CN114984011A - Application of pyrrolopyridine compound in preparation of medicine for treating lupus - Google Patents

Abstract

The invention belongs to the field of medicines, and particularly relates to application of a pyrrolopyridine compound in preparation of a medicine for treating lupus. The research of the invention finds that the pyrrolopyridine compound can effectively treat lupus and complications thereof, and can obtain a synergistic effect by combining the pyrrolopyridine compound with glucocorticoid.

Description

Application of pyrrolopyridine compounds in preparation of lupus medicine

technical field

The invention belongs to the field of medicine, in particular to the technical field of lupus treatment.

Background technique

Lupus erythematosus (LE) is a typical autoimmune disease, which produces a variety of autoantibodies due to cellular and humoral immune dysfunction, thereby accumulating skin, joint, muscle, kidney, cardiovascular, blood, Diseases of multiple organs and systems of the whole body such as the central nervous system. When lupus crisis occurs, it may endanger the patient's life if not timely and effective intervention. Rapid induction of lupus remission is one of the keys to the treatment of this disease.

The current clinical treatment regimen is like a double-edged sword. Although it can control the development of the disease on the one hand, it is also accompanied by many drug toxic effects. Such as long-term use of glucocorticoids can cause gastrointestinal damage, secondary Cushing syndrome infection, etc.; the use of large doses of glucocorticoids can lead to thalamo-pituitary-adrenal axis disorders. Immunosuppressive agents often lead to bone marrow suppression, liver and kidney damage, and secondary infections. The research and development of targeted monoclonal antibody biological agents has solved the problem of non-target effects very well, and has shown good therapeutic effects in clinical trials, but there are also some safety problems; and as biological agents, the price is relatively expensive; in addition , The occurrence and development of lupus erythematosus involves multiple systems and multiple factors, and the therapeutic effect obtained by targeted therapy of a single target is limited. Exploring more efficient and less off-target therapeutic drugs has important practical significance and development prospects for the treatment of LE.

SUMMARY OF THE INVENTION

In view of the above problems, the purpose of the present invention is to provide an application of a pyrrolopyridine compound in the preparation of a lupus medicament.

The second object of the present invention is to provide active ingredients and medicines for treating lupus containing pyrrolopyridine compounds.

Application of a pyrrolopyridine compound in the preparation of a lupus medicine, wherein the pyrrolopyridine compound has

The compound of formula 1;

In formula 1, the R is a C1-C6 carboxylic acid and its salt, a C2-C10 ester, a C2-C10 amide, a sulfonic acid and its salt.

The research of the present invention shows that the compound of formula 1 is helpful for alleviating the symptoms and complications of lupus.

In the present invention, the pyrrolopyridine compounds are compounds with the structure of formula 1-A:

In the application of the present invention, the lupus is at least one of systemic lupus erythematosus, discoid lupus erythematosus, and cutaneous lupus erythematosus; preferably, systemic lupus erythematosus. The research of the present invention shows that the compound of formula 1 can effectively relieve the symptoms and complications of systemic lupus erythematosus.

CD4⁺T细胞、

B细胞至少一种分化的治疗狼疮的药物。Preferably, in the application, the pyrrolopyridine compound is used to prepare at least one differentiation of Tfh, Th1, and antibody-secreting cells; and/or to inhibit autoantibody dsDNA antibody, IFN-β and IFN- secretion of at least one of gamma; and/or promoting Treg,

CD4 ⁺ T cells,

B cells differentiated from at least one drug for the treatment of lupus.

CD4⁺T细胞比例、促进

B细胞比例功能，如此能够有效缓解狼疮症状以及并发症。In the present invention, the compound of formula 1 can effectively inhibit Tfh cell differentiation, inhibit Th1 cell differentiation, inhibit antibody-secreting B cells, inhibit interferon secretion, inhibit autoantibody production, promote Treg cell differentiation, and promote

CD4 ⁺ T cell ratio, promotion

B cell ratio function, which can effectively relieve lupus symptoms and complications.

In the application of the present invention, the pyrrolopyridine compound is used to prepare a medicine for kidney injury caused by lupus.

In the application of the present invention, the pyrrolopyridine compound is used to prepare a medicine for lymphatic and/or spleen hyperplasia caused by lupus.

In a preferred application of the present invention, the pyrrolopyridine compound and glucocorticoid are combined to prepare a medicine for treating lupus. In the present invention, the combined use of the pyrrolopyridine compound and the glucocorticoid can achieve a combined synergistic effect, and a better therapeutic effect can be obtained.

In the application of the present invention, the pyrrolopyridine compound and pharmaceutically acceptable auxiliary materials are combined to prepare any pharmaceutically acceptable dosage form; preferably, the dosage form is an external preparation, an oral preparation or an injection preparation.

The present invention also provides a pharmaceutical active composition for treating lupus, comprising the compound of formula 1 and a glucocorticoid;

Preferably, the dosage ratio (eg, mass ratio) of the compound of formula 1 and glucocorticoid is 1-3:1.

The present invention also provides a medicine for treating lupus, comprising the active composition in a pharmaceutically effective amount.

The preferred medicine contains pharmaceutically acceptable excipients. Preferred drugs are in pharmaceutically acceptable dosage forms. The dosage form is, for example, any dosage form of granules, tablets, capsules, sprays, injections, suspensions, emulsions and the like.

Beneficial effects of the present invention:

CD4⁺T细胞，

B细胞的比例；抑制IFN-β，IFN-γ，抗dsDNA的产生；能够用于狼疮的治疗，缓解狼疮症状以及预防并发症。1. The compound of formula 1 can reduce the proportion of Tfh, Th1 and antibody-secreting B cells in draining lymph nodes; increase Treg,

CD4 ⁺ T cells,

The proportion of B cells; inhibit the production of IFN-β, IFN-γ, anti-dsDNA; can be used for the treatment of lupus, relieve lupus symptoms and prevent complications.

2. Combining the compound of formula 1 and glucocorticoid can achieve synergy and obtain better lupus treatment effect,

Description of drawings

Fig. 1 shows that formula 1-A in Example 1 can better inhibit the differentiation of Tfh compared with a variety of reference drugs;

Fig. 2 shows that formula 1-A in Example 1 can better inhibit the production of IL-21 compared with a variety of reference drugs;

Fig. 3 shows that compared with a variety of reference drugs, Chinese formula 1-A in Example 2 can better promote the differentiation of Treg cells;

CD4+T向Tfh细胞的分化；Figure 4 shows the inhibition of formula 1-A in Example 3

Differentiation of CD4+T into Tfh cells;

CD4+T向Th1细胞的分化；Figure 5 shows the inhibition of formula 1-A in Example 4

Differentiation of CD4+T into Th1 cells;

CD4+T向Treg细胞的分化；Fig. 6 is embodiment 5 Chinese formula 1-A promotes

Differentiation of CD4+T into Treg cells;

Figure 7 shows that Chinese formula 1-A in Example 6 improves the kidney damage of lupus and reduces the kidney damage score;

Fig. 8 is embodiment 6 Chinese formula 1-A improves spleen lymph node hyperplasia;

Figure 9 shows that formula 1-A in Example 6 reduces the proportion of Tfh cells in the draining lymph nodes;

Figure 10 shows that formula 1-A in Example 6 reduces the proportion of Th1 cells in the draining lymph nodes;

Figure 11 shows that formula 1-A in Example 6 reduces the proportion of antibody-secreting B cells in draining lymph nodes;

Figure 12 shows that formula 1-A in Example 6 increases the proportion of Treg cells in the draining lymph nodes;

CD4⁺T细胞的比例；Fig. 13 shows that the formula 1-A in Example 6 improves the drainage of lymph nodes in the

Proportion of CD4 ⁺ T cells;

B细胞的比例；Fig. 14 shows that the formula 1-A in Example 6 improves the drainage of lymph nodes in the

The proportion of B cells;

Figure 15 shows that Formula 1-A in Example 6 inhibits the production of IFN-β;

Figure 16 shows that Formula 1-A in Example 6 inhibits the production of IFN-γ;

Figure 17 shows that Formula 1-A in Example 6 inhibits the production of anti-dsDNA;

Figure 18 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of CD8 ⁺ TEM cells in the draining lymph nodes (DLN) than prednisolone alone;

Figure 19 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of CD8 ⁺ TCM cells in the draining lymph nodes than prednisolone alone;

CD8⁺T细胞；Figure 20 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better maintain the initial state of CD8 ⁺ T cells in the draining lymph nodes than prednisolone alone, i.e.

CD8 ⁺ T cells;

Figure 21 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of CD4 ⁺ TEM cells in the draining lymph nodes than prednisolone alone;

Figure 22 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of CD4 ⁺ TCM cells in the draining lymph nodes than prednisolone alone;

CD4⁺T细胞；Figure 23 shows that the combination of Chinese formula 1-A and glucocorticoid prednisolone in Example 7 can better maintain the initial state of CD4 ⁺ T cells in the draining lymph nodes than prednisolone alone, namely

CD4 ⁺ T cells;

Figure 24 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of CD4 ⁺ TCM cells in the spleen than prednisolone alone;

Figure 25 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of antibody-secreting cells ASC in the draining lymph nodes than prednisolone alone;

Figure 26 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better inhibit the differentiation of memory B cells in the draining lymph nodes than prednisolone alone;

Figure 27 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better maintain the initial state of B cells in the draining lymph nodes than prednisolone alone;

Figure 28 shows that the combination of Chinese formula 1-A and the glucocorticoid prednisolone in Example 7 can better promote the differentiation of antibody Treg in the spleen than prednisolone alone;

Detailed ways

Example 1: In vitro Tfh and IL-21 inhibition studies

100 ml of peripheral blood was drawn from healthy volunteers, and PBMCs were separated with Ficoll, and seeded in 24-well plates coated with anti-human CD3 one night in advance, and anti-human CD28 was added. Add solvent (DMSO), formula 1-A, or several reference drugs (Molibresib, I-BET762 carboxylic acid, BET-BAY002, PROTAC BET-binding moiety 2, BI-9564, (S)-JQ- 35), the final concentration was 1 μM, and cultured at 37°C for 3 days. The culture supernatant was collected, and the concentration of IL-21 was detected by human IL-21 ELISA detection kit; the collected cells were detected by flow cytometry. Proportion. Compared with the control group and various reference drugs, formula 1-A can more effectively inhibit the secretion of IL-21; and can more effectively inhibit the differentiation of Tfh, the results are shown in Figures 1 and 2. IL-21 and Tfh play an important role in promoting the occurrence and development of lupus erythematosus. Formula 1-A has better potential therapeutic effect than a variety of reference drugs.

The human IL-21 ELISA kit used in Example 1 was purchased from Wuhan Huamei Company, the anti-human CD3 and anti-human CD28 used were purchased from Miltenyi Company, and the flow-through antibodies used were purchased from BD Company.

Example 2: Differentiation study of Treg cells in vitro

100 ml of peripheral blood was drawn from healthy volunteers, and PBMCs were separated with Ficoll, and seeded in 24-well plates coated with anti-human CD3 one night in advance, and anti-human CD28 was added. Add vehicle (DMSO), formula 1-A, or several reference drugs (respectively, Alobresib, PFI-1, (Rac)-BAY1238097, Y06036) at a final concentration of 1 μM, culture at 37°C for 3 days, harvest cells for use The proportion of Treg cells in CD4+ T cells was detected by flow cytometry. Compared with the control group and various reference drugs, formula 1-A can more effectively promote the differentiation of Treg, and the results are shown in Figure 3. Treg cells play a role in suppressing the immune response, and can inhibit the differentiation of many cells that play a promoting role in the occurrence and development of lupus erythematosus, which is beneficial to the remission and treatment of the disease. potential therapeutic effect.

The anti-human CD3 and anti-human CD28 used in Example 2 were purchased from Miltenyi Company, and the flow-through antibodies used were purchased from BD Company.

Example 3: Effect of Formula 1-A on Tfh-induced differentiation

CD4+分选磁珠分离其中的

CD4+T细胞(按试剂盒说明书操作)，加入含有抗人CD28，IL-6，IL-12，IL-21，TGF-β的10％FBS的RPMI 1640培养基中，于提前包被有抗人CD3的24孔细胞培养板中培养，种板的细胞密度为1×10⁶/ml，培养3天后流式检测Tfh的比例。与对照组相比(DMSO)，实验组(式1-A)的Tfh分化比例显著减少(图4)。150ml of peripheral blood was extracted from 3 healthy volunteers, and the PBMCs of each volunteer were separated by Ficoll, a lymphocyte separation solution, and Miltenyi human

CD4+ sorting magnetic beads separate the

CD4+ T cells (operated according to the kit instructions) were added to RPMI 1640 medium containing anti-human CD28, IL-6, IL-12, IL-21, TGF-β in 10% FBS, and coated with anti- Human CD3 was cultured in a 24-well cell culture plate at a cell density of 1×10 ⁶ /ml, and the ratio of Tfh was detected by flow cytometry after 3 days of culture. Compared with the control group (DMSO), the proportion of Tfh differentiation in the experimental group (Formula 1-A) was significantly reduced (Figure 4).

The reagent consumables used are:

CD4分选磁珠，抗人CD28，抗人CD3，LS柱均购于美天旎；people

CD4 sorting magnetic beads, anti-human CD28, anti-human CD3, and LS columns were purchased from Miltenyi;

IL-6, IL-21, IL-12, TGF-β were purchased from Beijing Yiqiao Shenzhou Technology Co., Ltd.;

Flow-through antibodies were purchased from BD company, specifically CD4:FITC, CXCR5:PE, PD-1:PE-CY7.

Example 4: Effect of Formula 1-A on Th1-induced differentiation

CD4+分选磁珠分离其中的

CD4+T细胞(按试剂盒说明书操作)，，加入含有抗人CD28，IL-4，IL-2，IL-12的10％FBS的RPMI 1640培养基中，于提前包被有抗人CD3的24孔细胞培养板中培养，种板的细胞密度为1×10⁶/ml，3天后流式检测Th1的比例。与对照组相比(DMSO)，实验组(式1-A)的Th1的分化比例显著减少(图5)。与健康对照相比，红斑狼疮患者体内的Th1水平明显增高；Th1还能通过产生分泌IFN-γ加重疾病的发展。式1-A可通过抑制Th1的分化而缓解病情。150ml of peripheral blood was extracted from 3 healthy volunteers, and the PBMCs of each volunteer were separated by Ficoll, a lymphocyte separation solution, and Miltenyi human

CD4+ sorting magnetic beads separate the

CD4+ T cells (operated according to the kit instructions), added to RPMI 1640 medium containing 10% FBS of anti-human CD28, IL-4, IL-2, IL-12, and pre-coated with anti-human CD3 The cells were cultured in a 24-well cell culture plate, and the cell density of the seed plate was 1×10 ⁶ /ml, and the proportion of Th1 was detected by flow cytometry after 3 days. Compared with the control group (DMSO), the differentiation ratio of Th1 in the experimental group (Formula 1-A) was significantly reduced (Fig. 5). Compared with healthy controls, the level of Th1 in patients with lupus erythematosus is significantly increased; Th1 can also aggravate the development of the disease by producing and secreting IFN-γ. Formula 1-A can alleviate the disease by inhibiting the differentiation of Th1.

The reagent consumables used are:

CD4分选磁珠，抗人CD28，抗人CD3，LS柱均购于美天旎；people

CD4 sorting magnetic beads, anti-human CD28, anti-human CD3, and LS columns were purchased from Miltenyi;

IL-4, IL-2, and IL-12 were purchased from Beijing Yiqiao Shenzhou Technology Co., Ltd.;

Flow-through antibodies were purchased from BD Company, specifically CD4:FITC, IFN-γ:PE-CY7.

Example 5: Effect of Formula 1-A on Treg-induced differentiation

CD4+分选磁珠分离其中的

CD4+T细胞(按试剂盒说明书操作)，加入含有抗人CD28，IL-2，TGF-β的10％FBS的RPMI 1640培养基中，于提前包被有抗人CD3的24孔细胞培养板中培养，种板的细胞密度为1×10⁶/ml，3天后流式检测Treg的比例(图6)。与对照组相比(DMSO)，实验组(式1-A)的Treg的分化比例显著增加。150ml of peripheral blood was extracted from 3 healthy volunteers, and the PBMCs of each volunteer were separated by Ficoll, a lymphocyte separation solution, and Miltenyi human

CD4+ sorting magnetic beads separate the

CD4+ T cells (operated according to the kit instructions) were added to RPMI 1640 medium containing 10% FBS of anti-human CD28, IL-2 and TGF-β, and were pre-coated with anti-human CD3 in a 24-well cell culture plate The cell density of the seed plate was 1×10 ⁶ /ml, and the proportion of Treg was detected by flow cytometry after 3 days ( FIG. 6 ). Compared with the control group (DMSO), the differentiation ratio of Treg in the experimental group (Formula 1-A) was significantly increased.

The reagent consumables used are:

CD4分选磁珠，抗人CD28，抗人CD3，LS柱均购于美天旎；people

CD4 sorting magnetic beads, anti-human CD28, anti-human CD3, and LS columns were purchased from Miltenyi;

IL-2 and TGF-β were purchased from Beijing Yiqiao Shenzhou Technology Co., Ltd.;

Flow-through antibodies were purchased from BD Company, specifically CD4:FITC, CD25:APC, CD127:percep-cy5.5.

Example 6: Therapeutic effect of formula 1-A on spontaneous lupus mice

The 12-week-old spontaneous lupus model mice (MRL/lpr, Beijing Speifu) were randomly divided into two groups, the control group (6 mice) and the experimental group (6 mice). The dose of 10 mg/kg was intragastrically administered, and the control group was intragastrically administered with the same dose of vehicle. After 6 weeks of administration, the mice were sacrificed according to the guidelines of the animal ethics committee, and the weight of the mice, spleen and lymph nodes were weighed.

CD4⁺T细胞，

B细胞的比例；取左侧肾脏固定包埋切片，HE染色后显微镜下观察肾小球的损害程度，计算评分；ELISA检测血清中IFN-γ，IFN-β，抗dsDNA的水平(按各试剂盒的说明说进行操作，结果见图7～图17)。Tfh，Th1，抗体分泌B细胞，肾小球损害评分，IFN-γ，IFN-β和抗dsDNA都能加重疾病或与病情呈正相关，而Treg细胞，

CD4+T细胞，

B细胞与疾病呈负相关或对疾病有缓解作用。(CD4+CXCR5+PD-1+), Treg (CD4+CD25+FOXP3+), Th1 (CD4+IFN-γ+), antibody secreting B cells,

CD4 ⁺ T cells,

The proportion of B cells; the left kidney was fixed and embedded, and the damage degree of the glomerulus was observed under a microscope after HE staining, and the score was calculated; ELISA was used to detect the levels of IFN-γ, IFN-β, and anti-dsDNA in serum (according to each reagent). The description of the box says to operate, and the results are shown in Figure 7 to Figure 17). Tfh, Th1, antibody-secreting B cells, glomerular damage score, IFN-γ, IFN-β and anti-dsDNA all aggravated or were positively correlated with the disease, while Treg cells,

CD4+ T cells,

B cells are inversely associated with disease or have a disease-modifying effect.

The flow antibodies and reagents used for the flow analysis were purchased from BD Company, specifically:

CD4:Percp-cy5.5, IFN-γ:PE-CY7, CXCR5:PE-CY7, PD-1:PE, CD25BB515, FOXP3:APC, CD19:APC-CY7, B220:PE-CY7, IgD:FITC, CD138: APC, CD4: PE, CD44: APC-CY7, CD62L: PE-CY7; immobilized nuclear membrane breaking reagent, fixed envelope breaking reagent.

ELISA kits were purchased from Huamei Biological.

Example 7: The therapeutic effect of formula 1-A in synergy with glucocorticoid prednisolone (Pred) on spontaneous lupus mice

CD8+T(CD44-CD62L+CD8+)，TEM CD4+T(CD44+CD62L-CD4+)，TCM CD4+T(CD44+CD62L+CD4+)，

CD4+T(CD44-CD62L+CD4+)，抗体分泌细胞ASC(B220-IgD-CD138+)，记忆型B细胞(B220+CD138+IgD-)，

B细胞(B220+CD138-IgD+)；及脾脏中TCM CD4+T CD44+CD62L+CD4+)细胞，Treg(CD4+CD25+FOXP3+)的比例。TEM CD8+T细胞，TCM CD8+T细胞，TEMCD4+T细胞，TCM CD4+T细胞，抗体分泌细胞，记忆型B细胞能加重疾病或与病情呈正相关，而Treg细胞，

CD8+T细胞，

CD4+T细胞，

B细胞与疾病呈负相关或对疾病有缓解作用(结果见图18～图28)。The 12-week-old spontaneous lupus model mice (MRL/lpr, Beijing Speyford) were randomly divided into two groups: prednisolone group (6 mice) and formula 1-A combined with prednisolone group (6 mice), prednisolone group (6 mice). The group was given prednisolone suspension by gavage at a dose of 5 mg/kg per day, and the co-administration group was given prednisolone 5 mg/kg and formula 1-A 10 mg/kg by gavage per day. After 6 weeks of administration, the mice were sacrificed according to the guidelines of the animal ethics committee, and the weight of the mice, spleen and lymph nodes were weighed. CD44+CD62L-CD8+), TCM CD8+T (CD44+CD62L+CD8+),

CD8+T(CD44-CD62L+CD8+), TEM CD4+T(CD44+CD62L-CD4+), TCM CD4+T(CD44+CD62L+CD4+),

CD4+T (CD44-CD62L+CD4+), antibody secreting cells ASC (B220-IgD-CD138+), memory B cells (B220+CD138+IgD-),

The proportion of B cells (B220+CD138-IgD+); and TCM CD4+T CD44+CD62L+CD4+) cells, Treg (CD4+CD25+FOXP3+) in the spleen. TEM CD8+T cells, TCM CD8+T cells, TEMCD4+T cells, TCM CD4+T cells, antibody secreting cells, memory B cells can aggravate or positively correlate with the disease, while Treg cells,

CD8+ T cells,

CD4+ T cells,

B cells were negatively correlated with the disease or had a remission effect on the disease (the results are shown in Figure 18 to Figure 28 ).

The flow antibodies and reagents used for the flow analysis were purchased from BD Company, specifically:

CD4: PE, CD8: Percp-cy5.5, CD44: APC-CY7, CD62L: PE-CY7; CD19: APC-CY7, B220: PE-CY7, IgD: FITC, CD138: APC; CD4: Percp-cy5. 5. CD25: BB515, FOXP3: APC; immobilized nucleocapsid reagent, immobilized envelope rupturing reagent.

Claims (10)

1. the application of pyrrolopyridine compounds in the preparation of medicine for the treatment of lupus, wherein the pyrrolopyridine compounds are compounds with the structure of formula 1;

In formula 1, the R is a C1-C6 carboxylic acid and its salt, a C2-C10 ester, a C2-C10 amide, a sulfonic acid and its salt. 2. application as claimed in claim 1 is characterized in that, described pyrrolopyridine compound is the compound with formula 1-A structure:

3. The application according to claim 1, wherein the lupus is at least one of systemic lupus erythematosus, discoid lupus erythematosus and cutaneous lupus erythematosus. 4. The application according to claim 1, wherein the pyrrolopyridine compound is used to prepare at least one differentiation of inhibiting Tfh, Th1, and antibody-secreting cells; and/or inhibiting autoantibody dsDNA antibody, IFN - secretion of at least one of beta and IFN-gamma; and/or promotion of Tregs,

CD4 ⁺ T cells,

B cells differentiated from at least one drug for the treatment of lupus. 5. The application according to claim 1, wherein the pyrrolopyridine compound is used to prepare a medicine for kidney injury caused by lupus. 6. The application according to claim 1, wherein the pyrrolopyridine compound is used to prepare a medicine for lymphatic and/or spleen hyperplasia caused by lupus. 7. The application according to any one of claims 1 to 6, wherein the pyrrolopyridine compound and glucocorticoid are combined to prepare a medicine for treating lupus. 8. The application according to claim 1, wherein the pyrrolopyridine compound is combined with a pharmaceutically acceptable adjuvant to prepare any pharmaceutically acceptable dosage form; Preferably, the dosage form is an external preparation, an oral preparation or an injection preparation. 9. A pharmaceutical active composition for the treatment of lupus, characterized in that, comprising the compound of formula 1 and glucocorticoid described in the application of claim 1; Preferably, the dosage ratio of the compound of formula 1 and glucocorticoid is 1-3:1. 10. A medicine for the treatment of lupus, comprising the active composition of claim 9 in a pharmaceutically effective amount; Preferably, the medicament contains pharmaceutically acceptable excipients; Preferably, the medicament has a pharmaceutically acceptable dosage form, such as an injection preparation.

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