trans-4-Dimethylaminocrotonic Acid Hydrochloride CAS 848133-35-7 Purity >98.0% (HPLC) Afatinib Dimaleate Intermediate

trans-4-Dimethylaminocrotonic Acid Hydrochloride (CAS: 848133-35-7) is a reagent used in the preparation of tyrosine kinase inhibiting antitumor agents. trans-4-Dimethylaminocrotonic Acid Hydrochloride can be used as an intermediate of Afatinib (CAS: 439081-18-2), Afatinib Dimaleate (CAS: 850140-73-7), Neratinib (CAS: 698387-09-6). Afatinib is a drug approved for the treatment non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim. It acts as a angiokinase inhibitor. Like Lapatinib and Neratinib, Afatinib is a tyrosine kinase inhibitor (TKI) that also irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation TKIs likeerlotinib or gefitinib, but also against those not sensitive to these standard therapies. Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers. Neratinib developed by US Wyeth company is an irreversible epidermal growth factor receptor(EGFR) inhibitor. It is a multiple target point of small molecule tyrosine kinase inhibitors to HER 2 and HER1 after Lapatinib, and is an irreversible ErbB receptor tyrosine kinase inhibitor. Neratinib could selectively inhibit HER-1 and HER-2 of EGFR family(IC50 was 92 nmol/L and 59 nmol/L, respectively). Clinical research showed that Neratinib exerted significant therapeutic effect on non-small cell lung cancer, colon cancer, and breast cancer. The phaseⅡclinical trial indicated that Neratinib showed good efficacy and tolerance to HER-2 positive patients with advanced breast cancer who had been received or not Trastuzumab treatment. The phase Ⅲ breast cancer clinical trial was complete in September 2014.