Diaminomethylidene derivatives

• US 5,753,654 A
• Filed: 11/07/1996
• Issued: 05/19/1998
• Est. Priority Date: 05/18/1994
• Status: Expired due to Fees

• Current Assignee: Nisshin Seifun Group Incorporated
• Original Assignee: Nisshin Flour Milling Incorporated (Nisshin Seifun Group Incorporated)
• Inventors: Satoh, Hiroaki, Suzuki, Masashi, Arai, Takeo, Kikuchi, Haruhiko, Inomata, Kohei, Hagihara, Koichiro, Mino, Setsuko, Fukutomi, Ruta, Eguchi, Haruko
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Ngo, Tamthom T.
• Application Number:
  US08/737,133
• Time in Patent Office: 558 Days
• Field of Search: 544/105, 544/121, 544/162, 514/230.5
• US Class Current: 514/230.5
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07D 265/30 not condensed with other rings
• CPC Class Codes: C07D 265/36 condensed with one six-membered ring
• CPC Class Codes: C07D 413/00 Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms

Abstract

Novel diaminomethylidene derivatives represented by formula (I) ##STR1## wherein R¹ is a hydrogen atom, a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group and others, R² is a group of the following formula ##STR2## and others, R³ is a hydrogen atom, a C₁ -C₆ alkyl group and others, X is O, S, CHNO₂, C(COOR⁴)₂, C(COOR⁴)CN or C(CN)₂) or pharmacologically acceptable salts thereof.

The above-mentioned compounds are useful as a gastrointestinal prokinetic agent to be used for the treatment of digestive tract diseases.

Claims

1. A diaminomethylidene derivative represented by formula (I) ##STR44## wherein R¹ is a hydrogen atom, a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group, a C₃ -C₆ cycloalkyl C₁ -C₁ alkyl group, an aryl group or an aryl C₁ -C₄ alkyl group, in which the aryl moiety of the aryl group or aryl C₁ -C₄ alkyl group may be optionally substituted with a halogen atom, a C₁ -C₆ alkyl group, a halo C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group, a C₁ -C₆ alkoxycarbonyl group, a phenyl group or an amino group;

X is O, S, CHNO₂, C(COOR⁴)₂, C(COOR⁴)CN or C(CN)₂, in which R⁴ is a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group, an aryl group, or an aryl C₁ -C₄ alkyl group;

R² is a group of the following general formulae (II)-(III);

##STR45## wherein R⁵ is a C₁ -C₆ alkyl group, an aryl C₁ -C₄ alkyl group, or an aryloxy C₂ -C₆ alkyl group, or in which the aryl moiety of the said groups may be optionally substituted with a halogen atom, a C₁ -C₆ alkyl group, a halo C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group, a C₁ -C₆ alkoxycarbonyl group, a phenyl group or an amino group,

Z¹ and Z² are O;

R³ is a hydrogen atom, a C₁ -C₆ alkyl group or a C₁ -C₆ alkoxy C₂ -C₆ alkyl group;

provided that there is excluded a compound wherein R¹ is an aryl group, X is O, and R² is a group of formula (II) wherein R⁵ is a C₁ -C₂ alkyl group or a pharmacologically acceptable salt thereof.

2. The compound of claim 1, represented by formula (I) wherein

X is O, S, CHNO₂, C(COOR⁴)₂, C(COOR⁴)CN, or C(CN)₂, in which R⁴ is a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group, a phenyl group, or a phenyl C₁ -C₄ alkyl group;

when X is O, R¹ is a C₁ is a C₆ alkyl group, when X is S, CHNO₂, C(COOR⁴)₂, C(COOR⁴)CN or C(CN)₂, R¹ is a hydrogen atom, a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group, a phenyl group, a naphthyl group, a C₃ -C₆ cycloalkyl C₁ -C₄ alkyl group, or a phenyl C₁ -C₄ alkyl group, in which the phenyl moiety of the phenyl group, naphthyl group or phenyl C₁ -C₄ alkyl group may be optionally mono- to tri-substituted with a halogen atom, a C₁ -C₆ alkyl group, a halo C_1-6 alkyl group, a C_1-6 alkoxy group, a C_1-6 alkoxycarbonyl group, or a phenyl group;

R² is a group of formula (II) wherein R⁵ is a C₁ -C₆ alkyl group, a phenyl C₁ -C₄ alkyl group, a naphthyl C₁ -C₄ alkyl group, or a phenoxy C₂ -C₆ alkyl group, in which the phenyl, phenoxy or naphthyl moiety may be optionally mono- to tri-substituted with a halogen atom, a C₁ -C₆ alkyl group, a halo C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group, a C₁ -C₆ alkoxycarbonyl group, or a phenyl group, Z¹ is O;

R³ is a hydrogen atom, a C₁ -C₆ alkyl group or a C₁ -C₄ alkoxy C₂ -C₄ alkyl group or a pharmacologically acceptable salt thereof.

3. The compound of claim 1, represented by formula (I) wherein

R¹ is a hydrogen atom, a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group, a phenyl group, a naphthyl group, a C₃ -C₆ cycloalkyl C₁ -C₄ alkyl group, or a phenyl C₁ -C₄ alkyl group, in which the phenyl moiety of the phenyl group, naphthyl group or phenyl C₁ -C₄ alkyl group may be optionally mono- to tri-substituted with a halogen atom, a C₁ -C₆ alkyl group, a halo C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group, a C₁ -C6 alkoxycarbonyl group, or a phenyl group;

X is O, S, CHNO₂, C(COOR⁴)₂, C(COOR⁴)CN or C(CN)₂, in which R⁴ is a C₁ -C₆ alkyl group, a C₃ -C₆ cycloalkyl group, a phenyl group, or a phenyl C₁ -C₄ alkyl group;

R² is a group of formula (III) wherein R⁵ is a C₁ -C₆ alkyl group, a phenyl C₁ -C₄ alkyl group, a naphthyl C₁ -C₄ alkyl group, or a phenoxy C₂ -C₆ alkyl group, in which the phenyl, phenoxy or naphthyl moiety may be optionally mono- to tri-substituted with a halogen atom, a C₁ -C₆ alkyl group, a halo C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group, a C₂ -C₆ alkoxycarbonyl group, or a phenyl group, Z² is O;

R³ is a hydrogen atom, a C₁ -C₆ alkyl group or a C₁ -C₄ alkoxy C₂ -C₄ alkyl group or a pharmacologically acceptable salt thereof.

4. A gastrointestinal prokinetic pharmaceutical composition which comprises as an active ingredient a compound represented by formula (I) as defined in claim 1 or a pharmacologically acceptable salt thereof, if necessary, in admixture with a pharmaceutically acceptable additive.

5. The gastrointestinal prokinetic pharmaceutical composition of claim 4, for use in the therapy of digestive tract disorders derived from chronic gastritis, diabetes mellitus, post-gastrectomy and peptic ulcer and digestive tract diseases including reflux esophagitis, irritable bowel syndrome with constipation as a chief complaint and spurious ileus.