Je Il Pharmaceutical Co., Ltd.

In-Hae Ye

Jong-Hee Choi

Myung-Hwa Kim

Chun-Ho Park

Kwang-Woo Chun

Seung-Hyun Kim

Bo-Young Joe

Sae-Kwang Ku

Dong-il Kang

Dong-Kyu Ryu

Ji-Seon Park

Han-Chang Lee

Ji-So Choi

Young-Chul Kim

The present invention relates to a novel crystalline acid salt of a tricyclic derivative or a hydrate thereof and a production method thereof. The crystalline acid salt or the hydrate thereof according to the present invention is stable with respect to humidity and stable with respect to hygroscopicity, and the quality control during manufacturing drugs is favorable. In addition, the crystalline acid salt or the hydrate thereof may be used in a pharmaceutical composition for preventing or treating neuropathic pain, epilepsy, stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, schizophrenia, chronic and acute pain, ischemic brain injury, neuronal loss after hypoxia, trauma and nerve damage, which are medical conditions induced by PARP overactivity.

Crystalline forms of tricyclic compound acid salt or hydrate thereof, and method for making thereof

A pharmaceutical composition includes lipid nanoparticles which include two or more of a phospholipid, cholesterol, and an ionic lipid, and a tricyclic derivative, wherein the solubility of the tricyclic derivative is improved. It is possible to solubilize a partially soluble tricyclic derivative in a high concentration even without using a solubilization aid harmful to the human body, to maintain improved solubility even if water is added for the use as an injection, and to show stability even if stored for a long time, by preparing lipid nanoparticles. Therefore, the lipid nanoparticles of the present invention can be used for preparing a pharmaceutical preparation containing a partially soluble tricyclic derivative as an active ingredient.

Pharmaceutical composition in which solubility of partially soluble tricyclic derivative is improved

The present invention relates to a novel tricyclic derivative with efficient inhibitory activity against poly(ADP-ribose)polymerases (PARP) or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition containing the same. The tricyclic derivative of the invention is useful for the prevention or treatment of diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic nephropathy, inflammatory diseases, osteoporosis, and cancer, by inhibiting the activity of poly(ADP-ribose)polymerases.

Tricyclic derivative or pharmaceutically acceptable salts thereof, preparation method thereof, and pharmaceutical composition containing the same

The present invention relates to a method for preparing a tricyclic derivative, and more particularly, to a method for preparing a tricyclic derivative intermediate with high yield and purity, the method including: introducing a hydroxy group by esterifying and substituting 2-fluoroisophthalic acid compound; introducing a piperidyl group; introducing a hydroxy group through reduction reaction; and then hydrolyzing the resultant compound, and to a method for preparing the tricyclic derivative using said intermediate. According to the method of the present invention, it is possible to provide a tricyclic derivative and an intermediate thereof with high productivity and economic feasibility as well as high purity and yield, by purifying a compound using re-crystallization unlike typical methods of using column chromatography. In addition, the method of the present invention can be usefully used for industrial mass production because sodium borohydride or lithium aluminum hydride with low risk of a fire is used unlike typical methods of using lithium borohydride which is not industrially applicable due to high risk of a fire.

Method for preparing tricyclic derivatives

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Yongin-si, South Korea

In-Hae Ye