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Lu AE58054 novel crystal form and preparation method thereof

A technology of crystal form and name, applied in the field of pharmaceutical chemical crystallization, can solve the problems of poor chemical stability, high solubility residue, poor processability of preparations, etc., and achieve the effect of low hygroscopicity

Inactive Publication Date: 2019-10-11
SOLIPHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The free state of AE58054 is an amorphous oil, which has the disadvantages of difficult purification, poor chemical stability, high residual solubility, and poor processability of preparations

Method used

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  • Lu AE58054 novel crystal form and preparation method thereof
  • Lu AE58054 novel crystal form and preparation method thereof
  • Lu AE58054 novel crystal form and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0068] According to the method described in Example 402 of the patent document CN1610547A, Lu AE58054 free state oil was prepared.

[0069] 1 HNMR (500MHz, DMSO) δ (ppm): 10.74 (s, 1H), 7.33 (dd, J = 8.5, 5.5Hz, 1H), 7.21 (dd, J = 15.2, 7.3Hz, 2H), 7.06 (dd, J=10.1,2.1Hz,1H),6.92–6.83(m,2H),6.83–6.78(m,1H),6.75(dd,J=14.4,6.2Hz,1H),6.61(dt,J=51.9, 5.3Hz, 1H), 4.51(t, J=13.2Hz, 2H), 3.33(s, 2H), 2.41(d, J=7.3Hz, 3H), 1.81(s, 2H), shown as known Lu AE58054.

[0070] X-ray powder diffraction pattern as figure 1 shown. It shows that Lu AE58054 prepared according to the method described in Example 402 of patent document CN1610547A is amorphous.

preparation example 2

[0072] Lu AE58054 hydrochloride solid was prepared according to the method described in Example 402 of patent document CN1610547.

[0073] Weigh 39.8mg of LuAE58054 free state, add 0.4mL ether, add HCl ether solution dropwise while stirring at room temperature until the pH is about 3, obtain a solid, collect the solid after stirring for 1 hour, wash with ether, and dry under vacuum at 40°C to obtain LuAE58054 salt Salt solid 42mg, yield 84%.

Embodiment 1

[0075] Take 87 mg of the Lu AE58054 hydrochloride sample prepared in Preparation Example 2, add 0.22 mL of acetone to ultrasonically dissolve it, add 0.22 mL of n-heptane under stirring until the precipitation becomes cloudy, then add 5 mL of an aqueous solution containing 11.7 mg of sodium carbonate, and stir at room temperature for 5 days. The resulting solid was centrifuged and dried under vacuum at 40° C. for 24 hours to obtain 74.1 mg of the Lu AE58054 crystal form 1 with a yield of 93%.

[0076] Its X-ray powder diffraction pattern is as figure 2 shown.

[0077] Its DSC spectrum is as image 3 shown.

[0078] Its TGA spectrum is as Figure 4 shown.

[0079] Its adsorption isotherm is as follows: Figure 5 shown.

[0080] Its PLM map such as Image 6 shown.

[0081] Its IR spectrum is as Figure 7 shown.

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Abstract

The invention relates to a Lu AE58054 novel crystal form and a preparation method and application thereof. Compared with known Lu AE58054, the Lu AE58054 novel crystal form is advantageous in crystallinity, moisture adsorption, shape, appearance and the like. The invention further relates to the preparation method of the Lu AE58054 novel crystal form and application of the Lu AE58054 novel crystalform to preparation of medicines for treating cognitive disorders such as Alzheimer's disease and schizophrenia.

Description

technical field [0001] This application relates to the technical field of medicinal chemical crystallization. Specifically, the application relates to a new crystal form of Lu AE58054 and its preparation method and use. Background technique [0002] Lu AE58054 is a selective 5-HT6 receptor antagonist indicated for the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia. Phase II results of the drug show that Lu AE58054 helps improve the cognitive function of patients with moderate Alzheimer's disease treated with the drug donepezil. [0003] The chemical name of Lu AE58054 is N-[2-(6-fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine, English name Idalopirdine, the molecular formula is C 20 h 19 f 5 N 2 O, molecular weight is 398.14, its chemical structural formula is as follows: [0004] [0005] Patent CN1610547A discloses Lu AE58054 compound (ie free state), Lu AE58054 hydrochloride and its preparation method, and me...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/14C07D209/16A61K31/404A61P25/28A61P25/00
CPCA61P25/00A61P25/28C07B2200/13C07D209/14C07D209/16
Inventor 盛晓红盛晓霞饶珺
Owner SOLIPHARMA