JPH0331280A - New imidazopyridine compound - Google Patents

Abstract

NEW MATERIAL:A compound expressed by the formula or salts of said com pound (R<1> is lower alkynyl; R<2> is lower alkyl; R<3> is aryl containable of substitut ing group). EXAMPLE:8-(2,3-dimethylbenzamide)-3-(2-propynyl)-2-methylimidazo[1,2-a] pyridine. USE:Remedy for ulcer. PREPARATION:For instance, 8-amino-3-(2-propynyl)-2-methylimidazo[1,2-a] pyri dine is reacted with 2,3-dimethylbenzoyl chloride to afford the exemplified compound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] This invention relates to novel imidazopyridine compounds and salts thereof. More specifically, the present invention relates to a novel imidazopyridine compound having antiulcer activity [wherein R1 is a lower alkynyl group, R'' is a lower alkyl group, and R' is an optionally substituted aryl group] It can be shown as follows.

The object compound (1) or a salt thereof can be produced by the method described in Examples and Production Examples below.

Suitable salts of the target compound (1) are conventional non-toxic salts, such as organic acid salts such as maleate, tartrate, acetate, methanesulfonate, benzenesulfonate, formate, toluenesulfonate, etc. addition salts, such as inorganic acid addition salts such as hydrochlorides, hydrobromides, sulfates, phosphates; salts with bases such as salts with amino acids such as arginine, aspartic acid, glutamic acid; or Mention may be made of acid addition salts.

In the remainder of this specification and the following description, preferred examples and explanations of various definitions falling within the scope of this invention will be explained in detail below.

As used herein, "lower" means groups having 1 to 6 carbon atoms, unless otherwise specified.

Suitable "lower alkyl 7sJ" has 1 to 6 carbon atoms, and includes a methyl group, an ethyl group, a propyl group,
Examples include inpropyl group, n-butyl group, tertiary butyl group, pentyl group, hexyl group, etc. Among them, preferred are (C, ~C°4) alkyl groups, and A preferred example is a methyl group.

Suitable "lower alkynyl groups" have 2 to 6 carbon atoms, including ethynyl group, 1 (or 2) propynyl group, 1 (or 2 or 3) butynyl group, 1 (or 2 or 3) butynyl group,
Examples include l methyl-2propynyl Jλ, l (or 2 or 3 or 4)-benzenylno λ, l (or 2 or 3 or 4 or 5)-hexynyl group, among which preferred ones include: (C2~C,)
Examples include an alkynyl group, and a more preferred one is a 2-propynyl group.

Preferred "aryl groups" include phenyl group, tolyl group, xylyl group, 1-naphthyl group, 2-naphthyl group, 1-
Examples include anthryl group, among which the phenyl method is preferred.

"Suitable substituents for the aryl group J which may have a suitable substituent include, for example, the lower alkyl group described above.

The raw material compound used in the synthesis of the object compound (1) of the present invention or its salts can be obtained by the method described in the Production Examples.

The L1-type compound (1) and its salts of the present invention are new compounds and are used as anti-ulcer agents.

[In order to demonstrate the usefulness of compound (1), the pharmacological test results of target compound (1) are shown below.

Stress: 1α ■ Test method: Approximately 240 g of Sprague-Dawley (Sprague-Dawley)
Five rats of the guc-DawIey) strain were used as one group. Each rat was secured in a small cage and submerged in a water bath with breathing conditions. The temperature of the water bath is 22
It was kept at °C. Test compounds were administered orally just before immobilization.

After 7 hours, the rats were sacrificed and the stomachs were removed. The stomach was then treated with 2% formalin. Ulcer area was measured for each rat. The average area (-') of the test compound administration group was compared with the area of the control group.

Test compound (+)8. -(1-Methylbenzamide 3-3-(2propynyl)-2-methylimidazo N, 2a]pyridine test results 32■/kg injection 1.t Inhibition rate (%) 1U It is clear from the test results As such, the object compound of this invention (
1) is useful as an anti-ulcer agent.

When administering the compounds of this invention for therapeutic purposes,
Use in the form of conventional pharmaceutical preparations containing the compounds as active ingredients in admixture with pharmaceutically acceptable carriers such as organic or inorganic solid or liquid excipients suitable for oral or parenteral administration. be able to. Pharmaceutical formulations may be in solid form, such as capsules, tablets, dragees, ointments or suppositories, or liquid, such as solutions, suspensions or emulsicone. If desired, auxiliary agents, stabilizers, suspending or emulsifying agents, buffers and others, lactose, fumaric acid, citric acid, tartaric acid, stearic acid, maleic acid, cono-phosphoric acid, malic acid, stearin, may be added to the above formulation. Commonly used additives such as magnesium acid, 07, sucrose, corn starch, talc, gelatin, agar, pectin, fallen beef oil, olive oil, cocoa butter, ethylene glycol, etc. may be included.

Although the dosage of the compound varies depending on the age and condition of the patient, the compound of this invention is administered at an average dosage of about 5.
0■, 50■, 100■, 250■, 500g1g, ]
OOO+ag is effective for treatment. Generally, amounts between 1 mg/solid and about 20,001 Ig/solid or more may be administered per day.

The present invention will be explained below according to production examples and examples.

Production Example 1 A methanol (126-) solution of 2.3-diaminopyridine (62.8 g) and 3-menoxy-5-hexyn-2-one (109.5 g) is refluxed for 20 hours. The methanol is distilled off under reduced pressure, aqueous sodium bicarbonate solution is added to the residue, then the mixture is extracted with ethyl acetate, washed successively with water and aqueous sodium chloride solution and the solvent is distilled off under reduced pressure. The resulting residue was subjected to column chromatography using silica gel (310 g) and eluted with a mixture of methylene chloride and acetonitrile.

The eluates containing the target compound are combined and the solvent is distilled off under reduced pressure F. The residue was suspended in diethyl ether, the resulting precipitate was collected by filtration, and 8-amino 3-(2-propynyl)-2-methylimidazo[12-a]viridi7 (1
8.42 g) is obtained. The filtrate was evaporated and the residue was subjected to column chromatography using silica gel (120 g), again eluting with a mixture of methylene chloride and methanol. The eluates containing the target compound are combined and the solvent is distilled off under reduced pressure. The resulting residue was suspended in diethyl ether, and the resulting precipitate was collected by filtration to give 8-amino-5-(2
-propynyl)-2-methylimidazoN,2-a] pyridine (14, IOg) is obtained.

lR(Nujolcm-'):3410,327
5.3170.1625,155ONMR(CDCI,
, δ) : 2.05(Ill, t,
J□311z).

2,43(311,S), 3.72(211,d,
J = 311z), 4.51 (211, lu-do
S), 6.27 (Ill, dd, J=IIlz an
d 7Hz), 6.63 (III, t, J=7
11z), 7.49(IH, dd, Jzllllza
nd)! lz) Example 1゜2.3-dimethylbenzoyl chloride (0,334g)
A solution of methylene chloride (0.5n) was added to 8amino-5-(2
-propynyl)-2-methylimidazo[1,2-al
Pyridine (0.35g) and triethylamine (0.2g)
) in methylene chloride (45-) at room temperature. After stirring for 6 hours, the mixture is poured into water and extracted with chloroform.

The extract is washed with water, dried over magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue was subjected to column chromatography using silica gel (10 g), eluted with chloroform, and purified to obtain a solid, which was crystallized from a mixture of ethyl acetate and n-hexane. 8-12,3
dimethylbenzamide)-3(2propynyl)-2
Methylimidazo(1,2-al pyridine is obtained.

Melting point 187-188°C IR (Nujol cs-'): 3390.323
0.1675.1550.1520°N M R (CD
c l m, δ): 2,07 (III, L,
J3! lz).

2.31 (311,S), 2.38 (611,S)
, 3.75 (2H, d, 13Hz), 6.80 (I
II, L, J-7,511z), 6.93~7
．． 40 (311, *), 7.75 (III, d,
J・7.5+1z'), 8.22(III, d, J=
'1.5Hz), 8.63 (III, Broad 5) 7
).

Example 2 8-(2-Methylbenzamide)-3-(2propynyl)-2-methylimidazo[],2-a]pyridine Melting point 145-146°C IR (Nujol cm-'): 338G, 322
0,1675,1550.1525NMR(CDCI3
．． δ): 2.08 CIll, L, J 311
z).

2.41 (311,3), 2.53 (3+1.S)
, 3.78 (211, d, J 311z), 6.85
(III, L, J 7.5+17), 7.13~
7.70 (411, m), 7.82 (III, d, J
7.511z), 8.33(lit, d, 3 7.5
112), 8.87 (III, II-F S) Elemental analysis (%) Calculated value C as C+all+JJ: 75
．． 23. H; 5.65. N; 13.85 Actual value C.
75.15. lI:5.55. N: 13.82 Example 3 8-(3,4-dimethylbenzamide)-3-(2-propynyl)-2-methylimidazo[1°2-a] Pyridine Melting point 144-145°C l R (Nujol cm -'):3400,320
0,1675,1550. +525N M R (CD
CI 3.6): 2. rJ9(lLt, J 4
11z) 2.35 (6B, S), 2.45 (311,
S), 3.78 (211d, J-311z), 6
．． 86(ill, t, J-1,511z), 7
．． 27 (IIl, d, J□7.51+7.),
7.68~L 9G (3H, m), 8.33 (III
, d, J= 7.511z), 9.23(311
, S) Elemental analysis (%) Calculated value C as C*oll+5NsO: 75.69.11; 6.03. 13.
24 Actual measurement value C: 75.32. II:5.86. N:1
2,9G Example 4゜8(3,5-dimethylbenzamide) 3(2-propynyl)-2methylimidazo[1゜2-al Pyridine Melting point 171-172℃ I R(!1ujol cm-')+34 (15,3
18G, +685.1605.155052O N M R (CDCI 3. J): 2.06 (I
ll, L, J 311z).

2.39 (6+1.S), 2.44 (3H,S),
3.75 (211, d, J-3Hz), 6.80 (
III, L, L7.511z), 7.12 (Il
l, S), 7.52 (211, S), 7.75 (
III, dd, J-111z and 7.5Hz)
, 8.22 (!H, bu [I-do d, J-1,511z
).

9.07 (Ill, Pn-F S) Elemental analysis (%) Calculated value C as C,,H,,1130
: 75.69. II; 6.03. N; 13.24
Actual measurement value C: 76,00. II:6.23. N:I
3.42 Example 5゜8-(2,5-Dimethylbenzamide) 3(2-propynyl)-2-methylimidazo[1゜2-a 1 Pyridine Melting point 157-159°C + R (Nujol c m-') :3390,3
225. +680. ．． 1550.1525NMR (CI
) CI 3+ δ) : 2.07(II
I, L, J 311z).

2, 33 (3+1.S), 2.40 (3+1.S)
S), 2.46 (3+1.S).

3, 75 (211, d, J-311z), 6.79
(III, L, J 7.511z) 7, 08 (2+
1. S), 7.30 (III, S), 7.75
(III, d.

37, 51! z), 8.21(III, d, J□
7.511z), 8.67 (III.

711-deS) Example 6 8-(2,6-dimethylbenzamide)-3(2-propynyl)-2-methylimidazoN.

-a1 Melting point 160-161°C l R (Nujol c s-'): 3280,321
0,1665. Mouth 540.1520°28O NMR (CDCI 3.δ): 2.0? (l11
．． L, J-51iz).

2.37 (911, S), 3.75 (211, d,
J-3i1z), 6.70-7, 25 (411, m),
7.75 (Ill, d, J-7,511z),
8.32 (+11.d, J 7.511z), 8.5
4(III, p[1-F S')8- (2,/I-
dimethylbenzamide) 3(2-propynyl)
2 Methylimidazo 11゜2-81 Pyridine Melting point 155-156℃ l R (Nujol cm-'): 3380.321
5.1670.1545.152ON M R (CD
Cl s, d): 2.07 (III, t, J
411z).

2, 35 (311, S), 2.40 (3+1.
S), 2°50 (311, S).

3, 75' (2tl, d, J-311z), 6.
80 (III, t, J 7.51!z), 6.
90-7.10 (211, m), 7.43 (III,
d, J-811z).

7, 74 (III, d, J・7.5!IZ), 8
．． 20 (III, d, L-811z) 8.72 (I
ll, Putodo S)

Claims (1)

[Claims] Formula: ▲Mathical formula, chemical formula, table, etc.▼(I) [In the formula, R^1 is a lower alkynyl group, R^2 is a lower alkyl group, and R^3 has a substituent. Each refers to an optionally aryl group. ] Compounds or salts thereof.