ETHYLENEDIAMINE COMPOUND AND USE THEREOF

Abstract

The present invention relates to the field of medicinal chemistry, and relates to an ethylenediamine compound represented by Formula A, pharmaceutically acceptable salts, stereoisomers, tautomers or isomer mixtures, hydrates thereof, solvates thereof, or prodrugs thereof, and use thereof in the treatment of tuberculosis.

##STR00001##

Claims

1. A compound represented by Formula A, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof, ##STR00100## wherein, R.sup.a is hydrogen, C.sub.1-6 alkyl, C.sub.3-14 cycloalkyl, 6- to 14-membered aryl, 3- to 14-membered heterocyclyl, ##STR00101## R.sup.b is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, C.sub.2-10 alkylacyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group, phenyl-substituted C.sub.1-6 alkyl or indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4; X is —CH.sub.2—, —CHR.sub.2— or —C(O)—, wherein R.sub.2 is C.sub.1-6 alkyl; R.sup.c is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-10 alkylacyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group; R.sup.d is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, C.sub.2-12 alkylacyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group, phenyl-substituted C.sub.1-10 alkyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted benzoyl, indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4.

2. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1, wherein the compound is represented by Formula I, ##STR00102## wherein, R.sub.1 is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, C.sub.2-10 alkylacyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group, phenyl-substituted C.sub.1-6 alkyl or indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4; X is —CH.sub.2—, —CHR.sub.2— or —C(O)—, wherein R.sub.2 is C.sub.1-6 alkyl; R.sub.3 is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, C.sub.2-10 alkylacyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group, phenyl-substituted C.sub.1-10 alkyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted benzoyl, indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4; R.sub.4 is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-10 alkylacyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group.

3. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2, wherein, R.sub.1 is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, C.sub.2-12 alkylacyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group; R.sub.3 is hydrogen, C.sub.1-10 alkyl, C.sub.3-14 cycloalkyl, C.sub.2-12 alkenyl or polyenyl, C.sub.2-12 alkenylacyl or polyenylacyl, C.sub.2-12 alkylacyl, substituted or unsubstituted 6- to 14-membered aryl, substituted or unsubstituted 3- to 14-membered heterocyclyl, substituted or unsubstituted 7- to 12-membered bridged-ring group.

4. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2 wherein, X is —CH.sub.2— or —C(O)—.

5. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2, wherein, R.sub.1 is hydrogen, C.sub.3-10 alkyl, C.sub.4-12 dienyl, phenyl-substituted C.sub.1-4 alkyl or indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4.

6. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according claim 2, wherein, R.sub.3 is hydrogen, C.sub.1-4 alkyl-substituted sulfonyl, C.sub.1-4 alkyl-phenyl-substituted sulfonyl, C.sub.4-12 dienylacyl, benzoyl substituted by one or more methoxy groups, phenyl-substituted C.sub.1-4 alkyl, C.sub.3-10 alkyl, C.sub.2-12 alkylacyl, C.sub.3-6 cycloalkyl, or indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4.

7. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2, wherein, R.sub.4 is hydrogen, C.sub.4-12 dienyl, C.sub.4-12 dienylacyl, C.sub.1-4 alkyl-substituted sulfonyl, C.sub.2-10 alkylacyl, C.sub.3-10 alkyl, C.sub.3-6 cycloalkyl, C.sub.1-4 alkyl-phenyl-substituted sulfonyl.

8. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1, wherein the compound is represented by Formula II, ##STR00103## wherein, R.sub.5 is hydrogen, C.sub.1-6 alkyl, C.sub.3-14 cycloalkyl, 6- to 14-membered aryl, 3- to 14-membered heterocyclyl; R.sub.6 is hydrogen, C.sub.1-6 alkyl, C.sub.3-14 cycloalkyl, 6- to 14-membered aryl, 3- to 14-membered heterocyclyl, ##STR00104## R.sub.7 is hydrogen or substituted or unsubstituted sulfonyl.

9. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2, wherein, R.sub.1 is hydrogen, or —CH.sub.2(CH.sub.2).sub.6CH.sub.3, ##STR00105## X is —CH.sub.2— or —C(O)—; R.sub.4 is hydrogen, or ##STR00106## R.sub.3 is hydrogen, —CH.sub.2(CH.sub.2).sub.4CH.sub.3, —CH.sub.2(CH.sub.2).sub.6CH.sub.3, ##STR00107##

10. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 8, wherein, R.sub.5 is hydrogen or C.sub.1-4 alkyl; R.sub.6 is hydrogen, C.sub.1-4 alkyl, ##STR00108## R.sub.7 is hydrogen, C.sub.1-4 alkyl-substituted sulfonyl or C.sub.1-4 alkyl-phenyl-substituted sulfonyl.

11. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 8, wherein, R.sub.5 is hydrogen; R.sub.6 is hydrogen, ##STR00109## R.sub.7 is hydrogen, ##STR00110##

12. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1, wherein the compound is selected from the group consisting of: ##STR00111## ##STR00112## ##STR00113## ##STR00114##

13. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof claim 1, wherein the pharmaceutically acceptable salt is an inorganic acid salt such as hydrochloride, sulfate, phosphate, or organic acid salt such as methanesulfonate, trifluoromethanesulfonate, acetate, trifluoroacetate, benzoate, of the compound.

14. A pharmaceutical composition, comprising the compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1, and optionally one or more pharmaceutically acceptable carriers or excipients.

15-16. (canceled)

17. A method for treating tuberculosis, comprising administering to a subject in need a therapeutically effective amount of at least one of the compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1.

18. A method for inhibiting the growth or reproduction of Mycobacterium tuberculosis (such as drug-resistant Mycobacterium tuberculosis) in vivo or in vitro, comprising contacting the Mycobacterium tuberculosis (such as drug-resistant Mycobacterium tuberculosis) with the compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1.

19. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 1, wherein the compound is characterized by one or more of the following items: (i) R.sup.a is hydrogen, ##STR00115## (ii) R.sup.b is hydrogen, ##STR00116## —CH.sub.2(CH.sub.2).sub.6CH.sub.3, or ##STR00117## X is —CH.sub.2— or —C(O)—; (iii) R.sup.c is hydrogen, ##STR00118## CH.sub.2(CH.sub.2).sub.6CH.sub.3, or —CH.sub.2(CH.sub.2).sub.4CH.sub.3; (iv) R.sup.d is hydrogen, ##STR00119## —CH.sub.2(CH.sub.2).sub.6CH.sub.3.

20. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2, wherein R.sub.1 is hydrogen, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, ##STR00120## benzyl, phenylethyl, phenyl-n-propyl, phenyl-n-butyl, indol-3-yl-C(O)—, indol-3-yl-CH.sub.2—C(O)—, indol-3-yl-(CH.sub.2).sub.2—C(O)—, indol-3-yl-(CH.sub.2).sub.3—C(O)— or indol-3-yl-(CH.sub.2).sub.4—C(O)—.

21. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 2, wherein the compound is characterized by one or more of the following items: (i) R.sub.3 is hydrogen, C.sub.1-3 alkyl-substituted sulfonyl, C.sub.1-2 alkyl-phenyl-substituted sulfonyl, C.sub.8-12 dienylacyl, benzoyl substituted by one or more methoxy groups, phenyl-substituted C.sub.1-3 alkyl, C.sub.6-10 alkyl, C.sub.6-12 alkylacyl, C.sub.3-4 cycloalkyl, or indol-3-yl-(CH.sub.2).sub.n—C(O)—, wherein n is an integer between 0 and 4, (ii) R.sub.4 is hydrogen, methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, p-toluenesulfonyl, p-ethylbenzenesulfonyl, p-n-propylbenzenesulfonyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, cyclopropyl, cyclobutyl, ##STR00121##

22. The compound, a pharmaceutically acceptable salt, a stereoisomer, a tautomer or an isomer mixture, a hydrate, a solvate or a prodrug thereof according to claim 10, wherein the compound is characterized by one or more of the following items: (i) R.sub.5 is hydrogen, methyl, ethyl, n-propyl or isopropyl; (ii) R.sub.6 is hydrogen, methyl, ethyl, n-propyl, isopropyl, ##STR00122## (iii) R.sub.7 is hydrogen, methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, p-toluenesulfonyl, p-ethylbenzenesulfonyl or p-n-propylbenzenesulfonyl.

Description

SPECIFIC MODELS FOR CARRYING OUT THE APPLICATION

[0242] The embodiments of the present application will be described in detail below in combination with examples, but those skilled in the art will understand that the following examples are only used to illustrate the present application and should not be regarded as limiting the scope of the present application. If specific conditions are not indicated in the examples, it shall be carried out in accordance with the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used without the manufacturer's indication are all conventional products that can be purchased commercially.

Example 1

Preparation of 3,7-dimethyl-oct-2,6-dienoic acid [2-(adamantan-2-yl-amino)ethyl]amide (XHJ-2-32)

1) Synthesis of N-adamantan-2-yl-ethane-1,2-diamine

[0243] ##STR00091##

[0244] 22 ml (0.32 mol) of Ethylenediamine was dissolved in 30 ml of anhydrous methanol, placed in an ice bath and stirred to dissolve until clear, 2.0 g (0.013 mol) of 2-adamantanone was added under the protection of nitrogen to obtain a transparent and clear solution, which was stirred and reacted for 2 h, then 0.75 g (0.019 mol) of NaBH.sub.4 was slowly added in batches, and then stirred overnight at room temperature. After the reaction was completed, 50 ml of H.sub.2O was added into the reaction flask, then the resulting mixture was extracted with dichloromethane (100 ml×2), the extracting solution was washed with saturated brine (50 ml×2), dried with anhydrous Na.sub.2SO.sub.4, and the solvent was evaporated under reduced pressure to obtain 2.4 g of a colorless oil with a yield of 93%. After standing, the oil was solidified to obtain a white solid. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 2.790˜2.820 (t, 2H), 2.714 (s, 1H), 2.650˜2.679 (t, 2H), 1.953˜1.983 (d, 2H), 1.839˜1.860 (d, 6H), 1.69˜11.713 (m, 4H), 1.480˜1.509 (d, 2H), 1.424 (s, 3H).

2) Synthesis of 3,7-dimethyl-oct-2,6-dienoic acid [2-(adamantan-2-yl-amino)ethyl]amide (XHJ-2-32)

[0245] ##STR00092##

[0246] 3,7-Dimethyl-oct-2,6-dienylacyl chloride was obtained through the acylation reaction of 3,7-dimethyl-oct-2,6-dienoic acid with oxalyl chloride, in which 1.5 times the amount of oxalyl chloride was added dropwise to 3,7-dimethyl-oct-2,6-dienoic acid, after the reaction was completed, the reaction liquid was distilled off and the obtained solid could be directly used in the next reaction.

[0247] 0.35 g of N-adamantan-2-yl-ethane-1,2-diamine was added into a reaction flask, 10 ml of dry THF was added to dissolve the N-adamantan-2-yl-ethane-1,2-diamine, 0.6 g of potassium carbonate was added, then 0.3 g of 3,7-dimethyl-oct-2,6-dienylacyl chloride (dissolved in 5 ml of dry THF) was added slowly and dropwise under ice bath. After the addition was completed, the reaction solution turned from colorless to reddish-brown, and reacted under stirring until the reaction of 3,7-dimethyl-oct-2,6-dienylacyl chloride was completed, 50 ml of H.sub.2O was added into the reaction flask, then the resulting mixture was extracted with dichloromethane (100 ml×2), the extracting solution was washed with saturated brine (50 ml×2), dried with anhydrous Na.sub.2SO.sub.4, concentrated under reduced pressure, separated and purified by a silica gel column (eluent was the mixture of dichloromethane, methanol and ammonia, wherein dichloromethane:methanol:ammonia (v/v/v)=500:10:1) to obtain 154 mg of a pale yellow oil with a yield of 28%. The oil was salified by treatment with hydrogen chloride in ethyl ether to obtain a white solid, mp 150˜164° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.645 (s, 1H), 5.074 (t, 1H), 3.572˜3.584 (t, 2H), 2.964˜2.996 (d, 3H), 2.110˜2.155 (m, 10H), 1.881 (t, 4H), 1.682˜1.734 (t, 7H), 1.568˜1.605 (d, 5H). LC-MS, m/z (%):

Example 2

Preparation of N-(adamantan-2-yl)-N′-ethylsulfonyl-ethane-1,2-diamine (XHJ-3-46)

[0248] ##STR00093##

[0249] The synthesis steps of Example 1 were repeated, except that ethylsulfonyl chloride was used as a raw material in place of 3,7-dimethyl-oct-2,6-dienylacyl chloride, and the target product XHJ-3-46 was obtained after separation and purification, yield: 28%, Mp 172-174° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 3.1˜73.19 (t, 2H), 3.04˜3.10 (m, 2H), 2.82˜2.85 (t, 2H), 2.72 (s, 1H), 1.80˜1.93 (m, 8H), 1.68˜1.72 (d, 2H), 1.51˜1.54 (d, 2H), 1.36˜1.40 (t, 3H). LC-MS, m/z (%): 287.3 (M.sup.+)

Example 3

Preparation of N-(adamantan-2-yl)-N′-octyl-ethane-1,2-diamine Dihydrochloride (XHJ-5-3)

[0250] The synthesis steps of Example 1 were repeated, except that 1-bromooctane was used as a raw material in place of 3,7-dimethyl-oct-2,6-dienylacyl chloride, petroleum ether was used in place of dichloromethane during the extraction in post-treatment, a colorless oil N-(adamantan-2-yl)-N′-octyl-ethane-1,2-diamine was obtained after separation and purification, which was salified by treatment with hydrogen chloride in ethyl ether to obtain the target product XHJ-5-3, yield: 15.2%, mp 224-226° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 3.4˜43.48 (m, 5H), 3.06˜3.10 (t, 2H), 2.24 (s, 2H), 2.10˜2.13 (d, 2H), 2.00˜2.03 (d, 2H), 1.83˜1.93 (m, 6H), 1.72˜1.78 (m, 4H), 1.32˜1.41 (m, 10H), 0.88˜0.92 (t, 3H). LC-MS, m/z (%):307.4 (M.sup.+)

Example 4

Preparation of N-(adamantan-2-yl)-N′-hexyl-ethane-1,2-diamine Dihydrochloride (XHJ-5-5)

[0251] The synthesis steps of Example 3 were repeated, except that 1-bromohexane was used as a raw material in place of 1-bromooctane, after separation and purification, the product was salified by treatment with hydrogen chloride in ethyl ether to obtain the target product XHJ-5-5, yield: 18.0%, mp 212-216° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 3.4˜33.48 (m, 5H), 3.05˜3.09 (t, 2H), 2.22 (s, 2H), 2.08˜2.11 (d, 2H), 1.99˜2.02 (d, 2H), 1.93 (s, 2H), 1.83˜1.87 (m, 4H), 1.71˜1.77 (m, 4H), 1.33˜1.43 (m, 6H), 0.90˜0.94 (t, 3H). LC-MS, m/z (%):279.4 (M.sup.+)

Example 5

Preparation of N-(adamantan-2-yl)-N′-cyclopropyl-ethane-1,2-diamine (XHJ-5-18)

[0252] The synthesis steps of Example 3 were repeated, except that bromocyclopropane was used as a raw material in place of 1-bromooctane, after separation and purification, the target product XHJ-5-18 was obtained, yield: 37.4%, mp197-200° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 2.9˜43.16 (m, 3H), 2.77˜2.78 (d, 2H), 2.12˜2.15 (d, 2H), 1.99 (s, 2H), 1.68˜1.83 (m, 8H), 1.43˜1.47 (d, 2H), 1.07˜1.09 (m, 1H), 0.54˜0.55 (d, 2H), 0.35˜0.38 (t, 2H). LC-MS, m/z (%):234.2 (M.sup.+)

Example 6

Preparation of N,N-(adamantan-2-yl)-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-3-45)

[0253] The synthesis steps of Example 3 were repeated, except that geranyl chloride was used as a raw material in place of 1-bromooctane, the separated product contained positive drug SQ109 and target product XHJ-3-45, mp102-104° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.30˜5.34 (t, 1H), 5.04˜5.07 (t, 1H), 3.48˜3.50 (d, 2H), 3.11 (s, 4H), 3.00 (s, 1H), 2.01˜2.09 (m, 8H), 1.89˜1.92 (t, 4H), 1.68˜1.77 (m, 10H), 1.60˜1.64 (m, 3H). LC-MS, m/z (%):331.6 (M.sup.+)

Example 7

Preparation of N-geranyl-N-(2-aminoethyl)ethylsulfonylamide Hydrochloride (XHJ-2-39)

[0254] ##STR00094##

[0255] 1.06 g of N-geranyl-ethane-1,2-diamine was added into a reaction flask, 20 ml of dry THF and 0.8 ml of triethylamine were added, then 0.73 g of ethylsulfonyl chloride (dissolved in 10 ml) was added dropwise, after the addition was completed, the reaction was performed under stirring at room temperature until the reaction was completed, then 50 ml of H.sub.2O was added into the reaction flask, the resulting mixture was extracted with ethyl acetate (50 ml×3), the extracting solution was washed with saturated brine (50 ml×2), dried overnight with anhydrous Na.sub.2SO.sub.4, filtered under reduced pressure, and evaporated to remove the solvent to obtain 1.5 g of a yellow oil, the yellow oil was separated and purified by a silica gel column (eluent was the mixture of dichloromethane, methanol and ammonia, wherein dichloromethane:methanol:ammonia (v/v/v)=500:10:1) to obtain 420 mg of a pale yellow oil with a yield of 26.9%, which was salified by treatment with hydrogen chloride in ethyl ether to obtain a white solid, mp103-106° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.189˜5.223 (t, 1H), 5.067˜5.098 (t, 1H), 3.217˜3.234 (d, 2H), 3.166˜3.193 (t, 2H), 3.031˜3.087 (m, 2H), 2.789˜2.817 (t, 2H), 2.062˜2.098 (m, 2H), 2.012˜2.032 (t, 2H), 1.605˜1.682 (t, 9H), 1.357˜1.394 (t, 5H). LC-MS, m/z (%):289.3 (M.sup.+). LC-MS, m/z (%):289.3 (M.sup.+)

Example 8

Preparation of N-geranyl-N-(2-aminoethyl)-p-toluenesulfonamide Hydrochloride (XHJ-2-45)

[0256] The synthesis steps of Example 7 were repeated, except that p-toluenesulfonyl chloride was used as a raw material in place of ethylsulfonyl chloride, a pale yellow oil N-geranyl-N-(2-aminoethyl)-p-toluenesulfonamide was obtained after separation and purification, which was salified by treatment with hydrogen chloride in ethyl ether to obtain the target product XHJ-2-45 with a yield of 18.2%, mp 134-137° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 7.661˜7.682 (d, 2H), 7.380˜7.399 (d, 2H), 5.058˜5.072 (t, 2H), 5.067˜5.098 (m, 1H), 2.983˜3.000 (d, 2H), 2.749˜2.782 (t, 2H), 2.461˜2.477 (t, 2H), 2.380 (s, 3H), 1.996˜2.031 (m, 2H), 1.906˜1.943 (t, 2H), 1.633 (s, 3H), 1.531˜1.558 (d, 6H). LC-MS, m/z (%):351.3 (M.sup.+)

Example 9

Preparation of N-(dipyridin-2-yl-methyl)-N′-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-5-14)

[0257] ##STR00095##

[0258] 1.0 g (5 mmol) of N-geranyl-ethane-1,2-diamine was added into a reaction flask, 20 ml of anhydrous methanol was added to dissolve the N-geranyl-ethane-1,2-diamine, 1.1 g (5.9 mmol) of di-2-pyridyl ketone was added, the resulting reaction solution was reacted under stirring and N.sub.2 protection at room temperature for 4 h, then 0.3 g (7.9 mmol) of NaBH.sub.4 was slowly added in batches, and then the reaction solution was stirred at room temperature overnight. After the reaction was completed, 100 ml of H.sub.2O was added into the reaction flask, the reaction solution was extracted with petroleum ether (100 ml×3), the organic layer was washed with saturated brine (50 ml×2), dried with anhydrous Na.sub.2SO.sub.4, distilled under reduced pressure to remove the solvent and obtain 2.03 g of a pale yellow oil, which was subjected to column chromatography (CH.sub.2Cl.sub.2:CH.sub.3OH:NH.sub.3.H.sub.2O (v/v/v)=500:10:1) to obtain 0.36 g of a pale yellow oil with a yield of 19.7%. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 8.56˜8.57 (d, 2H), 7.60˜7.62 (t, 2H), 7.37˜7.39 (d, 2H), 7.13˜7.16 (m, 2H), 5.28˜5.29 (t, 1H), 5.06˜5.08 (t, 2H), 3.24˜3.28 (t, 2H), 2.81˜2.84 (m, 4H), 1.99˜2.07 (m, 4H), 1.59˜1.72 (m, 9H), 1.633 (s, 3H), 1.531˜1.558 (d, 6H). LC-MS, m/z (%):365.3 (M.sup.+)

Example 10

Preparation of N-(phenyl-pyridin-3-yl-methyl)-N′-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-5-8)

[0259] The synthesis steps of Example 9 were repeated, except that 3-benzoylpyridine was used as a raw material in place of di-2-pyridyl ketone, and sodium cyanoborohydride was used in place of sodium borohydride, and the target compound XHJ-5-8 was obtained after separation and purification. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 8.51 (d, 1H), 8.29˜8.30 (m, 1H), 7.80˜7.82 (m, 1H), 7.2˜37.36 (m, 5H), 7.15˜7.17 (m, 1H), 5.13˜5.15 (t, 1H), 5.01˜5.03 (t, 1H), 3.11˜3.13 (d, 2H), 2.59˜2.65 (m, 4H), 1.94˜2.03 (m, 5H), 1.48˜1.60 (m, 10H), 1.19˜1.20 (d, 1H), 1.10˜1.13 (t, 1H). LC-MS, m/z (%):364.2 (M.sup.+)

Example 11

Preparation of N-adamantan-2-yl-N′,N′-ethylsulfonyl-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-3-1)

[0260] ##STR00096##

[0261] 0.9 g (2.72 mmol) of SQ109 (N-adamantan-2-yl-N′-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine) was dissolved in 15 ml of dry THF, 0.6 g of potassium carbonate was added, and 0.35 g (2.7 mmol) of ethylsulfonyl chloride (dissolved in 5 ml of THF) was added dropwise at room temperature. After the dropwise addition was completed, the temperature was raised and the reaction was performed under refluxing for 4 h. After the reaction was completed, 50 ml of H.sub.2O was added into the reaction flask, the resulting mixture was extracted with petroleum ether (100 ml×2), the organic layer was washed with saturated brine (50 ml×2), dried overnight with anhydrous Na.sub.2SO.sub.4, filtered under reduced pressure, and evaporated to remove the solvent to obtain 1.0 g of a yellow liquid, which was separated and purified by a silica gel column (the eluent was the mixture of dichloromethane, methanol and ammonia; wherein dichloromethane:methanol:ammonia (v/v/v)=1000:10:1) to obtain 240 mg of a pale yellow oil, with a yield of 30.5%, which was salified by treatment with hydrogen chloride in ethyl ether to obtain a white solid, mp103-106° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.202˜5.235 (t, 1H), 5.042˜5.059 (t, 1H), 3.907˜3.925 (d, 2H), 3.302˜3.334 (t, 2H), 3.011˜3.067 (m, 2H), 2.760˜2.791 (t, 2H), 2.705 (t, 1H), 2.045˜2.106 (m, 4H), 1.930˜1.961 (d, 2H), 1.833˜1.851 (t, 6H), 1.603˜1.706 (m, 10H), 1.472˜1.502 (d, 2H), 1.336˜1.373 (t, 3H). LC-MS, m/z (%):423.4 (M.sup.+)

Example 12

Preparation of N-adamantan-2-yl-N′,N′-p-toluenesulfonyl-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-3-3)

[0262] The synthesis steps of Example 11 were repeated, except that p-toluenesulfonyl chloride was used as a raw material in place of ethylsulfonyl chloride, a pale yellow oil was obtained after separation and purification, which was salified by treatment with hydrogen chloride in ethyl ether to obtain a white solid, namely the target compound XHJ-3-3, mp179-182° C. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 7.706˜7.727 (d, 2H), 7.266˜7.297 (t, 2H), 5.003˜5.010 (t, 2H), 3.843˜3.860 (d, 2H), 3.189˜3.222 (t, 2H), 2.734˜2.767 (t, 2H), 2.666 (s, 1H), 2.417 (s, 3H), 1.912˜2.025 (m, 6H), 1.762˜1.841 (m, 6H), 1.668˜1.698 (d, 7H), 1.575˜1.610 (d, 6H), 1.452˜1.483 (d, 2H). LC-MS, m/z (%):485.6 (M.sup.+)

Example 13

Preparation of N-adamantan-2-yl-N′,N′-(3,7-dimethyl-oct-2,6-dienyl)-(3,7-dimethyl-oct-2,6-dienoyl)-ethane-1,2-diamine (XHJ-3-11)

[0263] The synthesis steps of Example 11 were repeated, except that 3,7-dimethyl-oct-2,6-dienoyl chloride was used as a raw material in place of ethylsulfonyl chloride, and a pale yellow oil was obtained after separation and purification, which was the target compound XHJ-3-11. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.779 (s, 1H), 5.051˜5.064 (t, 3H), 3.959˜3.975 (d, 2H), 3.645˜3.655 (t, 2H), 3.093 (s, 2H), 1.899˜2.146 (t, 19H), 1.572˜1.745 (m, 21H), 1.202˜1.226 (d, 1H). LC-MS, m/z (%):481.6 (M+).

Example 14

Preparation of N-adamantan-2-yl-N′,N′-(3-indolyl-propionyl)-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-3-27)

[0264] ##STR00097##

[0265] 0.4 g of 3-indolyl-propionic acid, 0.35 g of HOBT (1-hydroxybenzotriazole), and 0.32 g of DMAP (dimethylaminopyridine) were dissolved in 15 ml of DMF, 2 ml of triethylamine was added, and 0.75 g of SQ109 was added, then the resulting mixture was heated to 50° C., and then 0.57 of EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) was added, the resulting reaction solution was reacted until it was detected from TLC that the reaction was completed. After the reaction was completed, the reaction system was allowed to stand and be cooled, 100 ml of H.sub.2O was added into the reaction flask, the reaction solution was extracted with ethyl acetate (100 ml×2), the organic layer was washed with saturated brine (50 ml×2), dried overnight with anhydrous Na.sub.2SO.sub.4, filtered under reduced pressure, and evaporated to remove the solvent and obtain 0.82 g of a red-brown oil, which was separated and purified by silica gel column (the eluent was the mixture of dichloromethane, methanol and ammonia, wherein dichloromethane:methanol:ammonia (v/v/v)=1000:10:1) to obtain 110 mg of a pale yellow oil, which was frozen and solidified to obtain a white solid, with a yield of 9.4%. .sup.1HNMR (400 MHz, DMSO-D6), δ: 8.58 (s, 1H), 7.57˜7.62 (t, 1H), 7.32˜7.34 (d, 1H), 7.14˜7.18 (t, 1H), 7.06˜7.10 (t, 1H), 6.98 (s, 1H), 5.07˜5.13 (t, 1H), 4.98˜5.05 (t, 1H), 4.05˜4.06 (d, 1H), 3.83˜3.85 (d, 2H), 3.45˜3.49 (t, 1H), 3.27˜3.30 (t, 1H), 3.11˜3.17 (m, 2H), 2.65˜2.81 (m, 5H), 1.57˜2.08 (m, 25H), 1.43˜1.49 (t, 2H). LC-MS, m/z (%):502.6 (M.sup.+)

Example 15

Preparation of N-adamantan-2-yl-N′,N′-(3,4,5-trimethoxybenzoyl)-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-3-29)

[0266] The synthesis steps of Example 14 were repeated, except that 3,4,5-trimethoxybenzoic acid was used as a raw material in place of 3-indolyl-propionic acid, a pale yellow oil was obtained after separation and purification, which was frozen and solidified to obtain a pale yellow solid, namely the target compound XHJ-3-29. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 6.65 (s, 2H), 5.27˜5.30 (t, 1H), 5.07 (s, 1H), 4.18 (s, 1H), 3.82˜3.93 (m, 10H), 3.60 (s, 2H), 2.91 (s, 1H), 2.74˜2.77 (d, 2H), 2.04˜2.08 (d, 5H), 1.52˜1.84 (m, 20H). LC-MS, m/z (%):525.1 (M.sup.+)

Example 16

Preparation of N-adamantan-2-yl-N′,N′-undecanoyl-(3,7-dimethyl-oct-2,6-dienyl)-ethane-1,2-diamine (XHJ-3-31)

[0267] The synthesis steps of Example 14 were repeated, except that undecanoic acid was used as a raw material in place of 3-indolyl-propionic acid, a pale yellow oil was obtained after separation and purification, which was the target compound XHJ-3-31. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.06˜5.10 (m, 2H), 4.02˜4.03 (d, 1H), 4.92˜4.94 (d, 1H), 3.44˜3.47 (t, 1H), 3.34˜3.37 (t, 1H), 3.72˜3.77 (m, 3H), 2.36˜2.40 (t, 1H), 2.27˜2.31 (t, 1H), 1.59˜2.08 (m, 30H), 1.25˜1.29 (m, 16H), 0.86˜0.89 (t, 3H). LC-MS, m/z (%):513.8 (M.sup.+)

Example 17

Preparation of N,N-adamantan-2-yl-(3-indolylformyl)-N′,N′-(3,7-dimethyl-oct-2,6-dienyl)-(3-indolylformyl)-ethane-1,2-diamine (XHJ-3-15)

[0268] ##STR00098##

[0269] 1.0 g (3.0 mmol) of SQ109 was dissolved in 20 ml of dry THF, 0.7 ml of triethylamine was added, and 1.1 g (6.1 mmol) of 3-indolylformyl chloride (dissolved in 5 ml of THF) was added dropwise under ice bath; after the addition was completed, the reaction system was heated and refluxed for 2 h. After the reaction was completed, 50 ml of H.sub.2O was added to the reaction flask, the resulting mixture was extracted with dichloromethane (100 ml×2), the organic layer was washed with saturated brine (50 ml×2), dried overnight with anhydrous Na.sub.2SO.sub.4, filtered under reduced pressure, and evaporated to remove the solvent to obtain a yellow solid, which was recrystallized in methanol to obtain 1.12 g of a white solid, with a yield of 59.9%. mp248-252° C. .sup.1HNMR (400 MHz, DMSO-D6), δ: 11.61 (s, 1H), 11.48 (s, 1H), 7.73 (s, 1H), 7.40˜7.62 (m, 5H), 7.03˜7.16 (m, 4H), 4.96˜4.99 (t, 1H), 4.85˜4.88 (t, 1H), 3.73 (s, 4H), 1.54˜1.92 (m, 21H), 1.16 (s, 3H). LC-MS, m/z (%):618.8 (M.sup.+).

Example 18

Preparation of N,N-adamantan-2-yl-benzyl-N′,N′-(3,7-dimethyl-oct-2,6-dienyl)-benzyl-ethane-1,2-diamine (XHJ-4-11)

[0270] The synthesis steps of Example 17 were repeated, except that benzyl bromide was used as a raw material in place of 3-indolylformyl chloride, and a pale yellow oil was obtained by separation and purification, which was frozen and solidified to obtain the target compound XHJ-4-11. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 7.22˜7.29 (m, 10H), 5.17˜5.20 (t, 1H), 5.06˜5.10 (t, 1H), 3.62 (s, 2H), 3.40 (s, 2H), 2.89˜3.91 (d, 2H), 2.63˜2.67 (t, 2H), 2.37˜2.41 (t, 2H), 1.94˜2.12 (m, 8H), 1.79˜1.81 (t, 4H), 1.66˜1.71 (t, 6H), 1.60˜1.63 (d, 5H), 1.51˜1.53 (t, 3H), 1.35˜1.38 (d, 2H). LC-MS, m/z (%):511.8 (M.sup.+)

Example 19

Preparation of N,N-adamantan-2-yl-octyl-N′,N′-(3,7-dimethyl-oct-2,6-dienyl)-octyl-ethane-1,2-diamine (XHJ-4-15)

[0271] The synthesis steps of Example 17 were repeated, except that 1-bromooctane was used as a raw material in place of 3-indolylformyl chloride, and a pale yellow oil was obtained by separation and purification, which was the target compound XHJ-4-15. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.24˜5.25 (t, 1H), 5.09˜5.10 (t, 1H), 3.05˜3.06 (d, 2H), 2.63 (s, 2H), 2.40˜2.52 (d, 2H), 1.95˜2.06 (m, 8H), 1.60˜1.80 (m, 16H), 1.27˜1.40 (m, 25H), 0.86˜0.90 (t, 6H). LC-MS, m/z (%):555.7 (M.sup.+)

Example 20

Preparation of N-adamantan-2-yl-2-(3,7-dimethyl-oct-2,6-dienylamino)-acetamide Hydrochloride (XHJ-2-37)

[0272] ##STR00099##

1) Synthesis of Geranylamine

[0273] 2.51 g (16.2 mmol) of geraniol, 2.86 g (19.4 mmol) of phthalimide, and 5.12 g (19.5 mmol) of triphenylphosphine were dissolved in 50 ml of dry THF, 3.35 g (19.2 mmol) of DEAD (diethyl azodicarboxylate) was added dropwise under ice bath. After the addition was completed, the resulting reaction system was stirred and reacted at room temperature until the reaction was completed, then evaporated to remove the solvent and obtain a white solid, which was extracted with petroleum ether, separated and purified by a silica gel column (the eluent was the mixture of petroleum ether and ethyl acetate, wherein petroleum ether:ethyl acetate (v/v)=10:1) to obtain 3.0 g of an intermediate 2-(3,7,-dimethyl-oct-2,6-dienyl)-isoindole-1,3-dione, with a yield of 65.4%. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 7.817˜7.848 (m, 2H), 7.699˜7.713 (m, 2H), 5.249˜5.282 (t, 1H), 5.024˜5.058 (t, 1H), 4.272˜4.289 (d, 2H), 1.990˜2.075 (m, 4H), 1.830 (s, 3H), 1.631 (s, 3H), 1.566 (s, 3H).

[0274] 3.0 g (10.6 mmol) of 2-(3,7,-dimethyl-oct-2,6-dienyl)-isoindole-1,3-dione was dissolved in 70 ml of absolute ethanol, and 5 ml (85 mmol) of hydrazine hydrate was added, the resulting mixture was heated to 70° C. and reacted for 3 h. After the reaction was completed, 70 ml of H.sub.2O was added into the reaction flask, then the reaction solution was adjusted with concentrated hydrochloric acid to a pH of 2, washed with 80 ml of ethyl ether. The aqueous phase was adjusted with 2M sodium hydroxide solution to a pH of 12, and extracted with anhydrous ethyl ether (100×2).sup.[48], the extracting solution was washed with saturated brine (50 ml×2), dried overnight with anhydrous Na.sub.2SO.sub.4, filtered under reduced pressure, and evaporated to remove the solvent to obtain 1.0 g of a yellow liquid with a yield of 61.7%. .sup.1HNMR (400 MHz, CDCl.sub.3), δ: 5.243˜5.274 (t, 1H), 5.082˜5.099 (t, 1H), 3.269˜3.286 (d, 2H), 1.978˜2.117 (m, 4H), 1.606˜1.685 (m, 8H), 1.442 (s, 3H).

2) Synthesis of N-adamantan-2-yl-2-(3,7-dimethyl-oct-2,6-dienylamino)-acetamide hydrochloride

[0275] 0.11 g (0.48 mmol) of N-adamantyl-acetyl chloride was dissolved in 20 ml of dry THF, 0.3 g of potassium carbonate was added, and 0.63 g (4.11 mmol) of geranylamine was added, the resulting mixture was heated and reacted under refluxing for 4 h. After the reaction was completed, 30 ml of H.sub.2O was added into the reaction flask, the reaction solution was extracted with dichloromethane (50 ml×2), the organic layer was washed with saturated brine (30 ml×2), dried overnight with anhydrous Na.sub.2SO.sub.4, filtered under reduced pressure, and evaporated to remove the solvent to obtain 0.55 g of a red-brown liquid, which was separated and purified by silica gel column (the eluent was the mixture of dichloromethane, methanol and ammonia, wherein dichloromethane:methanol:ammonia (v/v/v)=500:10:1) to obtain 42 mg of a pale yellow oil with a yield of 26.2%, which was salified by treatment with hydrogen chloride in ethyl ether to obtain a white solid. .sup.1HNMR (400 MHz, DMSO-D6), δ: 7.825˜7.845 (t, 1H), 5.208˜5.243 (t, 1H), 5.064˜5.096 (t, 1H), 4.061˜4.082 (d, 1H), 3.245˜3.391 (m, 3H), 1.997˜2.096 (m, 4H), 1.816˜1.906 (t, 10H), 1.750 (s, 2H), 1.593˜1.684 (m, 12H). LC-MS, m/z (%):345.3 (M.sup.+)

Example 21

In Vitro Anti-Tuberculosis Activity Test of the Compound of the Present Invention

[0276] The Microplate Alamar Blue Assay (MABA) method was used to determine the minimum inhibitory concentration (MIC) of the compound against the standard strain H.sub.37Rv of Mycobacterium tuberculosis (see Collins L A, Franzblau S G., Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrobial Agents Chemother, 1997, 1004-1009). The compounds to be tested were the compounds prepared in the Examples 1 to 20 of the present application, and the positive control compounds rifampin (RFP) and isoniazid (INH).

[0277] Experimental method: sterile 96-well plates (Falcon3072; Becton Dickinson, Lincoln Park, N.J.) were used, the compound to be tested was dissolved in dimethyl sulfoxide to prepare an initial solution with a concentration of 5 mg/ml, 199 μl of 7H9 liquid culture medium (Difco) and 1 μl of the initial solution of the compound was added to the highest concentration well and mixed well; the concentrations of the remaining wells were gradiently reduced twice by dilution, in which the volume of the solution of the compound to be tested was 200 μl and the final concentrations of the test compound in each well were: 25, 12.5, 6.25, 3.125, 1.56, 0.78, 0.39, 0.2, 0.1, 0.05, 0.025, 0.0125 μg/ml. Mycobacterium tuberculosis H.sub.37Rv (preserved strain of Beijing Tuberculosis and Thoracic Tumor Research Institute) was cultured for 2 to 3 weeks to prepare a bacterial suspension, inoculated into 7H9 liquid medium containing 0.05% Tween 80 and 10% ADC (albumin-dextrose-catalase, ADC), subjected to static culture at 37° C. for 1 to 2 weeks; when growing to a turbidity of McFarland 1 (equivalent to 10.sup.7 CFU/ml), the dilution was performed by a volume ratio of 1:20, then 100 μl of bacterial suspension was taken and added to each well. The final concentration of bacterial solution in each well was about 10.sup.6 CFU/ml. For each plate, two growth control wells without antibiotics were set, the 96-well plates were incubated at 37° C. After 7 days, a mixture solution of 20 μl of 10×Alamar Blue (Setotec) and 50 μl of 5% Tween80 was added to the growth control wells, then incubation was performed at 37° C. for 24 hours. If the color changed from blue to pink, the above-mentioned amount of the mixture solution of Alamar Blue and Tween80 was added into the wells of each drug to be tested, and incubated at 37° C. for 24 hours, the color of each well was recorded, the fluorescence values of 530 nm and 590 nm was measured by a microplate reader, and MIC values were calculated. The results are shown in Table 1. MIC was defined as the lowest drug concentration that prevented the color change (from blue to pink).

TABLE-US-00002 TABLE 1 Results of minimum inhibitory concentration (MIC) of Mycobacterium tuberculosis standard strain H37Rv determined by Microplate Alamar Blue Assay (MABA) method Sample No. MIC (μg/ml) XHJ-2-37 <0.5 XHJ-2-32 7.754 XHJ-2-39 >32 XHJ-2-45 31.459 XHJ-3-1 6.961 XHJ-3-3 3.757 XHJ-3-11 >32 XHJ-3-15 >32 XHJ-3-27 1.963 XHJ-3-29 3.91 XHJ-3-31 2.844 XHJ-3-45 <0.5 XHJ-3-46 >32 XHJ-4-11 30.822 XHJ-4-15 >32 XHJ-5-3 0.986 XHJ-5-5 0.982 XHJ-5-8 16 XHJ-5-14 4 XHJ-5-18 >32 INH 0.05 RFP 0.048

[0278] It can be seen from the experimental data in Table 1 that the compounds of the present invention had good in vitro anti-tuberculosis activity. Under the premise of retaining the basic skeleton structure of SQ109, among the modifications of its structure, the linear amides showed good activity, and both mono-substituted amides and sulfonamides at the N position showed good activity, and such examples included XHJ-2-37, XHJ-2-32, XHJ-3-1, XHJ-3-3, XHJ-3-27, XHJ-3-29, XHJ-3-31. Among the isopentenyl substitution derivatives, when the isopentenyl was replaced with a linear alkyl, better activity was observed, and such examples included XHJ-5-3 and XHJ-5-5. Among the adamantyl substitution derivatives, XHJ-5-8 and XHJ-5-14 showed better activity, and the skeleton rearrangement derivative XHJ-3-45 had better activity.