Beta Pharma, Inc.

Charles Davis

Don Zhang

Yinxiang Wang

Guojian Xie

Wei He

Yong Liu

Wei Long

Yunyan Hu

Lieming Ding

Bin Han

Fenlai Tan

Haima Ai

Zhengzhuang Cheng

Hang Chen

Mehrnaz Kamal

Haima Al

The invention relates to 4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-quinazoline hydrochloride, its new crystalline forms, its therapeutic usage for treatment of diseases mediated by EGFR kinase and its combinatory therapeutic usage together with other therapeutic agents. The invention also provides synthetic methods for preparation of 4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-quinazoline hydrochloride, its new crystalline forms, and the relevant synthetic intermediates for synthesis of 4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-quinazoline hydrochloride.

Icotinib hydrochloride, synthesis, crystalline forms, pharmaceutical compositions, and uses thereof

The present invention is directed to a compound having the structure wherein A is a 7&#x2013;18 membered ring that comprises 0 to 6 heteroatoms selected from O, S, and N; Ris selected from the group consisting of hydrogen, halogen, substituted or unsubstituted Calkyl, substituted or unsubstituted Calkenyl, substituted or unsubstituted Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; m is an integer from 0 to 3; X is selected from the group consisting of NR, CHR, O, or S; wherein Rand Rare each individually H or Calkyl; R is selected from the group consisting of unsubstituted aryl, and substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl-(C)alkyl, substituted or unsubstituted aryl-(C)cycloalkyl, substituted or unsubstituted heteroaryl-(C)alkyl, and substituted or unsubstituted heteroaryl-(C)cycloalkyl; and pharmaceutically acceptable salts thereof; with the proviso that if A is a 7 or 8 membered ring, then Ris selected from the group consisting of other than H, C&#x2013;Calkyl, (C&#x2013;Calkoxy)C&#x2013;Calkyl, C&#x2013;Calkanoyl, C&#x2013;Calkoxy or &#x2014;S(O)(C&#x2013;Calkyl) wherein x is 0 to 2, and wherein said alkyl group and the alkyl moieties of said Rgroups are optionally substituted by 1 to 3 halogens. The present invention is also directed to pharmaceutical compositions comprising the above compound, and methods of treating patients suffering from tyrosine kinase-mediated disorders using the above compound.

Fused quinazoline derivatives useful as tyrosine kinase inhibitors

Growing community of inventors

Germantown, WI, United States of America

Charles Davis