TW593320B - Tetrahydro imidazonaphthyridine compounds - Google Patents

Abstract

Compounds of the formula I, in which the substituents have the meanings mentioned in the description, are suitable for the prevention and treatment of gastrointestinal diseases. A compound of the formula I, in which R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, R3 is hydrogen or halogen, one of the substituents R4a and R4b is hydrogen and the other is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or 1-4C-alkylcarbonyloxy, or in which R4a and R4b together are O (oxygen), one of the substituents R5a and R5b is hydrogen and the other is hydrogen, hydroxyl, 1-4C-alkoxy or 1-4C-alkylcarbonyloxy, or in which one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand is in each case hydrogen, and the other substituents in each case together form a methylenedioxy radical (-O-CH2-O-) or an ethylenedioxy radical (-O-CH2-CH2-O), where R4a, R4b, R5a and R5b are not simultaneously hydrogen, R6 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy or trifluoromethyl and R7 is hydrogen, halogen, 1-4C-alkyI or 1-4C-alkoxy, or its salts.

Description

593320 A7 B7 Patent Application No. 087104064 Chinese Specification Replacement Page (December 1992) V. Description of the Invention (1) Scope of Application of the Invention The present invention relates to novel compounds which are used in the pharmaceutical industry to prepare pharmaceuticals Active compound. Background of the U.S. Patent No. 4,468,400 describes a tricyclic imidazo [1,2-a] pyridine having different ring systems fused to the imidazopyridine parent structure, which should be suitable for the treatment of digestive cancer. DESCRIPTION OF THE INVENTION The present invention describes compounds of formula L and their salts

Where R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, R3 is hydrogen or halogen, and one of the substituents R4a and R4b is hydrogen and the other is hydrogen , Hydroxy, 1-4C-alkoxy, 1-4C-alkoxy-1-4C_alkoxy or 1-4C-alkylcarbonyloxy, or R4a and R4b together are 0 (oxy), the substituent One of R5a and R5b is hydrogen and the other is hydrogen, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy or 1-4C-alkylcarbonyloxy Paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 593320 92. 4. 17 A7 _____B7 V. Description of the invention (2) group, or R5a and R5b together are 0 (oxygen), or one of the substituents One of R4a and R4b and one of the substituents R5a and R5b on the other hand is hydrogen, and the other substituents together form a methylenedioxy group (CH2-O-) or ethylenedioxy (-O -CH2-CH2-O-), where R4a, R4b, R5a and R5b will not be hydrogen at the same time, R6 is hydrogen, halo, 1-4C-alkyl, 1-4C-alkoxy, i_4C-alkoxycarbonyl Amine, l-4C-: feoxy-l-4C-feoxycarbonylamino or trifluoromethyl and R7 are hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy. 1-4C-alkyl represents a straight or branched chain alkyl group containing 1 to 4 carbon atoms. Examples which may be mentioned are butyl, isobutyl, second butyl, third butyl, propyl, isopropyl, ethyl and methyl. Methyl is preferred. The hydroxy 1-4C-alkyl group represents the above-mentioned 1-4C-alkyl group, which may be substituted by a group. Known examples are hydroxymethyl, 2-hydroxyethyl and 3-hydroxypropyl. Preferred is hydroxymethyl. The autogen in the present invention is bromine, chlorine or fluorine. 1-4C-alkoxy represents a group of a linear or branched alkyl group containing 1 to 4 carbon atoms in addition to the oxygen atom. Examples which may be mentioned are butoxy, isobutoxy, second butoxy, third butoxy, propoxy, isopropoxy, and preferably ethoxy and methoxy. 1-4C-alkoxy-1-4C-alkoxy represents one of the above-mentioned 1-4C-alkoxy groups substituted with more 1-4C-alkoxy groups. Examples that can be mentioned are 2- (methoxy) ethoxy (CH3-0-CH2-CH2-〇) and 2- (ethoxy) ethoxy (CH3-CH2-0-CH2-CH2-0- ). -5- This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) 593320 oCi. 4. ί Α7 Β7 1-4C-alkoxycarbonyloxy represents the carbonyl group and the above l-4C- and alkyl groups. One of them is bound. A reproducible example is ethoxyl (CH3C0-0-). The 1-4C-alkoxycarbonylamino group represents an amine group substituted with the aforementioned 1-4C-alkoxycarbonyl group. Illustrative examples are ethoxycarbonylamino and methoxycarbonylamino. 1-4 C -membered oxy-1-4 C · Phenyloxy represents a bond to one of the above ί and 4 C «Phenoxy-1-4C-alkyloxy. Illustrative examples are 2- (methoxy) ethoxycarbonyl (CH3-0-CH2CH2-O-C0-) and 2- (ethoxy) ethoxycarbonyl (CH3CH2-O-CH2CH2-0-C0_). The 1-4C-alkoxy-1-4C-alkoxycarbonylamino group represents an amine group substituted with one of the aforementioned 1-4C-alkoxy-1-4C-alkoxycarbonyl groups. Illustrative examples are 2- (methoxy) ethoxycarbonylamino and 2- (ethoxy) ethoxycarbonylamino. Suitable salts of the compounds of the formula I depend on the substituents, especially all acid addition salts. Special mention is made of tolerable salts of inorganic and organic acids that are customarily used in the pharmaceutical industry. Suitable are those containing, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzyl) benzoic acid, butyric acid, and sulfonic acid. Salicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, chlorobromosilicic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid, or hydroxy_2_arsinic acid The water-soluble and non-water-soluble acid addition salts, in which the acid end used in the preparation of the salt is not related to the mono- or poly-acid and the end depends on what kind of salt is required, and so on. The proportion of the amount or different ways. When the product is processed, medically intolerable salts begin to be obtained, for example, when a compound is prepared on an industrial scale in accordance with the present invention, it can be converted into a pharmaceutically tolerable salt by those skilled in the art.

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-6- A7 B7 Patent Application No. 087104064 Patent Replacement Page of Chinese Specification (December 1992) 5. Description of the Invention (4) The compound of formula I has 3 palm centers. The present invention is related to all eight imaginable mirror isomers mixed with one another in any desired ratio, including pure mirror isomers, and this is a preferred subject of the present invention. If methylenedioxy or ethylenedioxy is formed by one of the substituents R4a and R4b on the one hand and by one of the substituents R5a and R5b on the other hand, the methylenedioxy group formed by this disubstituted group Or ethylenedioxy is preferably cis to each other. The compounds highlighted are compounds of formula I and their salts, where R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, R3 is hydrogen, and the substituents R4a and R4b One is hydrogen and the other is hydrogen, hydroxy or 1-4C-alkoxy, or where R4a and R4b are together 0 (oxygen), one of the substituents R5a and R5b is hydrogen and the other is hydrogen, hydroxy or 1-4C-alkoxy, or where R5a and R5b are collectively 0 (oxygen), where R4a, R4b, R5a and R5b are not both hydrogen, R6 is hydrogen, halogen or trifluoromethyl and R7 is hydrogen or halogen. Emphasized embodiments of the invention are compounds of formula I # and salts thereof

This paper size applies to China National Standard (CNS) A4 specifications (210X 297 mm) 593320 92 · 4 Α7 Β7 5. Description of the invention (5) where R1 is 1-4C-alkyl and R2 is 1-4C-alkyl or Hydroxy-1-4C-alkyl, R3 is hydrogen, one of the substituents R4a and R4b is hydrogen and the other is hydrogen, mesityl or 1-4C-alkoxy, one of the substituents R5a and R5b Is hydrogen and the other is hydrogen, hydroxy or 1-4C-alkoxy, wherein R4a, R4b, R5a and R5b are not both hydrogen, R6 is hydrogen, halogen or trifluoromethyl and R7 is hydrogen or halogen. Particularly emphasized embodiments of the present invention are compounds of formula Γ and salts thereof, wherein R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxyfluorenyl, R3 is hydrogen, R4a is hydrogen, and R4b is hydroxyl Or 1-4C-alkoxy, R5a is hydrogen, hydroxy or 1-4C-alkoxy, R5b is hydrogen, R6 is hydrogen, halogen or trifluoromethyl and R7 is hydrogen or halogen. The preferred embodiment of the present invention is a compound of formula Γ and a salt thereof, in which R1 is 1-4C-alkyl, -8- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 593320 4- i 1 A7 B7 V. Description of the invention (6) R2 is 1-4C-alkyl, R3 is hydrogen, R4a is hydrogen, 1141) is #i group, R5a is warp group, R5b is hydrogen, R6 is hydrogen, halogen or Trifluoromethyl and R7 is hydrogen or halogen. By the general formula Γ, the following exemplary compounds according to the present invention and the salts of the compounds described in Table 1 can be really proposed through the meaning of the substituents and the positions of the substituents R3, R6, and R7 shown in Table 1 below. -9- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X 297 mm) 593320 Patent Application No. 087104064 Chinese Specification Replacement Page (December 1992) A? B7 V. Description of Invention (7) Table 1

R1 R2 R3 R4a R4b R5a R5b RB y R7 CHa CHa H 0 HH Ή H CHS CHa HH OH HHHH CKa CHa H 0 HH 2-C1 H CHa CH3 HH OH HH 2-Cl · H CH3 ch3 H 0 HH 2-CI 6 -CI CHa Chfc HH OH HH 2-CJ 6-CI ch3 CH3 HH OCHn H t HHH ch3 ch3 HH OC2H5 H .HHA CH3 ch3, H 0 HH 2-CF5 H CH3 ch3 • H OH HH 2-CF3 H ch3 Ή 〇 OH HHH ch3 Cht HH OH · OH HHH CH, CHa 6-Br ^ 〇HHHH ch3 ch3 6-Br H OH HHHH ch3 CHa 6-C) H OH HHH • 丨 ch3 ch3 6-Cl H OH OH HHH ch3 ch3 HH OH OH H 2-CI H ch3 Chb HH OH OH H 2-CI SC! Chb CHa HH OH OH H 4-a H CH3 ch3 HH OH OH H 2-CF3 H CHi CHa HH. OH OH H 2-NHCOOCH3v e- CHs CHo ch3 HH OH OH H ^ -NHCOOC ^ KrOCH ^ 6-CHa ～ 1 H 0 HHHHHHH OH HHH h -10- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 593320 A7 B7 5 Description of the invention (8) Continued Table 1 R1 RZ R3 R4a R4b R5a R5b R6 R7 Chh ch2oh H 〇HHH ch3 ch2 0h HH OH .HH 2-Ci 'H CH ^ ch2oh H. 〇H,; H 2-C ( 5-CI Ch3 ChbOH HH OH H 、 H 2-Ci S-Ci ch3 c h2〇h HH 〇CH ^ H -HHH CHo CH ^ OH HH OC ^ Hs • HHHH ch3 ch2〇h H 0 HH 2-CF3 H CHy ch3oh HH OH HH 2-CF3 H CHi ch2oh H OHHH CHA CHi 〇HHH OH OH H〆HH ch3 CH: 〇H 5-Br 0 H.. HHH CH] CH2〇H 6-Br H OH HHHH ch3 ch2oh 5-C! H OH HH. H 'H CH) ch2oh θ-CI H OH • OH HHH CK, ch ^ oh HH OH OH H 1 2-Ci H ch3 CH ^ OH HH OH OH \ H 2C \ 5-CI CH: CHz〇HH • H OH OH HM ch3 • CHz〇HHH OH OH H 2-CF3 is called ch3 ch2〇h. H 1 H OH OH H 2-NHCO-OCH3 6-CH3 CH] ch2oh HH OH OH H ^ NHCO-OC ^ KrOC ^ The compounds according to the present invention can therefore be described by the following examples Alternatively, they can be prepared analogously starting with the appropriate starting compound. The starting compounds are known or can be prepared similar to known compounds. Depending on the substitutions (R4a / R4b or R5a / R5b) at positions 7 and 8, the compounds according to the invention can be prepared from known or prepared N-protected 8-amine imidazo [l, 2-a ] Pyridine (see, for example, European Patent EP-A-0 299 470 or Kaminski et al., J. Med. Chem. 1985, 28, 876-892) began to be prepared according to the following reaction scheme: -11-This Paper size applies to China National Standard (CNS) A4 specification (210X 297 mm) 2.593320 A7 B7 V. Description of invention (9) Figure 1:

NHPiv

-R1

R6

• N-protected by deprotonation of R1 at the 7th position (Piv in the figure and the following figures represents a general protecting group, preferably trimethylacetamido), 8-aminoimidazo [1,2- a] Say pyridine reacts with cinnamaldehyde. The addition product begins to be oxidized (for example, with manganese dioxide) and then epoxidized (for example, with hydrogen peroxide). Under strong base and then strong acid conditions, the protecting group is removed to cause ring closure. If necessary, the reduction of the ketone group can be followed by, for example, the use of borohydride. -12 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 593320 A7 B7

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593320 A7 B7 V. Description of the invention (11) Figure 3 ··

R

R1 〇 R7

R6 ^) R7 The figure above represents an example of mirror-selection manufacturing. As in Figure 1, the same N-protected imidazo [l, 2-a] pyridine is used as the starting material. The deprotonated imidazole [1,2-a] pyridine reacts with pure mirror dipyridinane, which initially produces condensation products. Under strong acid conditions, the protecting group is removed and cyclized. The ketone group was also reduced with sodium borohydride (see also Figure 1) to produce a final product showing over 90% mirror purity. -14-This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 593320 A7 B7 5. Description of the invention (12) Figure 4:

Starting from the above 8-aminoimidazo [1,2-A] pyridine, via alkylation using an alkylating agent to carry a substituent (eg R8a = hydrogen, R8b = halogen) or via an appropriately substituted ketone [R8a And R8b together are 0 (oxygen)] reductive alkylation with the aid of a reducing agent such as sodium cyanoborohydride, and under the catalysis of a base or an acid, it is a ring closure, producing a cyclic ketone, which is in a suitable chemistry Transformation can be converted into the desired target compound (see Figures 1 and 2 for example). If necessary, Co2R can also be reduced before cyclization (aldehyde stage), thus forming a substituted 7-hydroxy derivative which can be converted to the appropriate target compound via oxidation / reduction. -15- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 593320 A7 B7

593320

Description of the invention In the different methods listed in Figure 4 above, R5a * R8a = H (hydrogen) and R5b and R8b together = 0 (oxygen), 8-aminoimidazopyridine starts to react with the epoxy cinnamate derivative to choose The epoxide is turned on (A), and the product (C) is cyclized under non-protonic base conditions. The other is to hydrolyze the mixture to cyclize the free carboxylic acid derivative (D) under acidic conditions. In these two methods, the keto group can be reduced to an alcohol (G) as shown in Fig. 1, for example, using sodium borohydride. If 8-aminoimidazo [i, 2_a] pyridine reacts with the protected epoxy cinnamaldehyde derivative (B), the product can be closed-looped (F) under acidic conditions after removing the acetal protecting group. . Reduction of esters to aldehydes is also possible (£) with acid cyclization. Both the reduction of the ketone and the ring closure of the aldehyde stage can be mirror-selectively performed, so that when the corresponding mirror-pure epoxy derivative is used, it is possible to selectively manufacture the mirror. -17- This paper is again applicable to the national standard (CNS) A4 size of the towel (210 X 297 male D ------------ 593320 ¥) 2. 4. IT B7

593320

A7

And then activated. Because it is P + ± H i *, Aberdeen < products and 8-aminoimidazo [i, 2-a] pyridine

• The reaction ’is performed for 5 more cycles 1 L ·. ± L as in alkaline conditions. If necessary, perform steps similar to Figure 3 (reduction). Figure 7:

8-haloimidazo [1,2-a] pyridine (X = halogen) is reacted with a suitably substituted / 3-phenyl- / 3-amino acid under heavy metal catalysis (preferably Pd) to produce The substituted amine is cyclized according to FIG. 4. An aldehyde group can also be used in place of the COOR group (as mentioned in Figure 4), if necessary, in the form of an acetal. γ is europium (hydrogen) or a protecting group, which can be removed after the ring is closed. -19- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (21〇297297) 593320 A7 B7 V. Description of the invention (17 Figure 8: R3

N 、 R1 〇 Ά2 R 丨

COOR R3

N〆, R2

3H ROOC〆 R R6-j 0 R7 〇 < X HCT R3- ό • R1 starts from imidazole, which is known or can be prepared in a similar way, and the closed loop is easy to form the femine structure (equilibrium). After the double bond is added by oxidation, the reduction of the keto group to an alcohol can proceed as shown in FIG. In the figure above, "nR" is 1-4C-alkyl. The ester group (-COOR or -C02R) mentioned in the example may be replaced by another leaving group or the OR group or another group may be used instead of the ester. In the compound of formula I, R4a / R4b or R5a / R5b is 1-4C-alkoxy, 1-4C-alkane 20- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 593320. Description of the invention (18) The oxy-1-4C-alkoxy or alkylcarbonyloxy group can be derived by methods well known to the examples (such as calcination or enzymes. This technique R4a / R4 «R5a / R5b is Corresponding compound of ㈣, from which a substance according to the present invention is separated and purified by a known method, the solvent is distilled off, and recrystallized from a suitable solvent, a column chromatography method in which a proper carrier is contained in Shinji, a general purification method '&Quot; or, for example, dissolve the free compound in a suitable solvent, such as a chlorinated hydrocarbon, or chloroform, or contain the desired acid or continue and add the required acid: ethanol' isopropanol) ' Salt is obtained. After 遽, and then cooler ::; Luo agent precipitation addition salt or evaporation to obtain salt. The resulting ^ is converted into free compounds, and vice versa can be converted into salt. Non-tolerant salts can be converted into pharmaceutical tolerable salts. Pure mirror image isomers, 较 is the comparative of the present invention._ Lamp isomers can be obtained by familiarizing with the methods familiar to this artisan, for example, mirror image selection (For example, see Figure 3), the chromatographic conversion method on the separation column of the opposite palm is used to generate derivatives and then separate non-mirror isomers and remove the opposite palm auxiliary group by the opposite adjuvant. Palmitic acid forms a salt, and then separates the salt and releases the desired compound from the salt, or crystallizes it through a suitable solvent (fractionation). The present invention is more related to the method and intermediates described in the above figures', especially the figure 丨 small ^ The process of the small coffee can be separated before the cyclization step. The following examples are used to further illustrate the present invention without limiting it. Similarly, more compounds not specifically described in the preparation method can be similar or used here. It is prepared in the same way as the general operating techniques familiar to the technology. -21-This paper size is a standard of CNS A4 (210X297 mm 593320)

”Endogenous substance 1 * Phenyl-imidazolopyridine-7 · m 30 ml of dioxin, containing 4.5 grams of 2,3-dimethyl ^ (3-phenyl small oxygen I propenyl) _8 -Trimethylacetamido-amino imidazolium [1,2-a] pyridine solution was treated with 20 ml of concentrated hydrochloric acid, refluxed for 8 hours, and adjusted to pH 7.0 with 2N sodium hydroxide under cooling and 50 亳 L of ethyl acetate was extracted twice. The combined extracts were washed with water and dried over potassium carbonate and concentrated to dryness in Celite. The residual viscous oil was chromatographed on a silica gel using ethyl acetate / petroleum ether (1: 1) as the eluent. 26 g can be obtained with a melting point of 138_40 ° (: the title compound. 2 · Lactyl) -2,3-dibl "1.71 pyrimidine-7 · ketone, similar to Example 1 'can be 7- [3- (2 -Chlorophenyl M • oxy-2-propanyl] 8-trimethylethylamidoamino-2,3-dimethylimidazon, 2_a] pyridine yields 73%, melting point 80-2 ° The title compound of C. 9- (2,6--monochatyl) -2,3--methyl-7,8.9,10-tetraodorant hin.71 pyrimidin-7-one is similar to Example 1, and can be obtained by 7 -[3- (2,6-dichlorophenylbutoxy-2-propenyl] 8-trimethylacetamido-2,3-dimethylimidazo [i, 2-a ] ^ — 41% yield of the title compound with a melting point of 248-9 ° C. 4 · 9- (2-tris-methyl i + radical) -2, -3 di-,-$ radical-7 · 8Ή_ tetra- < Gas ^ "1,2-111" 1,71_Yodo-7-one is similar to Example 1 and can be determined by 7- [3- (2-trifluoromethylphenyl)-; twenty two-

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k fluorenyl] -8-trimethylethylfluorenylamino-2,3-dimethylimidazo [^ "pyridinium yields 41% yield, melting point 184-5 ° Ct. The title compound. 5'yl-2, 3 :: methyl-tetrahydroimidazo hl "1,71 pyrimidine at room temperature, containing 1 g of 2,2-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazole in 15 ml of methanol The suspension of [nh] [1,7] pyridinone was treated with a small amount of 450 mg of sodium borohydride. The resulting yellowish solution was stirred for 2 hours and then diluted with ice water. The deposited precipitate was decanted by suction filtration. After washing with some cold 2-propanol, the title compound having a melting point of 2〇_i2 < ti80000 g was obtained. Π, 2-ίι1Π · 71-4 A pyridine was similar to Example 5 and was obtained from 9- (2-chlorobenzene Base) _2,3_diamidino_7,8,9 ι〇_ Tetrachlorotantrol [l, 2-h] [1,7], naphthalene_7_one yielded 73% yield, 'solvent 150 -2 ° C title compound.. Me- 二四 氤 味 ^ and fl.2-hl 「1,71-Meridine is similar to Example 5 and can be obtained from 9- (2,6_dichlorobenzyl ^, dimethyl dimethylbenzene • 7,8,9,10-tetrahydroimidazopyridinone 1 ketone yields the title compound with a yield of 72 ^ and a melting point of 155-7 ° C. 8. 1_ (2-trifluoromethyl i benzene ^ 1〇_ tetra New 1 Zolo fl, 2-hl, l, 71- 崦 Wa Example 5: 72% can be obtained from 9- (2-trifluoromethylphenyl) _2,3_dimethyl · 7,8,9,10-tetrahydroimido [mnu] peak pyridin_7_one " Production -23-

593320 Replacement page of Chinese manual for patent applicant No. 0871〇4〇64 (December 1992) a? '! ------------- -_____ B7 V. Description of the invention (21 ^ "-I 'The title compound has a melting point of 145-7 ° C. 9 · Phenyl-7,8,9,10-tetrahydrogen 1 and n h_iru7i ^ 5 mg of absolute ethanol containing 500 mg 2, 3-dimethyl_7_ (2,3_epoxy-1-oxy-3-phenylpropyl) trimethylacetamido-aminoimido [1'2-a] p The solution was treated with violent stirring with 96 mg of hydroxide. 1: After 2 hours of warm stirring, it was cooled to 0 in an ice bath. The deposited crystals were filtered off by suction filtration and washed with some cold ethanol. Drying under high vacuum After the reaction, the solid was added to 5 ml of 90% strength sulfuric acid at room temperature and stirred for 1 hour. Then it was neutralized with 40% strength cold sodium hydroxide solution under ice-cold conditions. The precipitate precipitated during the operation The material was filtered off in vacuo and dried. 145 mg of the title compound with a melting point of 232-4 ° C were obtained. 1〇 工 』-二 转 Ju 基 -9- 茉 某 _7 · 8 · 9 · 10-Tetrapyrene Furo 4-Lio, 2-hl [l, 71 700 gram 8-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10 · tetrahydroimid And n, 2-h] [l, 7] pyrimidin-7-one was suspended in 15 ml of methanol and stirred at room temperature with a portion of 200 mg of sodium borohydride. After stirring for 2 hours, the mixture was poured Into 100 ml of ice-cold water. The deposited precipitate was filtered off, dried briefly under vacuum and recrystallized from some 2-propanol. 500 mg of the title compound having a melting point of 150-2 ° C was obtained. ， 9R) -2,3-dimethyl | Nandong Benzene_7,8,91〇_tetra-imidazolium Il, 2-2-hl "1.71 meridin-7-one will 10.8 g (24 mmol) Ear) 2,3-dimethyl-7-[(2S, 3R) -2,3-0-isopropylidene-3-phenylpropan-1-yl-1yl] trimethylacetamidoimidazole -24- This paper is suitable for National Standards (CNS) A4 size (210X29? Public love) of the country of wealth 593320 θ2 · "7 Α7

Description of the invention [1,2-a] P specific bite (ee: > 95% HPLC) was added to 50 ml of 70% strength sulfuric acid under ice-cooling conditions within 4 minutes. During this time a suspension ' was formed which turned to an orange solution after 30 minutes. After the addition is complete, remove the ice cream and stir off the mixture at room temperature. TLC was performed after 50 hours. The gradual reaction solution was added to ice water, and then dichloromethane was added. Then, the mixture was adjusted to pH 8 ° with 6 N sodium hydroxide solution and saturated sodium bicarbonate to separate the organic phase. The aqueous phase was extracted twice with dichloromethane. The organic phases were combined and washed with some distilled water. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in a vacuum rotary evaporator. The residue was concentrated with eluent: dichloromethane / methanol 1 00/1 in a flash gel chromatography. The main part was concentrated and treated with ethyl acetate, at which point the crystalline compound as a yellow solid crystallized. The precipitate was decanted by suction filtration and dried in a vacuum drying oven at 50 ° C to constant weight. Mass: 4 22 g (57 2% of theory), ee: > 95% (HPLC), melting point: 231-4C. 12. ^ 111,811,91〇-2.3-dimethyl-7,8-dioxo-9-aiseven-7,8,9.10-tetra1imidazo "1,2-hl" 1.71 6 g (19.52 mmol) (8R, 9R) -2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2- 11] [1,7] Pyridin-7-one (66: > 90% HPLC) suspended in 60 ml of methanol and cooled to 50 ° C in an ice-methanol bath. C to 0C. At this temperature 'the hydrogen was measured Steel (0.81 g, 21.47 mmol) was added with a spoon (releasing gas) over 0.5 hours. After the addition was complete, the mixture was stirred for another 10 minutes and then at 40 ° C bath temperature on a vacuum rotary evaporator. It was concentrated in water. The obtained oily residue was dissolved in distilled water and extracted three times with chloroform. The organic phases were combined and washed with some water and then dried over anhydrous sodium sulfate. -25- This paper applies to Chinese National Standard (CNS) A4 (210X297) (Centimeter)

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k W320 92. i., 11

,filter. The filtrate was concentrated in a vacuum rotary evaporator and combined with acetone to crystallize the title compound at this time. The precipitate was filtered off with suction and washed with acetone and diethyl ether and then at 50 ° C. 〇In a vacuum drying oven, dry to 2 weights. Available melting point: 20-6-9. (: Title compound of colorless crystals. Mass: 5.15 g (85.3% of theoretical value); 97% of the compound has a non-mirromeric purity and a mirror-isomeric purity exceeding ee: 93 8% (HpL compound

(A · oxy-2-propenyl) _8_trimethyl acetamidine [pyridine

Method A a) 7-Butyltinyl-2,3-dimethyl-8-trimethylethylamidoaminoimidazo [l, 2-a] pyridine

At -78 ° C, a solution of 40 liters of diethyl ether containing 1 g of 2,3-dimethyltrimethylethylamidoimidazo [丨, 2-a] pyridine was added in 8 ml of n-pentane. 5 Molar solution of butyllithium was added dropwise. Stir the mixture for $ 1 and then treat it with 3.3 ml di-n-butyltin chloride. Then the internal temperature was raised. The mixture was poured into ice water and extracted twice with ethyl acetate. The combined extracts were washed with some water and dried with potassium carbonate. The solvent was removed under vacuum to dissolve the oil. The solvent was ethyl acetate / petroleum ether (1: 3) and chromatographed on a silica gel. 13 grams of 7-tributyltin alkyl-2,3-dimethyltrimethylethylamidoamidoimidazopyridine was obtained as a viscous oil. b) 2,3-Dimethyl-7- (3-phenyl_ 丨 _oxypropylfluorenyl) -8_trimethylethylfluorenylamino and [1,2-a] p ratio -26-

593320 A7 B7 V. Description of the invention (24 15 liters of tetrahydrofuran contains 1 gram of 7-tributyltinalkyl_2,3 • dimethyl-8-dimethylethoxyaminoimidazolo [丨,] ^ ] The pyridine solution was treated with 85 mg of bell chloride, 60 g of bis (acetonitrile) palladium chloride, and 3400 g of cinnamon chloride in order. The mixture was stirred at 60 for 3 hours. After cooling to 0, it was filtered by suction. The pale yellow precipitate was filtered off and the strip was washed with some tetrahydrocondensation and diethyl pickling. After vacuum drying, 720 mg of the title compound of the salt of oxychloride having a melting point of 263_5 ° C (decomposition) were obtained.

Method B a) 2,3-dimethyl-7- (3-phenyl_1_hydroxy_2-propanyl) _8-trimethylethylamidoaminoimidazo [1,2-a] pyridine 41 grams of 8_trimethylethylamidoamino_ 2,3-monomethylimidazo [i, 2_a] pyridine will be vigorously stirred at -78 ° C under 320 ml of available commercial product The third butyl lithium containing 1.5 mol of n-pentane was added dropwise so that the temperature did not exceed -70 ° C. After stirring for an additional 15 minutes at -78 ° C, a solution containing 61 g of cinnamaldehyde in 50 ml of anhydrous diethyl ether was added dropwise (internal temperature < -68. ≪ 3). The mixture was warmed to room temperature again, carefully poured into ice water and extracted three times with a total of 500 ml of ethyl acetate. The pale red organic phase was washed with distilled water and dried over sodium sulfate and the falling off agent was removed in vacuo. The remaining pale yellow suspension was treated with diethyl ether. The obtained crystals were filtered off by suction filtration. 30 g of 2,3-dimethyl (3-phenyl-1-hydroxy-2-propenyltrimethylethylamidoamidoimidazo [l, 2-a] having a melting point of 194-5 ° C can be obtained Pyridine. B) 2,3-dimethyl-7- (3-phenyl-1-oxy-2-propanyl) -8-trimethylethylamidoaminoimidazo [1,2-a ] Pyridine-27-

A7

In 900 ml of trichloromethane, 35.5 g of 2,3-dimethyl · 7 — (3-phenyl — 1-¾yl-2-propenyl) -8-trimethylacetamidoimidazole The pyridine solution was treated with 60 g of manganese monoxide and stirred vigorously at room temperature for 20 hours. The mixture was then filtered and the filtrate was concentrated in vacuo to dryness and the resulting oil was treated with some diisopropyl ether. The crystals obtained in this process were decanted by suction filtration. 31.5 g of the title compound having a melting point of 108-100 ° C were obtained. β. Propyl-1-8-trimethylpropionylamine diamidinediimidazole is similar to Example A, Method A. After a reaction corresponding to 2-chlorocinnamonium chloride, a yield of 42% can be obtained. Melting point The title compound was hydrochloride at 158-60 ° C. C · -monooxy + a) -1 -Gas-2-propenyl 1 -8-Tris-methyl ethylhexylamine ^ -2,3--methyl-taste and f 1,2 -a The 1 p ratio is similar to Example A, Method A. The title compound was obtained in a yield of 51% and melting point of 21 8-191 by reaction with 2,6-dichlorocinnamonium chloride. D. 7 Digas, methylbenzyl) _ι · Gas_2_propenyl 1 -8_triamyl ^ Bakerylamino-2,3 · Dimethyl is savory and flj-alp is similar to bite Example A, Method A, through reaction corresponding to 2-trifluoromethylcinnamonium chloride, a yield of 12% and a melting point of 206-8 can be obtained. (: The title compound of hydrochloride. E. 2,3--Li-yl- 7- (2,3 -Epoxy-1-airyl-3-benzylpropyl) -8- = ethyl alcohol Aminoamido smells, "1,2-aV ratio bite 60 ml of acetone contains 4 g of 2,3-dimethyl-7- (3-phenyl-1-oxy-2-propan-28-

This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 593320 A7 _____ B7 V. Description of the invention (26) Foot base) 8-trimethylacetamidoimidazopyridine and 1 A mixture of 400 mg of sodium sulfonium oxide in 2 ml of water was added at 30. 〇 Add 5.6 ml of a 30% strength hydrogen peroxide aqueous solution of a commercially available product to the solution under vigorous stirring (20 minutes). After stirring for an additional 30 minutes at 30 ° C, the mixture was cooled to 0 ° C and treated with 60 ml of water, 3 g of sodium thiosulfate and 30 ml of acetic acid. After phase separation, the aqueous phase was extracted with 2.0 liters of ethyl acetate. The organic phases were combined, treated with some water and dried over potassium carbonate. After removing the solvent in vacuo, the residual oil was dried in high vacuum. 4 g of the title compound were obtained as an amorphous material. F. ^^ methyl bis (2.§ ^ 10-2.3-0- 砟 isopropyl-3-benzylpropan-1- 醯-[ylacetate) Remove the water and dissolve 60 g (0.245 mole) of 2,3-dimethyl-8-trimethylethylamidoamidoimidazo [ij-a] pyridine in 1.5 liters of anhydrous di under argon. In ether and cooled to -75 in an ice-acetone cooling bath, 408 ml (0.6 12 mol) of a tertiary-butyl lithium solution (1.5 M in n-pentane) was added dropwise with a curved needle so that The temperature does not exceed _65. 0 (3 () minutes). A red suspension is formed. After the addition is complete, the suspension is stirred for a further 30 minutes at -75 ° C. The temperature is then lower than -65 ° c for 30 minutes In the meantime, 145 g of methyl (23,311) -2,3-0-isopropylidene-3-phenylpropionate (ee: 99.05%) in 150 ml of anhydrous THF of 1/3 was slowly added dropwise. The remaining amount was added dropwise randomly (5 minutes), which brought the temperature to -60 ° C. After the addition was complete, the cooling bath was removed. When the internal temperature reached -30 ° C, 20 ml of methanol was added and internally At a temperature of 0C, 200 ml of distilled water was added. The aqueous phase was separated with a separatory funnel and the organic phase was added at a time of 100 ° C. 5-29- washed ml of distilled water suitable for the present paper China National Standard Scale (CNS) A4 size (2l〇 ^ r ^^ y bookbinding

593320 A7 _______ B7 __— 5. Description of the invention (27) times, and then extracted 3 times with 10% strength sulfuric acid (200 ml, 50 ml, 50 ml). The sulfuric acid phases were combined, treated with 200 ml of dichloromethane and adjusted vigorously to pH 2.3 with a sodium hydroxide solution (calibration electrode). Separate and remove the organic phase. The aqueous phase was extracted with 30 ml of dichloromethane. The combined dichloromethane phases were washed twice with some distilled water. The organic phase was dried over anhydrous sodium sulfate and the solvent was completely removed in vacuo. A brown oil was obtained and treated with 50 ml of diethyl ether. After the seed crystals were put in, they were left overnight, and the crystals formed were filtered off and washed with diethyl ether. After drying in vacuo, the title compound was obtained as a pale yellow powder with a melting point of 76-80 ° C. Mass: 57.7 g (52.5% of theory), ee > 99% (HPLC). 13. 1118,811,91〇-2,3-Dimethyl-7.8-dioxine-9-phenyl-7,8,9.10- ^ pyrazoloH, 2-hl Gel chromatography (eluent ·· ethyl acetate / methanol 19/1) 2 g of mother liquor of Example 12 to give 0.35 g of the title compound as an oil, which crystallized after adding ethyl acetate. Melting point: 199-200 ° C ( Ethyl acetate). 14 · H9RV3-methylfluorenyl-8-hydroxy-2-methyl-7-oxyl-9- 1 I -miO-tetrahydroimidazolium "i.2-hl" l, 71 pyridine Add (8R, 9R) -8-hydroxy-2,3-dimethyl-7-oxytolyl-7,8,9,10-tetrahydroimidazo [1,2-11] [1, 7] Pyridine (1 g) was dissolved in 20 ml of anhydrous chloroform, and 5 g of potassium permanganate was added. After the reaction mixture was stirred at room temperature for 40 days, the solid was filtered off. Eluent: Dichloromethane / methanol 13/1) The filtrate was twice to give 0.07 g of the title compound as a semi-solid. 15 · Chloromethyl-7,8-di-amino-2-methyl-9- BenQ--30- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ^ 3320

HA10-tetrahydroxanthene and n.2-hin.7l4 pyridine will be 0.07 g of (8R, 9R) -3 -methylamido-8-quinyl-2 -methyl-7 -oxy-9 · »phenyl -7,8,9,10-tetrahydroimidazo [1,24] [1,7] pyridine was dissolved in 5 ml of anhydrous methanol and then 0.1 g of sodium borohydride was added. The mixture was stirred for 30 minutes and concentrated in true 2. An oily residue was distributed between water and chloroform. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The product was purified by flash gel flash chromatography (eluent: dichloromethane / methanol 9/1) to give 0.05 g of the title compound as a semi-solid. 1H-NMR (CD30H, 400 MHz) 5 = 1.90 (s, 3H, 2-CH3), 3.87 (dd, J8, 9 = 9.5 Hz, J8, 7 = 8.0 Hz, 1H, 8-H), 4.45 (d , J9,8 = 9.4 Hz, 1H, 9-H), 4.79 (bs, 2H, 3-CH2), 5.42 (d, J7, 8 = 8.0 Hz, 1H, 7-H), 7.03 (d, J6, 5 = 6.9 Hz, 1H, 6-H), 7.35-7.42 (m, 3H, 9-Ph), 7.55 (d, J = 7.0 Hz, 2H, 9-Ph), 7.77 (d, J5, 6 = 7.0 Hz, 1H, 5-H). 16 · ai ^, 9R) -7,8-subisomeric and some two most usable 3_ dimethyl usbbenzyl-tetrahydroimidazolium n.2-hl, l, 71 pyrimidine will be 0.3 g (73, 8 911) -2,3-dimethyl-7,8-dihydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-1!] [1,7] Pyridine was dissolved in 5 ml of anhydrous acetone and 10 ml of anhydrous N, N-dimethylformamidine. 2,2-Dimethoxypropane (20 ml) and p-toluenesulfonic acid-hydrate (〇68 G) Add, and then mix at room temperature: mix the mixture for 20 hours. Separate the organic layer, wash with water and dry with hydrated sulfuric acid steel. After evaporating the solvent, chromatograph the gel (eluent: ethyl acetate / Methanol 20/1) residue, 0.2 g of the title compound with a melting point of 23 1-232 ° C (decomposition = ether) can be obtained as colorless needles. Commercial Use-31-This paper applies Chinese National Standard (CNS) A4 Specifications (210 X 297 mm)

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2. Description of the invention (29) The beneficial pharmaceutical properties of the compound of formula I and its salts are particularly beneficial. In particular, it shows significant inhibition on warm-blooded animals = can be used for commercial ... protection. Selective effects, favorable rhinoplasty effects, and excellent materials can be distinguished from high-selection side effects and broad treatment paradigms. Internal activity, no significant meaning for the prevention and treatment of gastrointestinal diseases, especially ulcers, gastritis, two Harm (: such as f ulcer, duodenal ulcer caused by, for example, micro-birth: (such as Er Er Le Er Guan's functional gastric disease), which can be W (such as the pi spiral pimple), bacterial toxins, anti-inflammatory agents and Anti-rheumatic agent), acetic acid "caused by the mouth force. Yu Luan such as ethanol), f acid or before pressing: The excellent properties of the compound of the present invention have been proved to be significantly better than those obtained from the unformed compound X It has been determined that anti-carcinogenic and anti-secretory chemical compounds are suitable for these properties. The compounds of formula 1 and their pharmaceutically tolerable salts are particularly useful in human and veterinary medicine, of which the stomach and / Treatment and / or prevention The compounds according to the present invention are used for the treatment and / or prevention of the aforementioned diseases. *. The present invention also includes the use of the compounds according to the present invention to prepare a medicament for the treatment and / or prevention of the aforementioned diseases. The present invention further relates to-or- A variety of magic compounds and / or pharmaceuticals that are resistant to double salts. The pharmaceuticals are prepared by known methods and are familiar to those skilled in the art. '_______ _- 32 _ This paper rule is used t 目 @ 家 鲜(CNS) A4 Secret V. Explanation of the invention (30) Human: The active pharmaceutical compound according to the present invention can be activated by using as a fungicide (form or preferably combined with a suitable medical adjuvant to form a remedy) , Coated tablets, gum volume, county, capsules, suppositories, patches (such as TTS), emulsions, ... two dollars, of which the active compound component is preferably between (U and 95% <, and it is through the appropriate choice of adjuvant With excipients can be truly suitable for the active: the compound and / or the pharmaceutical dosage form (such as intestinal type) required to trigger the effect. The skilled person is familiar with the expertise suitable for the required pharmaceutical formula = Or excipient. In addition to solvents, gelling In addition to suppository base, lozenge adjuvant, and its w-type compound carrier, it is possible to use anti-oxidants, dispersants, etc .; the final agent, flavoring agents, preservatives, dissolving agents, colorants are not penetration enhancers. And complexing agents (such as cyclodextrin). The active compound can be administered orally, parenterally or transdermally. It has been proven in human medicine that the active compound is usually administered orally at a daily dose of about 0.001 to About 20, preferably from 0.05 to 5, especially from 0.1 to 1 ^ g / kg body weight '#suitable in the form of several times, preferably 1 to 4 individual doses to obtain the required Results. General parenteral treatment = formula II can be used similarly or (especially for intravenous administration of the active compound) a lower dose of I. The appropriate dosage and method of administration of the active compound required in each case can be determined by anyone skilled in the art. Defined by its expertise. If a compound according to the present invention and / or a salt thereof is used to treat the above-mentioned diseases, the pharmaceutical preparation may also contain one or more other medicinal active ingredients. Examples that can be mentioned are: sedatives (for example, benzodiazapines such as Diazepam), antispasmodics (for example, V. Description of the Invention (31) bitamivedne ) Or camilofin, antiparasympathetic agents (such as oxyphencycHmine or phenycarbamide), local anesthetics (such as tetracaine (procaine) And, if appropriate, enzymes, vitamins or amino acids. Special emphasis here should be given to compounds according to the invention and pharmaceutical preparations that inhibit acid secretion, such as for example: Η: blockers (such as cimetidine) Ranitidine, H + / K + -ATPase inhibitors (such as omeprazole, pantoprazole), or even with so-called peripheral antiparasympathetic agents (such as pirrizone tablets) (Pirenzepine), Telenzepine, and a combination with gastrin antagonists to increase the main effect of enhancing or additional sensation and / or reduce side effects, or in addition to antibacterial active substances (such as cephalosporins) (Cephalosporin), tetracycline , Penicillin, macrolide, nitroimidazole, or other bismuth salts) to control Helicobacter pylori. Active combination ingredients that can be mentioned are, for example, mezlocillin, ampicillin, Amoxycillin, cefalothin, cefoxitin, cefotaxime, imipenem, gentamycin, amikacillin Amikacin, erythromycin, ciprofloxacin, metronidazole, clarithromycin, azithromycin, and combinations thereof ( Such as clarithromycin + metronidazole). Pharmacology-34- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) A7

: According to the compound of the present invention, it has an excellent gastric protective effect and inhibits the secretion of gastric acid. Based on the model shown below, the number provided by the Institute is equivalent to the number of these compounds. Tests on the stomach of injected rats The following Table A shows the effects of the rats perfused with a compound according to the present invention in vivo on the stimulation of pentagastrin acid secretion after intravenous administration. Table A Convention No. Dose (μmol / kg) Intravenous Inhibition of Acid Secretion 5 3 100 6 3 100 10 3 100 12 3 100 Method

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Anesthetized rats (CD rats, females' 200-250 g, · intramuscular injection of urethane 1.5 g / kg), after tracheotomy, open the abdominal cavity in the middle above the abdomen, and fix the PVC catheter through the esophagus through the mouth The other end passes through the pylorus so that the end of the catheter fits into the gastric cavity. The catheter leading from the pylorus is guided to the outside through the side opening and enters the right abdominal wall. After being thoroughly moistened (approximately 50-100 ml), warm physiological saline at 37 ° C continued to flow through the stomach (0.5 ml / min, pH 6.8-6.9; Braun-Unita 1). The effluent was collected at 15-minute intervals to determine the pH (pH meter 632, glass electrode EA 147; φ = 5 mm, Metrohm) and titrated to pH 7 by freshly prepared 0.01 N NaOH solution (Dossmet) 665 Mandro-35-I paper size uses the Chinese National Standard (CNS) A4 specification (21 × 297 mm) 593320 Patent Application No. 087104064 'Chinese manual replacement page (December 1992) A7 B7 V. Invention (33) (Dosimat 665 Metrohm)) to determine the secreted HC1. After the operation (for example, after the second part of the measurement), continuous intravenous injection of 1 microgram / kg (= 1.65 ml / hour) of pentagastrin (left femoral vein) for 30 minutes to stimulate gastric secretion. After starting the continuous injection of pentagastrin, the test substance was administered intravenously at a liquid volume of 1 ml / kg for 60 minutes. Animal body temperature is maintained at a constant 37.8 to 38 ° C with infrared radiation and a heat pad (automatic, non-segmented control with anal temperature sensor). This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

Claims (1)

593320 8 8 8 8 A B c D 9as.2〇 Patent application No. 087104064 Chinese patent application scope replacement (May 1993) VI. Application scope of patent 1. A compound of formula I or its salt R2 Where R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, R3 is hydrogen or halogen, one of the substituents R4a and R4b is hydrogen, and the other is hydrogen , Hydroxy, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkoxy, or 1-4C-alkylcarbonyloxy, or wherein R4a and R4b together are 0 (oxy), substituted One of the groups R5a and R5b is hydrogen, and the other is hydrogen, hydroxy'l-βί: -alkoxy or 1-40 alkylcarbonyloxy, or one of the substituents R4a and R4b and the other On the one hand one of the substituents R5a and R5b is hydrogen in each case, and the other substituent in each case together forms a methylenedioxy (-0-CH2-〇-) or ethylenedioxy (- O-CH2-CH2-o-). Among them, R4a, R4b, R5a, and R5b are not hydrogen at the same time. This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 593320 A 8 B8 C3 D8. The scope of patent application R6 is hydrogen, halogen, 1-4C -Alkyl, 1-4C-alkoxy or tris-methyl and R7 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy. 2. The compound or its salt according to item 1 of the scope of the patent application, wherein R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, and R3 is hydrogen, One of the substituents R4a and R4b is hydrogen, and the other is hydrogen, hydroxy, or 4C-fluorenyloxy, or wherein R4a and R4b are together 0 (oxy), and one of the substituents R5a and R5b is hydrogen, The other is hydrogen, hydroxy or 1-β0 alkoxy, wherein R4a, R4b, R5a and R5b are not hydrogen at the same time, R6 is hydrogen, halogen or trifluoromethyl and R7 is hydrogen or halogen. 3. The compound or its salt according to item 1 of the patent scope, which has the formula Γ R 1 is 1-4 C -alkyl, R2 is 1-4C-alkyl or hydroxy-1-4C-alkyl, and the common Chinese National Standards (CNS) A4 specifications (210 X 297 mm) for each acre size are 593320 A3 B8 C8 D8 々, the scope of the patent application R3 is hydrogen, one of the substituents R4a and R4b is hydrogen, and the other is hydrogen, meridian or B4C-alkoxy, and one of the substituents R5a and R5b is hydrogen And the other is hydrogen, hydroxy, or 1-4C-alkoxy, where R4a, R4b, R5a, and R5b are not hydrogen at the same time, R6 is hydrogen, halogen, or trifluoromethyl and R7 is 'argon · or'. 4. The compound or its salt according to item 3 of the scope of the patent application, wherein R1 is 1-4C-alkyl, R2 is 1-4C-alkyl or hydroxymethyl, R3 is hydrogen, R4a is hydrogen, and R4b is hydroxy or 1-4C-alkoxy, R5a is hydrogen, hydroxy or 1-4C-alkoxy, R5b is hydrogen, R6 is hydrogen, halogen or trifluoromethyl and R7 is hydrogen or halogen. 5. The compound or its salt according to item 3 of the scope of the patent application, wherein R1 is 1-4C-alkyl, R2 is 1-4C-alkyl, R3 is hydrogen, R4a is hydrogen, and paper and paper * standards are generally in Chinese. : Standard (CMS) A4 Specification (210X 297 Gem) 593320 R4b is hydroxy, R5a is hydroxy, R5b is hydrogen, R6 is hydrogen, halogen or trifluoromethyl, and R7 is gas or dentition. 6. The compound or a salt thereof according to item 丨 of the scope of the patent application, which is selected from the group consisting of 7,8-dihydroxy_2,3_dimethyl_9_phenyl_7,8,9,1〇_ Hydroimidazolium'2 h] [1,7] Oral anaesthesia, 2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo [l, 2-h] [ 1,7] pyrimidone, 9_ (2_chlorophenyl)> 2,3_dimethyl_di 8,9,1__tetrahydroimidazolidinone, 9_ (2,6-dichlorobenzene) ) -2,3-dimethyl-7,8,9,10-tetrahydroimidazo [1,2_} 1] [1,7] pyrimidin-7-one, 9- (2-trifluoro (Methyl) -2,3-dimethyl-7,8,9,10-tetrahydroimidazo [1,2-11] [1,7] peak lake-7-one, 7-hydroxy-2, 3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazolo n, 2-hni, 7] pyridine, 9_ (2-chlorophenyl) · 7_hydroxy-2,3 -Dimethyl-7,8,9,10-tetrahydroimidazopyridine, (2,6-dichlorophenyl) -7_hydroxy_2,3_dimethyl-7,8,9, 10 / tetrahydroimidazo [l, 2-hni, 7] pyridine, 9- (2-trifluoromethylphenyl) _7 • hydroxyJ, pyrenedimethyl-7,8,9,10-tetram Hydroimidazolopyridine and 8 • hydroxy_2,3_dimethylphenyl-7,8,9,10-tetrahydroimidazolopyridine · 7_ 嗣. 7 · Combination according to item 1 of the scope of patent application Or its salt, which has the chemical name (711,811,911) -7,8-dihydroxy-2,3-dimethyl-9-phenyl_7,891〇tetrahydroimidazo [l, 2-h] [1,7] Pyridine. '8 · A pharmaceutical composition for the treatment of θ fine disease', which contains the basis according to the Chinese National Standard (CNS) A4 (210 X 297) Fit 593320 Patented generic pharmaceutical adjuvants are intended for use in the preparation of compounds and / or salts thereof, and / or formulations. • The compound according to item 1 of the patent application or its prevention of gastrointestinal diseases. I 10 The compound or a salt thereof according to the item of the scope of patent application for the prevention and treatment of gastrointestinal diseases. The compound or its salt according to item 1 of the scope of the patent application, which is ('8R'9R) -7,8-isopropylidenedioxy-2,3-dimethyltolyl 7'8, 9,10-tetrahydroimidazo [1,24] [1,7] pyridine compound or a salt thereof. 12. The compound or its salt according to item 1 of the scope of patent application, which is (7R'8R, 9R) -2,3 · dimethyl-8-hydroxy-7- (2-methoxyethoxybenzene • 7,8,9,10_tetrahydroimidazopyridine compound or its salt. -5- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)