. Pat. No. 6,503,914. The kit may have a single container means, and/or it may have distinct container means for each compound.  
      Combination Treatments  
      In order to increase the effectiveness of with the disclosed thienopyrimidine-based compounds, it may be desirable to combine these compositions with other agents effective in the treatment of the disease as disclosed in U.S. Pat. No. 6,503,914. The disclosed thienopyrimidine-based compounds may also be combined with other agents, treatments and/or therapies in the treatment of hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, viral infections, and hyperproliferative disease. Such treatments and therapies that may be combined with the use of the disclosed compounds include chemotherapy, radiotherapy, immunotherapy, gene therapy, antisense, inducers of cellular proliferation, inhibitors or cellular proliferation, regulators of programmed cell death, surgery and other agents and treatment as discussed in U.S. Pat. No. 6,503,914, the references cited therein and the references cited herein.  
     EXAMPLES  
      The following examples are included to demonstrate preferred embodiments. It should be appreciated by those skilled in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the disclosed techniques, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the concept, spirit and scope of this disclosure. More specifically, it will be apparent that certain agents that are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of this disclosure.  
      The following Examples 1-6 provide a synthesis procedure for a specific disclosed compound shown in one of  FIGS. 2-7  identified by a reference number in parenthesis. The same reference numbers are used to identify the disclosed compounds in Tables 1-7 and  FIGS. 2-7 . It will be noted that the synthesis procedure are applicable to the compounds disclosed in Tables 1-6 immediately following the synthesis procedures explained in Examples 1-6 respectively.  
      Additionally, a number of compounds disclosed in Tables 1-7 and  FIGS. 2-7  require additional reagent modification before or after induction into the provided synthetic route. These reagent modifications and the related compounds will be addressed in a Reagent Modification Section after Table 6 and before Example 7.  
     Example 1  
     Synthesis of 4-(2-diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 160; See FIG.  2 )  
      3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165): Commercially available from Lancaster Synthesis Inc., Windham, N.H., USA.  
      3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166): Formic acid (60 mL) was added to acetic anhydride (90 mL) cooled in an ice bath. 3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165, 25.0 g, 0.146 mol) was added to the cold solution in small portions. The cooling bath was removed and the resulting suspension was stirred at room temperature for 4 hours. The reaction mixture was added to 150 g Na 2 CO 3  in water (500 mL) cooled in an ice bath. The solid product was collected by vacuum filtration, washed with water and dried over P 2 O 5  under vacuum overnight (28.5 g, 97% yield, white solid).  
      7-Methyl-3H-thieno[3,2-d]pyrimid-4-one (167): 3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166, 10.0 g, 50.0 mmol), ammonium formate 26.0 g, (400 mmol) and formamide (12 mL) were heated at 160° C. for 6 hours under N 2  and then cooled to room temperature. The precipitate was collected by vacuum filtration, washed with acetone, and dried over P 2 O 5  under vacuum overnight (6.0 g 72% yield, white needles).  
      4-Chloro-7-methylthieno[3,2-d]pyrimidine (168): A solution of 7-methyl-3H-thieno[3,2-d]pyrimid-4-one (167, 10.6 g, 64.0 mmol) in phosphorus oxychloride (42 mL) was refluxed under N 2  for 2 hours. The resulting solution was allowed to cool to room temperature and then neutralized by carefully pouring into a saturated aqueous solution of sodium carbonate (300 mL). The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine, before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue dried over P 2 O 5  under vacuum overnight (11.2 g, 95% yield, white solid).  
      4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169): Diisopropylamine (11 mL 77.8 mmol, 1.43 eq) was dissolved in anhydrous THF 100 mL, and the solution was chilled to −78° C. 22 mL 1.6 M BuLi in hexanes (70.8 mmol, 1.3 eq) was added, and the solution was stirred for 30 minutes at −78° C. A solution of 4-chloro-7-methylthieno[3,2-d]pyrimidine (168, 10.0 g 54.4 mmol) in 100 mL anhydrous THF was chilled to −78° C., and the LDA solution was then transferred via cannula to the cold solution of 168. The reaction mixture became a dark brown suspension as the LDA solution was added. After 2 hours at −78° C., a solution of I 2  (20.8 g 81.6 mmol, 1.5 eq) in 50 mL THF was cannulated to the anion solution. The reaction mixture was maintained at −78° C. for 2 hours and then warmed to room temperature overnight. After overnight stirring, the reaction mixture was diluted with EtOAc and washed three times with deionized H 2 O, twice with saturated Na 2 S 2 O 4 , once with deionized H 2 O, three times with 10% HCl, and once with saturated NaCl. The dark solution was dried over anhydrous Na 2 SO 4 , decolorized with activated carbon, and then filtered through silica gel. The resulting light yellow filtrate was concentrated by rotary evaporation, and a light yellow solid precipitated as the solution was concentrated. After concentrating to a small volume, the precipitate was collected via filtration and was washed twice with ice cold EtOAc (13.7 g, 82% yield).  
      4-Chloro-(6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidine (170): 4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169, 3.43 g, 11.0 mmol) and dichlorobis(triphenylphosphine)palladium (II) (0.38 g, 0.57 mmol) were placed in a mixture of 1,2-dimethoxyethane (160 mL) and distilled water (60 ml) and stirred at room temperature for 10 minutes under N 2 . 2-Ethoxy-4-fluorophenyl boronic acid (2.20 g, 12.0 mmol) and Cs 2 CO 3  (8.86 g, 45.93 mmol) were added to the reaction mixture. The suspension was heated at 80° C. for 20 hr, cooled to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography and the product was dried over P 2 O 5  under vacuum overnight (0.80 g, 23% yield, white solid).  
      (6-(2-Ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazine (171). A suspension of 4-chloro-(6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidine (170, 0.50 g, 1.06 mmol) and hydrazine monohydrate (0.75 mL) were refluxed in ethanol (15 mL) for 1 hour. After cooling to room temperature, the solid product was collected by vacuum filtration (0.43 g, 87% yield, white solid).  
      4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazone (160). A suspension of (6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidin-4-yl)hydrazine (171, 55.0 mg, 0.17 mmol) and 4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (60.8 mg, 2.16 mmol) were refluxed in ethanol (2 mL) for 4 hours. After cooling to room temperature, the solid product was collected by vacuum filtration (35.0 mg, 35% yield, white solid).  
      Compounds that can be made using the above procedure with the appropriate substitution of reagents are listed in Table 1. The synthesis of Compound 160 as illustrated above is also illustrated in  FIG. 2 .  
                               TABLE 1                                       Purity                       by       Compound   No   1H NMR   MS   HPLC                                                    Methyl 4-formylbenzoate (6-(2-   1   (300MHz, DMSO-d6),   M+1=446   99%       ethoxyphenyl)-7-methylthieno[3,2-       12.27(s, 1H), 8.62(s,   (ESI+)       d]pyrimidin-4-yl)hydrazone       1H), 8.25(s, 1H), 8.02(d,               J=8.4Hz, 2H), 7.89(d,               J=8.4Hz, 2H), 7.40-7.54(m,               2H), 7.21(d, J=8.4Hz,               1H), 7.10(t, J=7.5Hz,               1H), 4.15(q, J=7.2Hz,               2H), 3.85(s, 3H),               2.25(s, 3H), 1.27(t,               J=6.9Hz, 3H)       4-Carboxybenzaldehyde (6-(4-   2   (300MHz, DMSO-d6),   M+1=418   98%       aminomethyl)phenyl-7-       12.4(br s, 1H), 8.62(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.25(s, 1H), 7.99(d,       yl)hydrazone       J=8.1Hz, 2H), 7.88(d,               J=8.4Hz, 2H), 7.75(d,               J=8.4Hz, 2H), 7.65(d,               J=8.1Hz, 2H), 4.12(s,               2H), 2.44(s, 3H)       3-Pyridinecarboxaldehyde (6-(4-   3   (300MHz, DMSO-d6),   M−1=373   99%       aminomethyl)phenyl-7-       8.93(s, 1H), 8.60(s, 1H),   (ESI−)       methylthieno[3,2-d]pyrimidin-4-       8.55(dd, J=6Hz, J=1.5Hz,       yl)hydrazone       1H), 8.21(s, 1H),               8.14(dd, J=6Hz, J=1.5Hz,               1H), 7.61(d, J=8.4Hz,               2H), 7.49-7.54(m,               3H), 3.83(s, 2H), 2.42(s,               3H)       2-Thiophenecarboxaldehyde (6-(4-   4   (300MHz, DMSO-d6),   M+1=380   94%       aminomethyl)phenyl-7-       8.55(s, 1H), 8.35(s, 1H),   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       7.61(d, J=3Hz, 1H), 7.56(d,       yl)hydrazone       J=8Hz, 2H), 7.50(d,               J=8Hz, 2H), 7.42(d, J=3Hz,               1H), 7.12(dd, J=3Hz,               J=1.5Hz, 1H), 3.78(s,               2H), 2.41(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   5   (300MHz, DMSO-d6),   M+1=420   99%       (6-(4-aminomethyl)phenyl-7-       8.53(s, 1H), 8.04(s, 1H),   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       7.59(d, J=7.8Hz, 2H),       yl)hydrazone       7.51(d, J=8.1Hz, 2H),               7.27(s, 1H), 7.10(d,               J=6.6Hz, 2H), 6.99(d,               J=8.7Hz, 2H), 3.80(s,               5H), 2.40(s, 3H)       3-Pyridinecarboxaldehyde (6-(3-   6   (300MHz, DMSO-d6),   M+1=375   99%       aminomethyl)phenyl-7-       8.93(s, 1H), 8.62(s, 1H),   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       8.56(dd, J=4.5Hz, J=1.5Hz,       yl)hydrazone       1H), 8.23(s, 1H),               8.17(m, 1H), 7.64(s,               1H), 7.45-7.53(m, 3H),               3.82(s, 2H), 2.43(s, 1H)       3-Hydroxy-4-methoxybenzaldehyde   7   (300MHz, DMSO-d6),   M+1=420   ND       (6-(2-aminomethyl)phenyl-7-       8.55(s, 1H), 8.03(s, 1H),   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       7.69(d, J=8.1Hz, 1H,)       yl)hydrazone       7.49(t, J=7.2Hz, 1H),               7.32-7.39(m, 2H), 7.19(s,               1H), 7.07(dd, J=8.4Hz,               J=1.8Hz, 1H), 6.97(d,               J=8.1Hz, 1H), 3.77(s,               3H), 3.61(s, 2H), 2.11(s,               3H)       3-Pyridinecarboxaldehyde (6-(4-   8   (300MHz, DMSO-d6),   M+1=361   99%       aminophenyl)-7-methylthieno[3,2-       12.26(br s, 1H), 8.94(s,   (ESI+)       d]pyrimidin-4-yl)hydrazone       1H), 8.57(s, 1H), 8.21(s,               1H), 8.18(d, J=7.8Hz,               1H), 7.53(m, 1H), 7.35(d,               J=8.4Hz, 2H), 6.71(d,               J=8.4Hz, 2H), 2.40(s,               3H)       2-Thiophenecarboxaldehyde (6-(4-   9   (300MHz, DMSO-d6),   M+1=366   95%       aminophenyl)-7-methylthieno[3,2-       11.98(s, 1H), 8.51(s,   (ESI+)       d]pyrimidin-4-yl)hydrazone       1H), 8.33(s, 1H), 7.63(d,               J=5.4Hz, 1H), 7.41(d,               J=4.5Hz, 1H), 7.32(d,               J=8.7Hz, 2H), 7.11(m,               1H), 6.69(d, J=8.7Hz,               2H), 5.54(s, 2H), 2.38(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   10   (300MHz, DMSO-d6),   M+1=406   99%       (6-(4-aminophenyl)-7-       11.79(s, 1H), 9.28(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.48(s, 1H), 8.02(s,       yl)hydrazone       1H), 7.34(d, J=8.7Hz,               2H), 7.26(s, 1H), 7.10(d,               J=7.8Hz, 1H), 7.00(d,               J=7.8Hz, 1H), 5.54(s,               2H), 3.80(s, 3H), 2.38(s,               3H)       3-Pyridinecarboxaldehyde (6-(3-   11   (300MHz, DMSO-d6),   M+1=361   99%       aminophenyl)-7-methylthieno[3,2-       12.28(s, 1H), 8.94(s,   (ESI+)       d]pyrimidin-4-yl)hydrazone       1H), 8.60(s, 1H), 8.57(d,               J=4.2Hz, 1H), 8.22(s,               1H), 8.16(d, J=8.1Hz,               1H), 7.53(m, 1H), 7.17(t,               J=7.8Hz, 1H), 6.84(s,               1H), 6.76(d, J=8.1Hz,               1H), 6.66(d, J=7.5Hz,               1H), 5.40(br s, 2H), 2.42(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   12   (300MHz, DMSO-d6),   M+1=406   99%       (6-(3-aminophenyl)-7-methylthieno       11.87(s, 1H), 9.28(s,       [3,2-d]pyrimidin-4-       1H), 8.52(s, 1H), 8.04(s,       yl)hydrazone       1H), 7.11-7.23(m, 3H),               7.01(d, J=8.7Hz, 1H),               6.83(s, 1H), 6.75(d,               J=6.6Hz, 1H), 6.65(d,               J=9.0Hz, 1H), 5.35(br s,               2H), 3.80(s, 3H), 2.39(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   13   (300MHz, DMSO-d6),   M+1=406   99%       (6-(2-aminophenyl)-7-methylthieno       11.83(br s, 1H), 9.26(s,   (ESI+)       [3,2-d]pyrimidin-4-       1H), 8.53(s, 1H), 8.02(s,       yl)hydrazone       1H), 6.97-7.19(m, 5H),               6.78(d, J=8.1Hz, 1H),               6.62(d, J=7.5Hz, 1H),               5.03(s, 2H), 3.78(s, 3H),               2.17(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   14   (300MHz, DMSO-d6),   M+1=414   99%       (7-methyl-6-(morpholin-4-yl)methylthieno       11.80(s, 1H), 9.16(s,   (ESI+)       [3,2-d]pyrimidin-4-       1H), 8.48(s, 1H), 8.02(s,       yl)hydrazone       1H), 7.31(s, 1H), 7.13(d,               J=2.4Hz, 1H), 7.00(d,               J=8.4Hz, 1H), 3.83(s,               3H), 3.64(s, 2H), 2.31(s,               3H)       3-Pyridinecarboxaldehyde (7-methyl-   15   (300MHz, DMSO-d6),   M+1=369   99%       6-(morpholin-4-yl)methyllthieno       12.20(s, 1H), 9.01(s,   (ESI+)       [3,2-d]pyrimidin-4-       1H), 8.58(d, J=1.8Hz,       yl)hydrazone       1H), 8.54(s, 1H), 8.17(m,               2H), 7.53(m, 1H),               3.86(s, 3H), 3.64(m,               4H), 2.31(s, 3H)       4-Methyl-5-imidazolecarboxaldehyde   16   (300MHz, DMSO-d6),   M+1=372   ND       (7-methyl-6-(morpholin-4-yl)methyllthieno       12.20(s, 1H), 11.50(s,   (ESI+)       [3,2-d]pyrimidin-4-       1H), 8.42(s, 1H), 8.16(s,       yl)hydrazone       1H), 7.59(s, 1H), 3.80(s,               3H), 3.60(m, 4H), 2.61(s,               3H), 2.27(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   17   (300MHz, DMSO-d6),   M+1=490   99%       (7-methyl-6-(3-(morpholin-4-       11.93(s, 1H), 9.27(s,   (ESI+)       yl)methyl)phenylthieno[3,2-       1H), 8.54(s, 1H), 8.04(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.43-7.58(m, 4H),               7.27(s, 1H), 7.09(d,               J=8.4Hz, 1H), 6.97(d,               J=8.4Hz, 1H), 3.80(s,               3H), 3.58(s, 2H), 2.41(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   18   (300MHz, DMSO-d6),   M+1=420   99%       (7-methyl-6-       11.76(s, 1H), 9.18(s,   (ESI+)       (phenylamino)methylthieno[3,2-       1H), 8.47(s, 1H), 7.96(s,       d]pyrimidin-4-yl)hydrazone)       1H), 7.17(d, J=2.1Hz,               1H), 7.08(m, 3H), 6.91(d,               J=8.4Hz, 1H), 6.67(d,               J=7.5Hz, 2H), 6.54(t,               J=7.5Hz, 1H), 6.38(t,               J=7.5Hz, 1H), 4.58(d,               J=5.4Hz, 2H, 3.82(s,               3H), 2.37(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   19   (300MHz, DMSO-d6)   M+1=434   ND       (6-(3-aminocarbonylphenyl)-7-       11.95(s, 1H, NH), 9.29(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.56(s, 1H), 8.31(m,       yl)hydrazone       2H), 8.07(s, 1H),               8.00(d, J=8.0Hz, 1H),               7.88(d, J=8.0Hz, 1H),               7.65(t, J=8.0Hz, 1H),               7.54(s, 1H), 7.28(d,               J=8.0Hz, 1H), 7.11(d,               J=8.0Hz, 1H), 6.99(d,               J=8.0Hz, 1H), 3.80(s,               3H), 2.41(s, 3H)       2-Thiophenecarboxaldehyde (6-(3-   20   (300MHz, DMSO-d6)   M+1=394   ND       aminocarbonylphenyl)-7-       12.17(s, 1H, NH), 8.98(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.58(s, 1H), 8.36(s,       yl)hydrazone       1H), 8.05(m, 1H),               7.77(m, 2H), 7.45(m,               2H), 7.2(m, 1H), 2.44(s,               3H)       3-Pyridinecarboxaldehyde (6-(3-   21   (300MHz, DMSO-d6)   M+1=389   ND       aminocarbonylphenyl)-7-       12.36(s, 1H, NH), 8.94(d,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       J=1.8Hz, 1H), 8.63(s,       yl)hydrazone       1H) 8.57(s, 1H), 8.57(d,               J=8.0Hz, 1H) 8.21(m,               3H), 8.02(m, 2H), 7.78(m,               2H), 7.50(m, 2H),               2.45(s, 3H)       4-Carboxybenzaldehyde (6-(3-   22   300MHz, DMSO-d6)   M+1=432   ND       aminocarbonylphenyl)-7-       12.33(s, 1H, NH), 8.64(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.26(s, 1H),       yl)hydrazone       8.10-7.66(m, 6H), 7.65-               7.40(m, 2H), 2.45(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   23   (300MHz, DMSO-d6)   M+1=434   ND       (6-(4-aminocarbonylphenyl)-7-       11.96(s, 1H, NH), 9.33(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.57(s, 1H), 8.06(m,       yl)hydrazone       4H), 7.77(m, 2H),               7.50(s, 1H), 7.29(s, 1H),               7.10(d, J=8.0Hz, 1H),               6.99(d, J=8.0Hz, 1H),               3.80(s, 3H), 2.41(s, 3H)       3-Pyridinecarboxaldehyde (6-(4-   24   (300MHz, DMSO-d6)   M+1=389   ND       aminocarbonylphenyl)-7-       12.36(s, 1H, NH), 8.94(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.63(s, 1H) 8.57(d,       yl)hydrazone       J=4.7Hz, 1H), 8.40-               7.84(m, 6H) 7.75(d,               J=8.1Hz, 1H), 7.45(m,               2H), 2.45(s, 3H)       2-Thiophenecarboxaldehyde (6-(4-   25   (300MHz, DMSO-d6)   M+1=394   ND       aminocarbonylphenyl)-7-       12.17(s, 1H, NH), 8.98(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.58(s, 1H), 8.37(s,       yl)hydrazone       1H), 8.02(m, 3H),               7.70(m, 2H), 7.48(m,               2H), 7.13(d, J=4.1,Hz               1H), 2.44(s, 3H)       4-Carboxybenzaldehyde (6-(4-   26   300MHz, DMSO-d6)   M+1=432   ND       aminocarbonylphenyl)-7-       12.19(s, 1H, NH), 8.63(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.25(s, 1H),       yl)hydrazone       8.10-7.92(m, 5H), 7.84(d,               J=8.0Hz, 1H), 7.69(d,               J=8.0Hz, 1H), 7.45(s,               1H) 2.45(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   27   (300MHz, DMSO-d6)   M+1=416   86%       (6-(3-cyanophenyl)-7-       11.99(s, 1H, NH), 9.35(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.57(s, 1H), 7.98(m,       yl)hydrazone       3H), 7.77(t, J=8.0Hz,               1H), 7.31(s, 1H),               7.11(d, J=8.0Hz, 1H),               6.98(d, J=8.0Hz, 1H),               3.80(s, 3H), 2.42(s, 3H)       2-Thiophenecarboxaldehyde (6-(3-   28   (300MHz, DMSO-d6)   M+1=376   ND       cyanophenyl)-7-methylthieno[3,2-       12.19(s, 1H, NH), 9.02(s,   (ESI+)       d]pyrimidin-4-yl)hydrazone       1H), 8.37(s, 1H), 8.05(d,               J=5.0Hz, 2H), 7.92(d,               J=8.5Hz, 2H), 7.90(d,               J=5.0Hz, 1H), 7.44(d,               J=3.0Hz, 1H), 7.2(m,               1H), 2.37(s, 3H)       3-Pyridinecarboxaldehyde (6-(3-   29   (300MHz, DMSO-d6)   M+1=371   ND       cyanophenyl)-7-methylthieno[3,2-       12.37(s, 1H, NH), 8.92(d,   (ESI+)       d]pyrimidin-4-yl)hydrazone       J=1.8Hz, 1H), 8.57(s,               1H), 8.58(d, J=8.0Hz,               1H) 8.20(m, 3H), 7.95(m,               2H), 7.75(m, 1H),               7.50(d, J=8.0Hz, 1H),               2.46(s, 3H)       4-Carboxybenzaldehyde (6-(3-   30   (300MHz, DMSO-d6)   M+1=414   ND       cyanophenyl)-7-methylthieno[3,2-       12.38(s, 1H, NH), 8.64(s,   (ESI+)       d]pyrimidin-4-yl)hydrazone       1H), 8.24(s, 1H),               8.02-8.03(m, 4H), 7.90-               7.60(m, 4H), 2.43(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   31   (300MHz, DMSO-d6)   M+1=416   ND       (6-(2-cyanophenyl)-7-       12.06(s, 1H, NH), 9.29(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.60(s, 1H), 8.06(m,       yl)hydrazone       2H), 7.90(m, 2H),               7.75(m, 2H), 7.21(s,               1H), 7.10(d, J=8.0Hz,               1H), 6.95(d, J=8.0Hz,               1H), 3.78(s, 2H), 2.26(s,               3H)       3-Pyridinecarboxaldehyde (6-   32   300MHz, DMSO-d6)   M+1=388   ND       benzamidin-3-yl)-7-methylthieno[3,2-       12.30(s, 1H, NH), 9.76(s,   (ESI+)       d]pyrimidin-4-yl]-hydrazone       1H), 8.97(s, 1H), 8.60(s,               1H), 8.56(d, J=8.0Hz,               2H), 8.20(s, 1H),               8.12(d, J=8.0Hz, 2H),               7.90(s, 1H) 7.89(d, J=7.4Hz,               1H), 7.81(d, J=8.0Hz,               1H), 7.70(d, J=8.0Hz,               1H), 7.69(m, 1H),               6.00(s, 2H), 2.39(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   36   (300MHz, DMSO-d6),   M+1=409   99%       (6-(4-fluorophenyl)-7-       11.92(s, 1H), 9.31(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.54(s, 1H), 8.04(s,       yl)hydrazone       1H), 7.71(dd, J=9Hz,               J=5.4Hz, 2H), 7.41(dd,               J=8.7Hz, J=8.7Hz, 2H),               7.27(d, J=1.8Hz, 1H),               7.10(dd, J=81Hz, J=1.8Hz,               1H), 6.99(d, J=8.7Hz,               1H), 3.80(s, 3H),               2.39(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   38   (300MHz, DMSO-d6),   M+1=407   97%       (6-(4-hydroxyphenyl)-7-       11.86(s, 1H), 9.90(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 9.31(s, 1H), 8.51(s,       yl)hydrazone       1H), 8.03(s, 1H), 7.48(d,               J=8.7Hz, 2H), 7.26(s,               1H), 7.11(d, J=28.4Hz,               1H), 7.00(d, J=8.1Hz,               1H), 6.93(d, J=7.5Hz,               2H), 3.80(s, 3H), 2.38(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   39   (300MHz, DMSO-d6),   M+1=436   82%       (6-(4-nitrophenyl)-7-       12.04(s, 1H), 9.33(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.58(s, 1H), 8.39(d,       yl)hydrazone       J=8.7Hz, 2H), 8.06(s,               1H), 7.96(d, J=9.0Hz,               2H), 7.29(s, 1H), 7.02(d,               J=8.4Hz, 1H), 6.99(d,               J=8.4Hz, 1H), 3.80(s,               3H), 2.44(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   42   (300MHz, DMSO-d6),   M+1=434   ND       (6-(4-N,N-dimethylaminophenyl)-7-       11.80(s, 1H), 9.28(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.48(s, 1H), 8.01(s,       yl)hydrazone       1H), 7.48(d, J=8.7Hz,               2H), 7.24(s, 1H), 7.10(d,               J=9.3Hz, 1H), 6.99(d,               J=7.5Hz, 1H), 6.85(d,               J=8.1Hz, 2H), 4.36(q,               J=6.9Hz, 2H), 3.79(s,               3H), 2.98(s, 6H), 2.39(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   43   (300MHz, DMSO-d6),   M+1=448   ND       (6-(4-N-acetylaminophenyl)-7-       11.87(s, 1H), 10.16(s,   (ESI+)       methythieno[3,2-d]pyrimidin-4-       1H), 9.31(s, 1H), 8.50(s,       yl)hydrazone       1H), 8.01(s, 1H), 7.74(d,               J=9.3Hz, 2H), 7.58(d,               J=9.3Hz, 2H), 7.25(s,               1H), 7.07(d, 1H), 6.99(d,               1H), 3.79(s, 3H), 2.39(s,               3H), 2.07(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   45   300MHz, DMSO-d6)   M+1=449   ND       (6-(benzamidin-3-yl)-7-       11.89(s, 1H, NH), 9.17(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-yl]-       1H), 8.34(s, 1H), 8.00(s,       hydrazone       1H), 7.89(d, J=8.3Hz,               2H), 7.64(d, J=8.3Hz,               2H), 7.27(s, 1H) 7.11(d,               J=7.5Hz, 1H), 6.78(d,               J=7.4Hz, 1H), 5.96(s,               3H), 3.89(s, 3H), 2.32(s,               3H)       3-Hydroxy-4-methoxybenzaldehyde   46   (300MHz, DMSO-d6)   M+1=490   ND       (6-(4-(morpholin-4-yl)methyl-       11.98(s, 1H, NH), 9.31(s,   (ESI+)       phenyl)-7-methylthieno[3,2-       1H), 8.57(s, 1H), 8.06(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.77(br, 4H),               7.31(s, 1H), 7.08(d,               J=8.0Hz 1H), 6.99(d,               J=8.0Hz, 1H), 4.43(br,               2H), 3.81(s, 3H), 3.33(m,               4H), 2.49(m, 7H)       3-Hydroxy-4-methoxybenzaldehyde   48   (300MHz, DMSO-d6),   M+1=434   ND       (6-(4-N-ethylaminophenyl)-7-       11.78(s, 1H), 9.28(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.48(s, 1H), 8.02(s,       yl)hydrazone       1H), 7.40(d, J=8.4Hz,               2H), 7.26(d, J=1.8Hz,               1H), 7.11(d, J=9.0Hz,               1H), 7.00(d, J=8.4Hz,               1H), 6.69(d, J=9.3Hz,               2H), 6.05(s, 1H), 3.80(s,               3H), 3.10(q, J=6.9Hz,               2H), 2.39(s, 3H), 1.20(t,               J=6.9Hz, 3H)       3-Pyridinecarboxaldehyde (6-(N-   49   300MHz, DMSO-d6)   M+1=404   ND       hydroxy-benzamidin-3-yl)-7-       12.28(s, 1H, NH), 9.78(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.92(s, 1H),       yl)hydrazone       8.62-(s, 1H), 8.56(d,               J=8.0Hz, 2H), 8.22(s,               1H), 8.15(d, J=8.0Hz,               2H), 7.94(s, 1H) 7.88(d,               J=7.5Hz, 1H), 7.80(d,               J=8.0Hz, 1H), 7.71(d,               J=8.0Hz, 1H), 7.63(m,               1H), 5.96(s, 2H), 2.43(s,               3H)       3-Pyridinecarboxaldehyde (6-(N-   50   300MHz, DMSO-d6)   M+1=404   ND       hydroxy-benzamidin-4-yl)-7-       12.28(s, 1H, NH), 9.78(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.94(s, 1H),       yl)hydrazone       8.62-(s, 1H), 8.56(d,               J=5.0Hz, 2H), 8.23(s,               1H), 8.15(d, J=8.0Hz,               2H), 7.67(d, J=8.0Hz,               1H), 7.50(m, 1H),5.93(s,               2H), 2.44(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   51   300MHz, DMSO-d6)   M+1=449   ND       (6-(N-hydroxy-benzamidin-4-yl)-7-       11.91(s, 1H, NH), 9.29(s,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       1H), 8.55(s, 1H),       yl)hydrazone       8.05-(s, 1H), 7.85(d,               J=8.3Hz, 2H), 7.67(d,               J=8.3Hz, 2H), 7.29(s,               1H) 7.12(d, J=7.5Hz,               1H), 6.99(d, J=7.5Hz,               1H), 5.93(s, 2H), 3.80(s,               3H), 2.43(s, 3H)       4-Methoxy-3-(2-(morpholin-4-yl)-   52   (300MHz, DMSO-d6),   M+1=547   97%       ethoxy)-benzaldehyde (6-(2-       8.54(s, 1H), 8.07(s, 1H),   (ESI+)       ethoxyphenyl)-7-methylthieno[3,2-       7.54(d, J=1.5Hz, 1H),       d]pyrimidin-4-yl)hydrazone       7.38-7.49(m, 2H), 7.18(d,               J=8.4Hz, 2H), 7.07(t,               J=8.1Hz, 1H), 7.01(d,               J=8.4Hz, 1H),       3,4-Dimethoxybenzaldehyde (6-(2-   53   (300MHz, DMSO-d6),   M+1=448   99%       ethoxyphenyl)-7-methylthieno[3,2-       8.55(s, 1H), 8.08(s, 1H),   (ESI+)       d]pyrimidin-4-yl)hydrazone       7.53(d, J=1.5Hz, 1H),               7.38-7.48(m, 2H), 7.15-               7.24(m, 2H), 6.97-7.12(m,               2H), 4.11(q, J=6.9Hz,               2H), 3.78(s, 3H),               3.73(s, 3H), 2.23(s, 3H),               1.25(t, J=6.9Hz, 3H)       3-Methoxy-4-(2-(morpholin-4-yl)-   54   (300MHz, DMSO-d6),   M+1=547   99%       ethoxy)-benzaldehyde (6-(2-       8.54(s, 1H), 8.08(s, 1H),   (ESI+)       ethoxyphenyl)-7-methylthieno[3,2-       7.52(s, 1H), 7.39-7.48(m,       d]pyrimidin-4-yl)hydrazone       2H), 7.15-7.24 (m,               2H), 6.99-7.10(m, 2H),               4.01-4.15(m, 4H), 3.73(s,               3H), 3.52-3.60(m,               4H), 2.68(t, J=6.9Hz,               2H), 2.46(m, 4H), 2.23(s,               3H), 1.25(t, J=6.6Hz,               3H)       3-Hydroxy-4-methoxybenzaldehyde   55   (300MHz, DMSO-d6),   M+1=434   99%       (6-(2-ethoxyphenyl)-7-       8.53(s, 1H), 8.04(s, 1H),   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       7.39-7.51(m, 3H), 7.19(d,       yl)hydrazone       J=7.5Hz, 1H), 6.99-               7.11(m, 2H), 6.81(d,               J=8.1Hz, 1H), 4.10(q,               J=6.6Hz, 2H), 3.74(s,               3H), 2.23(s, 3H), 1.26(t,               J=6.6Hz, 3H)       3-Hydroxy-4-methoxybenzaldehyde   57   300MHz, DMSO-d6)   M+1=352   ND       (6-(2-ethoxy-4-fluorophenyl)-7-       11.89(s, 1H), 9.25(s, 1H,   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       NH), 8.53(s, 1H), 8.03(s,       yl)hydrazone       1H), 7.45-6.92(m, 6H),               3.79(m, 3H), 2.20(s, 3H)       3,4,5-Trimethoxybenzaldehyde (6-(2-   63   (300MHz, DMSO-d6),   M+1=478   95%       ethoxyphenyl)-7-methylthieno[3,2-       8.56(s, 1H), 8.07(s, 1H),   (ESI+)       d]pyrimidin-4-yl)hydrazone       7.39-7.47(m, 2H), 7.12-               7.21(m, 3H), 7.05(t,               J=7.8Hz, 1H), 4.08(q,               J=6.9Hz, 2H), 3.76(s,               6H), 3.67(s, 3H), 2.23(s,               3H), 1.24(t, J=6.9Hz,               3H)       3,4-Dimethoxy-5-   64   (300MHz, DMSO-d6),   M+1=464   99%       hydroxybenzaldehyde (6-(2-       8.55(s, 1H), 8.00(s, 1H),   (ESI+)       ethoxyphenyl)-7-methylthieno[3,2-       7.39-7.48(m, 2H), 7.18(d,       d]pyrimidin-4-yl)hydrazone       J=7.8Hz, 1H), 7.06(t,               J=8.1Hz, 1H), 7.00(d,               J=1.8Hz, 1H), 6.83(d,               J=1.5Hz, 1H), 4.09(q,               J=6.9Hz, 2H), 3.75(s,               3H), 3.68(s, 3H), 2.23(s,               3H), 1.25(t, J=6.9Hz,               3H)       3,5-Dimethoxy-4-   65   (300MHz. DMSO-d6),   M+1=464   99%       hydroxybenzaldehyde (6-(2-       8.53(s, 1H), 8.03(s, 1H),   (ESI+)       ethoxyphenyl)-7-methylthieno[3,2-       7.39-7.47(m, 2H), 7.02-       d]pyrimidin-4-yl)hydrazone       7.19(m, 4H), 4.08(q,               J=6.9Hz, 2H), 2.23(s,               3H), 1.25(t, J=7.2Hz,               3H)       2,3-Dihydro-benzo[1,4]dioxine-6-   66   (300MHz, DMSO-d6),   M+1=446   99%       carbaldehyde (6-(2-ethoxyphenyl)-7-       8.53(s, 1H), 8.04(s, 1H),   (ESI+)       methylthieno[3,2-d]pyrimidin-4-       7.35-7.51(m, 2H), 7.30(d,       yl)hydrazone       J=2.1Hz, 1H), 7.18(m,               2H), 7.07(t, J=8.1Hz,               1H), 6.91(d, J=8.7Hz,               1H),       3-Pyridinecarboxaldehyde (6-(4-   75   (300MHz, DMSO-d6),   M+1=362   ND       hydroxyphenyl)-7-methylthieno[3,2-       12.25(s, 1H), 9.90(s,   (ESI+)       d]pyrimidin-4-yl]hydrazone       1H), 8.93(s, 1H), 8.57(m,               2H), 8.21(s, 1H),               8.16(d, J=7.8Hz, 1H),               7.46-7.54(m, 3H), 6.94(d,               J=8.7Hz, 2H), 2.40(s,               3H)       4-Carboxybenzaldehyde (6-(4-   76   (300MHz, DMSO-d6),   M+1=405   ND       hydroxyphenyl)-7-methylthieno[3,2-       13.05(br s, 1H), 12.25(br   (ESI+)       d]pyrimidin-4-yl]hydrazone       s, 1H), 9.91(s, 1H), 8.78(s,               1H), 8.59(s, 1H), 8.06(s,               1H), 7.96-8.06(m,               4H), 7.87(d, J=8.4Hz,               2H), 7.51(d, J=8.7Hz,               2H), 6.95(d, J=8.7Hz,               2H), 2.41(s, 3H)       2-Chlorobenzaldehyde (6-(2-   77   (300MHz, DMSO-d6),   ND   97%       ethoxyphenyl)-7-methylthieno[3,2-       12.30(s, 1H), 8.61(s,       d]pyrimidin-4-yl)hydrazone       1H), 8.59(s, 1H), 8.11(d,               J=7.8Hz, 1H), 7.38-7.58(m,               3H), 7.20(d, J=8.7Hz,               1H), 7.08(t, J=7.2Hz,               1H), 4.13(q, J=6.9Hz,               2H), 2.25(s, 3H),               1.27(t, J=6.6Hz, 3H)       2-Fluorobenzaldehyde (6-(2-   78   (300MHz, DMSO-d6),   ND   97%       ethoxyphenyl)-7-methylthieno[3,2-       12.22(s, 1H), 8.60(s,       d]pyrimidin-4-yl)hydrazone       1H), 8.40(s, 1H), 8.02(t,               J=7.2Hz, 1H), 7.38-7.50(m,               3H), 7.23-7.36(m,               2H), 7.20(d, J=8.4Hz,               1H), 7.08(t, J=7.2Hz,               1H), 4.13(q, J=6.9Hz,               2H), 2.25(s, 3H), 1.27(t,               J=6.9Hz, 3H)       2,4-Dimethoxybenzaldehyde (6-(2-   79   (300MHz, DMSO-d6),   ND   99%       ethoxyphenyl)-7-methylthieno[3,2-       11.89(s, 1H), 8.52(s,       d]pyrimidin-4-yl)hydrazone       1H), 8.43(s, 1H), 7.88(d,               J=8.7Hz, 1H), 7.36-7.52(m,               2H), 7.19(d, J=7.8Hz,               1H), 7.08(t, J=8.1Hz,               1H), 6.61-7.75(m,               2H), 4.12(q, J=7.2Hz,               2H), 3.86(s, 3H), 3.80(s,               3H), 2.22(s, 3H), 1.26(t,               J=6.6Hz, 3H)       3-Hydroxy-4-methoxybenzaldehyde   80   (300MHz, DMSO-d6),   ND   ND       (6-(2-allyloxyphenyl)-7-       11.88(s, 1H), 9.24(s,       methylthieno[3,2-d]pyrimidin-4-       1H), 8.53(s, 1H), 8.02(s,       yl)hydrazone       1H), 7.30-7.46(m, 3H),               7.17-7.23(m, 2H), 7.10(t,               J=7.5Hz, 1H), 6.97(d,               J=8.1Hz, 1H), 5.9-6.1(m,               1H), 5.27(d, J=17.7Hz,               1H), 5.16(d, J=11.7Hz,               1H) 4.64(d,               J=4.5Hz, 1H), 3.78(s,               1H), 2.20(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   81   (300MHz, DMSO-d6),   ND   ND       (6-(2-benzyloxyphenyl)-7-       11.87(s, 1H), 9.29(s,       methylthieno[3,2-d]pyrimidin-4-       1H), 8.50(s, 1H), 8.03(s,       yl)hydrazone       1H), 7.05-7.49(m, 11H),               6.96(d, J=8.7Hz, 1H),               5.17(s, 2H), 3.78(s, 3H),               2.19(s, 3H)       3-Pyridinecarboxaldehyde (6-(2-   82   (300MHz, DMSO-d6),   ND   ND       benzyloxyphenyl)-7-       12.25(s, 1H), 8.93(s,       methylthieno[3,2-d]pyrimidin-4-       1H), 8.59(s, 1H), 8.54(d,       yl)hydrazone       J=5.1Hz, 1H), 8.21(s,               1H), 8.13(d, J=8.1Hz,               1H), 7.05-7.55(m, 10H),               5.18(s, 2H), 2.22(s, 3H)       3-Hydroxy-4-methoxybenzaldehyde   83   (300MHz, DMSO-d6),   ND   ND       (7-methyl-6-(2-       11.86(s, 1H), 9.22(s,       propoxyphenyl)thieno[3,2-       1H), 8.52(s, 1H), 8.02(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.36-7.46(m, 2H),               7.08-7.18(m, 2H), 7.05-               7.08(m, 2H), 6.97(d,               J=9.3Hz, 1H), 4.00(m,               2H), 3.78(s, 3H), 2.21(s,               3H), 1.64(sextet, J=6.6Hz,               2H), 0.84(t, J=7.2Hz,               3H)       3-Hydroxy-4-methoxybenzaldehyde   84   (300MHz, DMSO-d6),   ND   ND       (6-(2-hydroxyphenyl)-7-       11.84(s, 1H), 9.87(s,       methylthieno[3,2-d]pyrimidin-4-       1H), 9.24(s, 1H), 8.52(s,       yl)hydrazone       1H), 8.03(s, 1H), 7.26-               7.33(m, 2H), 7.21(s,               1H), 7.09(d, J=7.8Hz,               1H), 6.96-7.05(m, 2H),               6.92(d, J=7.5Hz, 1H),               3.78(s, 3H), 2.20(s, 3H)       2-Thiophenecarboxaldehyde (6-(2-   106   (300MHz, DMSO-d6)   M+1=464   ND       ethoxy-4-fluorophenyl)-7-       12.06(s, 1H, NH), 8.58(s,   (ESI+)       methythieno[3,2-d]pyrimidin-4-       1H), 8.37(s, 1H),       yl)hydrazone       7.62(d, J=5.0Hz, 1H),               7.44(m, 2H), 7.13(m,               2H), (td, J=8.2Hz,               J=3.8, J=2.4Hz, 1H),               4.14(q, J=6.5Hz, 2H)               2.21(s, 3H), 1.28, (t,               J=7.0Hz, 3H)       4-Methoxy-3-(2-(morpholin-4-yl)-   158   (300MHz, DMSO-d6),   ND   98%       ethoxy)-benzaldehyde (6-(2-       11.98(br s, 1H), 8.53(s,       ethoxyphenyl)-7-methylthieno[3,2-       1H), 8.07(s, 1H),       d]pyrimidin-4-yl)hydrazone       7.50(s, 1H), 7.36-7.47(m,               2H), 7.16(d, J=8.4Hz,               1H), 6.95-7.10(m,               2H), 4.07(q, J=7.2Hz,               2H), 3.95(t, J=6.9Hz,               2H), 3.76(s, 3H), 2.62(t,               J=6.9Hz, 2H), 2.37(q,               J=6.9Hz, 4H), 2.20(s,               3H), 1.23(t, J=6.9Hz,               3H), 0.83(t, J=7.2Hz,               6H)       4-(2-Diethylamino-ethoxy)-3,5-   160   (300MHz, DMSO-d6)   ND   ND       dimethoxy-benzaldehyde (6-(2-       12.20(s, 1H, NH), 8.57(s,       ethoxy-4-fluorophenyl)-7-       1H), 8.08(s, 1H),       methylthieno[3,2-d]pyrimidin-4-       7.48(t, d, J=8.2Hz,       yl)hydrazoned(160)       1H), 7.12(M, 3H), 6.90(t,               J=8.2Hz, 1H), 4.10(q,               J=6.5Hz, 2H), 3.95(t,               J=5.9Hz, 2H), 3.78(s,               6H), 2.81(br, 2H),               2.63(br, 4H), 2.23(s,               3H), 1.24(t, J=7.0Hz,               3H), 0.99(s, 6H),                  
 
     Example 2  
     Synthesis of 2-thiophenecarboxaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 107; See FIG.  3 )  
      3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165): Commercially available from Lancaster Synthesis Inc., Windham, N.H., USA.  
      3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166): Formic acid (60 mL) was added to acetic anhydride (90 mL) cooled in an ice bath. 3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165, 25.0 g, 0.146 mol) was added to the cold solution in small portions. The cooling bath was removed and the resulting suspension was stirred at room temperature for 4 hours. The reaction mixture was added to 150 g Na 2 CO 3  in water (500 mL) cooled in an ice bath. The solid product was collected by vacuum filtration, washed with water and dried over P 2 O 5  under vacuum overnight (28.5 g, 97% yield, white solid).  
      7-Methyl-3H-thieno[3,2-d]pyrimid-4-one (167): 3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166, 10.0 g, 50.0 mmol), ammonium formate 26.0 g, (400 mmol) and formamide (12 mL) were heated at 160° C. for 6 hours under N 2  and then cooled to room temperature. The precipitate was collected by vacuum filtration, washed with acetone, and dried over P 2 O 5  under vacuum overnight (6.0 g 72% yield, white needles).  
      4-Chloro-7-methylthieno[3,2-pyrimidine (168): A solution of 7-methyl-3H-thieno[3,2-d]pyrimid-4-one (167, 10.6 g, 64.0 mmol) in phosphorus oxychloride (42 mL) was refluxed under N 2  for 2 hours. The resulting solution was allowed to cool to room temperature and then neutralized by carefully pouring into a saturated aqueous solution of sodium carbonate (300 mL). The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine, before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue dried over P 2 O 5  under vacuum overnight (11.2 g, 95% yield, white solid).  
      4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169): Diisopropylamine (11 mL 77.8 mmol, 1.43 eq) was dissolved in 100 mL anhydrous THF, and the solution was chilled to −78° C. 22 mL 1.6 M BuLi in hexanes (70.8 mmol, 1.3 eq) was added, and the solution was stirred for 30 minutes at −78° C. A solution of 4-chloro-7-methylthieno[3,2-d]pyrimidine (168, 10.0 g 54.4 mmol) in anhydrous THF 100 mL was chilled to −78° C., and the LDA solution was then transferred via cannula to the cold solution of 168. The reaction mixture became a dark brown suspension as the LDA solution was added. After 2 hours at −78° C., a solution of I 2  (20.8 g, 81.6 mmol, 1.5 eq) in 50 mL THF was cannulated to the anion solution. The reaction mixture was maintained at −78° C. for 2 hours and then warmed to room temperature overnight. After overnight stirring, the reaction mixture was diluted with EtOAc and washed three times with deionized H 2 O, twice with saturated Na 2 S 2 O 4 , once with deionized H 2 O, three times with 10% HCl, and once with saturated NaCl. The dark solution was dried over anhydrous Na 2 SO 4 , decolorized with activated carbon, and then filtered through silica gel. The resulting light yellow filtrate was concentrated by rotary evaporation, and a light yellow solid precipitated as the solution was concentrated. After concentrating to a small volume, the precipitate was collected via filtration and was washed twice with ice cold EtOAc (13.7 g, 82% yield).  
      4-Chloro-(6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidine (170): 4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169, 3.43 g, 11.0 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.38 g, 0.57 mmol) were placed in a mixture of 1,2-dimethoxyethane (160 mL) and distilled water (60 ml) and stirred at room temperature for 10 minutes under N 2 . 2-Ethoxy-4-fluorophenyl boronic acid (2.20 g, 12.0 mmol) and Cs 2 CO 3  (8.86 g, 45.93 mmol) were added to the reaction mixture. The suspension was heated at 80° C. for 20 hr, cooled to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography and the product was dried over P 2 O 5  under vacuum overnight (0.80 g, 23% yield, white solid).  
      7-Bromomethyl-4-chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidine (172): 4-Chloro-(6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidine (170, 2.30 g, 5.75 mmol) was dissolved in 10 mL CCl 4 . NBS (1.40 g, 7.78 mmol, 1.3 eq) was added to the solution, and the suspension was stirred under a 250 W sun lamp until the reaction was complete (about 1 hr). Upon completion of the reaction, the crude suspension was filtered through Celite, and the filter pad was washed with 2 small portions of CCl 4 . The filtrate was absorbed on to silica gel by rotovaporation and the product was chromatographed through a silica gel plug with 10% EtOAc/hexanes (2.30 g. 99% yield, tan solid).  
      4-Chloro-6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethyl-thieno-3,2-d]pyrimidine (173): 7-Bromomethyl-4-chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidine (172, 2.50 g 6.22 mmol) was suspended in 160 mL dioxane/160 ml H 2 O. To the suspension was added CaCO 3  (3.13 g, 31.3 mmol 5 eq), refluxed overnight, and then diluted with EtOAc/H 2 O. The EtOAc phase was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (2.10 g. 99% yield, white solid).  
      (6-(2-Ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazine (174): A suspension of 4-Chloro-6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno-3,2-d]pyrimidine (173, 0.50 g, 1.48 mmol) and hydrazine monohydrate (0.75 mL) were refluxed in ethanol (15 mL) for 1 hour. After cooling to room temperature, the solid product was collected by vacuum filtration (0.42 g, 85% yield, white solid).  
      2-Thiophenecarboxaldehyde(6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazone (107). A suspension of (6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno[3,2-d]pyrimidin-4-yl)hydrazine (174, 60.0 mg, 0.18 mmol) and 2-thiophenecarboxaldehyde (28 mg, 0.18 mmol) were refluxed in ethanol (2 mL) for 4 hours. After cooling to room temperature, the solid product was collected by vacuum filtration (20.0 mg, 26% yield, white solid).  
      Compounds that can be made using the above procedure with the appropriate substitution of reagents are listed in Table 2. The synthesis of Compound 107 as illustrated above is also illustrated in  FIG. 3 .  
                               TABLE 2                                       Purity                       by       Compound   No   1H NMR   MS   HPLC                                                    3-Hydroxy-4-   33   (300MHz, DMSO-d6), 11.89(s,   M+1=433   99%       methoxybenzaldehyde (7-       1H), 9.21(s, 1H), 8.53(s,   (ESI+)       hydroxymethyl-6-(2-       1H), 8.03(s, 1H), 7.62(d,       ethoxyphenyl)thieno[3,2-       J=6.0Hz, 1H), 7.43(t, J=7.2Hz,       d]pyrimidin-4-       1H), 7.27(d, J=2.1Hz,       yl)hydrazone       1H), 7.19(d, J=7.5Hz, 1H),               7.06-7.12(m, 2H), 6.98(d,               J=8.4Hz, 1H), 4.94(t, J=4.8Hz,               1H), 4.57(d, J=4.8Hz,               1H), 4.14(q, J=6.9Hz, 2H),               3.79(s, 3H), 1.26(t, J=6.9Hz,               3H)       3-Hydroxy-4-   44   (300MHz, DMSO-d6), 12.85(s,   M−1=477   ND       methoxybenzaldehyde       1H), 9.0(s, 1H), 8.52(s,   (ESI−)       (7-ethoxymethyl (6-(2-       1H), 8.03(s, 1H), 7.54(d,       ethoxyphenyl)       ND, H), 7.45(t, 1H), 6.94-       thieno[3,2-d] pyrimidin-       7.27(m, ND, H), 4.51(s, 2H),       4-yl)hydrazone       4.11(q, J=ND, 2H), 3.78(s,               3H), 1.13(t, J=ND, 3H),               1.03(t, J=ND, 3H)       3-Hydroxy-4-   56   (300MHz, acetone-d6), 8.51(s,   M+1=525   95%       methoxybenzaldehyde(7-       1H), 8.15(s, 1H), 7.60(d,   (ESI+)       ((±)-4,5-dihydroxy-2-       J=7.5Hz, 1H), 7.44-7.50(m,       oxopentyl) (6-(2-       2H), 7.17-7.24(m, 2H), 7.10(t,       ethoxyphenyl) thieno[3,2-       J=7.5Hz, 1H), 7.02(d, J=8.4Hz,       d]pyrimidin-4-       1H), 4.69(dd, J=18.3Hz,       yl)hydrazone       J=10.2Hz, 2H), 4.19(q, J=6.9Hz,               2H), 3.88(s, 3H), 3.77(t,               J=6Hz, 1H), 3.46-3.65(m,               4H), 1.36(t, J=6.6Hz, 3H)       3-Hydroxy-4-   58   (300MHz, DMSO-d6), 11.79(br   M+1=422   ND       methoxybenzaldehyde (6-       s, 1H), 9.27(br s, 1H),   (ESI+)       (4-aminophenyl)-7-       8.49(s, 1H), 8.03(s, 1H), 7.55(d,       hydroxymethylthieno[3,2-       J=8.4Hz, 2H), 7.29(d, J=2.1Hz,       d]pyrimidin-4-       1H), 7.11(dd, J=8.4Hz,       yl)hydrazone       1.8Hz, 1H), 7.01(d, J=8.1Hz,               1H), 6.70(d, J=8.7Hz, 2H),               5.58(s, 2H), 5.12(t, J=5.1Hz,               1H), 4.63(d, J=5.1Hz, 2H),               3.81(s, 3H),       3-Hydroxy-4-   60   (300MHz, DMSO-d6) 11.89(s,   M+1=453   ND       methoxybenzaldehyde (6-       1H, NH), 9.22(s, 1H), 8.53(s,   (ESI+)       (2-ethoxy-4-       1H), 8.03(s, 1H), 7.67(dd,       fluorophenyl)-7-       J=8.5Hz, J=1.8Hz, 1H), 7.29(d,       hydroxymethylthieno[3,2-       J=1.7Hz, 1H) 7.11(m,       d]pyrimidin-4-       2H), 6.93(m, 6H), 4.97(t,       yl)hydrazone       J=5.3Hz, 1H) 4.56(d, 2.47               J=5.Hz, 2H), 4.15(q, J=6.5Hz,               2H) 3.80(s, 3H), 1.26, (t,               J=7.0Hz, 3H)       3-Pyridinecarboxaldehyde   70   (300MHz, DMSO-d6), 12.45(br   M−1=404   ND       (6-(2-ethoxyphenyl)-7-       s, 1H), 8.95(d, J=2.1Hz,   (ESI−)       hydroxymethylthieno[3,2-       1H), 8.63(s, 1H), 8.57(d,       d]pyrimidin-4-       J=3.3Hz, 1H), 8.24(s, 1H),       yl)hydrazone       8.17(d, J=7.8Hz, 1H), 7.64(d,               J=7.2Hz, 1H), 7.43-7.53(m,               2H), 7.20(d, J=8.1Hz, 1H),               7.09(t, J=7.5Hz, 1H), 4.59(s,               2H), 4.14(q, J=6.9Hz, 2H),               1.27(t, J=6.9Hz, 3H)       2-   71   (300MHz, DMSO-d6), 12.08(s,   M−1=409   99%       Thiophenecarboxaldehyde       1H), 8.55(s, 1H), 8.35(s,   (ESI−)       (6-(2-ethoxyphenyl)-7-       1H), 7.56-7.61(m, 2H), 7.39-       hydroxymethylthieno[3,2-       7.43(m, 2H), 7.18(d, J=8.7Hz,       d]pyrimidin-4-       1H), 7.04-7.17(m, 2H),       yl)hydrazone       4.93(t, J=5.7Hz, 1H), 4.55(d,               J=4.8Hz, 2H), 4.01(q, J=7.5Hz,               2H), 1.27 (t, J=6.9Hz, 3H)       4-Carboxybenzaldehyde   72   (300MHz, DMSO-d6), 12.35(br   M−1=447   ND       (6-(2-ethoxyphenyl)-7-       s, 1H), 8.61(s, 1H), 8.24(s,   (ESI−)       hydroxymethylthieno[3,2-       1H), 7.99(d, J=7.2Hz, 2H),       d]pyrimidin-4-       7.88(d, J=8.1Hz, 2H), 7.67(d,       yl)hydrazone       J=7.5Hz, 1H), 7.46(t, J=8.1Hz,               1H), 7.20(d, J=8.4Hz,               1H), 7.09(t, J=7.2Hz, 1H),               4.59(s, 2H), 4.14(q, J=7.5Hz,               2H), 1.28(t, J=6.6Hz, 3H)       2-   107   (300MHz, DMSO-d6) 12.06(s,   ND   ND       Thiophenecarboxaldehyde       1H, NH), 8.55(s, 1H), 8.36(s,       (6-(2-ethoxy-4-       1H), 7.83(m, 1Hz), 7.67(d,       fluorophenyl)-7-       J=5.0Hz, 1H), 7.47(d, J=4.4Hz,       hydroxymethylthieno[3,2-       1H), 7.12(m, 3H), 6.91(m,       d]pyrimidin-4-       1H), 4.56(s, 2H), 4.23(q, J=6.5Hz,       yl)hydrazone       2H) 1.28, (t, J=7.0Hz, 3H)                  
 
     Example 3  
     Synthesis of 4-(2-diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 159; See FIG.  4 )  
      3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165): Commercially available from Lancaster Synthesis Inc., Windham, N.H., USA.  
      3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166): Formic acid (60 mL) was added to acetic anhydride (90 mL) cooled in an ice bath. 3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165, 25.0 g, 0.146 mol) was added to the cold solution in small portions. The cooling bath was removed and the resulting suspension was stirred at room temperature for 4 hours. The reaction mixture was added to 150 g Na 2 CO 3  in water (500 mL) cooled in an ice bath. The solid product was collected by vacuum filtration, washed with water and dried over P 2 O 5  under vacuum overnight (28.5 g, 97% yield, white solid).  
      7-Methyl-3H-thieno[3,2-d]pyrimid-4-one (167): 3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166, 10.0 g, 50.0 mmol), ammonium formate 26.0 g, (400 mmol) and formamide (12 mL) were heated at 160° C. for 6 hours under N 2  and then cooled to room temperature. The precipitate was collected by vacuum filtration, washed with acetone, and dried over P 2 O 5  under vacuum overnight (6.0 g 72% yield, white needles).  
      4-Chloro-7-methylthieno[3,2-d]pyrimidine (168): A solution of 7-methyl-3H-thieno[3,2-d]pyrimid-4-one (167, 10.6 g, 64.0 mmol) in phosphorus oxychloride (42 mL) was refluxed under N 2  for 2 hours. The resulting solution was allowed to cool to room temperature and then neutralized by carefully pouring into a saturated aqueous solution of sodium carbonate (300 mL). The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine, before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue dried over P 2 O 5  under vacuum overnight (111.2 g, 95% yield, white solid).  
      4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169): Diisopropylamine (11 mL 77.8 mmol, 1.43 eq) was dissolved in anhydrous THF 100 mL, and the solution was chilled to −78° C. 22 mL 1.6 M BuLi in hexanes (70.8 mmol, 1.3 eq) was added, and the solution was stirred for 30 minutes at −78° C. A solution of 4-chloro-7-methylthieno[3,2-d]pyrimidine (168, 10.0 g 54.4 mmol) in 100 mL anhydrous THF was chilled to −78° C., and the LDA solution was then transferred via cannula to the cold solution of 168. The reaction mixture became a dark brown suspension as the LDA solution was added. After 2 hours at −78° C., a solution of I 2  (20.8 g 81.6 mmol, 1.5 eq) in 50 mL THF was cannulated to the anion solution. The reaction mixture was maintained at −78° C. for 2 hours and then warmed to room temperature overnight. After overnight stirring, the reaction mixture was diluted with EtOAc and washed three times with deionized H 2 O, twice with saturated Na 2 S 2 O 4 , once with deionized H 2 O, three times with 10% HCl, and once with saturated NaCl. The dark solution was dried over anhydrous Na 2 SO 4 , decolorized with activated carbon, and then filtered through silica gel. The resulting light yellow filtrate was concentrated by rotary evaporation, and a light yellow solid precipitated as the solution was concentrated. After concentrating to a small volume, the precipitate was collected via filtration and was washed twice with ice cold EtOAc (13.7 g, 82% yield).  
      4-Chloro-(6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidine (170): 4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169, 3.43 g, 11.0 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.38 g, 0.57 mmol) were placed in a mixture of 1,2-dimethoxyethane (160 mL) and distilled water (60 ml) and stirred at room temperature for 10 minutes under N 2 . 2-Ethoxy-4-fluorophenyl boronic acid (2.20 g, 12.0 mmol) and Cs 2 CO 3  (8.86 g, 45.93 mmol) were added to the reaction mixture. The suspension was heated at 80° C. for 20 hr, cooled to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography and the product was dried over P 2 O 5  under vacuum overnight (0.80 g, 23% yield, white solid).  
      7-Bromomethyl-4-chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidine (172): 4-Chloro-(6-(2-ethoxy-4-fluorophenyl)-7-methylthieno[3,2-d]pyrimidine (170, 2.30 g, 5.75 mmol) was dissolved in 10 mL CCl 4 . NBS (1.40 g, 7.78 mmol, 1.3 eq) was added to the solution, and the suspension was stirred under a 250 W sun lamp until the reaction was complete (about 1 hr). Upon completion of the reaction, the crude suspension was filtered through Celite, and the filter pad was washed with 2 small portions of CCl 4 . The filtrate was absorbed on to silica gel by rotovaporation and the product was chromatographed through a silica gel plug with 10% EtOAc/hexanes (2.30 g. 99% yield, tan solid).  
      4-Chloro-6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethyl-thieno-3,2-d]pyrimidine (173): 7-Bromomethyl-4-chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidine (172, 2.50 g, 6.22 mmol) was suspended in 160 mL dioxane/160 ml H 2 O. To the suspension was added CaCO 3  (3.13 g, 31.3 mmol 5 eq), refluxed overnight, and then diluted with EtOAc/H 2 O. The EtOAc phase was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (2.10 g. 99% yield, white solid).  
      4-Chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde (175): Oxalyl chloride (0.48 mL, 5.50 mmol 1.1 eq) was dissolved in 10 mL of dry CH 2 Cl 2 , and the solution was chilled to −60° C. Dry DMSO (0.86 mL, 11.4 mmol 2.4 eq) was added, and stirring was maintained for 15 min. at −60 C. After 15 min, a solution of 4-chloro-6-(2-ethoxy-4-fluorophenyl)-7-hydroxymethylthieno-[3,2-d]pyrimidine (173, (1.70 g, 5.00 mmol) in 15 mL CH 2 Cl 2  (plus 5 mL rinse) was added via syringe. The reaction was maintained at −60° C. for 1 hr, and TEA (3.36 mL, 24.2 mmol 4.8 eq) was added. The reaction was allowed to warm up gradually to RT and was then diluted with CH 2 Cl 2 /H 2 O. The CH 2 Cl 2  extract was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (1.6 g, 82% yield, tan solid).  
      4-Chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidin-7-ol (176): 4-Chloro-6-(2-ethoxy-4-fluorophenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde (175, 0.77 g, 2.30 mmol) was dissolved in CH 2 Cl 2  (31 mL), and MCPBA (0.85 g, 3.40 mmol 1.5 eq) was added. The reaction was stirred overnight at RT. The reaction was diluted with CH 2 Cl 2  and was washed twice with sat. NaHCO 3 , once with H 2 O, and once with sat. NaCl. The extract was dried over Na 2 SO 4  and on a placed on a rotovaporator until dry. The crude product was dissolved in MeOH (33 mL). TEA (0.76 mL, excess) was added, and the reaction was stirred overnight at RT. After overnight stirring, the reaction was diluted with EtOAc and was washed twice with 10% HCl and once with H 2 O. The extract was dried over Na 2 SO 4  and placed on a placed on a rotovaporator until dry (0.75 g, 99% yield, white solid).  
      6-(2-Ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazine (177): A suspension of 4-Chloro-6-(2-ethoxy-4-fluorophenyl-7-hydroxythieno-[3,2-d]pyrimidine (176, 0.40 g, 1.20 mmol) and hydrazine monohydrate (1.2 mL) were refluxed in ethanol (12 mL) for 1 hour. After cooling to room temperature, the solid product was collected by vacuum filtration (0.35 g, 89% yield, white solid).  
      4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazone (159): A suspension of (6-(2-ethoxy-4-fluorophenyl)-7-hydroxythieno[3,2-d]pyrimidin-4-yl)hydrazine (177, 55.0 mg, 0.17 mmol) and 4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde (60.0 mg, 2.16 mmol) were refluxed in ethanol (2 mL) for 4 hours. After cooling to room temperature, the solid product was collected by vacuum filtration (65.0 mg, 65% yield, white solid).  
      Compounds that can be made using the above procedure with the appropriate substitution of reagents are listed in Table 3. The synthesis of Compound 159 as illustrated above is also illustrated in  FIG. 4 .  
                               TABLE 3                                       Purity                       by       Compound   No   1H NMR   MS   HPLC                                                    3-Hydroxy-4-   37   (300MHz, DMSO-d6), 11.89(s,   M−H=435   99%       methoxybenzaldehyde (6-(2-       1H), 9.20(s, 1H), 8.51(s,   (ESI−)       ethoxyphenyl)-7-       1H), 8.02(s, 1H), 7.91(dd,       hydroxythieno[3,2-d]pyrimidin-       J=8.1Hz, J=1.8Hz, 1H), 7.30-       4-yl)hydrazone       7.38(m, 2H), 7.15(dd, J=8.7Hz,               1.5Hz, 1H), 6.96-7.08(m,               3H), 4.20(q, J=6.9Hz, 2H),               3.82(s, 3H), 1.35(t, J=7.2Hz,               3H)       3-Hydroxy-4-   61   (300MHz, DMSO-d6) 11.88(s,   M+1=469   ND       methoxybenzaldehyde (6-(2-       1H, NH), 9.19(s, 1H), 8.51(s,   (ESI+)       ethoxy-4-fluorophenyl)-7-       1H), 8.02(s, 1H), 7.92(t,       hydroxythieno[3,2-d]pyrimidin-       J=7.0Hz, 1H), 7.31(d, J=1.8Hz,       4-yl)hydrazone       1H) 7.09(m, 2H), 6.98(d,               J=8.5Hz, 1H), 6.87(td, J=8.2Hz,               J=3.8Hz, J=2.4 1H), 4.20(q,               J=6.7Hz, 2H) 3.80(s, 3H),               1.34, (t, J=6.7Hz, 3H)       3-Pyridinecarboxaldehyde (6-   73   (300MHz, DMSO-d6), 12.28(s,   M+1=392   ND       (2-ethoxyphenyl)-7-       1H), 10.06(br s, 1H),   (ESI+)       hydroxythieno[3,2-d]pyrimidin-       9.01(d, J=2.1Hz, 1H), 8.57(m,       4-yl)hydrazone       2H), 8.16-8.21(m, 2H), 8.00(d,               J=7.2Hz, 1H), 7.50(dd, J=8.1Hz,               J=4.5Hz, 1H), 7.34(t,               J=7.5Hz, 1H), 7.16(d, J=8.7Hz,               1H), 7.05(t, J=7.8Hz, 1H),               4.22(q, J=7.2Hz, 2H), 1.36(t,               J=6.9Hz, 3H)       4-Carboxybenzaldehyde (6-(2-   74   (300MHz, DMSO-d6), 13.05(br   M+1=435   ND       ethoxyphenyl)-7-       s, 1H), 12.27(br s, 1H),   (ESI+)       hydroxythieno[3,2-d]pyrimidin-       10.05(br s, 1H), 8.59(s, 1H),       4-yl)hydrazone       8.23(s, 1H), 7.91-8.02(m, 3H),               7.91(d, J=8.4Hz, 2H), 7.34(t,               J=6.9Hz, 1H), 7.16(d, J=8.4Hz,               1H), 7.05(t, J=7.8Hz, 1H),               4.24(q, J=7.2Hz, 2H), 1.38(t,               J=6.9Hz, 3H)       2-Thiophenecarboxaldehyde (6-   85   (300MHz, DMSO-d6), 12.05(br   ND   ND       (2-ethoxyphenyl)-7-       s, 1H), 8.53(s, 1H), 8.34(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.84(d, J=7.8Hz, 1H),       4-yl)hydrazone       7.65(d, J=4.8Hz, 1H), 7.43(d,               J=3.6Hz, 1H), 7.34(t, J=7.2Hz,               1H), 7.10-7.17(m, 2H),               7.04(t, J=7.2Hz, 1H), 4.19(q,               J=6.9Hz, 2H), 1.36(t, J=6.9Hz,               3H)       4-Hydroxy-3-   88   (300MHz, DMSO-d6), 11.93(br   ND   ND       methoxybenzaldehyde (6-(2-       s, 1H), 9.51(br s, 1H), 8.50(s,       ethoxyphenyl)-7-       1H), 8.04(s, 1H), 7.83(d,       hydroxythieno[3,2-d]pyrimidin-       J=7.5Hz, 1H), 7.45(s, 1H),       4-yl)hydrazone       7.33(t, J=7.8Hz, 1H), 7.10-               7.21(m, 2H), 7.04(t, J=6.6Hz,               1H), 6.83(d, J=8.1Hz, 1H),               4.14(q, J=7.2Hz, 2H), 3.79(s,               3H), 1.30(t, J=6.9Hz, 3H)       3-Bromo-4-hydroxy-5-   89   (300MHz, DMSO-d6), 12.15(br   ND   ND       methoxybenzaldehyde (6-(2-       s, 1H), 9.95(br s, 1H),       ethoxyphenyl)-7-       8.53(s, 1H), 8.03(s, 1H), 7.82(d,       hydroxythieno[3,2-d]pyrimidin-       J=7.2Hz, 1H), 7.56(s, 1H),       4-yl)hydrazone       7.44(s, 1H), 7.33(t, J=7.2Hz,               1H), 7.13(d, J=7.8Hz, 1H),               7.04(t, J=7.8Hz, 1H), 4.15(q,               J=6.9Hz, 2H), 3.85(s, 3H),               1.29(t, J=7.2Hz, 3H)       3-Chloro-4-   92   (300MHz, DMSO-d6), 11.98(s,   ND   ND       hydroxybenzaldehyde (6-(2-       1H), 10.68(br s, 1H), 8.52(s,       ethoxyphenyl)-7-       1H), 8.05(s, 1H), 7.94(dd,       hydroxythieno[3,2-d]pyrimidin-       J=7.5Hz, J=1.8Hz, 1H), 7.83(d,       4-yl)hydrazone       J=2.1Hz, 1H), 7.56(dd,               J=8.1Hz, J=1.8Hz, 1H), 7.33(t,               J=6.9Hz, 1H), 7.15(d, J=7.8Hz,               1H), 7.01-7.07(m, 2H),               4.20(q, J=7.2Hz, 2H), 1.36(t,               J=7.2Hz, 3H)       3-Thiophenecarboxaldehyde (6-   93   (300MHz, DMSO-d6), 11.95(br   ND   ND       (2-ethoxyphenyl)-7-       s, 1H), 8.52(s, 1H), 8.19(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.96(dd, J=7.5Hz, 1.5Hz,       4-yl)hydrazone       1H), 7.86-7.90(m, 1H),               7.68 (s, 1H), 7.67(s, 1H), 7.33(t,               J=8.4Hz, 1H), 7.15(d, J=8.4Hz,               1H), 7.04(t, J=7.2Hz, 1H),               4.20(q, J=7.2Hz, 2H), 1.37(t,               J=7.2Hz, 3H)       3,5-Dimethoxy-4-   96   (300MHz, DMSO-d6), 12.01(br   ND   ND       hydroxybenzaldehyde (6-(2-       s, 1H), 8.85(br s, 1H),       ethoxyphenyl)-7-       8.51(s, 1H), 8.02(s, 1H), 7.75(d,       hydroxythieno[3,2-d]pyrimidin-       J=7.8Hz, 1H), 7.33(t, J=7.8Hz,       4-yl)hydrazone       1H), 7.01-7.14(m, 4H),               4.10(q, J=7.5Hz, 2H), 1.25(t,               J=7.2Hz, 3H)       2-Imidazolecarboxaldehyde (6-   97   (300MHz, DMSO-d6), 12.02(br   ND   ND       (2-ethoxyphenyl)-7-       s, 1H), 8.53(s, 1H), 8.08(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.81(d, J=7.2Hz, 1H),       4-yl)hydrazone       7.44(s, 1H), 7.33(t, J=7.8Hz,               1H), 6.99-7.22(m, 4H), 4.12(q,               J=6.9Hz, 2H), 1.29(t, J=6.9Hz,               3H)       3,4-Dimethoxy-5-   100   (300MHz, DMSO-d6), 12.02(s,   ND   ND       hydroxybenzaldehyde (6-(2-       1H), 9.80(br s, 1H), 9.35(s,       ethoxyphenyl)-7-       1H), 8.53(s, 1H), 7.99(s, 1H),       hydroxythieno[3,2-d]pyrimidin-       7.81(d, J=7.2Hz, 1H), 7.32(t,       4-yl)hydrazone       J=7.2Hz, 1H), 7.13(d, J=8.4Hz,               1H), 6.96(m, 2H), 6.91(s,               1H), 4.12(q, J=6.9Hz, 2H),               1.28(t, J=6.9Hz, 3H)       4-(1H-imidazol-1-   101   (300MHz, DMSO-d6), 12.18(s,   ND   ND       yl)benzaldehyde (6-(2-       1H), 9.98(br s, 1H), 8.57(s,       ethoxyphenyl)-7-       1H), 8.35(s, 1H), 8.21(s, 1H),       hydroxythieno[3,2-d]pyrimidin-       7.94(d, J=8.4Hz, 2H), 7.75-       4-yl)hydrazone       7.92(m, 4H), 7.35(t, J=7.2Hz,               1H), 7.12-7.19(m, 2H), 7.05(t,               J=8.1Hz, 1H), 4.22(q, J=6.6Hz,               2H), 1.36(t, J=7.2Hz, 3H)       4-Hydroxybenzaldehyde (6-(2-   104   (300MHz, DMSO-d6), 11.85(s,   ND   ND       ethoxyphenyl)-7-       1H), 9.94(br s, 1H), 9.90(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.50(s, 1H), 8.06(s, 1H),       4-yl)hydrazone       7.98(d, J=8.1Hz, 1H), 7.64(d,               J=8.7Hz, 2H), 7.33(t, J=8.1Hz,               1H), 7.15(d, J=8.4Hz,               1H), 7.04(t, J=8.1Hz, 1H),               6.85(d, J=8.1Hz, 2H), 4.22(q,               J=6.6Hz, 2H), 1.38(t, J=7.2Hz,               3H)       3-Hydroxybenzaldehyde (6-(2-   105   (300MHz, DMSO-d6), 12.01(s,   ND   ND       ethoxyphenyl)-7-       1H), 9.97(br s, 1H), 9.61(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.54(s, 1H), 8.07(s, 1H),       4-yl)hydrazone       7.94(d, J=6.0Hz, 1H), 7.02-               7.35(m, 6H), 6.80(d, J=6.3Hz,               1H), 4.20(q, J=6.9Hz, 2H),               1.35(t, J=7.2Hz, 3H)       2-Thiophenecarboxaldehyde (6-   109   (300MHz, DMSO-d6) 12.06(s,   ND   ND       (2-ethoxy-4-fluorophenyl)-7-       1H, NH), 8.54(s, 1H), 8.35(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.88(m, 1H), 7.66(d,       4-yl)hydrazone       J=4.7Hz, 1H), 7.44(d, J=3.1Hz,               1H), 7.08(m, 2H), 6.90(m,               1H), 4.22(q, J=6.5Hz, 2H),               1.37, (t, J=7.0Hz, 3H)       4-Pyridinecarboxaldehyde (6-   112   (300MHz, DMSO-d6), 12.40(s,   ND   ND       (2-ethoxyphenyl)-7-       1H), 10.05(br s, 1H), 8.67(d,       hydroxythieno[3,2-d]pyrimidin-       J=6.0Hz, 2H), 8.61(s, 1H),       4-yl)hydrazone       8.15(s, 1H), 7.98(dd, J=7.8Hz,               1.8Hz, 1H), 7.74(d, J=6.3Hz,               2H), 7.35(t, J=7.8Hz, 1H),               7.16(d, J=7.8Hz, 1H), 7.05(t,               J=7.8Hz, 1H), 4.23(q, J=7.2Hz,               2H), 1.36(t, J=7.2Hz, 3H)       2,4-Dioxo-1,2,3,4-tetrahydro-   113   (300MHz, DMSO-d6), 11.97(s,   ND   ND       pyrimidine-5-carbaldehyde (6-       1H), 11.46(m, 2H), 9.90(br       (2-ethoxyphenyl)-7-       s, 1H), 8.51(s, 1H), 8.04(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.81-7.90(m, 2H), 7.33(t,       4-yl)hydrazone       J=6.9Hz, 1H), 7.14(d, J=7.8Hz,               1H), 7.03(t, J=7.8Hz, 1H),               4.14(q, J=6.9Hz, 2H), 1.32(t,               J=6.9Hz, 3H)       3-Carboxybenzaldehyde (6-(2-   116   (300MHz, DMSO-d6), 12.18(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 9.98(br s, 1H),       hydroxythieno[3,2-d]pyrimidin-       8.57(s, 1H), 8.35(s, 1H), 8.24(s,       4-yl)hydrazone       1H), 8.06(d, J=7.8Hz, 1H),               7.89-7.96(m, 2H), 7.60(t,               J=8.1Hz, 1H), 7.34(t, J=7.8Hz,               1H), 7.13(d, J=7.5Hz,               1H), 7.04(t, J=8.4Hz, 1H),               4.18(q, J=6.9Hz, 2H), 1.30(t,               J=6.9Hz, 3H)       4-Methyl-5-   117   (300MHz, DMSO-d6), 11.59(s,   ND   ND       imidazolecarboxaldehyde (6-(2-       1H), 8.46(s, 1H), 8.17(s,       ethoxyphenyl)-7-       1H), 7.80(d, J=7.8Hz, 1H),       hydroxythieno[3,2-d]pyrimidin-       7.57(s, 1H), 7.32(t, J=7.8Hz,       4-yl)hydrazone       1H), 7.11(d, J=8.7Hz, 1H),               7.02(t, J=7.2Hz, 1H), 4.12(q,               J=6.6Hz, 2H), 2.34(s, 3H),               1.30(t, J=7.5Hz, 3H)       Methyl 4-formyl benzoate (6-   120   (300MHz, DMSO-d6), 12.29(s,   ND   ND       (2-ethoxyphenyl)-7-       1H), 10.08 (br s, 1H), 8.59(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.23(s, 1H), 7.90-       4-yl)hydrazone       8.08(m, 5H), 7.34(t, J=7.2Hz, 1H),               7.16(d, J=7.2Hz, 1H), 7.05(t,               J=7.8Hz, 1H), 4.23(q, J=6.9Hz,               2H), 3.87(s, 3H), 1.37(t,               J=6.3Hz, 3H)       2-Furancarboxaldehyde (6-(2-   121   (300MHz, DMSO-d6), 12.01(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 9.95(br s, 1H),       hydroxythieno[3,2-d]pyrimidin-       8.53(s, 1H), 8.04(s, 1H), 9.57(d,       4-yl)hydrazone       J=7.5Hz, 1H), 7.82(s, 1H),               7.32(t, J=6.9Hz, 1H), 7.14(d,               J=8.1Hz, 1H), 7.03(t, J=7.5Hz,               1H), 6.89(d, J=3.6Hz,               1H), 6.65(dd, J=3.3Hz, J=1.8Hz,               1H), 4.18(q, J=7.2Hz,               2H), 1.41(t, J=7.2Hz)       3-Methyl-2-   124   (300MHz, DMSO-d6), 11.91(br   ND   ND       thiophenecarboxaldehyde (6-(2-       s, 1H), 8.51(s, 1H), 8.40(s,       ethoxyphenyl)-7-       1H), 7.83(d, J=7.8Hz, 1H),       hydroxythieno[3,2-d]pyrimidin-       7.54(d, J=5.4Hz, 1H), 7.34(t,       4-yl)hydrazone       J=9.0Hz, 1H), 7.14(d, J=8.7Hz,               1H), 7.03(t, J=8.1Hz, 1H),               6.95(d, J=5.1Hz, 1H), 4.18(q,               J=7.5Hz, 2H), 2.32(s, 3H),               1.36(t, J=7.2Hz, 3H)       3-Chloro-4-fluorobenzaldehyde   125   (300MHz, DMSO-d6), 12.22(br   ND   ND       (6-(2-ethoxyphenyl)-7-       s, 1H), 8.57(s, 1H), 8.14(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.03(dd, J=7.5Hz, 2.1Hz,       4-yl)hydrazone       1H), 7.93(dd, J=7.8Hz,               1.8Hz, 1H), 7.76-7.84(m, 1H),               7.54(t, J=9.0Hz, 1H), 7.34(td,               J=8.4Hz, 1.8Hz, 1H), 7.14(d,               J=8.7Hz, 1H), 7.04(t, J=7.5Hz,               1H), 4.19(q, J=6.9Hz,               2H), 1.33(t, J=6.9Hz, 3H)       5-Methyl-2-   128   (300MHz, DMSO-d6), 11.99(s,   ND   ND       thiophenecarboxaldehyde (6-(2-       1H), 9.84(s, 1H), 8.51(s,       ethoxyphenyl)-7-       1H), 8.23(s, 1H), 7.87(dd,       hydroxythieno[3,2-d]pyrimidin-       J=8.1Hz, 1.8Hz, 1H), 7.33(t,       4-yl)hydrazone       J=8.7Hz, 1H), 7.21(d, J=3.3Hz,               1H), 7.15(d, J=8.4Hz,               1H), 7.03(t, J=7.5Hz, 1H),               6.82(dd, J=3.6Hz, J=1.2Hz,               1H),       3-Furancarboxaldehyde(6-(2-   129   (300MHz, DMSO-d6), 11.93(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 9.90(br s, 1H), 8.51(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.13(s, 1H), 8.10(s,       4-yl)hydrazone       1H), 7.93(d, J=7.5Hz, 1H),               7.80(d, J&lt;1Hz, 1H), 7.33(t,               J=8.4Hz, 1H), 7.15(d, J=8.7Hz,               1H), 7.04(t, J=7.8Hz, 1H),               6.94(d, J&lt;1Hz, 1H), 4.18(q,               J=7.2Hz, 2H), 1.35(t, J=6.6Hz,               3H)       4-Acetamidobenzaldehyde (6-   132   (300MHz, DMSO-d6), 11.99(s,   ND   ND       (2-ethoxyphenyl)-7-       1H), 10.13(s, 1H), 10.00(br       hydroxythieno[3,2-d]pyrimidin-       s, 1H), 8.53(s, 1H), 8.10(s,       4-yl)hydrazone       1H), 8.02(dd, J=7.5Hz, 1.5Hz,               1H), 7.74(d, J=8.7Hz,               2H), 7.68(d, J=8.7Hz, 2H),               7.33(t, J=8.1Hz, 1H), 7.17(d,               J=8.1Hz, 1H), 7.05(t, J=8.1Hz,               1H), 4.23(q, J=6.9Hz,               2H), 2.07(s, 3H), 1.40(t, J=7.2Hz,               3H)       4-N,N-   133   (300MHz, DMSO-d6), 11.78(s,   ND   ND       Dimethylaminobenzaldehyde       1H), 9.83(br s, 1H), 8.47(s,       (6-(2-ethoxyphenyl)-7-       1H), 8.03(s, 1H), 7.93(dd,       hydroxythieno[3,2-d]pyrimidin-       J=7.5Hz, 1.8Hz, 1H), 7.63(d,       4-yl)hydrazone       J=9.0Hz, 2H), 7.33(t, J=6.9Hz,               1H), 7.15(d, J=8.7Hz,               1H), 7.04(t, J=7.5Hz, 1H),               6.76(d, J=8.7Hz, 2H), 4.21(q,               J=6.9Hz, 2H), 2.97(s, 6H),               1.39(t, J=6.9Hz, 3H)       5-Methyl-2-   136   (300MHz, DMSO-d6), 11.89(br   ND   ND       furancarboxaldehyde (6-(2-       s, 1H), 8.50(s, 1H), 7.96(s,       ethoxyphenyl)-7-       1H), 7.92(d, J=8.1Hz, 1H),       hydroxythieno[3,2-d]pyrimidin-       7.32(t, J=7.2Hz, 1H), 7.13(d,       4-yl)hydrazone       J=8.1Hz, 1H), 7.03(t, J=7.8 HZ,               1H), 6.78(d, J=3.3Hz,               1H), 6.27(d, J=3.3Hz, 1H),               4.17(q, J=6.6Hz, 2H), 2.34(s,               3H), 1.38(t, J=6.9Hz, 3H)       4-Fluorobenzaldehyde (6-(2-   137   (300MHz, DMSO-d6), 12.12(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 10.01(br s, 1H),       hydroxythieno[3,2-d]pyrimidin-       8.55(s, 1H), 8.17(s, 1H),       4-yl)hydrazone       7.95(d, J=7.8Hz, 1H), 7.87(dd,               J=8.7Hz, J=5.4Hz, 2H), 7.27-               7.38(m, 3H), 7.15(d, J=8.4Hz,               1H), 7.07(t, J=7.5Hz, 1H),               4.21(q, J=6.9Hz, 2H), 1.35(t,               J=6.9Hz, 3H)       1-Methyl-2-   140   (300MHz, DMSO-d6), 11.97(s,   ND   ND       imidazolecarboxaldehyde (6-(2-       1H), 9.99(br s, 1H), 8.55(s,       ethoxyphenyl)-7-       1H), 8.21(s, 1H), 7.88(d, J=6.3Hz,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.28-7.40(m, 2H),       4-yl)hydrazone       7.13(d, J=7.8Hz, 1H), 7.00-               7.07(m, 2H), 4.14(q, J=7.2Hz,               2H), 4.06(s, 3H), 1.29(t, J=7.2Hz,               3H)       3-Fluorobenzaldehyde (6-(2-   141   (300MHz, DMSO-d6), 12.22(s,   ND   ND       ethoxyphenyl)-7-       1H), 10.08(br s, 1H), 8.58(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.17(s, 1H), 7.99(d,       4-yl)hydrazone       J=7.5Hz, 1H), 7.49-7.70(m,               3H), 7.21-7.38(m, 2H), 7.16(d,               J=8.1Hz, 1H), 7.05(t, J=7.5Hz,               1H), 4.21(q, J=6.6Hz,               2H), 1.36(t, J=6.9Hz, 3H)       4-Cyanobenzaldehyde (6-(2-   144   (300MHz, DMSO-d6), 12.38(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 8.61(s, 1H), 8.22(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.95(m, 5H), 7.34(t,       4-yl)hydrazone       J=7.8Hz, 1H), 7.17(d, J=8.7Hz,               1H), 7.05(t, J=7.8Hz, 1H),               4.22(q, J=6.9Hz, 2H), 1.34(t,               J=6.9Hz, 3H)       3-Cyanobenzaldehyde (6-(2-   145   (300MHz, DMSO-d6), 12.35(s,   ND   ND       ethoxyphenyl)-7-       1H), 10.05(br s, 1H), 8.60(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.20-8.24(m, 2H), 8.14(d,       4-yl)hydrazone       J=7.8Hz, 1H), 7.96(d,               J=8.1Hz, 1H), 7.87(d, J=8.1Hz,               1H), 7.70(t, J=8.1Hz, 1H),               7.35(t, J=9.0Hz, 1H), 7.16(d,               J=8.1Hz, 1H), 7.05(t, J=6.6Hz,               1H), 4.22(q, J=6.6Hz,               2H), 1.35(t, J=6.9Hz, 3H)       4-Bromobenzaldehyde (6-(2-   148   (300MHz, DMSO-d6), 12.17(s,   ND   ND       ethoxyphenyl)-7-       1H), 10.00(br s, 1H), 8.56(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.15(s, 1H), 7.95(d,       4-yl)hydrazone       J=7.5Hz, 1H), 7.75(d, J=8.4Hz,               2H), 7.67(d, J=8.4Hz,               2H), 7.34(t, J=7.8Hz, 1H),               7.15(d, J=8.1Hz, 1H), 7.04(t,               J=7.8Hz, 1H), 4.21(q, J=6.9Hz,               2H), 1.35(t, J=6.9Hz, 3H)       3-Bromobenzaldehyde (6-(2-   149   (300MHz, DMSO-d6), 12.21(s,   ND   ND       ethoxyphenyl)-7-       1H), 8.57(s, 1H), 8.14(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.04(s, 1H), 7.93(d, J=7.8Hz,       4-yl)hydrazone       1H), 7.77(d, J=6.6Hz,               1H), 7.59(d, J=9.0Hz, 1H),               7.42(t, J=8.1Hz, 1H), 7.33(t,               J=7.8Hz, 1H), 7.14(d, J=8.4Hz,               1H), 7.04(t, J=7.5Hz, 1H),               4.20(q, J=7.2Hz, 2H), 1.35(t,               J=7.2Hz, 3H)       2-Pyridinecarboxaldehyde (6-   152   (300MHz, DMSO-d6), 12.32(s,   ND   ND       (2-ethoxyphenyl)-7-       1H), 10.06(br s, 1H), 8.60(m,       hydroxythieno[3,2-d]pyrimidin-       2H), 8.22(s, 1H), 8.13(d,       4-yl)hydrazone       J=8.1Hz, 1H), 7.91-8.02(m,               2H), 7.30-7.42(m, 2H), 7.16(d,               J=8.1Hz, 1H), 7.05(t, J=8.4Hz,               1H), 4.21(q, J=6.9Hz,               2H), 1.36(t, J=6.9Hz, 3H)       3-   153   (300MHz, DMSO-d6), 11.64(s,   ND   ND       Tetrahydrofurancarboxaldehyde       1H), 9.82(br s, 1H), 8.46(s,       (6-(2-ethoxyphenyl)-7-       1H), 7.97(d, J=7.8Hz, 1H),       hydroxythieno[3,2-d]pyrimidin-       7.48(d, J=4.8Hz, 1H), 7.30(t,       4-yl)hydrazone       J=7.2Hz, 1H), 7.11(d, J=8.1Hz,               1H), 7.02(t, J=7.2Hz, 1H),               4.14(q, J=6.9Hz, 2H), 3.6-               3.9(m, ?H), 2.00-2.13(m, 2H),               1.38(t, J=6.6Hz, 3H)       4-Methoxybenzaldehyde (6-(2-   156   (300MHz, DMSO-d6), 11.92(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 8.52(s, 1H), 8.11(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.95(dd, J=8.4Hz, J=1.5Hz,       4-yl)hydrazone       1H), 7.75(d, J=8.7Hz,               2H), 7.31(t, J=6.9Hz, 1H),               7.15(d, J=7.5Hz, 1H), 7.00-               7.11(m, 3H), 4.21(q, J=6.9Hz,               2H), 3.80(s, 3H), 1.37(t, J=7.2Hz,               3H)       3-Methoxybenzaldehyde (6-(2-   157   (300MHz, DMSO-d6), 12.15(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 8.55(s, 1H), 8.12(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 7.91(d, J=7.8Hz, 1H),       4-yl)hydrazone       7.28-7.43(m, 4H), 7.05(d,               J=8.4Hz, 1H), 7.00-7.09(m,               2H), 4.17(q, J=6.9Hz, 2H),               3.78(s, 3H), 1.32(t, J=7.2Hz,               3H)       4-(2-Diethylamino-ethoxy)-   159   (300MHz, DMSO-d6) 12.14(s,   ND   ND       3,5-dimethoxy-benzaldehyde       1H, NH), 8.54(s, 1H), 8.06(s,       (6-(2-ethoxy-4-fluorophenyl)-       1H), 7.76(t, J=8.0Hz, 1H),       7-hydroxythieno[3,2-       7.16(s, 2H), 7.03(d, J=11.2Hz,       d]pyrimidin-4-yl)hydrazone       1H), (6.88(t, J=8.5Hz,               1H), 4.09(q, J=6.7Hz,               2H), 3.92(t, J=4.5Hz, 2H),               3.78(s, 6H), 2.70(t, J=6.5Hz, 2H),               2.50(m, 4H), 1.23(t, J=6.7Hz,               3H), 0.94(s, 6H),       2-Fluorobenzaldehyde (6-(2-   162   (300MHz, DMSO-d6), 12.19(br   ND   ND       ethoxyphenyl)-7-       s, 1H), 8.57(s, 1H), 8.39(s,       hydroxythieno[3,2-d]pyrimidin-       1H), 8.13(t, J=8.1Hz, 1H),       4-yl)hydrazone       7.98(d, J=8.1Hz, 1H), 7.43-               7.51(m, 1H), 7.25-7.37(m,               3H), 7.15(d, J=8.4Hz, 1H),               7.04(t, J=6.9Hz, 1H), 4.21(q,               J=6.9Hz, 2H), 1.36(t, J=6.9Hz,               3H)                  
 
     Example 4  
     Synthesis of 3-hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methoxythieno[3,2-d]pyrimidin-yl)hydrazone (Compound 40; See FIG.  5 )  
      3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165): Commercially available from Lancaster Synthesis Inc., Windham, N.H., USA.  
      3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166): Formic acid (60 mL) was added to acetic anhydride (90 mL) cooled in an ice bath. 3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165, 25.0 g, 0.146 mol) was added to the cold solution in small portions. The cooling bath was removed and the resulting suspension was stirred at room temperature for 4 hours. The reaction mixture was added to 150 g Na 2 CO 3  in water (500 mL) cooled in an ice bath. The solid product was collected by vacuum filtration, washed with water and dried over P 2 O 5  under vacuum overnight (28.5 g, 97% yield, white solid).  
      7-Methyl-3H-thieno[3,2-d]pyrimid-4-one (167): 3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166, 10.0 g, 50.0 mmol), ammonium formate 26.0 g, (400 mmol) and formamide (12 mL) were heated at 160° C. for 6 hours under N 2  and then cooled to room temperature. The precipitate was collected by vacuum filtration, washed with acetone, and dried over P 2 O 5  under vacuum overnight (6.0 g 72% yield, white needles).  
      4-Chloro-7-methylthieno[3,2-d]pyrimidine (168): A solution of 7-methyl-3H-thieno[3,2-d]pyrimid-4-one (167, 10.6 g, 64.0 mmol) in phosphorus oxychloride (42 mL) was refluxed under N 2  for 2 hours. The resulting solution was allowed to cool to room temperature and then neutralized by carefully pouring into a saturated aqueous solution of sodium carbonate (300 mL). The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine, before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue dried over P 2 O 5  under vacuum overnight (11.2 g, 95% yield, white solid).  
      4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169): Diisopropylamine (11 mL, 77.8 mmol, 1.43 eq) was dissolved in anhydrous THF 100 mL, and the solution was chilled to −78° C. 22 mL 1.6 M BuLi in hexanes (70.8 mmol, 1.3 eq) was added, and the solution was stirred for 30 minutes at −78° C. A solution of 4-chloro-7-methylthieno[3,2-d]pyrimidine (168, 10.0 g 54.4 mmol) in 100 mL anhydrous THF was chilled to −78° C., and the LDA solution was then transferred via cannula to the cold solution of 168. The reaction mixture became a dark brown suspension as the LDA solution was added. After 2 hours at −78° C., a solution of I 2  (20.8 g 81.6 mmol, 1.5 eq) in 50 mL THF was cannulated to the anion solution. The reaction mixture was maintained at −78° C. for 2 hours and then warmed to room temperature overnight. After overnight stirring, the reaction mixture was diluted with EtOAc and washed three times with deionized H 2 O, twice with saturated Na 2 S 2 O 4 , once with deionized H 2 O, three times with 10% HCl, and once with saturated NaCl. The dark solution was dried over anhydrous Na 2 SO 4 , decolorized with activated carbon, and then filtered through silica gel. The resulting light yellow filtrate was concentrated by rotary evaporation, and a light yellow solid precipitated as the solution was concentrated. After concentrating to a small volume, the precipitate was collected via filtration and was washed twice with ice cold EtOAc (13.7 g, 82% yield).  
      4-Chloro-(6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidine (178): 4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169, 7.00 g, 22.5 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.79 g, 0.11 mmol) were placed in a mixture of 1,2-dimethoxyethane (94 mL) and distilled water (31 mL) and stirred at room temperature for 10 minutes under N 2 . 2-Ethoxyphenyl boronic acid (4.12 g, 24.80 mmol) and Cs 2 CO 3  (18.40 g, 0.11 mmol) were added to the reaction mixture. The suspension was heated at 80° C.: for 20 hr, cooled to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography and the product was dried over P 2 O 5  under vacuum overnight (5.60 g, 82% yield, white solid).  
      7-Bromomethyl-4-chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine (179): 4-Chloro-(6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidine (178, 0.50 g, 1.70 mmol) was dissolved in CCl 4 8.0 mL. NBS (0.33 g, 1.83 mmol eq 1.1) was added to the solution, and the suspension was stirred under a 250 W sun lamp until the reaction was complete (about 1 hr). Upon completion of the reaction, the crude suspension was filtered through Celite, and the filter pad was washed with 2 small portions of CCl 4 . The filtrate was absorbed on to silica gel by rotovaporation and the product was chromatographed through a silica gel plug with 10% EtOAc/hexanes (0.56 g. 93% yield).  
      4-Chloro-6-(2-ethoxyphenyl)-7-hydroxymethylthieno-3,2-d]pyrimidine (180): 7-Bromomethyl-4-chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine (179, 0.52 g, 1.34 mmol) was suspended in 15 mL dioxane/15 mL H 2 O. To the suspension was added CaCO 3  (0.67 g, 6.72 mmol, 5 eq) refluxed overnight, and then diluted with EtOAc/H 2 O. The EtOAc phase was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (0.40 g, 94% yield).  
      4-Chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde (181): Oxalyl chloride (1.60 mL, 18.33 mmol, 1.1 eq) was dissolved in 80 mL of dry CH 2 Cl 2 , and the solution was chilled to −60° C. Dry DMSO (2.80 mL, 38.10 mmol, 2.4 eq) was added, and stirring was maintained for 15 min. at −60° C. After 15 min, a solution of 4-chloro-6-(2-ethoxyphenyl)-7-hydroxymethylthieno-3,2-d]pyrimidine (180, 0.54 g, 16.7 mmol) in 50 mL CH 2 Cl 2  (plus 10 mL rinse) was added via syringe. The reaction was maintained at −60° C. for 1 hr, TEA (11.0 ml, 79.22 mmol, 4.8 eq) was added. The reaction was allowed to warm up gradually to RT and was then diluted with CH 2 Cl 2 /H 2 O. The CH 2 Cl 2  extract was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (5.30 g, 99% yield).  
      4-Chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-7-ol (182): 4-Chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde (181, 84.0 mg, 0.28 mmol) was dissolved in CH 2 Cl 2  (5 mL), and MCPBA (72.0 mg, 0.42 mmol, 1.5 eq) was added. The reaction was stirred overnight at RT. The reaction was diluted with CH 2 Cl 2  and was washed twice with sat. NaHCO 3 , once with H 2 O, and once with sat. NaCl. The extract was dried over Na 2 SO 4  and on a placed on a rotovaporator until dry. The crude product was dissolved in MeOH (8 mL). TEA (0.20 mL, excess) was added, and the reaction was stirred overnight at RT. After overnight stirring, the reaction was diluted with EtOAc and was washed twice with 10% HCl and once with H 2 O. The extract was dried over Na 2 SO 4  and placed on a placed on a rotovaporator until dry (65.0 mg, 59% yield).  
      4-Chloro-6-(2-ethoxyphenyl)-7-methoxythieno-3,2-d]pyrimidine (183): 4-Chloro-6-(2-ethoxyphenyl)-thieno[3,2-d]pyrimidin-7-ol (182, 34.0 mg, 0.11 mmol) was dissolved in acetone (2 ml). K 2 CO 3  (152.0 mg, 1.10 mmol 10 eq) and MeI (62.0 mg, 0.44 mmol, 4 eq) were added to the solution. After refluxing for 4 hours, the reaction was diluted with EtOAc and was washed twice with H 2 O. The extract was dried over Na 2 SO 4  and reduced to dryness on a rotovaporator (31.0 mg, 87% yield).  
      6-(2-Ethoxyphenyl)-7-methoxythieno[3,2-d]pyrimidin-4-yl)hydrazine (184): A suspension of 4-chloro-6-(2-ethoxyphenyl)-7-methoxythieno-3,2-d]pyrimidine (183, 31.0 mg, 0.10 mmol) and hydrazine monohydrate (54 mg, 1.0 mmol) were refluxed in ethanol (1 mL) for 1 hour. After cooling to room temperature, the solid product was collected by vacuum filtration (11.0 mg, 36% yield).  
      3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-methoxythieno[3,2-d]pyrimidin-4-yl)hydrazone (40): A suspension of (6-(2-ethoxyphenyl)-7-methoxythieno[3,2-d]pyrimidin-4-yl)hydrazine (184, 11.0 mg, 0.04 mmol) and 3-hydroxy-4-methoxybenzaldehyde (7.0 mg, 0.05 mmol) were refluxed in ethanol (0.50 mL) for 4 hours. After cooling to near 0 C, the solid product was collected by vacuum filtration (3.5 mg, 22% yield,).  
      Compounds that can be made using the above procedure with the appropriate substitution of reagents are listed in Table 4. The synthesis of Compound 40 as illustrated above is also illustrated in  FIG. 5 .  
                               TABLE 4                                       Purity                       by       Compound   No   1H NMR   MS   HPLC                  3-Hydroxy-4-   40   (300MHz, DMSO-d6),   M+1=451   99%       methoxybenzaldehyde(6-(2-       11.93(br s, 1H), 9.23(s,   (ESI+)       ethoxyphenyl)-7-       1H), 8.50(s, 1H), 8.02(s,       methoxythieno[3,2-       1H), 7.62(d, J=8.4Hz, 1H),       d]pyrimidin-4-yl)hydrazone       7.41(t, J=8.4Hz, 1H),               7.28(s, 1H), 6.95-7.20(m, 4H),               4.17(q, J=6.9Hz, 3H), 4.00(s,               2H), 3.80(s, 3H), 1.30(t,               J=6.9Hz, 3H)       3-Hydroxy-4-   41   (300MHz, DMSO-d6),   M+1=550   ND       methoxybenzaldehyde(6-(2-       12.10(br s, 1H), 9.24(s,   (ESI+)       ethoxyphenyl)-7-(2-(morpholin-       1H), 8.05(s, 1H), 7.44(m,       4-yl)-ethoxy)thieno[3,2-       ND, H), 7.29(s, 1H), 6.95-7.19(m,       d]pyrimidin-4-yl)hydrazone       ND, H), 4.20(q,               J=6.9Hz, 2H), 3.80(s, 3H)               1.30(t, J=6.9Hz, 3H)                  
 
     Example 5  
     Synthesis of 3-fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl) thieno[3,2-d]pyrimidin-4yl)hydrazone (Compound 139; See FIG.  6 )  
      3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165): Commercially available from Lancaster Synthesis Inc., Windham, N.H., USA.  
      3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166): Formic acid (60 mL) was added to acetic anhydride (90 mL) cooled in an ice bath. 3-Amino-4-methyl-2-thiophenecarboxylic acid methyl ester (165, 25.0 g, 0.146 mol) was added to the cold solution in small portions. The cooling bath was removed and the resulting suspension was stirred at room temperature for 4 hours. The reaction mixture was added to 150 g Na 2 CO 3  in water (500 mL) cooled in an ice bath. The solid product was collected by vacuum filtration, washed with water and dried over P 2 O 5  under vacuum overnight (28.5 g, 97% yield, white solid).  
      7-Methyl-3H-thieno[3,2-d]pyrimid-4-one (167): 3-(Formylamino)-4-methyl-2-thiophenecarboxylic acid methyl ester (166, 10.0 g, 50.0 mmol), ammonium formate 26.0 g, (400 mmol) and formamide (12 mL) were heated at 160° C. for 6 hours under N 2  and then cooled to room temperature. The precipitate was collected by vacuum filtration, washed with acetone, and dried over P 2 O 5  under vacuum overnight (6.0 g 72% yield, white needles).  
      4-Chloro-7-methylthieno[3,2-d]pyrimidine (168): A solution of 7-methyl-3H-thieno[3,2-d]pyrimid-4-one (167, 10.6 g, 64.0 mmol) in phosphorus oxychloride (42 mL) was refluxed under N 2  for 2 hours. The resulting solution was allowed to cool to room temperature and then neutralized by carefully pouring into a saturated aqueous solution of sodium carbonate (300 mL). The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine, before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue dried over P 2 O 5  under vacuum overnight (11.2 g, 95% yield, white solid).  
      4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169): Diisopropylamine (11 mL, 77.8 mmol, 1.43 eq) was dissolved in 100 mL anhydrous THF, and the solution was chilled to −78° C. 22 mL 1.6 M BuLi in hexanes (70.8 mmol, 1.3 eq) was added, and the solution was stirred for 30 minutes at −78° C. A solution of 4-chloro-7-methylthieno[3,2-d]pyrimidine (168, 10.0 g 54.4 mmol) in 100 mL anhydrous THF was chilled to −78° C., and the LDA solution was then transferred via cannula to the cold solution of 168. The reaction mixture became a dark brown suspension as the LDA solution was added. After 2 hours at −78° C., a solution of I 2  (20.8 g 81.6 mmol, 1.5 eq) in 50 mL THF was cannulated to the anion solution. The reaction mixture was maintained at −78° C. for 2 hours and then warmed to room temperature overnight. After overnight stirring, the reaction mixture was diluted with EtOAc and washed three times with deionized H 2 O, twice with saturated Na 2 S 2 O 4 , once with deionized H 2 O, three times with 10% HCl, and once with saturated NaCl. The dark solution was dried over anhydrous Na 2 SO 4 , decolorized with activated carbon, and then filtered through silica gel. The resulting light yellow filtrate was concentrated by rotary evaporation, and a light yellow solid precipitated as the solution was concentrated. After concentrating to a small volume, the precipitate was collected via filtration and was washed twice with ice cold EtOAc (13.7 g, 82% yield).  
      4-Chloro-(6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidine (178): 4-Chloro-6-iodo-7-methylthieno[3,2-d]pyrimidine (169, 7.00 g, 22.5 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.79 g, 0.11 mmol) were placed in a mixture of 1,2-dimethoxyethane (94 mL) and distilled water (31 mL) and stirred at room temperature for 10 minutes under N 2 . 2-Ethoxyphenyl boronic acid (4.12 g, 24.80 mmol) and Cs 2 CO 3  (18.40 g, 0.11 mmol) were added to the reaction mixture. The suspension was heated at 80° C. for 20 hr, cooled to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography and the product was dried over P 2 O 5  under vacuum overnight (5.60 g, 82% yield, white solid).  
      7-Bromomethyl-4-chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine (179): 4-Chloro-(6-(2-ethoxyphenyl)-7-methylthieno[3,2-d]pyrimidine (178, 0.50 g, 1.70 mmol) was dissolved in CCl 4  8.0 mL. NBS (0.33 g, 1.83 mmol eq 1.1) was added to the solution, and the suspension was stirred under a 250 W sun lamp until the reaction was complete (about 1 hr). Upon completion of the reaction, the crude suspension was filtered through Celite, and the filter pad was washed with 2 small portions of CCl 4 . The filtrate was absorbed on to silica gel by rotovaporation and the product was chromatographed through a silica gel plug with 10% EtOAc/hexanes (0.56 g. 93% yield).  
      4-Chloro-6-(2-ethoxyphenyl)-7-hydroxymethylthieno-3,2-d]pyrimidine (180): 7-Bromomethyl-4-chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine (179, 0.52 g, 1.34 mmol) was suspended in 15 mL dioxane/15 mL H 2 O. To the suspension was added CaCO 3  (0.67 g, 6.72 mmol, 5 eq). The reaction was refluxed overnight. The reaction was diluted with EtOAc/H 2 O. The EtOAc phase was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (0.40 g, 94% yield).  
      4-Chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde (181): Oxalyl chloride (1.60 mL, 18.33 mmol, 1.1 eq) was dissolved in 80 mL of dry CH 2 Cl 2 , and the solution was chilled to −60° C. Dry DMSO (2.80 mL, 38.10 mmol, 2.4 eq) was added, and stirring was maintained for 15 min. at −60° C. After 15 min, a solution of 4-chloro-6-(2-ethoxyphenyl)-7-hydroxymethylthieno-3,2-d]pyrimidine (180, 0.54 g, 16.7 mmol) in 50 mL CH 2 Cl 2  (plus 10 mL rinse) was added via syringe. The reaction was maintained at −60° C. for 1 hr, then TEA (11.0 ml, 79.22 mmol, 4.8 eq) was added. The reaction was allowed to warn up gradually to RT and was then diluted with CH 2 Cl 2 /H 2 O. The CH 2 Cl 2  extract was washed once more with H 2 O and once with sat. NaCl. The extract was dried over Na 2 SO 4  and placed on a rotovaporator until dry (5.30 g, 99% yield).  
      4-Chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde oxime (185): 4-Chloro-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde (181, 3.25 g, 10.20 mmol) was suspended in 90 mL EtOH/45 mL H 2 O. To the suspension was added hydroxylamine hydrochloride (0.74 g, 10.7 mmol, 1.05 eq) and sodium acetate (1.05 g, 12.80 mmol, 1.25 eq). The suspension was refluxed for 1 hr, and then chilled in ice and filtered. The residue was washed with ice cold EtOH. A second crop of product was collected by concentration of the filtrate (2.87 g, 85% yield,).  
      (4-Chloro-7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine (186): 4-Chloro-6-(2-ethoxy-phenyl)thieno[3,2-d]pyrimidine-7-carbaldehyde oxime (185, 2.87 g, 8.23 mmol) was suspended in Ac 2 O (30 mL) and heated to 125 C for 4 hours. The reaction mixture was diluted with EtOAc and was washed with sat. NaHCO 3  until effervescence ceased. The extract was dried over Na 2 SO 4  and chromatographed (1.89 g, 73% yield, a yellow solid).  
      7-Cyano-6-(2-Ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazine (187): A suspension of (4-chloro-7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidine (186, 1.89 g, 5.99 mmol) and hydrazine monohydrate (3.49 g, 70.0 mmol) were refluxed in ethanol (40 mL) for 1 hour. After cooling to room temperature, the solid product was collected by vacuum filtration (1.61 g, 86% yield, a yellow solid).  
      3-Fluorobenzaldehyde (7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone (139): A suspension of 7-cyano-6-(2-ethoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazine (187, (20.0 mg, 0.06 mmol) and 3-fluorobenzaldehyde (10.0 mg, 0.06 mmol) were refluxed in ethanol (1.0 mL) for 4 hours. After cooling to room temperature, the solid product was collected by vacuum filtration (23.0 mg, 86% yield).  
                               TABLE 5                                          Purity                       by       Compound   No   1H NMR   MS   HPLC               3-Hydroxy-4-   47   (300MHz, DMSO-d6),   M−1=444   ND       methoxybenzaldehyde(7-       12.29(s, 1H), 9.32(s, 1H),   (ESI−)       cyano-6-(2-ethoxyphenyl)       8.60(s, 1H), 8.09(s, 1H),       thieno[3,2-d]pyrimidin-4-       7.74(d, J=7.5Hz, 1H), 7.58(t,       yl)hydrazone       J=ND, 1H), 7.30(m, 2H),               7.09-7.19(m, 2H), 6.99(d,               J=8.4Hz, 1H)       3-Hydroxy-4-   59   (300MHz, DMSO-d6),   M+1=417   99%       methoxybenzaldehyde(6-(4-       12.10(br s, 1H), 9.43(br s,   (ESI+)       aminophenyl)-7-       1H), 8.52(s, 1H), 8.06(s,       cyanothieno[3,2-d]pyrimidin-4-       1H), 7.74(d, J=8.7Hz, 2H),       yl)hydrazone.       7.31(s, 1H), 7.12(d, J=8.4Hz,               1H), 7.02(d, J=8.4Hz,               1H), 6.74(d, J=8.4Hz, 2H),               6.12(s, 2H), 3.82(s, 3H)       3-Hydroxy-4-   62   (300MHz, DMSO-d6) 12.28(s,   M+1=455   ND       methoxybenzaldehyde(7-       1H, NH), 9.32(s, 1H),   (ESI+)       cyano-6-(2-ethoxy-4-       8.60(s, 1H), 8.10(s, 1H),       fluorophenyl)thieno[3,2-       7.80(dd, J=6.8Hz, J=2.0Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.27(m, 2H) 7.05(m,               3H), 4.24(q, J=7.0Hz,               2H) 3.81(s, 3H), 1.34,(t,               J=7.0Hz, 3H)       3-Pyridinecarboxaldehyde(7-   67   (300MHz, DMSO-d6),   M+1=401   99%       cyano-6-(2-ethoxyphenyl)       12.63(br s, 1H), 8.96(s,   (ESI+)       thieno[3,2-d]pyrimidin-4-       1H), 8.66(s, 1H), 8.58(dd,       yl)hydrazone       J=4.5Hz, J=1.8Hz, 1H),               8.27(s, 1H), 8.16(d, J=7.8Hz,               1H), 7.78(dd, J=7.5Hz,               J=1.8Hz, 1H), 7.48-7.58(m,               2H), 7.30(d, J=8.4Hz, 1H),               7.17(t, J=7.2Hz, 1H), 4.24(q,               J=7.2Hz, 2H), 1.34(t,               J=6.9Hz, 3H)       4-Carboxybenzaldehyde(7-   68   (300MHz, DMSO-d6),   M−1=442   96%       cyano-6-(2-       12.62(br s, 1H), 8.68(s,   (ESI−)       ethoxyphenyl)thieno[3,2-       1H), 8.30(s, 1H), 8.01(d,       d]pyrimidin-4-yl)hydrazone       J=8.4Hz, 2H), 7.89(d, J=8.4Hz,               2H), 7.89(dd, J=7.8Hz,               J=1.8Hz, 1H), 7.60(t, J=6.6Hz,               1H), 7.31(d, J=8.1Hz,               1H), 7.18(t, J=8.7Hz, 1H),               4.26(q, J=6.9Hz, 2H), 1.36(t,               J=6.9Hz, 3H)       2-Thiophenecarboxaldehyde(7-   69   (300MHz, DMSO-d6),   M+1=444   85%       cyano-6-(2-       12.05(br s, 1H), 8.60(br s,   (ESI+)       ethoxyphenyl)thieno[3,2-       1H), 8.40(s, 1H), 7.68(m,       d]pyrimidin-4-yl)hydrazone       2H), 7.58(t, J=8.7Hz, 1H),               7.48(m, 1H), 7.30(d, J=8.7Hz,               1H), 7.10-7.20(m, 2H),               4.01(q, J=6.9Hz, 2H), 1.17(t,               J=7.5Hz, 3H)       4-Hydroxy-3-   86   (300MHz, DMSO-d6), 8.60(s,   ND   ND       methoxybenzaldehyde(7-       1H), 8.11(s, 1H), 7.72(d,       cyano-6-(2-       J=6.9Hz, 1H), 7.58(t, J=6.6Hz,       ethoxyphenyl)thieno[3,2-       1H), 7.45(s, 1H), 7.28(d,       d]pyrimidin-4-yl)hydrazone       J=9.3Hz, 1H), 7.12-7.28(m,               2H), 6.84(d, J=7.8Hz,               1H), 4.19(q, J=6.9Hz, 2H),               3.77(s, 3H), 1.34(t, J=6.9Hz,               3H)       3-   87   (300MHz, DMSO-d6),   ND   ND       Bromo-4-hydroxy-5-       12.45(br s, 1H), 8.63(s,       methoxybenzaldehyde(7-       1H), 8.10(s, 1H), 7.74(d,       cyano-6-(2-       J=7.5Hz, 1H), 7.51-7.64(m,       ethoxyphenyl)thieno[3,2-       2H), 7.44(s, 1H), 7.29(d,       d]pyrimidin-4-yl)hydrazone       J=8.4Hz, 1H), 7.16(t, J=7.5Hz,               1H), 4.20(q, J=7.5Hz,               2H), 3.84(s, 3H), 1.33(t,               J=7.2Hz, 3H)       3-Chloro-4-   90   (300MHz, DMSO-d6),   ND   ND       hydroxybenzaldehyde(7-cyano-       12.36(br s, 1H), 11.78(br s,       6-(2-ethoxyphenyl)thieno[3,2-       1H), 8.61(s, 1H), 8.12(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.78(m, 2H), 7.56(m,               2H), 7.31(d, J=9.0Hz, 1H),               7.18(r, J=8.4Hz, 1H), 7.04(d,               J=8.4Hz, 1H), 4.24(q,               J=6.9Hz, 2H), 1.35(t, J=7.2Hz,               3H)       3-Thiophenecarboxaldehyde(7-   91   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.35(br s, 1H), 8.61(s,       ethoxyphenyl)thieno[3,2-       1H), 8.26(s, 1H), 7.96(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.61-7.77(m, 2H),               7.45-7.58(m, 2H), 7.30(d,               J=8.4Hz, 1H), 7.17(t, J=6.6Hz,               1H), 4.24(q, J=6.9Hz,               2H), 1.35(t, J=7.2Hz, 3H)       3,5-Dimethoxy-4-   94   (300MHz, DMSO-d6),   ND   ND       hydroxybenzaldehyde(7-cyano-       12.40(br s, 1H), 8.60(s,       6-(2-ethoxyphenyl)thieno[3,2-       1H), 8.10(s, 1H), 7.70(d,       d]pyrimidin-4-yl)hydrazone       J=7.8Hz, 1H), 7.57(t, J=7.8Hz,               1H), 7.28(d, J=8.7Hz,               1H), 7.17(t, J=7.2Hz, 1H),               7.11(s, 2H), 4.17(q, J=6.9Hz,               2H), 3.78(s, 6H), 1.32(t,               J=7.2Hz, 3H)       2-Imidazolecarboxaldehyde(7-   95   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.19(s, 1H), 8.62(s, 1H),       ethoxyphenyl)thieno[3,2-       8.14(s, 1H), 7.67(d, J=8.1Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.57(t, J=7.8Hz,               1H), 7.24-7.30(m, 2H),               7.09-7.19(m, 2H), 4.18(q,               J=6.3Hz, 2H), 1.32(t, J=7.2Hz,               3H)       3,4-Dimethoxy-5-   98   (300MHz, DMSO-d6),   ND   ND       hydroxybenzaldehyde(7-cyano-       12.41(br s, 1H), 9.45(s,       6-(2-ethoxyphenyl)thieno[3,2-       1H), 8.62(s, 1H), 8.07(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.71(d, J=7.8Hz, 1H),               7.57(t, J=7.5Hz, 1H), 7.28(d,               J=8.4Hz, 1H), 7.17(t,               J=7.2Hz, 1H), 6.97(s, 1H),               6.90(s, 1H), 4.18(q, J=7.5Hz,               2H), 1.32(t, J=6.6Hz,               3H)       4-(1H-imidazol-1-   99   (300MHz, DMSO-d6),   ND   ND       yl)benzaldehyde(7-cyano-6-(2-       12.55(s, 1H), 8.67(s, 1H),       ethoxyphenyl)thieno[3,2-       8.35(s, 1H), 8.28(s, 1H),       d]pyrimidin-4-yl)hydrazone       7.92(d, J=7.5Hz, 2H), 7.76-7.84(m,               4H), 7.60(t, J=7.5Hz,               1H), 7.32(d, J=7.80Hz,               1H), 7.31(t, J=7.8Hz, 1H),               7.12(s, 1H), 4.25(q, J=7.2Hz,               2H), 1.35(t, J=6.6Hz,               3H)       4-Hydroxybenzaldehyde(7-   102   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.27(s, 1H), 9.99(s, 1H),       ethoxyphenyl)thieno[3,2-       8.59(s, 1H), 8.14(s, 1H),       d]pyrimidin-4-yl)hydrazone       7.77(d, J=6.3Hz, 1H), 7.54-7.63(m,               3H), 7.31(d, J=8.1Hz,               1H), 7.17(t, J=7.8Hz,               1H), 6.85(d, J=8.4Hz, 2H),               4.24(q, J=6.9Hz, 2H), 1.36(t,               J=6.6Hz, 3H)       3-Hydroxybenzaldehyde(7-   103   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.40(s, 1H), 9.68(s, 1H),       ethoxyphenyl)thieno[3,2-       8.64(s, 1H), 8.15(s, 1H),       d]pyrimidin-4-yl)hydrazone       7.76(dd, J=7.5Hz, J=1.5Hz,               1H), 7.58(t, J=9.0Hz,               1H), 7.12-7.32(m, 5H), 6.83(d,               J=6.9Hz, 1H), 4.23(q,               J=7.2Hz, 2H), 1.34(t, J=6.6Hz,               3H)       2-Thiophenecarboxaldehyde(7-   108   (300MHz, DMSO-d6) 12.48(s,   ND   ND       cyano-6-(2-ethoxy-4-       1H, NH), 8.63(s, 1H),       fluorophenyl)thieno[3,2-       8.42(s, 1H), 7.76(dd, J=8.8Hz,       d]pyrimidin-4-yl)hydrazone       J=2.0Hz, 1H), 7.68(d,               J=5.0Hz, 1H), 7.49(d, J=3.9Hz,               1H), 7.25(dd, J=9.1Hz,               J=2.3Hz, 1H), 7.14(dd,               J=4.9Hz, J=1.4Hz, 1H),               7.04(td, J=10.5Hz, J=8.5Hz,               J=2.3 1H), 4.24(q, J=6.7Hz,               2H) 1.37,(t, J=6.7Hz,               3H)       4-Pyridinecarboxaldehyde(7-   110   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.74(s, 1H), 8.71(s, 1H),       ethoxyphenyl)thieno[3,2-       8.67(d, J=6.0Hz, 2H), 8.23(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.79(dd, J=8.1Hz,               1.8Hz, 1H), 7.72(d, J=6.0Hz,               2H), 7.60(t, J=8.1Hz,               1H), 7.31(d, J=9.0Hz, 1H),               7.182(t, J=8.1Hz, 1H), 4.25(q,               J=6.9Hz, 2H), 1.35(t,               J=6.9Hz, 3H)       2,4-Dioxo-1,2,3,4-tetrahydro-   111   (300MHz, DMSO-d6),   ND   ND       pyrimidine-5-carbaldehyde(7-       12.34(s, 1H), 11.48(s, 1H),       cyano-6-(2-       11.39(br s, 1H), 8.60(s,       ethoxyphenyl)thieno[3,2-       1H), 8.10(s, 1H), 7.89(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.69(dd, J=7.5Hz, 1.8Hz,               1H), 7.57(t, J=6.6Hz,               1H), 7.29(d, J=8.1Hz, 1H),               7.15(t, J=7.5Hz, 1H), 4.20 (q,               J=6.9Hz, 2H), 1.33(t,               J=6.9Hz, 3H)       3-Carboxybenzaldehyde(7-   114   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.59(s, 1H), 8.67(s, 1H),       ethoxyphenyl)thieno[3,2-       8.42(s, 1H), 8.31(s, 1H),       d]pyrimidin-4-yl)hydrazone       7.94-8.02(m, 2H), 7.76(dd,               J=7.5Hz, J=1.5Hz, 1H),               7.54-7.65(m, 2H), 7.29(d,               J=7.8Hz, 1H), 7.18(t, J=7.2Hz,               1H), 4.22(q, J=6.9Hz,               2H), 1.31(t, J=6.6Hz, 3H)       4-Methyl-5-   115   (300MHz, DMSO-d6),   ND   ND       imidazolecarboxaldehyde(7-       12.22(br s, 1H), 12.06(s,       cyano-6-(2-       1H), 8.56(s, 1H), 8.22(s,       ethoxyphenyl)thieno[3,2-       1H), 7.62-7.68(m, 2H), 7.57(t,       d]pyrimidin-4-yl)hydrazone       J=8.7Hz, 1H), 7.28(d,               J=8.4Hz, 1H), 7.15(t, J=7.8Hz,               1H), 4.19(q, J=7.2Hz,               2H), 2.42(s, 3H), 1.34(t,               J=6.9Hz, 3H)       Methyl 4-formyl benzoate(7-   118   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.67(s, 1H), 8.69(s, 1H),       ethoxyphenyl)thieno[3,2-       8.31(s, 1H), 8.04(d, J=8.7Hz,       d]pyrimidin-4-yl)hydrazone       2H), 7.92(d, J=8.4Hz,               2H), 7.78(d, J=8.1Hz, 1H),               7.60(t, J=7.8Hz, 1H), 7.31(d,               J=8.1Hz, 1H), 7.19(t,               J=7.5Hz, 1H), 4.26(q, J=6.6Hz,               2H), 3.87(s, 3H), 1.35(t,               J=6.9Hz, 3H)       2-Furancarboxaldehyde(7-   119   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.42(s, 1H), 8.62(s, 1H),       ethoxyphenyl)thieno[3,2-       8.09(s, 1H), 8.67(d, J=1.2Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.74(dd, J=7.5Hz,               1.8Hz, 1H), 7.58(t, J=7.2Hz,               1H), 7.29(d, J=7.8Hz,               1H), 7.16(t, J=7.8Hz, 1H),               6.95(d, J=3.9Hz, 1H), 6.65(dd,               J=3.6Hz, J=1.8Hz,               1H), 4.22(q, J=6.9Hz, 2H),               1.37(t, J=7.2Hz, 3H)       3-Methyl-2-   122   (300MHz, DMSO-d6),   ND   ND       thiophenecarboxaldehyde(7-       12.33(s, 1H), 8.61(s, 1H),       cyano-6-(2-       8.46(s, 1H), 7.68(d, J=7.5Hz,       ethoxyphenyl)thieno[3,2-       1H), 7.54-7.60(m, 2H),       d]pyrimidin-4-yl)hydrazone       7.29(d, J=7.8Hz, 1H), 7.17(t               J=7.8Hz, 1H), 6.97(d,               J=4.8Hz, 1H), 4.21(q, J=6.9Hz,               2H), 2.33(s, 3H), 1.36(t,               J=6.9Hz, 3H)       3-Chloro-4-fluorobenzaldehyde   123   (300MHz, DMSO-d6),   ND   ND       (7-cyano-6-(2-       12.60(s, 1H), 8.67(s, 1H),       ethoxyphenyl)thieno[3,2-       8.22(s, 1H), 8.00(d, J=7.2Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.72-7.85(m, 2H),               7.50-7.62(m, 2H), 7.30(d,               J=7.8Hz, 1H), 7.18(t, J=7.2Hz,               1H), 4.23(q, J=6.9Hz,               2H), 1.34(t, J=6.6Hz, 3H)       5-Methyl-2-   126   (300MHz, DMSO-d6),   ND   ND       thiophenecarboxaldehyde(7-       12.39(s, 1H), 8.60(s, 1H),       cyano-6-(2-       8.31(s, 1H), 7.71(d, J=8.1Hz,       ethoxyphenyl)thieno[3,2-       1H), 7.58(t, J=6.3Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.26-7.34(m, 2H), 7.17(t,               J=6.9Hz, 1H), 6.83(d,               J&lt;1Hz, 1H), 4.24(q, J=7.2Hz,               2H), 1.39(t, J=6.9Hz,               3H)       3-Furancarboxaldehyde(7-   127   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.37(s, 1H), 8.61(s, 1H),       ethoxyphenyl)thieno[3,2-       8.18(s, 2H), 7.80(s, 1H),       d]pyrimidin-4-yl)hydrazone       7.74(d, J=7.5Hz, 1H), 7.58(t,               J=7.8Hz, 1H), 7.29(d,               J=7.8Hz, 1H), 7.16(t, J=7.2Hz,               1H), 6.87(s, 1H), 4.21(q,               J=6.6Hz, 2H), 1.35(t,               J=6.6Hz, 3H)       4-Acetamidobenzaldehyde(7-   130   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.37(br s, 1H), 10.14(s,       ethoxyphenyl)thieno[3,2-       1H), 8.61(s, 1H), 8.17(s,       d]pyrimidin-4-yl)hydrazone       1H), 7.77(d, J=7.8Hz, 1H),               7.67-7.72(m, 4H), 7.59(t,               J=8.1Hz, 1H), 7.32(d, J=8.4Hz,               1H), 7.18(t, J=8.1Hz,               1H), 4.25(q, J=6.9Hz, 2H),               2.06(s, 3H), 1.37(t, J=7.2Hz,               3H)       4-N,N-   131   (300MHz, DMSO-d6),   ND   ND       Dimethylaminobenzaldehyde       12.19(s, 1H), 8.56(s, 1H),       (7-cyano-6-(2-       8.09(s, 1H), 7.74(dd, J=7.5Hz,       ethoxyphenyl)thieno[3,2-       1.5Hz, 1H), 7.56-7.63(m,       d]pyrimidin-4-yl)hydrazone       3H), 7.30(d, J=8.1Hz,               1H), 7.17(t, J=8.1Hz, 1H),               6.76(d, J=9.0Hz, 2H), 4.24(q,               J=7.2Hz, 2H), 2.97(s,               6H), 1.36(t, J=7.2Hz, 3H)       5-Methyl-2-   134   (300MHz, DMSO-d6),   ND   ND       furancarboxaldehyde(7-cyano-       12.37(s, 1H), 8.60(s, 1H),       6-(2-ethoxyphenyl)thieno[3,2-       8.01(s, 1H), 7.73(d, J=6.3Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.30(t, J=7.2Hz,               1H), 7.28(d, J=8.4Hz, 1H),               7.16(t, J=7.5Hz, 1H), 6.84(d,               J=3.0Hz, 1H), 6.28(d,               J=2.7Hz, 1H), 4.21(q, J=6.6Hz,               2H), 2.33(s, 3H), 1.37(t,               J=6.9Hz, 3H)       4-Fluorobenzaldehyde(7-   135   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.48(s, 1H), 8.65(s, 1H),       ethoxyphenyl)thieno[3,2-       8.24(s, 1H), 7.84(dd, J=8.7Hz,       d]pyrimidin-4-yl)hydrazone       J=5.4Hz, 2H), 7.76(dd,               J=7.8Hz, J=1.5Hz, 1H),               7.59(t, J=7.5Hz, 1H), 7.27-7.38(m,               3H), 7.17(t, J=7.5Hz,               1H), 4.24(q, J=7.2Hz,               2H), 1.34(t, J=6.6Hz, 3H)       1-Methyl-2-   138   (300MHz, DMSO-d6),   ND   ND       imidazolecarboxaldehyde(7-       12.37(br s, 1H), 8.63(s,       cyano-6-(2-       1H), 8.26(s, 1H), 7.69(d,       ethoxyphenyl)thieno[3,2-       J=7.8Hz, 1H), 7.57(t, J=7.2Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.34(s, 1H), 7.28(d,               J=8.4Hz, 1H), 7.14(t,               J=7.8Hz, 1H), 7.07(s, 1H),               4.19(q, J=7.2Hz, 2H), 3.99(s,               3H), 1.33(t, J=6.9Hz,               3H)       3-Fluorobenzaldehyde(7-   139   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.60(s, 1H), 8.67(s, 1H),       ethoxyphenyl)thieno[3,2-       8.24(s, 1H), 7.79(dd, J=7.8Hz,       d]pyrimidin-4-yl)hydrazone       1.8Hz, 1H), 7.50-7.64(m,               4H), 7.21-7.37(m, 2H),               7.20(t, J=7.5Hz, 1H), 4.24(q,               J=6.9Hz, 2H), 1.35(t,               J=6.9Hz, 3H)       4-Cyanobenzaldehyde(7-cyano-   142   (300MHz, DMSO-d6),   ND   ND       6-(2-ethoxyphenyl)thieno[3,2-       12.74(s, 1H), 8.70(s, 1H),       d]pyrimidin-4-yl)hydrazone       8.30(s, 1H), 7.96(m, 4H),               7.77(d, J=7.8Hz, 1H), 7.60(t,               J=8.1Hz, 1H), 7.32(d,               J=8.4Hz, 1H), 7.18(t, J=7.2Hz,               1H), 4.25(q, J=6.6Hz,               2H), 1.34(t, J=6.9Hz, 3H)       3-Cyanobenzaldehyde(7-cyano-   143   (300MHz, DMSO-d6),   ND   ND       6-(2-ethoxyphenyl)thieno[3,2-       12.68(br s, 1H), 8.69(s,       d]pyrimidin-4yl)hydrazone       1H), 8.28(s, 1H), 8.21(s,               1H), 8.12(d, J=7.5Hz, 1H),               7.99(d, J=7.8Hz, 1H), 7.79(d,               J=7.8Hz, 1H), 7.70(t,               J=7.8Hz, 1H), 7.59(t, J=7.8Hz,               1H), 7.31(d, J=8.7Hz,               1H), 7.18(t, J=7.5Hz, 1H),               4.25(q, J=6.9Hz, 2H), 1.34(t,               J=6.6Hz, 3H)       4-Bromobenzaldehyde(7-   146   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.57(s, 1H), 8.66(s, 1H),       ethoxyphenyl)thieno[3,2-       8.22(s, 1H), 7.61-7.79(m,       d]pyrimidin-4-yl)hydrazone       5H), 7.59(t, J=9.0Hz, 1H),               7.30(d, J=8.1Hz, 1H), 7.17(t,               J=7.5Hz, 1H), 4.24(q,               J=7.2Hz, 2H), 1.36(t, J=6.9Hz,               3H)       3-Bromobenzaldehyde(7-   147   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.61(s, 1H), 8.67(s, 1H),       ethoxyphenyl)thieno[3,2-       8.21(s, 1H), 8.02(s, 1H),       d]pyrimidin-4-yl)hydrazone       8.02(t, J=1.8Hz, 1H), 7.78(dd,               J=7.8Hz, 1H), 7.51-7.66(m,               2H), 7.44(t, J=7.8Hz,               1H), 7.30(d, J=8.1Hz,               1H), 7.18(t, J=7.5Hz, 1H),               4.24(q, J=6.6Hz, 2H), 1.35(t,               J=6.9Hz, 3H)       2-Pyridinecarboxaldehyde(7-   150   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.68(br s, 1H), 8.69(s,       ethoxyphenyl)thieno[3,2-       1H), 8.62(d, J=4.5Hz, 1H),       d]pyrimidin-4-yl)hydrazone       8.28(s, 1H), 8.05(d, J=7.8Hz,               1H), 7.93(t, J=7.5Hz,               1H), 7.78(d, J=7.5Hz, 1H),               7.59(t, J=7.2Hz, 1H), 7.37-7.43(m,               1H), 7.31(d, J=7.8Hz,               1H), 7.18(t, J=7.2Hz,               1H), 4.24(q, J=6.9Hz, 2H),               1.34(t, J=6.9Hz, 3H)       3-   151   (300MHz, DMSO-d6),   ND   ND       Tetrahydrofurancarboxaldehyde       12.06(s, 1H), 8.56(s, 1H),       (7-cyano-6-(2-       7.71(d, J=6.3Hz, 1H), 7.53-7.58(m,       ethoxyphenyl)thieno[3,2-       2H), 7.27(d, J=8.1Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.15(t, J=7.8Hz,               1H), 4.19(q, J=6.6Hz, 2H),               3.6-3.8(m, ?H), 2.05(m,               ?H), 1.79(m, ?H)       4-Methoxybenzaldehyde(7-   154   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.37(s, 1H), 8.60(s, 1H),       ethoxyphenyl)thieno[3,2-       8.18(s, 1H), 7.70-7.78(m,       d]pyrimidin-4-yl)hydrazone       3H), 7.57(t, J=6.9Hz, 1H),               7.30(d, J=7.8Hz, 1H), 7.17(t,               J=8.1Hz, 1H), 7.04(d,               J=8.7Hz; 2H), 4.24(q, J=6.9Hz,               2H), 3.80(s, 3H), 1.35(t,               J=6.6Hz, 3H)       3-Methoxybenzaldehyde(7-   155   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.52(br s, 1H), 8.63(s,       ethoxyphenyl)thieno[3,2-       1H), 8.20(s, 1H), 7.75(d,       d]pyrimidin-4-yl)hydrazone       J=8.1Hz, 1H), 7.58(t, J=7.2Hz,               1H), 7.26-7.42(m, 4H),               7.16(t, J=7.5Hz, 1H), 7.00(d,               J=8.4Hz, 1H), 4.21(q,               J=6.6Hz, 2H), 3.77(s, 3H),               1.34(t, J=6.9Hz, 3H)       2-Fluorobenzaldehyde(7-   161   (300MHz, DMSO-d6),   ND   ND       cyano-6-(2-       12.58(s, 1H), 8.65(s, 1H),       ethoxyphenyl)thieno[3,2-       8.45(s, 1H), 8.03(t, J=5.4Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.76(d, J=6.6Hz,               1H), 7.58(t, J=7.5Hz, 1H),               7.41-7.53(m, 1H), 7.27-7.40(m,               2H), 7.17(t, J=7.8Hz,               1H), 4.24(q, J=6.9Hz, 2H),               1.34(t, J=6.6Hz, 3H)       3-[Bis-(2,3-dihydroxy-propyl)-   163   300MHz, acetone-d6), 8.58(s,   ND   ND       amino]-benzaldehyde(7-cyano-       1H), 8.22(s, 1H), 7.80(d,       6-(2-ethoxyphenyl)thieno[3,2-       J=7.2Hz, 1H), 7.57(t, J=7.5Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.06-7.30(m, 4H),               6.77(d, J=6.9Hz, 1H), 5.05(m,               1H), 4.28(q, J=6.6Hz,               2H), 3.45-4.00(m, ND, H)       3-Dimethylamino-4-   164   (300MHz, DMSO-d6),   ND   ND       (morpholin-4-yl)-benzaldehyde       12.39(br s, 1H), 8.59(s,       (7-cyano-6-(2-       1H), 8.11(s, 1H), 7.66(d,       ethoxyphenyl)thieno[3,2-       J=7.8Hz, 1H), 7.57(t, J=7.8Hz,       d]pyrimidin-4-yl)hydrazone       1H), 7.47(s, 1H), 7.28(d,               J=9.0Hz, 1H), 7.12-7.23(m,               2H), 6.90(d, J=8.4Hz,               1H), 4.18(q, J=6.6Hz, 2H),               3.75(m, 4H), 3.09(m, 4H),               2.75(s, 6H), 1.33(t, J=7.2Hz,               3H)                  
 
     Example 6  
     Synthesis of 3-hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-vinylthieno[3,2-d]pyrimidin-4-yl)hydrazone (Compound 34; See FIG.  7 )  
      3-Amino-2-thiophenecarboxylic acid methyl ester (188): Commercially available from Aldrich Chemical Company, Milwaukee, Wis., USA.  
      3-(Formylamino)-2-thiophenecarboxylic acid methyl ester (189): Formic acid (40 mL) was added to acetic anhydride (60 mL) while cooling in an ice bath. Solid 3-amino-2-thiophenecarboxylic acid methyl ester (188, 10.3 g, 66 mmol) was added to the cold solution in small portions. The cooling bath was removed and the resulting suspension was stirred at room temperature for 4 hours. The reaction mixture was diluted with water (100 mL) and the solid product collected by vacuum filtration to yield 3-(formylamino)-2-thiophenecarboxylic acid methyl ester (10.3 g, 85% yield) as a white solid.  
      3H-Thieno[3,2-d]pyrimid-4-one (190): To a solution of ammonium formate (9.4 g, 0.15 mol) in formamide (14 mL) at 150° C. was added 3-(formylamino)-2-thiophenecarboxylic acid methyl ester (189, 5.2 g, 28 mmol) as a solid in small portions. The resulting solution was heated at 150° C. for 4 hours and then allowed to stand at room temperature for 12 hours. The precipitate that formed was collected by vacuum filtration to give 3H-thieno[3,2-d]pyrimid-4-one (2.7 g, 63% yield) as white needles.  
      7-Bromo-3H-thieno[3,2-d]pyrimid-4-one (191): To a solution of 3H-thieno[3,2-d]pyrimid-4-one (190, 0.98 g, 6.40 mmol) in acetic acid (3.4 mL) was added a solution of bromine (1 mL) in acetic acid (3 mL). The reaction mixture was heated at reflux for 8 hours. The resulting suspension was allowed to cool to room temperature and then poured into a saturated aqueous solution of sodium bicarbonate to neutralize. The solid product was collected by vacuum filtration to give 7-bromo-3H-thieno[3,2-d]pyrimid-4-one (0.94 g, 64% yield) as a pale yellow solid.  
      7-Bromo-4-chloro-thieno[3,2-d]pyrimidine (192): A solution of 7-bromo-3H-thieno[3,2-d]pyrimid-4-one (191, 153.0 mg, 0.66 mmol) in phosphorus oxychloride (2 mL) was refluxed under N 2  for 2 hours. The resulting solution was allowed to cool to room temperature and then neutralized by carefully pouring into a saturated aqueous solution of sodium carbonate. The aqueous mixture was extracted with ethyl acetate and the organic layer washed with water and brine, before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue dried over P 2 O 5  under vacuum overnight (156.0 mg, 95% yield, white solid).  
      7-Bromo-4-methoxythieno[3,2-d]pyrimidine (193): To a suspension of sodium methoxide (4.33 g, 80.0 mmol) in dioxane (32 mL) under N 2 , was added 7-Bromo-4-chloro-thieno[3,2-d]pyrimid-4-one (192, 4.30 g, 16.0 mmol) as a solid in one portion. The reaction mixture was stirred at room temperature for 12 hours followed by removal of the solvent by rotary evaporation. The resulting residue was diluted with water and then extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to yield 7-bromo-4-methoxythieno[3,2-d]pyrimidine (2.07 g, 53%) as a white solid.  
      4-Methoxy-7-vinylthieno[3,2-d]pyrimidine (194): 7-Bromo-4-methoxythieno[3,2-d]pyrimidine (193, 1.13 g, 4.61 mmol) and tetrakis(triphenylphosphine)palladium (0) (450.0 mg, 0.46 mmol, 0.1 eq) were dissolved in dry DMF (50 mL). Next was added SnBu 3 (CHCH 2 ) (1.75 g, 5.53 mmol, 1.2 eq), and the reaction mixture was heated at 80° C. for 12 h. The suspension was diluted with water, and the product was extracted into ethyl acetate. The extract was washed 3 times more with water and twice with sat. NaCl and then dried over Na 2 SO 4 . The solvent was removed by rotary evaporation and the product was purified by chromatography to yield 4-methoxy-7-vinylthieno[3,2-d]pyrimidine (0.67 g, 75% yield).  
      6-Iodo-4-methoxy-7-vinylthieno[3,2-d]pyrimidine (195): Diisopropylamine (0.51 mL, 3.63 mmol, 1.43 eq) was dissolved in anhydrous THF (20 mL), and the solution was chilled to −78° C. N-Butyl lithium (1.20 mL of 1.6M in THF, 1.92 mmol) was added, and the solution was stirred for 30 minutes at −78° C. A solution of 4-methoxy-7-vinylthieno[3,2-d]pyrimidine (194, 0.50 g, 2.60 mmol) in dry THF (20 mL) was chilled to −78° C., and the LDA solution was then transferred via cannula to the cold solution of 194. The reaction mixture became a dark brown suspension as the LDA solution was added. After 2 hours at −78° C., a solution of I 2  (1.0 g, 3.94 mmol) in dry THF (15 mL) was cannulated to the anion solution. The reaction mixture was maintained at −78° C. for 2 hours and then warmed to room temperature overnight. After overnight stirring, the reaction mixture was diluted with EtOAc and washed three times with deionized H 2 O, twice with saturated Na 2 S 2 O 4 , once with deionized H 2 O, three times with 10% HCl, and once with saturated NaCl. The dark solution was dried over anhydrous Na 2 SO 4 , decolorized with activated carbon, and then filtered through silica gel. The resulting light yellow filtrate was concentrated by rotary evaporation, and a light yellow solid precipitated as the solution was concentrated. After concentrating to a small volume, the precipitate was collected via filtration and was washed twice with ice cold EtOAc (412.0 mg, 51% yield,).  
      6-(2-Ethoxyphenyl)-4-methoxy-7-vinylthieno[3,2-d]pyrimidine (196): 6-Iodo-4-methoxy-7-vinylthieno[3,2-d]pyrimidine (195, 412.0 mg, 1.30 mmol) and tetrakis(triphenylphosphine)palladium(0) (75 mg, 0.07 mmol) in 1,2-dimethoxyethane (13 mL) were stirred at room temperature for 10 minutes under N 2 . 2-Ethoxyphenyl boronic acid 236.0 mg, (1.40 mmol) and 2M NaHCO 3  (1.7 mL) sparged with N 2  were added. The suspension was heated at 70° C. for 20 hr, cooled to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate, and the organic layer washed with water and brine before drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by chromatography, and the product was dried over P 2 O 5  under vacuum overnight (404.0 mg, 99% yield,).  
      6-(2-Ethoxyphenyl)-7-vinylthieno[3,2-d]pyrimidin-4-yl)hydrazine (197): A suspension of 6-(2-Ethoxyphenyl)-4-methoxy-7-vinylthieno[3,2-d]pyrimidine (196, 81.0 mg, 0.26 mmol) and hydrazine monohydrate (1.7 mg, 5.20 mmol) were refluxed in ethanol (2 mL) for 24 hours. After cooling to room temperature, the solid product was collected by vacuum filtration (47.0 mg, 58% yield).  
      3-Hydroxy-4-methoxybenzaldehyde (6-(2-ethoxyphenyl)-7-vinylthieno[3,2-d]pyrimidin-4-yl)hydrazone (34): A suspension of 6-(2-ethoxyphenyl)-7-vinylthieno[3,2-d]pyrimidin-4-yl)hydrazine (197, 47.0 mg, 0.15 mmol) and 3-hydroxy-4-methoxybenzaldehyde (29.0 mg, 0.19 mmol) were refluxed in ethanol (2 mL) for 4 hours. After cooling to room temperature, the solid product was collected by vacuum filtration (11.0 mg, 16% yield,).  
      Compounds that can be made using the above procedure with the appropriate substitution of reagents are listed in Table 6. The synthesis of Compound 34 as illustrated above is also illustrated in  FIG. 7 .  
                               TABLE 6                                          Purity                       by       Compound   No   1H NMR   MS   HPLC               3-Hydroxy-4-   34   (300MHz, DMSO-d6), 11.94(s,   M+1=447   99%       methoxybenzaldehyde(6-(2-       1H), 9.24(s, 1H), 8.58(s,   (ESI+)       ethoxyphenyl)-7-       1H), 8.04(s, 1H), 7.47(t,       vinylthieno[3,2-d]pyrimidin-4-       J=6.9Hz, 1H), 7.36(d, J=8.1Hz,       yl)hydrazone       1H), 7.06-7.23(m, 4H),               6.98(d, J=8.1Hz, 1H), 6.54,(m,               2H), 5.35(d, J=14.7Hz,               1H), 4.08(q, J=6.9Hz, 2H),               3.79(s, 3H), 1.22(t, J=6.9Hz,               3H)       3-Hydroxy-4-   35   (300MHz, DMSO-d6), 11.86(s,   M+1=449   99%       methoxybenzaldehyde(7-ethyl-       1H), 9.21(br s, 1H), 8.52(s,   (ESI+)       6-(2-ethoxyphenyl)thieno[3,2-       1H), 8.02(s, 1H), 7.45(t,       d]pyrimidin-4-yl)hydrazone       J=7.2Hz, 1H), 7.35(d, J=5.7Hz,               1H), 7.16-7.23(m, 2H),               7.06-7.10(m, 2H), 6.97(d,               J=8.1Hz, 1H), 4.10(q, J=6.9Hz,               2H), 2.66(q, J=7.8Hz),               1.22(t, J=6.9Hz, 3H), 1.11(t,               J=7.8Hz, 3H)                  
 
     Reagent Modifications  
      The reagents for compounds 1, 19-31, 33-40, 47, 53, 55, 63-74, 77-79, 85-105, 110-157, (108 total compounds), required no modification. 24 reagents were modified before or after induction into the synthesis of the remaining 56 compounds, 19 modifications at the R 2  position, 3 modifications at the R 1  position, and 4 modifications at the R 3  position. The modifications are as follows:  
      For compounds (2-6) the commercially available 4-aminomethylphenylboronic acid and 3-aminomethylphenylboronic acid were BOC protected under standard conditions (Wei et al., 2000) and the appropriate boronic acid was used at the Suzuki coupling stage in the synthesis of compounds (2-6). The BOC group was removed with 4 M HCl in dioxane at RT after hydrazone coupling; 
          For compound (7) the commercially available 2-hydroxymethylphenylboronic acid was converted to the mesylate with MsCl in CH 2 Cl 2  for 18 hrs at 0° C. using TEA as the base. Displacement of the mesylate with NaN 3  in DMSO at 100° C. for 12 hrs gave the 2-azidomethylphenylboronic acid which was reduced under Staudinger conditions (PPh 3 , MeOH/H 2 O) to give 2-aminomethylphenylboronic acid. The boronic acid was then BOC protected under standard conditions (See above compounds 2-6) used at the Suzuki coupling stage, and the BOC group was removes with 4 M HCl in dioxane at RT after hydrazone coupling;     For compounds (8-13, 58, 59) the commercially available 4-aminophenylboronic acid, 3-aminomethylphenylboronic acid and 2-aminophenylboronic acid were BOC protected under standard conditions (See above compounds 2-6) and the appropriate boronic acid was used at the Suzuki coupling stage in the synthesis of compounds (2-6). The BOC group was removed with: 4 M HCl in dioxane at RT after hydrazone coupling;     For compounds (14-16) the 4-chloro-6-iodo-7-methyl-thieno[3,2-d]pyrimidine compound (synthesized via Example 1) was lithiated with LDA in THF at −78° C., then quenched with DMF to give the 4-chloro-7-methyl-thieno[3,2-d]pyrimidine-6-carbaldehyde compound which was converted to the desired 4-chloro-7-methyl-6-morpholin-4-ylmethyl-thieno[3,2-d]pyrimidine under reductive amination conditions (Mitchell and Finney 2001) with morpholine in 1,2-dichloroethane with NaBH(OAc) 3 . The 4-chloro-7-methyl-6-morpholin-4-ylmethyl-thieno[3,2-d]pyrimidine was converted to the hydrazine and hydrazone under conditions given in Example 1;     For compounds (17, 46) the [3-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenyl]-methanol compound (synthesized via Example 1) was converted to the mesylate using MsCl in CH 2 Cl 2  at 0° C. The mesylate was then reacted with morpholine to give the 4-chloro-7-methyl-6-(3-morpholin-4-ylmethyl-phenyl)-thieno[3,2-d]pyrimidine compound. 4-Chloro-7-methyl-6-(3-morpholin-4-ylmethyl-phenyl)-thieno[3,2-d]pyrimidine was converted to the hydrazine and hydrazone under conditions given in Example 1;     For compound (18) the 4-chloro-6-iodo-7-methyl-thieno[3,2-d]pyrimidine compound (synthesized via Example 1) was lithiated with LDA in THF at −78 C, then quenched with DMF to give the 4-chloro-7-methyl-thieno[3,2-d]pyrimidine-6-carbaldehyde compound which was converted to the desired (4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-ylmethyl)-phenyl-amine under reductive amination conditions (See above compounds 14-16) with morpholine in 1,2-dichloroethane with NaBH(OAc) 3 . The (4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-ylmethyl)-phenyl-amine was converted to the hydrazine and hydrazone under conditions given in Example 1;     For compound (32) the 4-[7-methyl-4-(N′-pyridin-3-ylmethylene-hydrazino)-thieno[3,2-d]pyrimidin-6-yl]-benzonitrile compound (synthesized via Example 1) was treated with HCL(g) in absolute EtOH at 0° C. for 16 hr., EtOH and excess HCL removed under reduced pressure, and treated with (NH 4 ) 2 CO 3  in absolute EtOH for 24 hr. to give the amidine (Qi et al., 2000), 3-pyridinecarboxaldehyde (6-(benzamidin-3-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl]-hydrazone;     For compound (41) the 4-chloro-6-(2-ethoxy-phenyl)-thieno[3,2-d]pyrimidin-7-ol compound (synthesized via Example 3) was treated with K 2 CO 3  in DMSO and alkylated with 4-(2-chloroethyl)-morpholine hydrochloride in DMSO at 70° C. for 1 hr (Gibson et al., 2002) to give 4-chloro-6-(2-ethoxy-phenyl)-7-(2-morpholin-4-yl-ethoxy)-thieno[3,2-d]pyrimidine which was converted to the hydrazine and hydrazone under conditions given in Example 3;     For compound (42) the 4-chloro-7-methyl-6-phenyl-thieno[3,2-d]pyrimidine compound (synthesized via Example 1) was nitrated (Olah et al., 1992) HNO 3 /H 2 SO 4  at 0° C. and reduced with H 2  Pd/C in EtOH for 2 days (Ram and Ehrenkaufer, 1984) to give 4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenylamine. The phenylamine was treated with MeI/K 2 CO 3  (Dillard et al., 1987) for 21 hr. to give [4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenyl]-dimethylamine which was converted to the hydrazine and hydrazone under conditions given in Example 1;     For compound (43) the 4-chloro-7-methyl-6-phenyl-thieno[3,2-d]pyrimidine compound (synthesized via Example 1) was nitrated with HNO 3 /H 2 SO 4  at 0° C. and reduced with H 2  Pd/C in EtOH (See above compound 42) for 2 days to give 4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenylamine. The phenylamine was treated with Ac 2 O and DMAP in pyridine at RT for 8 hr. to give the N-[4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenyl]-acetamide which converted to the hydrazine and hydrazone under conditions given in Example 1;     For compound (44) the 7-bromomethyl-4-chloro-6-(2-ethoxy-phenyl)-thieno[3,2-d]pyrimidine compound (synthesized via Example 2) was reacted with NaOEt in EtOH for 18 hr. at RT (Larock et al., 1989) to give 4-ethoxy-7-ethoxymethyl-6-(2-ethoxy-phenyl)-thieno[3,2-d]pyrimidine with an ethoxide at C-7 position CH 2  and at C-4 position. The C-4 position ethoxide was converted to the hydrazine under conditions given in Example 2, except reaction was conducted for 30 hr. instead of the usual 1 hr. The hydrazine was converted to the hydrazone under conditions given in Example 2;     For compounds (45, 49) the 3-(4-hydrazino-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-benzonitrile compound, for compounds (50, 51) the, 4-(4-hydrazino-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-benzonitrile compound (all synthesized via Example 1) were individually treated with NH 2 —OH*HCL in DMF at 80° C. for 12 hr. (Batt et al. 2000,) to give the respective (4-hydrazino-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-N-hydroxy-benzamidine compounds which converted to the respective hydrazone under conditions given in Example 1;     For compound (48) the 4-chloro-7-methyl-6-phenyl-thieno[3,2-d]pyrimidine compound (synthesized via Example 1) was nitrated with HNO3/H2SO4 at 0° C. and reduced with H 2  Pd/C in EtOH for 2 days to give 4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenylamine (See above compound 43). The phenylamine was treated with Ac 2 O and DMAP in pyridine at RT for 8 hr. (See above compound 43) to give the N-[4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenyl]-acetamide. The acetamide was reduced with BH 3 /THF in THF at reflux for 4 hr. (Salerno et al., 2000) to give [4-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenyl]-ethyl-amine which converted to the hydrazine and hydrazone under conditions given in Example 1;     For compound (52) the commercially available 3-hydroxy-4-methoxy-benzaldehyde and for compound (54) the commercially available 4-Hydroxy-3-methoxy-benzaldehyde was individually Alkylated with 4-(2-chloroethyl)morpholine hydrochloride in DMSO using K 2 CO 3  as the base (See above compound 41) to give the respective methoxy (2-morpholin-4-yl-ethoxy)-benzaldehydes which were individually coupled with the respective hydrazine to give the hydrazone under conditions given in Example 1;     For compound (56) the commercially available acetic acid 2-acetoxy-3-hydroxy-propyl ester was deprotonated with NaH in DMSO at RT and transferred to solution of 7-bromomethyl-4-chloro-6-(2-ethoxy-phenyl)-thieno[3,2-d]pyrimidine (synthesized via Example 2) in DMSO and heated at 75° C. to give 4-(1,2-Bis-isopropenyloxy-ethoxy)-7-(1,2-bis-isopropenyloxy-ethoxymethyl)-6-(2-ethoxy-phenyl)-thieno[3,2-d]pyrimidine (See above compound 41). This compound was converted to the hydrazine under conditions given in Example 2, except reaction was conducted for 30 hr instead of the usual 1 hr. The hydrazine was converted to the hydrazone under conditions given in Example 2;     For compounds (57, 60-62, 106-109, 159, 160) the commercially available 4-fluorophenylboronic acid was treated with EtI/K 2 CO 3  in acetone at reflux for 12 hr. (See above compound 42) to give the alkylated product 4-ethoxyphenylboronic acid. This boronic acid was used at the Suzuki coupling stage in the synthesis of compounds (57, 60-62, 106-109, 159, 160).     For compounds (75, 76, 84), the commercially available 4-hydroxyphenylboronic acid was treated was treated with Ac 2 O and DMAP in pyridine at RT for 8 hr to give the boronic acid acetic acid phenyl ester. This boronic acid was used at the Suzuki coupling stage in the synthesis of compounds (75, 76, 84). Deprotection occurred in situ due to during Suzuki coupling conditions (See Suzuki coupling conditions Example 1);     For compound (80) the commercially available 2-hydroxyphenylboronic acid was treated was treated with Ac 2 O and DMAP in pyridine at RT for 8 hr. to give the boronic acid acetic acid phenyl ester. This boronic acid was used at the Suzuki coupling stage in the synthesis of compound (80) and deprotection occurred in situ due to during Suzuki coupling conditions (See Suzuki coupling conditions Example 1) to give 2-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenol. This phenol was alkylated with alkyl bromide in acetone (K 2 CO 3 ) at RT (Seley et al.,) to give 6-(2-allyloxy-phenyl)-4-chloro-7-methyl-thieno[3,2-d]pyrimidine which converted to the hydrazine and hydrazone under conditions given in Example 1;     For compounds (81, 82), the commercially available 2-hydroxyphenylboronic acid was treated was treated with Ac 2 O and DMAP in pyridine at RT for 8 hr. (See above compounds 75, 76, 84) to give the boronic acid acetic acid phenyl ester. This boronic acid was used at the Suzuki coupling stage in the synthesis 1,0: of compound (81, 82) and deprotection occurred in situ due to during Suzuki coupling conditions (See Suzuki coupling conditions Example 1) to give 2-(4-chloro-7-methyl-thieno[3,2-d]pyrimidin-6-yl)-phenol. This phenol was alkylated with benzyl bromide in acetone (K 2 CO 3 ) at RT (See above compound 80) to give 6-(2-benzyloxy-phenyl)-4-chloro-7-methyl-thieno[3,2-d]pyrimidine which; converted to the hydrazine and hydrazone under conditions given in Example 1;     For compounds (83) the commercially available 2-hydroxyphenylboronic acid was treated with Ac 2 O and DMAP in pyridine at RT for 8 hr. (See above compounds 75, 76, 84) to give the boronic acid acetic acid phenyl ester. This boronic acid was used at the Suzuki coupling stage in the synthesis of compound (83) and deprotection occurred in situ due to during Suzuki coupling conditions (See Suzuki coupling conditions Example 1) to give 2-(4-chloro-7-methylthieno[3,2-d]pyrimidin-6-yl)-phenol. This phenol was alkylated with alkyl bromide in acetone (K 2 CO 3 ) at RT (See above compound 80) to give 6-(2-allyloxy-phenyl)-4-chloro-7-methyl-thieno[3,2-d]pyrimidine which converted to the hydrazine and hydrazone under conditions given in Example 1. The alkyl ether of hydrazone was hydrogenated in EtOH using Pd/C catalyst (See above compound 42) to give the final product, 3-hydroxy-4-methoxybenzaldehyde (7-methyl-6-(2-propoxyphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazone;     For compounds (158), the commercially available 3-hydroxy-4-methoxy-benzaldehyde was alkylated with the (2-chloro-ethyl)-diethyl-amine hydrochloride salt in DMSO using K 2 CO 3  at 70° C. (See above compound 41) to give 3-(2-Diethylamino-ethoxy)-4-methoxy-benzaldehyde. This aldehyde was coupled with the respective hydrazine to give the hydrazone under conditions given in Example 1;     For compounds (161, 162), the commercially available 4-hydroxy-3,5-dimethoxy-benzaldehyde was alkylated with the (2-chloro-ethyl)-diethyl-amine hydrochloride salt in DMF using Cs 2 CO 3  at 65° C. for 24 hr. (Lee et al., 1995) to give 4-(2-Diethylamino-ethoxy)-3,5-dimethoxy-benzaldehyde. This aldehyde was coupled with the respective hydrazine to give the hydrazone under conditions given in Example 1;     For compound (163) the commercially 3-nitrobenzaldehyde was converted to the cyclic acetal, 2-(3-nitro-phenyl)-[1,3]dioxolane using ethylene glycol and TsOH in refluxing benzene under Dean-Stark conditions. The nitro group of the 1.0 dioxolane was then reduced via H 2  Pd/C reduction in EtOH (See above compound 42) for 4 hrs to give the phenylamine, 3-[1,3]dioxolan-2-yl-phenylamine. The phenylamine was alkylated with 2 eq 3-chloro-1,2-propanediol in EtOH using K 2 CO 3  at RT (See above compound 41) for 48 hr. (to give 3-[(2,3-dihydroxy-propyl)-(3-[1,3]dioxolan-2-yl-phenyl)-amino]-propane-1,2-diol. The cyclic acetal of this dioxolane deprotected using 1 M HCl in THF for 20 min to give 3-[bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde. This aldehyde was coupled with the respective hydrazine to give the hydrazone under conditions given in Example 5;     For compound (164) the commercially 4-chloro-3-nitrobenzaldehyde was treated with K 2 CO 3  in EtOH at reflux for 24 hr. to give 4-morpholin-4-yl-3-nitro-benzaldehyde (See above compound 41) which was converted to the cyclic acetal, 4-(4-[1,3]dioxolan-2-yl-2-nitro-phenyl)-morpholine using ethylene glycol and TsOH in refluxing benzene under Dean-Stark conditions. The nitro group of the dioxolane was then reduced via H 2  Pd/C reduction in EtOH (See above compound 42) to give the phenylamine, 3-amino-4-morpholin-4-yl-benzaldehyde with loss of the ethylene glycol protecting group during the reduction. This aldehyde was alkylated in EtOH with MeI, and K 2 CO 3  at reflux (See above compound 41) for 18 hrs to give 3-dimethylamino-4-morpholin-4-yl-benzaldehyde. This aldehyde was converted to the hydrazine and hydrazone under conditions given in Example 5;        

     Example 7  
     Specificity of Thienopyrimidine-Based Inhibitors for Src  
      Recombinant human Src was expressed using the baculovirus-insect cell system and purified as published (Budde et al., 1993 and 2000). Recombinant Csk and the FGF receptor (FGFr) were expressed as glutathione-5-transferase fusion proteins using the pGEX expression vector and  E. coli , and purified as described (Sun &amp; Budde, 1995).  
      The tyrosine kinase activity of Src, Csk and FGFr was determined using poly E 4 Y and  32 P-ATP. Briefly, enzymes were assayed in a reaction mixture 0.5 consisting of 0.15 M EPPS-NaOH (pH 8.0) with 6 mM MgCl 2 , 0.2 mM γ 32 P-ATP (0.2-0.4 mCi/μmol), 10% glycerol, 0.1% Triton X-100, and poly E 4 Y. Poly E 4 Y is a synthetic peptide whose phosphorylation is measured in this assay by the addition of the radioactively labeled phosphate from the ATP (Budde et al., 1995). For screening assays, 50 μg/ml poly E 4 Y was used, and for K i  determinations variable concentrations (0, 20, 30, 75, and 150 μg/ml) of poly E 4 Y were used. When ATP was varied (0, 50, 100 and 250 μM), poly E 4 Y was kept constant at 150 μg/ml.  
      Compounds were identified as especially good inhibitors of Src if they possessed an IC 50  of 2 μM or less. One or more disclosed thienopyrimidine-based compounds in the category include compounds 34, 37, 42, 96, 104, and 105, all of the disclosed compounds have excellent potential, and numerous other commercial candidates will emerge after further experimentation (See Table 7).  
                                       TABLE 7                                           IC 50  Value                               (μM)       Cmpd.   R1   R2   R3   Csk   FGFr   Src                                                            1   methyl   2-ethoxyphenyl   methyl 4-formylbenzoate   ND   ND   ND       2   methyl   4-aminomethyphenyl   4-carboxybenzaldehyde   ND   ND   0.024       3   methyl   4-aminomethylphenyl   3-pyridinecarboxaldehyde   ND   ND   0.024       4   methyl   4-aminomethylphenyl   2-thiophenecarboxaldehyde   ND   ND   0.028       5   methyl   4-aminomethyphenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.032       6   methyl   3-aminomethyphenyll   3-pyridinecarboxaldehyde   ND   ND   0.016       7   methyl   2-aminomethylphenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.12       8   methyl   4-aminophenyl   3-pyridinecarboxaldehyde   ND   ND   0.0096       9   methyl   4-aminophenyl   2-thiophenecarboxaldehyde   ND   ND   0.019       10   methyl   4-aminophenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.0087       11   methyl   3-aminophenyl   3-pyridinecarboxaldehyde   ND   ND   0.0049       12   methyl   3-aminophenyl)   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.0012       13   methyl   2-aminophenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.038       14   methyl   morpholinyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.35       15   methyl   morpholinyl   3-pyridinecarboxaldehyde   ND   ND   0.32       16   methyl   morpholinyl   5-Methyl-3H-imidazole-4-carbaldehyde   ND   ND   0.62       17   methyl   3-morpholin-4-   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.026               ylmethylphenyl       18   methyl   phenylaminomethyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.55       19   methyl   3-aminocarbonylphenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.014       20   methyl   3-aminocarbonylphenyl   2-thiophenecarboxaldehyde   ND   ND   0.054       21   methyl   3-aminocarbonylphenyl   3-pyridinecarboxaldehyde   ND   ND   0.091       22   methyl   3-aminocarbonylphenyl   4-carboxybenzaldehyde   ND   ND   0.041       23   methyl   4-aminocarbonylphenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.020       24   methyl   4-aminocarbonylphenyl   3-pyridinecarboxaldehyde   ND   ND   0.013       25   methyl   4-aminocarbonylphenyl   2-thiophenecarboxaldehyde   ND   ND   0.026       26   methyl   4-aminocarbonylphenyl   4-carboxybenzaldehyde   ND   ND   0.036       27   methyl   3-cyanophenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.058       28   methyl   3-cyanophenyl   2-thiophenecarboxaldehyde   ND   ND   1.4       29   methyl   3-cyanophenyl   3-pyridinecarboxaldehyde   ND   ND   0.027       30   methyl   3-cyanophenyl   4-carboxybenzaldehyde   ND   ND   0.16       31   methyl   2-cyanophenyl   3-hydroxy-4-methoxybenzaldehyde   ND   ND   0.074       32   methyl   3-benzamidine   3-pyridinecarboxaldehyde   ND   ND   0.041       33   hydroxymethyl   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   10   NI   0.011       34   vinyl   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   1.35   NI   0.039       35   ethyl   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.014       36   methyl   4-fluorophenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.057       37   hydroxy   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   1.28   NI   0.0026       38   methyl   4-hydroxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.015       39   methyl   4-nitrophenyl   3-hydroxy-4-methoxybenzaldehyde   23   NI   0.16       40   methoxy   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.022       41   morpholin-4-   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.34           yl-ethoxy       42   methyl   4-N,N-dimethylaminophenyl   3-hydroxy-4-methoxybenzaldehyde   0.46   NI   0.072       43   methyl   4-N-acetylaminophenyl   3-hydroxy-4-methoxybenzaldehyde   112   NI   0.012       44   ethoxymethyl   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.079       45   methyl   3-N-hydroxy-benzamidine   3-hydroxy-4-methoxybenzaldehyde   26.8   NI   0.019       46   methyl   4-morpholin-4-ylmethyl-   3-hydroxy-4-methoxybenzaldehyde   102   102   0.0055               phenyl       47   cyano   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.0015       48   methyl   4-N-ethylaminophenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.064       49   methyl   3-N-hydroxy-benzamidine   3-pyridinecarboxaldehyde   124   NI   0.0041       50   methyl   4-N-hydroxy-benzamidine   3-pyridinecarboxaldehyde   42   NI   0.025       51   methyl   4-N-hydroxy-benzamidine   3-hydroxy-4-methoxybenzaldehyde   47   NI   0.011       52   methyl   2-ethoxyphenyl   3-(2-(morpholin-4-yl)-ethoxy)-4-methoxy-benzaldehyde   46   NI   0.0011       53   methyl   2-ethoxyphenyl   3,4-dimethoxybenzaldehyde   NI   NI   0.0046       54   methyl   2-ethoxyphenyl   3-methoxy-4-(2-(morpholin-4-yl)-ethoxy)-benzaldehyde   110   NI   0.0014       55   methyl   2-ethoxyphenyl   3-methoxy-4-hydroxybenzaldehyde   NI   NI   0.0033       56   4,5-dihydroxy-2-   2-ethoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.12           oxopentyl       57   methyl   2-ethoxy-4-fluorophenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.0049       58   hydroxymethyl   4-aminophenyl   3-hydroxy-4-methoxybenzaldehyde   12   NI   0.043       59   cyano   4-aminophenyl   3-hydroxy-4-methoxybenzaldehyde   10   NI   0.016       60   hydroxymethyl   2-ethoxy-4-fluorophenyl   3-hydroxy-4-methoxybenzaldehyde   210   NI   0.036       61   hydroxy   2-ethoxy-4-fluorophenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.006       62   cyano   2-ethoxy-4-fluorophenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.0015       63   methyl   2-ethoxyphenyl   3,4,5-trimethoxybenzaldehyde   NI   NI   0.0013       64   methyl   2-ethoxyphenyl   3-hydroxy-4,5-dimethoxybenzaldehyde   NI   NI   0.0012       65   methyl   2-ethoxyphenyl   4-Hydroxy-3,5-dimethoxy-benzaldehyde   NI   NI   0.00099       66   methyl   2-ethoxyphenyl   2,3-dihydro-benzo[1,4]dioxine-6-carbaldehyde   NI   NI   0.0064       67   cyano   2-ethoxyphenyl   3-pyridinecarboxaldehyde   NI   NI   0.0012       68   cyano   2-ethoxyphenyl   4-carboxybenzaldehyde   26   NI   0.0014       69   cyano   2-ethoxyphenyl   2-thiophenecarboxaldehyde   NI   NI   0.0041       70   hydroxymethyl   2-ethoxyphenyl   3-pyridinecarboxaldehyde   NI   NI   0.020       71   hydroxymethyl   2-ethoxyphenyl   2-thiophenecarboxaldehyde   NI   NI   0.028       72   hydroxymethyl   2-ethoxyphenyl   4-carboxybenzaldehyde   NI   NI   0.032       73   hydroxy   2-ethoxyphenyl   3-pyridinecarboxaldehyde   NI   NI   0.003       74   hydroxy   2-ethoxyphenyl   4-carboxybenzaldehyde   NI   NI   0.00029       75   methyl   4-hydroxyphenyl   3-pyridinecarboxaldehyde   NI   NI   0.021       76   methyl   4-hydroxyphenyl   4-carboxybenzaldehyde   NI   NI   0.041       77   methyl   2-ethoxyphehyl   2-chlorobenzaldehyde   NI   NI   1.4       78   methyl   2-ethoxyphenyl   2-fluorobenzaldehyde   NI   NI   0.00084       79   methyl   2-ethoxyphenyl   2,4-dimethoxybenzaldehyde   NI   NI   0.25       80   methyl   2-allyloxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.0065       81   methyl   2-benzyloxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   NI       82   methyl   2-benzyloxyphenyl   3-pyridinecarboxaldehyde   NI   NI   3.9       83   methyl   2-propoxyphenyl   3-hydroxy-4-methoxybenzaldehyde   NI   NI   0.029       84   methyl   2-hydroxyphenyl   3-hydroxy-4-methoxybenzaldehyde   500   NI   0.18       85   hydroxy   2-propoxyphenyl   2-thiophenecarboxaldehyde   17.7   7.5   0.0048       86   cyano   2-ethoxyphenyl   3-methoxy-4-hydroxybenzaldehyde   NI   NI   0.0014       87   cyano   2-ethoxyphenyl   3-Bromo-4-hydroxy-5-methoxy-benzaldehyde   NI   NI   0.00031       88   hydroxy   2-ethoxyphenyl   3-methoxy-4-hydroxybenzaldehyde   3.4   2.3   0.0025       89   hydroxy   2-ethoxyphenyl   3-Bromo-4-hydroxy-5-methoxy-benzaldehyde   2.9   1.9   0.0025       90   cyano   2-ethoxyphenyl   3-chloro-4-hydroxybenzaldehyde   NI   NI   0.0021       91   cyano   2-ethoxyphenyl   3-thiophenecarboxaldehyde   NI   NI   0.00058       92   hydroxy   2-ethoxyphenyl   3-chloro-4-hydroxybenzaldehyde   11.3   27.7   0.0042       93   hydroxy   2-ethoxyphenyl   3-thiophenecarboxaldehyde   NI   NI   0.0028       94   cyano   2-ethoxyphenyl   3,5-dimethoxy-4-hydroxybenzaldehyde   NI   NI   0.00034       95   cyano   2-ethoxyphenyl   2-imidazolecarboxaldehyde   NI   NI   0.025       96   hydroxy   2-ethoxyphenyl   3,5-dimethoxy-4-hydroxybenzaldehyde   0.58   NI   0.00073       97   hydroxy   2-ethoxyphenyl   2-imidazolecarboxaldehyde   NI   NI   0.055       98   cyano   2-ethoxyphenyl   3,4-dimethoxy-5-hydroxybenzaldehyde   NI   NI   0.0010       99   cyano   2-ethoxyphenyl   1-imidazolecarboxaldehyde   NI   6.2   0.010       100   hydroxy   2-ethoxyphenyl   3,4-dimethoxy-5-hydroxybenzaldehyde   2.1   NI   0.0013       101   hydroxy   2-ethoxyphenyl   4-(1H-imidazol-1-yl)benzaldehyde   NI   NI   0.00042       102   cyano   2-ethoxyphenyl   4-hydroxybenzaldehyde   NI   NI   0.0015       103   cyano   2-ethoxyphenyl   3-hydroxybenzaldehyde   13   NI   0.0015       104   hydroxy   2-ethoxyphenyl   4-hydroxybenzaldehyde   0.98   NI   0.0016       105   hydroxy   2-ethoxyphenyl   3-hydroxybenzaldehyde   0.9   NI   0.0043       106   methyl   2-ethoxy-4-fluorophenyl   2-thiophenecarboxaldehyde   NI   NI   0.0095       107   hydroxymethyl   2-ethoxy-4-fluorophenyl   2-thiophenecarboxaldehyde   NI   NI   0.055       108   cyano   2-ethoxy-4-fluorophenyl   2-thiophenecarboxaldehyde   NI   NI   0.0085       109   hydroxy   2-ethoxy-4-fluorophenyl   2-thiophenecarboxaldehyde   NI   NI   0.0011       110   cyano   2-ethoxyphenyl   4-pyridinecarboxaldehyde   NI   NI   0.0019       111   cyano   2-ethoxyphenyl   2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbaldehyde   NI   NI   0.012       112   hydroxy   2-ethoxyphenyl   4-pyridinecarboxaldehyde   7.2   NI   0.0040       113   hydroxy   2-ethoxyphenyl   2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbaldehyde   NI   NI   0.028       114   cyano   2-ethoxyphenyl   3-carboxybenzaldehyde   NI   NI   0.0032       115   cyano   2-ethoxyphenyl   5-Methyl-3H-imidazole-4-carbaldehyde   NI   NI   0.0026       116   hydroxy   2-ethoxyphenyl   3-carboxybenzaldehyde   7.1   NI   0.0050       117   hydroxy   2-ethoxyphenyl   5-Methyl-3H-imidazole-4-carbaldehyde   5.5   NI   0.0050       118   cyano   2-ethoxyphenyl   4-Formyl-benzoic acid methyl ester   NI   NI   0.022       119   cyano   2-ethoxyphenyl   2-furancarboxaldehyde   NI   NI   0.0047       120   hydroxy   2-ethoxyphenyl   methyl 4-formyl benzoate   NI   NI   0.0059       121   hydroxy   2-ethoxyphenyl   2-furancarboxaldehyde   5   NI   0.0060       122   cyano   2-ethoxyphenyl   3-methyl-2-thiophenecarboxaldehyde   NI   NI   0.0052       123   cyano   2-ethoxyphenyl   3-chloro-4-fluorobenzaldehyde   NI   NI   0.027       124   hydroxy   2-ethoxyphenyl   3-methyl-2-thiophenecarboxaldehyde   15   NI   0.009       125   hydroxy   2-ethoxyphenyl   3-chloro-4-fluorobenzaldehyde   NI   NI   0.045       126   cyano   2-ethoxyphenyl   5-methyl-2-thiophenecarboxaldehyde   NI   NI   0.0049       127   cyano   2-ethoxyphenyl   3-furancarboxaldehyde   NI   NI   0.003       128   hydroxy   2-ethoxyphenyl   5-methyl-2-thiophenecarboxaldehyde   NI   NI   0.0028       129   hydroxy   2-ethoxyphenyl   3-furancarboxaldehyde   NI   NI   0.0034       130   cyano   2-ethoxyphenyl   4-acetamidobenzaldehyde   NI   NI   0.0018       131   cyano   2-ethoxyphenyl   4-N,N-dimethylaminobenzaldehyde   NI   NI   0.13       132   hydroxy   2-ethoxyphenyl   4-acetamidobenzaldehyde   NI   NI   0.0024       133   hydroxy   2-ethoxyphenyl   4-N,N-dimethylaminobenzaldehyde   NI   NI   0.0062       134   cyano   2-ethoxyphenyl   5-Methyl-furan-2-carbaldehyde   NI   NI   0.0026       135   cyano   2-ethoxyphenyl   4-fluorobenzaldehyde   NI   NI   0.0040       136   hydroxy   2-ethoxyphenyl   5-Methyl-furan-2-carbaldehyde   ND   ND   ND       137   hydroxy   2-ethoxyphenyl   4-fluorobenzaldehyde   ND   ND   ND       138   cyano   2-ethoxyphenyl   1-Methyl-1H-imidazole-2-carbaldehyde   NI   NI   0.018       139   cyano   2-ethoxyphenyl   3-fluorobenzaldehyde   NI   NI   0.0047       140   hydroxy   2-ethoxyphenyl   1-Methyl-1H-imidazole-2-carbaldehyde   ND   ND   ND       141   hydroxy   2-ethoxyphenyl   3-fluorobenzaldehyde   ND   ND   ND       142   cyano   2-ethoxyphenyl   4-cyanobenzaldehyde   ND   ND   ND       143   cyano   2-ethoxyphenyl   3-cyanobenzaldehyde   ND   ND   ND       144   hydroxy   2-ethoxyphenyl   4-cyanobenzaldehyde   ND   ND   ND       145   hydroxy   2-ethoxyphenyl   3-cyanobenzaldehyde   ND   ND   ND       146   cyano   2-ethoxyphenyl   4-bromobenzaldehyde   ND   ND   ND       147   cyano   2-ethoxyphenyl   3-bromobenzaldehyde   ND   ND   ND       148   hydroxy   2-ethoxyphenyl   4-bromobenzaldehyde   ND   ND   ND       149   hydroxy   2-ethoxyphenyl   3-bromobenzaldehyde   ND   ND   ND       150   cyano   2-ethoxyphenyl   2-pyridinecarboxaldehyde   ND   ND   ND       151   cyano   2-ethoxyphenyl   3-tetrahydrofurancarboxaldehyde   ND   ND   ND       152   hydroxy   2-ethoxyphenyl   2-pyridinecarboxaldehyde   ND   ND   ND       153   hydroxy   2-ethoxyphenyl   3-tetrahydrofurancarboxaldehyde   ND   ND   ND       154   cyano   2-ethoxyphenyl   4-methoxybenzaldehyde   ND   ND   ND       155   cyano   2-ethoxyphenyl   3-methoxybenzaldehyde   ND   ND   ND       156   hydroxy   2-ethoxyphenyl   4-methoxybenzaldehyde   ND   ND   ND       157   hydroxy   2-ethoxyphenyl   3-methoxybenzaldehyde   ND   ND   ND       158   methyl   2-ethoxyphenyl   3-(2-diethylamino-ethoxy)-4-methoxy-benzaldehyde   NI   NI   0.000015       159   hydroxy   2-ethoxy-4-fluorophenyl   3,5-dimethoxy-4-(2-diethylamino-ethoxy)-benzaldehyde   NI   NI   0.00056       160   methyl   2-ethoxy-4-fluorophenyl   3,5-dimethoxy-4-(2-diethylamino-ethoxy)-benzaldehyde   NI   NI   0.00030       161   cyano   2-ethoxyphenyl   2-fluorobenzaldehyde   ND   ND   ND       162   hydroxy   2-ethoxyphenyl   2-fluorobenzaldehyde   ND   ND   ND       163   cyano   2-ethoxyphenyl   3-[Bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde   ND   ND   ND       164   cyano   2-ethoxyphenyl   3-dimethylamino-4-(morpholin-4-yl)-benzaldehyde   ND   ND   ND                 ND = not determined            NI = no inhibition             
 
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