KR890012969A - New compounds - Google Patents

Abstract

No content.

Description

New compounds

Since this is an open matter, no full text was included.

Claims (16)

Compounds of the following general formula (I), or salts or solvent compounds thereof; Wherein RCO is an acyl group where the R group contains a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring and R ₁ and R ₂ are independently hydrogen, C _1-6 alkyl, C _2-6 alkenyl Or C _3-6 cycloalkyl or C _4-12 cycloalkylalkyl groups or together form a C _2-8 branched or linear polymethylene or C _2-6 alkenylene group (optionally substituted by a hetero atom); R ₃ is hydrogen, C _1-6 alkyl, or phenyl, or together with R ₁ , R ₃ forms a-(CH ₂ ) ₃ -or-(CH ₂ ) ₄ -group; R ₄ and R ₅ may be the same or different and may be attached to the same or different carbon atoms of the isoquinoline nucleus, each being hydrogen, halogen, hydroxy, C _1-6 alkyl, aryl, or R ₄ together with R ₅ Forms a-(CH ₂ ) _p -group, where _p is an integer from 1-5 and one or more-(CH ₂ ) _-moieties are optionally substituted with a C _1-6 alkyl group, and R ₆ and R _6a are May be the same or different, hydrogen C _1-6 alkyl, —CH ₂ OR ₆ b, halogen, hydroxy, C _1-6 alkoxy, C _1-6 alkoxycarbonyl, thiol, C _1-6 alkylthio, , -NHCOR _6d R _6e , NHSO ₂ R _6e , -CH ₂ SO ₂ NR _6f R _6g , wherein each of R _6a -R _6g is independently hydrogen, C _1-6 , alkyl aryl or aryl or aralkyl )ego; Provided that R ₄ , R ₅ , R ₆ and R _6a are not simultaneously hydrogen. The compound of claim 1, wherein each of R ₁ and R ₂ is methyl, ethyl, propyl, butyl, pentyl or hexyl. The compound of claim 1, wherein R ₁ and R ₂ together form a propylene, butylene, pentylene or hexylene group, or —CH ₂ —CH═CH—CH ₂ — group. The compound of any one of claims 1-3, wherein R is of the general formula (II): Wherein n is 0,1 or 2; m is 0,1 or 2; m 'is 0,1 or 2 (where m + m'≤2); X is a direct bond, or O, S or NR ₈ where R ₈ is hydrogen or C _1-6 alkyl; Ar is a substituted or unsubstituted carbocyclic or heterocyclic aromatic group; each of R ₇ and R _7a is C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _2-6 haloalkenyl, C _2-6 haloalkynyl, aryl, aralkyl, hydroxy, C _1-6 alkoxy , Thiol, C _1-6 alkylthio, C _1-6 haloalkoxy, C _1-6 haloalkylthio, halogen, NO ₂ , CN, CF ₃ , -OCF ₃ , -OCHF ₁ , -OCF ₂ CF ₁ H, -OCC _l2 CF ₃ , -COOR ₉ , -CONR ₁₀ R ₁₁ , -SO ₃ R ₁₂ , -SO ₂ NR ₁₃ R ₁₄ and -COR ₁₅ , wherein each of R ₉ -R ₁₅ is independently hydrogen, C _1-6 alkyl, aryl or aralkyl; or, when m is 2 and m 'is 0, two R ₇ ′ form a C _1-6 polymethylene group; R _7b is hydrogen or C _{1- 6} alkyl). The compound of claim 4, wherein Ar is phenyl. 6. The compound of claim 5, wherein R ₇ or R _7a is chlorine, bromine, NO ₂ or CF ₃ in a meta- or para-position. 7. The compound of claim 1, wherein R ₆ or R _6a is hydroxy, methyl, methoxy, colo, fluoro, methylthio or methoxy carbonyl. 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-3-methyl-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-4-methyl-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-5-chloro-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-5-fluoro-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-5-methel-1,2,3,4-tetrahydro isoquinoline; 1-dimethyl amino methyl-2- (3,4-dichloro phenyl) acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1-dimethyltyl amino methyl-2- (3,4-dichloro phenyl) acetyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; 1-dimethyltyl amino methyl-2- (3,4-dichloro phenyl) acetyl-5-chloro-1,2,3,4-tetrahydro isoquinoline; 1-dimethyltyl amino methyl-2- (3,4-dichloro phenyl) acetyl-6-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1-dimethyl amino methyl-2- (3,4-dichloro phenyl) acetyl-6-methoxy-1,2,3,4-tetrahydro isoquinoline; 1-dimethyltyl amino methyl-2- (3,4-dichloro phenyl) acetyl-6-chloro-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-6-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-6-chloro-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-7-hydrocy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-7-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-7-chloro-1,2,3,4-tetrahydro isoquinoline; 1-dimethyl aamino methyl-2- (3,4-dichloro phenyl) acetyl-7-methoxy-1,2,3,4-tetrahydro isoquinoline; 1-dimethyl aamino methyl-2- (3,4-dichloro phenyl) acetyl-7-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1-dimethyl aamino methyl-2- (3,4-dichloro phenyl) acetyl-7-chloro-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-8-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-8-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-8-chloro-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) eth-1-yl-2- (3,4-dichloro phenyl) acetyl-1,2,3,4-tetrahydro isoquinoline; 1-dimethyl aamino-eth-1-yl-2- (3,4-dichloro phenyl) -acetyl-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) acetyl-5-methylthio-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (4-trifluoro methyl phenyl) -acetyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (4-trifluoro methyl phenyl) -acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1- (piperidin-1-yl) methyl-2- (4-trifluoro methyl phenyl) acetyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (piperidin-1-yl) methyl-2- (3,4-dichloro methyl phenyl) -acetyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; 1- (piperidin-1-yl) methyl-2- (3,4-trifluoro methyl phenyl) -acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1- (piperidin-1-yl) methyl-2- (4-trifluoromethyl phenyl) -acetyl-5,6-dimethoxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-5,6-dihydroxy-1,2,3,4-tetrahydro isoquinoline; (+) 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-3-methyl-1,2,3,4-tetrahydro isoquinoline; (-)-1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-3-methyl-1,2,3,4-tetrahydro isoquinoline; (+)-1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-4-methyl-1,2,3,4-tetrahydro isoquinoline; (-)-1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-4-methyl-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-3,4-dimethyl-1,2,3,4-tetrahydro isoquinoline; 1- (piperidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-3,4-dimethyl) -1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-4-phenyl-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-5-acetoxy-1,2,3,4-tetrahydro isoquinoline; (+)-1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; (-)-1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro benzoyl) -acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (3,4-dichloro phenyl) -acetyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2- (2-thiophencarbonyl) -5-hydroxy-1,2,3,4-tetrahydro isoquinoline. A compound of formula (III); Wherein R ₁ ′ and R ₂ ′ are independently hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _3-6 cycloalkyl or C _4-12 cycloalkyl groups or together C _2-8 branched Or a linear polymethylene or C _2-6 alkenylene group (optionally substituted with a hetero atom); R ₃ ′ is hydrogen, C _1-6 alkyl, or phenyl, or R ₃ ′ with R ₁ ′-( CH ₂ ) ₃ )-or-(CH ₂ ) ₄ -to form a group; R ₄ ′ and R ₅ ′ may be the same or different and may be attached to the same or different carbon atoms of the isoquinoline nucleus, each being hydrogen, halogen, hydroxy, C _1-6 alkyl, aryl, or together with R ₅ ′ R ₄ ′ forms a — (CH ₂ ) _p group, where p is an integer from 1-5 and one or more — (CH ₂ ) _-moieties are optionally substituted with a C _1-6 alkyl group, and R ₆ ′ And R ⁶ _a ′ may be the same or different, hydrogen C _1-6 alkyl, —CH ₂ OR _6b , halogen, hydroxy, C _1-6 alkoxy, C _1-6 alkoxycarbonyl, thiol, C _{1 -6} alkylthio, , -NHCOR _6d , -NHSO ₂ R _6e , -CH ₂ SO ₂ NR _6f R _g , wherein each of R ₆₆ -R _6g is independently hydrogen, C _1-6 , alkyl, aryl or aralkyl ; Provided that R ₄ ′, R ₅ ′, R ₆ ′, and R _6a ′ are not hydrogen at the same time, or each may be converted to R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R _6, or R _6a Group or atom) with a general formula R ′ CO.OH compound wherein R ′ is a group containing a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring or convertable to R) or an active derivative thereof By reacting a compound of formula (Ia): And then, a) R ', R ₁ ', R ₂ ', R ₃ ', R ₄ ', R ₅ ', R ₆ 'and R _6a are R, R ₁ , R ₂ , R ₃ , R _4, R _5, R ₆ or when R6a different _{from, R ', R 1',} R 2 ', R 3, R 4', R 5 ', R 6' and R _6a 'to R, R _1, R ₂ Converting to R ₃ , R ₄ , R ₅ , R ₆ or R _6a to generalize to obtain the compound of general formula (I), b) R ', R1', R2 ', R3', R4 ', R5', When R6 'and R6a are R, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ or R _6a , R, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ or Converting R _6a to another R, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ or R _6a to obtain a compound of formula (I), (c) a compound of formula (I) obtained A process for preparing a compound according to any one of claims 1 to 8 comprising suitably carrying out one of the steps of forming a salt and / or a solvent compound. Compound of general formula (III): Wherein R ₁ ′ and R ₂ ′ are independently hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _3-6 cycloalkyl or C _4-12 cycloalkyl groups or together C _2-8 branched or To form a linear polymethylene or C _1-6 alkenylene group (optionally substituted with a heteroatom); R ₂ ′ is hydrogen, C _1-6 alkyl, phenyl, or together with R ₁ ′ R ₃ ′ forms a — (CH ₂ ) ₃ — or — (CH ₂ ) ₄ — group; R ₃ ′ is hydrogen, C _1-6 alkyl, or phenyl, or together with R ₁ ′ R ₃ ′ forms a — (CH ₂ ) ₃ —or- (CH ₂ ) ₄ — group; R ₄ ′ and R ₅ ′ may be the same or different and may be attached to the same or different carbon atoms of the isoquinoline nucleus, each being hydrogen, halogen, hydroxy, C _1-6 alkyl, aryl, or together with R ₅ ′ R ₄ ′ forms a — (CH ₂ ) _p— group where _p is an integer from 1-5 and one or more — (CH ₂ ) _-moieties are optionally substituted with a C _1-6 alkyl group, and R ₆ 'And R _6b ' may be the same or different, and hydrogen, C _1-6 and R _6G 'may be the same or different, respectively, hydrogen, C _1-6 alkyl, CH ₂ OR _6b , halogen, hydroxy, C _1-6 alkoxy, C _1-6 alkoxycarbonyl, thiol, C _1-6 alkylthio, , -NHCOR _6d , -NHSO ₂ R _6e , -CH ₂ SO ₂ NR _6f R _6e , wherein each of R _6b -R _6g is independently hydrogen, C _1-6 alkyl, aryl or aralkyl; Provided that R ₄ ′, R ₅ ′, R ₆ ′, and R _6a ′ are not simultaneously hydrogen, or each is converted to R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R _6, or R ₆ ⁽ Possible groups or atoms. 1- (pyrrolidin-1-yl) methyl-3-methyl-1,2,3,4-tetrahydro isoquinoline; 1-dimethylamino methyl-7-hydroxy-1,2,3,4--tetrahydro isoquinoline; 1- (pyrrolidin-1-yl) methyl-2-benzyloxycarbonyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; (-)-1- (pyrrolidin-1-yl) methyl-2-benzyloxycarbonyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; (+)-1- (pyrrolidin-1-yl) methyl-2-benzyloxycarbonyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; (+)-1- (pyrrolidin-1-yl) methyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; (-)-1- (pyrrolidin-1-yl) methyl-5-methoxy-1,2,3,4-tetrahydro isoquinoline; (+)-1- (pyrrolidin-1-yl) methyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; (-)-1- (pyrrolidin-1-yl) methyl-5-hydroxy-1,2,3,4-tetrahydro isoquinoline; Compound selected from. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. The unit dosage form and composition according to claim 12. The compound according to claim 1, for use as an active therapeutic substance. The compound of claim 1 for use in the treatment of pain. Use of a compound according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment of pain. ※ Note: The disclosure is based on the initial application.