NEW 4-METHOXY PYRROL DERIVATIVES OR THEIR SALTS, AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM

Abstract

The present invention relates to a 4-methoxypyrrole derivative or its pharmaceutically acceptable salt, its preparation process, and a pharmaceutical composition comprising it. The 4-methoxypyrrole derivatives or their pharmaceutically acceptable salts according to the present invention exhibit not only excellent proton pump inhibitory activity, gastric lesion inhibition activity, and defensive factor enhancement activity, but also excellent eradication activity against <em>h. Pylori < / em> Therefore, pyrrole 4-methoxy derivatives or their pharmaceutically acceptable salts can be used effectively for the prevention and treatment of gastrointestinal lesions due to gastrointestinal tract ulcers, gastritis, reflux esophagitis, or <em> h. Pylori< / em>Furthermore, pyrrole 4-methoxy derivatives or their pharmaceutically acceptable salts exhibit inhibitory activities against gpcr and can therefore be used effectively for the prevention and treatment of diseases induced by the 5-ht receptor or the muscarinic acetylcholine receptor.<!--endfragment-->

Description

prevention and treatment of diseases induced by the 5-HT receptor or the muscarinic acetylcholine receptor.

Claims

Demands 1. Compound represented by the following chemical formula 1 or pharmaceutically acceptable salt thereof: [Chemical formula 1] in chemical formula 1, Ri, Rg, and R3 are each independently hydrogen or halogen, provided that Ri, Rg, and R3 cannot be hydrogen simultaneously, and R4 and Rs are each independently hydrogen, halogen, alkyl in Ci-4, alkoxy in Ci-4, haloalkyl in Ci-4, haloalkoxy in Ci-4, provided that R^ and R 3 cannot be hydrogen simultaneously. Or born of 2. A pharmaceutically acceptable compound or salt thereof according to claim 1, wherein Ri, Rz and R3 are each independently hydrogen, fluoro, or chloro, provided that Ri, Rz and R3 cannot be hydrogen simultaneously.

3. A pharmaceutically acceptable compound or salt thereof according to claim 1, in which R4 and R are each independently hydrogen, chloro, fluoro, methyl, trifluoromethyl, methoxy or difluoromethoxy, provided that R4 and Rs cannot be hydrogen simultaneously.

4. A pharmaceutically acceptable compound or salt thereof according to claim 1, in which Ri is halogen, and R2 and R3 are each independently hydrogen, or halogen.

5. A pharmaceutically acceptable compound or salt thereof according to claim 1, in which Ri is fluoro, and R2 and R3 are each independently hydrogen, fluoro, or chloro, or Ri is chloro, and R2 and R3 are hydrogen.

6. Pharmaceutically acceptable compound or salt of this one according to claim 1, ل in which R4 is a halogen, and Rs is chloro, fluoro, methyl, trifluoromethyl, methoxy or difluoromethoxy, or R4 and R5 are each independently chloro, or fluoro.

7. A pharmaceutically acceptable compound or salt thereof according to claim 1, in which Ri is fluoro, and R2 and R3 are each independently hydrogen, or fluoro, R4 is hydrogen, and R1 is chloro, or trifluoromethyl.

8. Pharmaceutically acceptable compound or salt of this one according to claim 1, I the compound being chosen from the group represented by the following chemical formulas 1-2 to 1-4: [Chemical formula 1-2] [Chemical Form 1 1-4] in chemical formulas 1-2 to 1-4, R-, to R.', are as defined in claim 1.

9. A pharmaceutically acceptable compound or salt thereof according to claim 1, The compound chosen from the group constitutes the following compounds: 1) 1-(5-(2-fluorophenyl)-4-methoxy-l-((3-chlorophenyl) sulfonyl) _lH-pyrrol-3-yl) -N-methylmethanamine; 2) 1-(5-(2-fluorophényl)-4-méthoxy-l- ((3- (trifluoromethyl)phenyl)sulfonyl)_lH-pyrrol-3-yl)-N-méthyléthanamine ; 3) 1-(5-(2-fluorophenyl)-4-méthoxy-l-((3-methoxyphenyl)sulfonyl)_lH-pyrrol-3-yl)-N-methylméthanamine ; 4) 1-(5-(2-fluorophényl)-4-méthoxy-l-((3-difluorométhoxyphényl)sulfonyl)-lH-pyrro!-3-yl)-N-methyl éthanamine ; 5) 1-(5-(2-chlorophényl)-4-méthoxy-l-((3-méthoxyphenyl) sulfonyl)-lH-pyrro!-3-yl)-N-méthylméthanamine ; 6) 1-(5-(2-fluoro-4-chlorophènyl) -4-m <âthoxy-l- ( (3-chiorophenyi)sulfonyl)-lh-pyrro!-3-yl)-n-méthylméthanamine ;7) 1-(5-(2-fluoro-4-chlorophenyl)-4-methoxy-l-((3-(trifluoromethyl)phenyl)sulfonyi)-lH-pyrrol--3-yl)-N-methylmethanamine; 8) 1-(5-(2,4-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methyloxy-1H-pyrrol-3-y!)-N-methylmethanamine; 9) 1- (5- (2,4-difluorophenyl)-1- ( (3- ب (trifluoromethyl)phenyl)sulfonyl)-4-methoxy-1H-pyrro.l_ 3-yl)-N-methylmethanamine; 10) 1-(5-(2,4-difluorophenyl)-1-((3- methylphenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 11) 1- (5- (2,4-difluorophenyl)-1- ( (3-methoxyphenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 12) 1-(5-(2,4-difluorophenyl)-1-((3-difluoromethoxyphenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 13) 1-(5-(2,6-difluorophenyl)-1-((3- fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 14) 1-(5-(2,6-difluorophenyl)-1-((3- chlorophenyl(sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N methylmethanamine; '" 15) 1-(5-(2,6-difluorophenyl)-1-((3-(trifluoromethyl)phenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 16) 1-(5-(2,6-difluorophenyl)-1-((3- methylphenyl) sulfonyl)-4-methoxy-1H-pyrrol_3-yl)-N-methylmethanamine; 17) 1-(5-(2,6-difluorophenyl)-1-((3-methoxyphenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmeth ana mine,- 18) 1-(5-(2, 6-difluorophenyl)-1-((3-chloro-4-fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 19) 1-(5-(2,6-difluorophenyl)-1-((3,4-difluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine,• 20) 1-(5-(2-fluoro-6-chlorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N? methylmethanamine ,- 21) 1-(5-(2-fluoro-6-chlorophenyl)-1- ( (3-chlorophenyl) sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; 22) 1-(1-((3-fluorophenyl)sulfonyl)-4-methoxy-5- (2,4,6-trifluorophenyl)-1H-pyrro!-3-yl)-N- methylmethanamine, 23) 1-(1-((3-chlorophenyl)sulfonyl)-4-methoxy-5- (2,4,6-trifluorophenyl)-1H-pyrro-3-yl)-N-methylmethanamine; 24) 1-(1-((3-trifluoromethylphenyl)sulfonyl)-4-methoxy-5-(2,4,6-trifluorophenyl)-1H-pyrro-3-yl)-N-methylmethanamine; 25) 1-(1-((3-methoxyphenyl)sulfonyl)-4-methoxy-5- (2,4,6-trifluorophenyl)-1H-pyrro-3-yl)-N-methylmethanamine 26) 1-(1-((3, 4-difluorophenyl)sulfonyl)-4-methoxy-5- (2,4,6-trifluorophenyl)1H-pyrrol-3-yl)-N-methanamine; 27) 1-(1-((3-fluorophenyl)sulfonyl)-4-methoxy-5- (2,3,6-trifluorophenyl)-1H-pyrro-3-yl)-N-methylmethanamine 28) 1-(1-((3-chlorophenyl)sulfonyl)-4-methoxy-5- (2,3,6-trifluorophenyl)-1H-pyrro-3-yl)-N-methylmethanamine 29) 1-(1-((3-trifluoromethylphenyl)sulfonyl)-4-methoxy-5-(2,3,6-trifluorophenyl)_lH-pyrrol-3-yl)-N-methylmethanamine; 30) 3) ) -1) - Ά-methoxyphenyl) sulfony-l) -4-methoxy-5- (2,3,6-trifluorophenyl)-1H-pyrro!-3-yl)-N-methylmethanamine; 31) 1-(5-(2,5-difluorophenyl)-1-((3- fluorophenyl) sulfonyl)-4-methoxy-1H-pyrrol-3-yl) -N^; methylmethanamine; 32) 1-(5-(2,5-difluorophenyl)-1-((3-trifluoromethylphenyl)sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine; And 33) 1-(5-(2,5-difluorophenyl)-1-((3-methoxyphenyl) sulfonyl)-4-methoxy-1H-pyrrol-3-yl)-N-methylmethanamine.

10. A pharmaceutically acceptable compound or salt thereof according to claim 1, The pharmaceutically acceptable salt is a hydrochloride or fumarate salt.

11. Pharmaceutical composition for use in the prevention and treatment of gastrointestinal lesions due to gastrointestinal tract ulcer, gastritis, peptic esophagitis or H. pylori, comprising the compound or pharmaceutically acceptable salt thereof according to any one of the claims therein.

12. Pharmaceutical composition for use in the prevention and treatment of diseases mediated by 5-HT receptors or mediated by muscarinic acetylcholine receptors selected from depression, manic-depression, schizophrenia, autism, obsessive-compulsive neurosis, anxiety disorder, migraine, hypertension, eating disorder, irritable bowel syndrome (IBS), peptic ulcer, diabetic neuropathy, asthma and overactive bladder, comprising the compound or a pharmaceutically acceptable salt according to any one of claims 1 to 10.