AIMTo establish new methods for the chiral separation and preparation of three new drugs, alfuzosin, terazosin and doxazosin.

METHODSBy optimizing factors which affect the chiral separation, modifier of solvent, chiral additive, pH of mobile phase, modifier of organic base and stationary phase, the optimum condition for chiral separation were selected. The preparation of enantiomers was carried out on semi-preparative reverse phase column (7.8 mm x 250 mm C4 5 microns). Acetonitrile-water modified by the addition of carboxymethyl-beta-cyclodextrin (2%-5%, w/v) was applied as chiral mobile phase.

RESULTSThe enantiomers of three new drugs were base-line-separated and milligram-scale samples of enantiomer were obtained.

CONCLUSIONThe newly established method can be used in research and development of the enantiomers of three new drugs.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Doxazosin ; isolation & purification ; Molecular Structure ; Prazosin ; analogs & derivatives ; isolation & purification ; Quinazolines ; isolation & purification

During past several years, a novel class of antihyperglycemic agents, dipeptidyl peptidase-4 (DPP-4) inhibitors, has become one of the most important options in the management of type 2 diabetes. These agents have unique insulinotropic actions as well as other advantages such as lower hypoglycemia and a weight-neutral effect compared to traditional insulin secretagogues. To date, 6 different DPP-4 inhibitors have been introduced: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin and gemiglitin. This review provides a summary of the clinical data for each DPP-4 inhibitor, and discusses the similarities and differences between them.
Adamantane ; Diabetes Mellitus ; Dipeptides ; Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemia ; Hypoglycemic Agents ; Incretins ; Insulin ; Nitriles ; Piperidines ; Purines ; Pyrazines ; Pyrrolidines ; Quinazolines ; Triazoles ; Uracil ; Linagliptin ; Sitagliptin Phosphate

Anagrelide is an effective drug for essential thrombocythaemia, and its adverse cardiovascular effects are relatively rarely reported. We experienced a 73 year-old man with essential thrombocythaemia developed anagrelide-induced dilated cardiomyopathy. After discontinuation of anagrelide, the patient's left ventricular systolic function was completely recovered.
Cardiomyopathies ; Cardiomyopathy, Dilated ; Quinazolines

Spontaneous pneumothorax (SPTx) associated with primary lung cancer is quite rare, but has been reported as the initial presentation or a complication of disease progression. Moreover, chemotherapy-related SPTx in primary lung cancer occurs at a very low frequency, accounting for less than 0.05% of all cases. Here, we report the first case of erlotinib-related SPTx in a patient with advanced lung adenocarcinoma in Korea. After 3 cycles of cisplatin-based chemotherapy as first-line therapy, erlotinib was administered as second-line treatment. Asymptomatic SPTx accompanied by a significant decrease in tumor size was observed in the left lung 7 weeks later. The patient received continuous administration of erlotinib, without additional treatment. This case showed that SPTx can occur in patients with primary lung cancer receiving erlotinib, and asymptomatic chemotherapy-related SPTx in primary lung cancer may not require therapeutic intervention.
Accounting ; Adenocarcinoma ; Disease Progression ; Humans ; Korea ; Lung ; Lung Neoplasms ; Pneumothorax ; Quinazolines ; Erlotinib Hydrochloride

Erlotinib (Tarceva(R)) has been considered to be a new, promising oral chemotherapy agent for local advanced or metastatic non-small cell lung cancer (NSCLC). Erlotinib is regarded as relatively safe, but interstitial lung disease (ILD) related to erlotinib has been reported on an infrequent basis in Asia. We report an histologically confirmed case of recurrent erlotinib-induced ILD. Although, the patient was highly responsive to the first erlotinib treatment, the therapy was discontinued due to erlotinib-induced ILD. After intravenous high dose methylpredinisolone treatment, ILD was improved rapidly by radiologic studies, but the particular lung cancer re-emerged. We restarted the patient erlotinib on low-dose oral methylpredinisolone, resulting in a recurrence of erlotinib-induced ILD. Our case suggests that re-administration of erlotinib should be performed on a limited basis in patients that have developed ILD on previous use, even if a therapeutic effect can be estimated.
Asia ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Diseases, Interstitial ; Lung Neoplasms ; Quinazolines ; Recurrence ; Erlotinib Hydrochloride

Erlotinib (Tarceva(R)) has been considered to be a new, promising oral chemotherapy agent for local advanced or metastatic non-small cell lung cancer (NSCLC). Erlotinib is regarded as relatively safe, but interstitial lung disease (ILD) related to erlotinib has been reported on an infrequent basis in Asia. We report an histologically confirmed case of recurrent erlotinib-induced ILD. Although, the patient was highly responsive to the first erlotinib treatment, the therapy was discontinued due to erlotinib-induced ILD. After intravenous high dose methylpredinisolone treatment, ILD was improved rapidly by radiologic studies, but the particular lung cancer re-emerged. We restarted the patient erlotinib on low-dose oral methylpredinisolone, resulting in a recurrence of erlotinib-induced ILD. Our case suggests that re-administration of erlotinib should be performed on a limited basis in patients that have developed ILD on previous use, even if a therapeutic effect can be estimated.
Asia ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Diseases, Interstitial ; Lung Neoplasms ; Quinazolines ; Recurrence ; Erlotinib Hydrochloride

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Humans ; Korea ; Lung ; Lung Neoplasms ; Patient Selection ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Erlotinib Hydrochloride

Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor (EGFR). There have been many reports of the mucocutaneous side effects related to several EGFR inhibitors (EGFRIs). However, no case of black hairy tongue (BHT) associated with EGFRI has been reported. Herein, we report the first case of erlotinib-induced BHT in a 61-year-old man with advanced lung cancer. Considering recent use of EGFRIs worldwide, dermatologists should recognize the possible occurrence of BHT associated with EGFRIs such as erlotinib.
Butylated Hydroxytoluene ; Humans ; Lung ; Lung Neoplasms ; Middle Aged ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Tongue, Hairy ; Erlotinib Hydrochloride

Although failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) is generally believed to be associated with cross-resistance to other EGFR TKI, the benefit of administering erlotinib as a second EGFR TKI after resistance of gefitinib as the first TKI has been well known. However, good response to gefitinib after an initial response to erlotinib has been rare. We report that a 45-year-old woman (never smoked), with lung adenocarcinoma and EGFR mutation, showed an initial response to erlotinib, and then responded to gefitinib again.
Adenocarcinoma ; Female ; Humans ; Lung ; Lung Neoplasms ; Middle Aged ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Erlotinib Hydrochloride

BACKGROUND/AIMS: Lung cancer is the leading cause of cancer death worldwide. There are significant gender differences in lung cancer: most females with lung cancer are non-smokers and they are diagnosed with adenocarcinoma. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in female lung cancer patients, but the results with gefitinib and erlotinib differ. This study compared the therapeutic response and toxicity of gefitinib and erlotinib in female lung cancer patients. Method: We retrospectively reviewed the clinical information on patients treated with gefitinib or erlotinib for more than one month at Kosin University Gospel Hospital from February 2004 to November 2007. RESULTS: Forty-two patients (26 gefitinib vs. 16 erlotinib) were enrolled during this period. Their median age was 58 years. Thirty-six patients (85%) were non-smokers and 35 patients (83%) had adenocarcinoma. There were 24% at stage IIIb and 76% at stage IV. The median survival time was 793 days. In the gefitinib group, 69% of the patients received 3rd-line chemotherapy, while 12 of 16 (87.5%) in the erlotinib group received 2nd-line chemotherapy. There were no significant differences in the overall response rate (gefitinib 39% vs. erlotinib 31%, p=0.524), median survival time (gefitinib 605 days vs. erlotinib 510 days, p=0.455), and time to progression (gefitinib 186 days vs. erlotinib 262 days, p=0.660). Rashes were more common in the erlotinib group (73.3% vs. 27%, p<0.001). CONCLUSIONS: There were no significant differences in the response rate, overall survival, and time to progression between the two groups. Rashes were more common in the erlotinib group.
Adenocarcinoma ; Exanthema ; Female ; Humans ; Lung ; Lung Neoplasms ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Erlotinib Hydrochloride