EP1107944A1 - Derives d'aminoalcool et leur utilisation comme agonistes du recepteur beta-3-adrenergique - Google Patents

Derives d'aminoalcool et leur utilisation comme agonistes du recepteur beta-3-adrenergique

Info

Publication number
EP1107944A1
EP1107944A1 EP99938596A EP99938596A EP1107944A1 EP 1107944 A1 EP1107944 A1 EP 1107944A1 EP 99938596 A EP99938596 A EP 99938596A EP 99938596 A EP99938596 A EP 99938596A EP 1107944 A1 EP1107944 A1 EP 1107944A1
Authority
EP
European Patent Office
Prior art keywords
amino
alkyl
phenyl
hydroxy
bis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99938596A
Other languages
German (de)
English (en)
Inventor
Kiyoshi Taniguchi
Naoaki Fujii
Minoru Sakurai
Yasuyo Tomishima
Hisashi Takasugi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujisawa Pharmaceutical Co Ltd
Original Assignee
Fujisawa Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd
Publication of EP1107944A1 publication Critical patent/EP1107944A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
    • C07C215/54—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
    • C07C217/30—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/58—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/64—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
    • C07C217/66—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain
    • C07C217/72—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
    • C07C217/84—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
    • C07C217/86—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
    • C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/43—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
    • C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/28—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
    • C07C317/36—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atoms of the amino groups bound to hydrogen atoms or to carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/31—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/32—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to an acyclic carbon atom of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Definitions

  • This invention relates to new aminoalcohol derivatives and salts thereof which are ⁇ adrenergic receptor agonists and useful as a medicament.
  • This invention relates to new aminoalcohol derivatives which are ⁇ adrenergic receptor agonists and salts thereof.
  • new aminoalcohol derivatives and salts thereof which have gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic, anti-urinary incontinence and anti-pollakiuria activities, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of gastro-intestinal disorders caused by smooth muscle contractions in human beings or animal.
  • One object of this invention is to provide new and useful aminoalcohol derivatives and salts thereof which have gut selective sympathomimetic, anti-ulcerous, lipolytic, anti-urinary incontinence and anti-pollakiuria activities.
  • Another object of this invention is to provide processes for the preparation of said aminoalcohol derivatives and salts thereof.
  • the object aminoalcohol derivatives of this invention are new and can be represented by the following general formula [I] :
  • A is a heterocyclic group or aryl, each of which may have
  • substituent (s) selected from a group consisting of halogen, hydroxy, amino, lower alkyl, lower alkylsulfonylamino, phenyl (lower) alkoxy and phenyl (lower) alkoxycarbonylamino,
  • -X- is bond, -CH 2 -, -CH 2 -CH 2 -, -NH-CH 2 -, -0-CH 2 -, -S-CH 2 -, -SO-CH 2 - or -S0 2 -CH 2 -,
  • RH J - i- is hydrogen, hydroxy, lower alkoxy or acyloxy
  • R6 R8 -Z- is -(CH n -c- CH 2 J m -c :CH 2 ) k ⁇ r (CH 2'n /- ⁇ :CH* m
  • R 11 R 10 R 11 R 10 R 10 wherein R 10 is hydrogen or lower alkyl, and R is lower alkyl, R , R , R° and R" are each independently hydrogen, hydroxy, lower alkyl, lower alkenyl, lower alkoxy, lower alkoxy (lower) alkyl or aryl which may have 1 to 3 lower alkoxy, n, m and k is each independently 0 to 6, p is 0 to 4, q is 1 to 4, and r is 2 to 7) and
  • R 1 is hydrogen or an amino protective group
  • R , R , R 4 and R 5 are each independently hydrogen; lower alkyl; lower alkylthio; lower alkylsulfonyl; hydroxy; lower alkoxy; amino; lower alkylamino; acylamino; N- (lower alkyl) acylamino; carboxy; lower alkoxycarbonyl; carbamoyl optionally substituted with one or two lower alkyl; hydroxy (lower) alkyl; lower alkoxy (lower) alkyl;
  • N-acylamino (lower) alkyl N- (lower alkyl) -N- acylamino (lower) alkyl; carboxy (lower) alkyl; lower alkoxycarbonyl (lower) alkyl; carbamoyl (lower) alkyl optionally substituted with one or two lower alkyl; or
  • R 12 and R 13 are each independently hydrogen or lower alkyl, or R and R may be bonded to form a lower alkylene chain, and j is 0 to 6) .
  • the object compound [I] or a salt thereof can be prepared by the following processes. rocess 1
  • lower is intended to mean a group having 1 to 6 carbon atom(s), unless otherwise provided.
  • lower alkyl and “lower alkyl” moiety may include straight or branched one having 1 to 6 carbon atom(s), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylpentyl, tert-pentyl, neo-pentyl, hexyl, isohexyl and the like.
  • Suitable "lower alkenyl” may include vinyl, l-(or 2-)propenyl, l-(or 2- or 3-)butenyl, l-(or 2- or 3- or 4-)pentenyl, l-(or 2- or 3- or 4- or 5-)hexenyl, methylvinyl, ethylvinyl, l-(or 2- or 3-)methyl-l- (or 2-)propenyl, l-(or 2- or 3-) ethyl-1- (or 2-)propenyl, l-(or 2- or 3- or 4-)methyl-l- (or 2- or 3-)butenyl, and the like, in which more preferable example may be C -C 4 alkenyl.
  • Suitable "lower alkoxy” and “lower alkoxy” moiety may be a straight or branched one such as methoxy, ethoxy, propoxy, isopropoxy, 1-ethylpropoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, neopentyloxy, tert-pentyloxy, hexyloxy, and the like, in which the preferred one may be C ⁇ -C ⁇ j alkoxy, and the most preferred one may be methoxy.
  • halogen may be fluoro, chloro, bromo and iodo.
  • aryl and “ar” moiety may include phenyl, naphthyl, anthryl, and the like, in which the preferred one may be phenyl.
  • heterocyclic group may include unsaturated 3 to 8-membered (more preferably 5 or 6- membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1, 2, 4-triazolyl, 1H-1,2,3- triazolyl, 2H-1, 2, 3-triazolyl, etc.), tetrazolyl (e.g., 1H- tetrazolyl, 2H-tetrazolyl, etc.), etc.; saturated 3 to 8-membered (more preferably 5 or 6- membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolidinyl, imid
  • sulfur atom(s) for example, benzothienyl, benzodithiinyl, etc.
  • amino protective group may be common amino protective group such as acyl, for example, substituted or unsubstituted lower alkanoyl [e.g. formyl, acetyl, propionyl, trifluoroacetyl, etc.], phthaloyl, lower alkoxycarbonyl [e.g. tert-butoxycarbonyl, tert-amyloxy- carbonyl, etc.], substituted or unsubstituted aralkyloxy- carbonyl [e.g. benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, etc.], substituted or unsubstituted arenesulfonyl [e.g.
  • benzenesulfonyl, tosyl, etc.] nitrophenylsulfenyl, ar (lower) alkyl [e.g. trityl, benzyl, etc.], and the like, in which preferable one is phenyl (lower ) alkyl such as benzyl.
  • Suitable "acyl” and “acyl” moiety may be carboxy; esterified carboxy; carbamoyl optionally substituted with one or two lower alkyl; lower alkylsulfonyl [e.g. methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl, hexylsulfonyl, etc.]; substituted or unsubstituted lower alkanoyl [e.g.
  • esterified carboxy may be substituted or unsubstituted lower alkoxycarbonyl [e.g.
  • 2-naphthyloxycarbonyl, etc.] substituted or unsubstituted ar (lower) alkoxycarbonyl e.g. benzyloxycarbonyl, phenethyloxycarbonyl , benzhydryloxycarbonyl , 4-nitrobenzyloxycarbonyl, etc.
  • ar (lower) alkoxycarbonyl e.g. benzyloxycarbonyl, phenethyloxycarbonyl , benzhydryloxycarbonyl , 4-nitrobenzyloxycarbonyl, etc.
  • lower alkylsulfonylamino may include methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, butylsulfonylamino, pentylsulfonylamino, hexylsulfonylamino, and the like, in which the preferred one may be (C ⁇ _-C 4 ) alkylsulfonylamino, and the most preferred one may be methylsulfonylamino.
  • heterocyclic group in A can be referred to aforementioned “heterocyclic group", in which the preferred one may be unsaturated 3 to 8-membered (more preferably 5 or ⁇ -membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s) or unsaturated condensed heterocyclic group containing 1 to 4 nitrogen atom(s), and the most preferred one may be pyridyl, indolyl or 2-oxo-2, 3-dihydro- lH-benzimidazolyl .
  • the lower alkylene chain formed by R' and R° is a straight or branched chain alkylene having 1 to 6 carbon atoms and is exemplified by methylene, ethylene, trimethylene, propylene, butylene, 1, 2-dimethylethylene, pentamethylene and hexamethylene .
  • A is pyridyl, indolyl, 2-oxo-2, 3-dihydro-lH-benzimidazolyl or phenyl, each of which may have 1 to 3 same or different substituent (s) selected from a group of hydroxy, amino lower alkyl (more preferably methyl), lower alkylsulfonylamino (more preferably methanesulfonylamino) , phenyl (lower) alkoxy (more preferably benzyloxy) and phenyl (lower) alkoxycarbonylamino (more preferably benzyloxycarbonylamino) ,
  • -X- is bond, -CH 2 -, -CH 2 -CH 2 -, -0-CH 2 - or -S0 2 ⁇ CH 2 -,
  • ⁇ Y -_ is _ C - (in which R is hydrogen or hydroxy)
  • -Z- is -(CH 2 ) n -C-(CH 2 ) m -C-(CH 2 ) k -, "(CH 2 ) n -—C—-(CH 2 ) m - or
  • -Q- is -CH-CO-N- or -CH-CH 2 -N-, wherein
  • R ⁇ is hydrogen or lower alkyl (more preferably methyl) and
  • RU is lower alkyl (more preferably methyl) ,
  • R! is hydrogen or ar (lower) alkyl (more preferably benzyl), and R 2 , R , R 4 and R 5 are each independently hydrogen; lower alkyl (more preferably methyl) ; lower alkylthio (more preferably methylthio) ; lower alkylsulfonyl (more preferably methanesulfonyl) ; hydroxy; lower alkoxy (more preferably methoxy or ethoxy) ; amino; lower alkylamino (more preferably methylamino) ; acylamino (more preferably lower alkoxycarbonylamino, lower alkylsulfonylamino, lower alkanoylamino, ureido or trifluoroacetylamino, most preferably methoxycarbonylamino, ethoxycarbonylamino, methanesulfonylamino, formylamino, acetylamino or propionylamino) ; N
  • A is phenyl each of which may have 1 to 3 same or different substituent (s) selected from a group of hydroxy, amino, lower alkylsulfonylamino (more preferably methanesulfonylamino) and phenyl (lower) alkoxy (more preferably benzyloxy)
  • -X- is bond, -CH 2 -, -CH 2 -CH 2 ⁇ , -0-CH - or -S0 2 -CH 2 -, ⁇ Y; is ⁇ 9 C ⁇ -- (i- n which R 11 is hydrogen or hydroxy),
  • R , R , R 8 and R are each independently hydrogen, lower alkyl (more preferably methyl) or phenyl which may have 1 to 3 lower alkoxy (more preferably methoxy) , n, m and k is each independently 0 or 1), R is hydrogen or phenyl (lower) alkyl (more preferebly benzyl) , and
  • R , R , R 4 and R 5 are each independently hydrogen; lower alkyl (more preferably methyl); lower alkylthio (more preferably methylthio) ; lower alkylsulfonyl (more preferably methanesulfonyl) ; hydroxy; lower alkoxy (more preferably methoxy or ethoxy) ; amino; lower alkylamino
  • Suitable salts of the object aminoalcohol derivatives [I] are pharmaceutically acceptable salts and include conventional non-toxic salts such as an inorganic acid addition salt [e.g. hydrochloride, hydrobromide, sulfate, phosphate, etc.], an organic acid addition salt [e.g. formate, acetate, trifluoroacetate, oxalate, maleate, fumarate, tartrate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.], an alkali metal salt [e.g. sodium salt, potassium salt, etc.] or the like.
  • an inorganic acid addition salt e.g. hydrochloride, hydrobromide, sulfate, phosphate, etc.
  • an organic acid addition salt e.g. formate, acetate, trifluoroacetate, oxalate, maleate, fumarate, tartrate, methanesulfonate, benzen
  • the object compound [I] or a salt thereof can be prepared by reacting a compound [II] with a compound [III] or a salt thereof.
  • Suitable salt of the compound [III] may be the same as those exemplified for the compound [I] .
  • the reaction is preferably carried out in the presence of a base such as an alkali metal carbonate [e.g. sodium carbonate, potassium carbonate, etc.], an alkaline earth metal carbonate [e.g. magnesium carbonate, calcium carbonate, etc.], an alkali metal bicarbonate [e.g. sodium bicarbonate, potassium bicarbonate, etc.], tri (lower) alkylamine [e.g. trimethylamine, triethylamine, etc.], picoline or the like.
  • the reaction is usually carried out in a conventional solvent, such as an alcohol [e.g. methanol, ethanol, propanol, isopropanol, etc.], diethyl ether, tetrahydrofuran, dioxane, or any other organic solvent which does not adversely influence the reaction.
  • the reaction temperature is not critical, and the reaction can be carried out under cooling to heating.
  • the object compound [lb] or a salt thereof can be prepared by subjecting a compound [la] or a salt thereof to elimination reaction of the amino protective group.
  • Suitable salts of the compounds [la] and [lb] may be the same as those exemplified for the compound [I].
  • This reaction is carried out in accordance with a conventional method such as hydrolysis, reduction or the like.
  • the hydrolysis is preferably carried out in the presence of a base or an acid including Lewis acid.
  • Suitable base may include an inorganic base and an organic base such as an alkali metal [e.g. sodium, potassium, etc.], an alkaline earth metal [e.g. magnesium, calcium, etc.], the hydroxide or carbonate or bicarbonate thereof, hydrazine, trialkylamine [e.g. trimethylamine, triethylamine, etc.], picoline, 1, 5-diazabicyclo [4.3.0] non-5-ene, 1, 4-diazabicyclo [2.2.2] octane, 1, 8-diazabicyclo [5.4.0] undec- 7-ene, or the like.
  • an alkali metal e.g. sodium, potassium, etc.
  • an alkaline earth metal e.g. magnesium, calcium, etc.
  • the hydroxide or carbonate or bicarbonate thereof hydrazine
  • trialkylamine e.g. trimethylamine, triethylamine, etc.
  • picoline 1, 5-diazabicyclo [
  • Suitable acid may include an organic acid [e.g. formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.], an inorganic acid [e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, hydrogen fluoride, etc.] and an acid addition salt compound [e.g. pyridine hydrochloride, etc. ] .
  • organic acid e.g. formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.
  • an inorganic acid e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, hydrogen fluoride, etc.
  • an acid addition salt compound e.g. pyridine hydrochloride, etc.
  • trihaloacetic acid e.g. trichloroacetic acid, trifluoroacetic acid, etc.
  • cation trapping agents e.g. anisole, phenol, etc.
  • the reaction is usually carried out in a solvent such as water, an alcohol [e.g. methanol, ethanol, etc.], methylene chloride, chloroform, tetrachloromethane, tetrahydrofuran, a mixture thereof or any other solvent which does not adversely influence the reaction.
  • a liquid base or acid can be also used as the solvent.
  • the reaction temperature is not critical and the reaction is usually carried out under cooling to heating.
  • the reduction method applicable for the elimination reaction may include chemical reduction and catalytic reduction.
  • Suitable reducing agents to be used in chemical reduction are a combination of metal [e.g. tin, zinc, iron, etc.] or metallic compound [e.g. chromium chloride, chromium acetate, etc.] and an organic or inorganic acid [e.g. formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, etc. ] .
  • metal e.g. tin, zinc, iron, etc.
  • metallic compound e.g. chromium chloride, chromium acetate, etc.
  • organic or inorganic acid e.g. formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, etc.
  • Suitable catalysts to be used in catalytic reduction are conventional ones such as platinum catalysts [e.g. platinum plate, spongy platinum, platinum black, colloidal platinum, platinum oxide, platinum wire, etc.], palladium catalysts [e.g. spongy palladium, palladium black, palladium oxide, palladium on carbon, colloidal palladium, palladium on barium sulfate, palladium on barium carbonate, etc.], nickel catalysts [e.g. reduced nickel, nickel oxide, Raney nickel, etc.], cobalt catalysts [e.g. reduced cobalt, Raney cobalt, etc.], iron catalysts [e.g. reduced iron, Raney iron, etc.], copper catalysts [e.g.
  • platinum catalysts e.g. platinum plate, spongy platinum, platinum black, colloidal platinum, platinum oxide, platinum wire, etc.
  • palladium catalysts e.g. spongy palladium, palladium black, palladium oxide, palladium on carbon
  • the reduction is preferably carried out in the presence of a combination of palladium catalysts [e.g. palladium black, palladium on carbon, etc.] and formic acid or its salt [e.g. ammonium formate, etc.].
  • the reduction is usually carried out in a conventional solvent which does not adversely influence the reaction such as water, an alcohol [e.g. methanol, ethanol, propanol, etc.], chlorobenzene, N,N-dimethylformamide, or a mixture thereof.
  • a solvent which does not adversely influence the reaction
  • an alcohol e.g. methanol, ethanol, propanol, etc.
  • chlorobenzene N,N-dimethylformamide, or a mixture thereof.
  • the above-mentioned acids to be used in chemical reduction are in liquid, they can also be used as a solvent.
  • a suitable solvent to be used in catalytic reduction may be the above-mentioned solvent, and other conventional solvent such as diethyl ether, dioxane, tetrahydrofuran, etc. or a mixture thereof.
  • the reaction temperature of this reduction is not critical and the reaction is usually carried out under cooling to heating.
  • the compounds obtained by the above processes can be isolated and purified by a conventional method such as pulverization, recrystallization, column chromatography, reprecipitation, or the like, and converted to the desired salt in conventional manners, if necessary.
  • the compound [I] and the other compounds may include one or more stereoisomers due to asymmetric carbon atoms, and all of such isomers and mixture thereof are included within the scope of this invention.
  • isomerization or rearrangement of the object compound [I] may occur due to the effect of the light acid, base or the like, and the compound obtained as the result of said isomerization or rearrangement is also included within the scope of the present invention.
  • the solvating form of the compound [I] e.g. hydrate, etc.
  • any form of the crystal of the compound [I] are included within the scope of the present invention.
  • the object compound [I] or a salt thereof possesses gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic and anti-pollakiuria activities, and are useful for the treatment and/or prevention of gastro-intestinal disorders caused by smooth muscle contractions in human beings or animals, and more particularly to methods for the treatment and/or prevention of spasm or hyperanakinesia in case of irritable bowel syndrome, gastritis, gastric ulcer, duodenal ulcer, enteritis, cholecystopathy, cholangitis, urinary calculus and the like; for the treatment and/or prevention of ulcer such as gastric ulcer, duodenal ulcer, peptic ulcer, ulcer causes by non steroidal anti-inflammatory drugs, or the like; for the treatment and/or prevention of dysuria such as pollakiuria, urinary incontinence or the like in case of nervous pollakiuria, neurogenic bladder dysfunction, nocturia, unstable bladder, cystospasm, chronic cystitis,
  • reaction mixture was poured into IN hydrochloric acid and the mixture was stirred under ice cooling for 20 minutes.
  • the organic layer was separated, washed with an aqueous solution of sodium fluoride and a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate, and evaporated in vacuo.
  • reaction mixture was worked up in the usual manner and purified by a silica gel column chromatography to give (2S) -l-phenoxy-3- [ (3RS) -1, 1-bis [4- (methylthio) phenyl] -l-hydroxy-3-butyl] amino-3-propanol (58.5 mg) .
  • Example 7 The following compounds were obtained according to a similar manner to that of Example 6.
  • Example 11 The following compound was obtained according to a similar manner to that of Example 10.
  • Example 15 To a mixture of (2S) -l-phenoxy-3- [3, 3-bis (4- methoxyphenyl) -3-hydroxypropyl] amino-2-propanol (34 mg) , triethylsilane (0.5 ml) and dichloromethane (1 ml), trifluoroacetic acid (0.1 ml) was added dropwise at room temperature. The reaction mixture was worked up immediately in the usual manner and purified by silica gel preparative TLC (eluent; 10% methanol/dichloromethane) to give (2S)-1- phenoxy-3- [3, 3-bis (4-methoxyphenyl) propyl] amino-2-propanol trifluoroacetate (21 mg) .
  • (2S) -l-Phenoxy-3- [N- (benzyl- [ (3RS) -1, 1-bis [4- [ (methoxycarbonyl) amino] phenyl] -1-hydroxy-3-butyl] amino] -2- propanol (99 mg) was hydrogenated in the usual manner to give (2S) -l-phenoxy-3- [ (3RS) -1, 1-bis [4- [ (methoxycarbonyl) amino] - phenyl] -3-butyl] amino-2-propanol (58 mg) .
  • (2S) -l-Phenoxy-3- [ (3RS) -1, 1-bis [4- [N-methyl- (methoxycarbonyl) amino] phenyl] -l-hydroxy-3-butyl] amino-2- propanol (30 mg) was obtained from (2S) -l-phenoxy-3- [N- benzyl- [ (3RS) -1, 1-bis [4- [N-methyl- (methoxycarbonyl) amino] - phenyl] -l-hydroxy-3-butyl] amino] -2-propanol (60 mg) by the usual hydrogenation.
  • Example 45 Under nitrogen, to a solution of 4, 4-bis (4- methoxyphenyl) -2-butanone (187 mg) and ( IRS) -2-amino-l- (2- methylpyridin-6-yl) ethanol (100 mg) prepared from 6- methylpyridin-2-carboxaldehyde and trimethylsilylcyanide catalized with zinc iodide followed by reduction with lithium aluminum hydride, in 1, 2-dichloroethane (10 ml) was added sodium triacetoxyborohydride (257 mg) at room temperatue, and the mixture was stirred at the same temperature for 24 hours. The resulting mixture was poured into saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate.
  • Example 52 The following compounds were obtained according to a similar manner to that of Example 51.
  • (2S) -l-Phenoxy-3- [N-benzyl- [3, 3-bis [4- [ (methoxycarbonyl) amino] phenyl] propyl] amino] -2-propanol (18.8 mg) was hydrogenated in a usual manner to give (2S) -l-phenoxy-3- [ [3, 3-bis [4- [ (methoxycarbonyl) amino] phenyl] propyl] amino] -2- propanol (8.1 mg) .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyridine Compounds (AREA)
  • Indole Compounds (AREA)

Abstract

La présente invention concerne de nouveaux dérivés d'aminoalcool et leurs sels, représentés par la formule (I), dans laquelle chaque symbole est tel que défini dans le descriptif. Lesdits dérivés et leurs sels font office d'agonistes du récepteur β3-adrénergique, et ils exercent, de ce fait, une activité sélective pour le tube digestif, sympathomimétique, anti-ulcéreuse, anti-pancréatite, lipolytique, anti-incontinence urinaire et antipollakiurie. L'invention concerne également des procédés de préparation de ces composés, une composition pharmaceutique les contenant, ainsi qu'un procédé de prévention et/ou de traitement des maladies indiquées dans le descriptif chez l'homme ou chez l'animal.
EP99938596A 1998-08-26 1999-08-23 Derives d'aminoalcool et leur utilisation comme agonistes du recepteur beta-3-adrenergique Withdrawn EP1107944A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AUPP5499A AUPP549998A0 (en) 1998-08-26 1998-08-26 New compound
AUPP549998 1998-08-26
PCT/JP1999/004538 WO2000012462A1 (fr) 1998-08-26 1999-08-23 Derives d'aminoalcool et leur utilisation comme agonistes du recepteur beta-3-adrenergique

Publications (1)

Publication Number Publication Date
EP1107944A1 true EP1107944A1 (fr) 2001-06-20

Family

ID=3809726

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99938596A Withdrawn EP1107944A1 (fr) 1998-08-26 1999-08-23 Derives d'aminoalcool et leur utilisation comme agonistes du recepteur beta-3-adrenergique

Country Status (12)

Country Link
EP (1) EP1107944A1 (fr)
JP (1) JP2002523484A (fr)
KR (1) KR20010082178A (fr)
CN (1) CN1323289A (fr)
AR (1) AR020276A1 (fr)
AU (1) AUPP549998A0 (fr)
BR (1) BR9913377A (fr)
CA (1) CA2341458A1 (fr)
HK (1) HK1042081A1 (fr)
HU (1) HUP0103347A3 (fr)
TW (1) TW482753B (fr)
WO (1) WO2000012462A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPQ407699A0 (en) * 1999-11-16 1999-12-09 Fujisawa Pharmaceutical Co., Ltd. Aminoalcohol derivatives
AUPQ575300A0 (en) * 2000-02-21 2000-03-16 Fujisawa Pharmaceutical Co., Ltd. New compound
AUPR034000A0 (en) 2000-09-25 2000-10-19 Fujisawa Pharmaceutical Co., Ltd. Aminoalcohol derivatives
AUPR120400A0 (en) * 2000-11-02 2000-11-23 Fujisawa Pharmaceutical Co., Ltd. New compound
JP4044740B2 (ja) * 2001-05-31 2008-02-06 信越化学工業株式会社 レジスト材料及びパターン形成方法
WO2003024483A1 (fr) * 2001-09-11 2003-03-27 Fujisawa Pharmaceutical Co., Ltd. Potentialisateur d'effets inhibiteurs sur la frequence des mictions et l'incontinence urinaire
CN101039902B (zh) * 2004-09-21 2010-11-10 安斯泰来制药有限公司 氨基醇衍生物
DE102004050952A1 (de) * 2004-10-18 2006-04-20 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmazeutische Zusammensetzung zur Behandlung von Beschwerden, die mit krankhaften Veränderungen oder Irritationen der Prostata verbunden sind
EP2096105A1 (fr) * 2008-02-28 2009-09-02 Laboratorios Almirall, S.A. Dérivés de 4-(2-amino-1-hydroxyethyl)phénol en tant qu'antagonistes du récepteur adrénergique b2

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5451677A (en) * 1993-02-09 1995-09-19 Merck & Co., Inc. Substituted phenyl sulfonamides as selective β 3 agonists for the treatment of diabetes and obesity
US5726165A (en) * 1994-07-29 1998-03-10 Smithkline Beecham P.L.C. Derivatives of 4-(2-aminoethyl)phenoxymethyl-phosphonic and -phosphinic acid and pharmaceutical and veterinary uses therefor
PL318381A1 (en) * 1994-07-29 1997-06-09 Smithkline Beecham Plc Derivatives of aryloxy- and arylothiopropanoloamine useful as agonists of beta3-adrenoreceptor and antagonists of beta1 and beta2 adrenoreceptors and their pharmaceutic composition
US5541204A (en) * 1994-12-02 1996-07-30 Bristol-Myers Squibb Company Aryloxypropanolamine β 3 adrenergic agonists
FR2746395B1 (fr) * 1996-03-22 1998-04-17 Adir Nouveaux derives d'arylethanolamine et d'aryloxypropanolamine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0012462A1 *

Also Published As

Publication number Publication date
AR020276A1 (es) 2002-05-02
KR20010082178A (ko) 2001-08-29
AUPP549998A0 (en) 1998-09-17
CA2341458A1 (fr) 2000-03-09
BR9913377A (pt) 2001-10-02
TW482753B (en) 2002-04-11
HK1042081A1 (zh) 2002-08-02
HUP0103347A3 (en) 2002-08-28
WO2000012462A1 (fr) 2000-03-09
JP2002523484A (ja) 2002-07-30
CN1323289A (zh) 2001-11-21
HUP0103347A2 (hu) 2002-05-29

Similar Documents

Publication Publication Date Title
US20030073846A1 (en) Aminoalcohol derivatives
US7629366B2 (en) Aminoalcohol derivatives
EP0749424B1 (fr) Derives de naphtalene utilises comme agonistes de la prostaglandine i2
WO2001036375A1 (fr) Dérivés d'amino alcools utiles pour le traitement de troubles gastro-intestinaux
US7217706B2 (en) Propanolamine derivatives
WO2000012462A1 (fr) Derives d'aminoalcool et leur utilisation comme agonistes du recepteur beta-3-adrenergique
EP1389185A2 (fr) Derives d'amino-alcool
US20040138462A1 (en) Aminoalcohol derivatives
US7417060B2 (en) Aminoalcohol derivatives
US20030181726A1 (en) Aminoalcohol derivatives and their use as beta 3 adrenergic agonists
US20040106653A1 (en) Aminoalcohol derivatives
US20030032834A1 (en) Aminoalcohol derivatives
AU5305199A (en) Aminoalcohol derivatives and their use as beta 3 adrenergic agonists
WO1994025427A1 (fr) Derives d'ethanolamine utilises pour le traitement de troubles gastro-intestinaux
MXPA01002132A (en) Aminoalcohol derivatives and their use as beta 3 adrenergic agonists
WO2005110981A1 (fr) Dérivés d'aminoalcools

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010214

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

17Q First examination report despatched

Effective date: 20020213

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20050804