The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Harold Mastalerz - One of the best experts on this subject based on the ideXlab platform.
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5-((4-Aminopiperidin-1-yl)methyl)Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Brian E. Fink, Ashvinikumar V. Gavai, Wen-ching Han, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Kenneth J. LeavittAbstract:Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.
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Novel C-5 aminomethyl Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ashvinikumar V. Gavai, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Punit Marathe, Arvind Mathur, Simone Oppenheimer, James G. TarrantAbstract:Novel C-5 aminomethyl Pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket.
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New C-5 substituted Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Pierre Dextraze, Brian E. Fink, Ashvinikumar V. Gavai, Bindu Goyal, Wen-ching Han, Johnson Walter Lewis, David R. LangleyAbstract:Novel C-5 substituted Pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket.
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Pyrrolotriazine 5 carboxylate ester inhibitors of egfr and her2 protein tyrosine kinases and a novel one pot synthesis of c 4 subsitituted pyrrole 2 3 dicarboxylate diesters
Canadian Journal of Chemistry, 2006Co-Authors: Harold Mastalerz, Brian E. Fink, Ashvinikumar V. Gavai, James G. Tarrant, Charles Struzynski, Gregory D Vite, Tai W Wong, Guifen Zhang, Dolatrai M VyasAbstract:Pyrrolotriazines with an ester group at C-5 were prepared and evaluated as inhibitors of the EGFR and HER2 receptor tyrosine kinases, validated targets for cancer therapy. The C-5 ester (15) was at...
David R. Langley - One of the best experts on this subject based on the ideXlab platform.
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5-((4-Aminopiperidin-1-yl)methyl)Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Brian E. Fink, Ashvinikumar V. Gavai, Wen-ching Han, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Kenneth J. LeavittAbstract:Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.
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Novel C-5 aminomethyl Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ashvinikumar V. Gavai, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Punit Marathe, Arvind Mathur, Simone Oppenheimer, James G. TarrantAbstract:Novel C-5 aminomethyl Pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket.
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New C-5 substituted Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Pierre Dextraze, Brian E. Fink, Ashvinikumar V. Gavai, Bindu Goyal, Wen-ching Han, Johnson Walter Lewis, David R. LangleyAbstract:Novel C-5 substituted Pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket.
Ashvinikumar V. Gavai - One of the best experts on this subject based on the ideXlab platform.
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5-((4-Aminopiperidin-1-yl)methyl)Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Brian E. Fink, Ashvinikumar V. Gavai, Wen-ching Han, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Kenneth J. LeavittAbstract:Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.
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Novel C-5 aminomethyl Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ashvinikumar V. Gavai, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Punit Marathe, Arvind Mathur, Simone Oppenheimer, James G. TarrantAbstract:Novel C-5 aminomethyl Pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket.
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New C-5 substituted Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Pierre Dextraze, Brian E. Fink, Ashvinikumar V. Gavai, Bindu Goyal, Wen-ching Han, Johnson Walter Lewis, David R. LangleyAbstract:Novel C-5 substituted Pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket.
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Pyrrolotriazine 5 carboxylate ester inhibitors of egfr and her2 protein tyrosine kinases and a novel one pot synthesis of c 4 subsitituted pyrrole 2 3 dicarboxylate diesters
Canadian Journal of Chemistry, 2006Co-Authors: Harold Mastalerz, Brian E. Fink, Ashvinikumar V. Gavai, James G. Tarrant, Charles Struzynski, Gregory D Vite, Tai W Wong, Guifen Zhang, Dolatrai M VyasAbstract:Pyrrolotriazines with an ester group at C-5 were prepared and evaluated as inhibitors of the EGFR and HER2 receptor tyrosine kinases, validated targets for cancer therapy. The C-5 ester (15) was at...
Ming Chang - One of the best experts on this subject based on the ideXlab platform.
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5-((4-Aminopiperidin-1-yl)methyl)Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Brian E. Fink, Ashvinikumar V. Gavai, Wen-ching Han, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Kenneth J. LeavittAbstract:Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.
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Novel C-5 aminomethyl Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ashvinikumar V. Gavai, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Punit Marathe, Arvind Mathur, Simone Oppenheimer, James G. TarrantAbstract:Novel C-5 aminomethyl Pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket.
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New C-5 substituted Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Pierre Dextraze, Brian E. Fink, Ashvinikumar V. Gavai, Bindu Goyal, Wen-ching Han, Johnson Walter Lewis, David R. LangleyAbstract:Novel C-5 substituted Pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket.
Johnson Walter Lewis - One of the best experts on this subject based on the ideXlab platform.
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5-((4-Aminopiperidin-1-yl)methyl)Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Brian E. Fink, Ashvinikumar V. Gavai, Wen-ching Han, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Kenneth J. LeavittAbstract:Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.
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Novel C-5 aminomethyl Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ashvinikumar V. Gavai, Johnson Walter Lewis, David R. Langley, Francis Y. Lee, Punit Marathe, Arvind Mathur, Simone Oppenheimer, James G. TarrantAbstract:Novel C-5 aminomethyl Pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket.
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New C-5 substituted Pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
Bioorganic & medicinal chemistry letters, 2007Co-Authors: Harold Mastalerz, Ming Chang, Ping Chen, Pierre Dextraze, Brian E. Fink, Ashvinikumar V. Gavai, Bindu Goyal, Wen-ching Han, Johnson Walter Lewis, David R. LangleyAbstract:Novel C-5 substituted Pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket.
