Santen Pharmaceutical Co., Ltd.

Ayumi Pharmaceutical Corporation

Miwa Takai

Toshiyuki Mori

Masatomo Kato

Mamoru Matsuda

Masato Nagatsuka

Sachiko Kobayashi

Minoru Yamamoto

Kenji Kawashima

Tomoko Oda

Takahiro Matsuyama

Tatsuji Kurose

Yumi Hagiwara

Hiroyuki Aono

Kenji Oki

Atsuyoshi Dota

Kenji Imoto

A 1,2,3,4-tetrahydroquinoxaline compound represented by the following formula: In the formula (1), Rrepresents substituents such as a halogen, an alkyl, a cycloalkyl, an aryl or a heterocyclic group; p represents 0 to 5; Rrepresents substituents such as a halogen, an alkyl, a hydroxyl or an alkoxy group; q represents 0 to 2; Rrepresents substituents such as hydrogen, an alkyl, an alkenyl, an alkylcarbonyl or an arylcarbonyl group; Rand Rindependently represent substituents such as hydrogen, a halogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl or a heterocyclic group; Rrepresents substituents such as hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl or a heterocyclic group; A represents an alkylene; Rrepresents OR, NRR, SR, S(O)R, S(O)R; Rand Rindependently represent substituents such as hydrogen, an alkyl or an alkenyl; and X represents O or S.

1,2,3,4-tetrahydroquinoxaline compounds having glucocorticoid receptor binding activity

The object aims to find a novel pharmacological activity of a novel 1,2,3,4-tetrahydroquinoxaline derivative which contains, as a substituent, a phenyl group having a sulfonic acid ester structure introduced therein. A compound represented by general formula (1) or a salt thereof is useful as a glucocorticoid receptor agonist, particularly as a therapeutic agent for diseases against which a glucocorticoid receptor agonist (e.g., a steroid) is believed to be effective, such as inflammatory bone/joint diseases, inflammatory ophthalmic diseases (inflammatory ophthalmic diseases in the anterior or posterior segment of an eye). Rrepresents a group represented by general formula (2a), (3a), (4a) or (5a); Rrepresents a lower alkyl group which may have a substituent, a lower cycloalkyl group which may have a substituent, or the like; Rrepresents a lower alkyl group; R, R, Ror Rrepresent a halogen atom, a lower alkyl group which may have a substituent, a hydroxy group, a lower alkoxy group which may have a substituent, or the like; and m, n, p or q represents a number of 0, 1 or 2. 

Method for treating an inflammatory disease by administering a 1,2,3,4- tetrahydroquinoxaline compound containing a phenyl group having a sulfonic acid ester structure introduced therein as a substituent

A method for preventing or treating a disease related to the glucocorticoid receptor involving administering a pharmacologically effective amount of a 1,2-dihydroquinoline compound.

Method for treating a disease related to the glucocorticoid receptor

A method for preventing or treating a metabolic disorder, an inflammatory disease, an autoimmune disease, an allergic disease, a central nervous system disease, a cardiovascular disease, a homeostasis-related disease or glaucoma, involving administering a compound or a salt thereof, the compound having the following formula (1): wherein Rrepresents alkyl, cycloalkyl, aryl, heterocyclic or aralkyl; Rrepresents cycloalkyl, aryl or heterocyclic; W represents oxygen or NR, Y represents alkylene, Z represents oxygen, sulfur, OCO or NR; R, R, R, R, Rand Rrepresent hydrogen or alkyl.

Method for treating a homeostasis-related disease or glaucoma by administering a 1,2,3,4-tetrahyroquinoxaline compound

A method for preventing or treating a disease related to the glucocorticoid receptor involving administering a pharmacologically effective amount of a 1,2-dihydroquinoline compound or a pharmaceutically acceptable salt thereof.

Method for preventing or treating a disease related to the glucocorticoid receptor

An object of the present invention is to synthesize a novel 1,2,3,4-tetrahydroquinoxaline derivative represented by formula (1) and to find a pharmacological action of the derivative. In the formula, the Rrepresents a halogen, an alkyl, cycloalkyl, aryl or heterocyclic group, or the like; p represents 0 to 5; Rrepresents a halogen, an alkyl, hydroxyl or alkoxy group, or the like; q represents 0 to 2; Rrepresents hydrogen, an alkyl, alkenyl, alkylcarbonyl or arylcarbonyl group, or the like; Rand Rindependently represent hydrogen, a halogen, an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclic group, or the like; Rrepresents hydrogen, an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclic group, or the like; A represents an alkylene; Rrepresents OR, NRR, SR, S(O)R, S(O)R; and X represents O or S. 

1,2,3,4-tetrahydroquinoxaline derivative having glucocorticoid receptor binding activity

A method for treating a disease related to the glucocorticoid receptor involving administering a pharmacologically effective amount of a 1,2-hydroquinoline compound.

The present invention is related to glucocorticoid receptor agonists comprised of a compound represented by formula (1) which is 2,2,4-trimethyl-6-phenyl-1,2-dihydroquinoline derivative or a salt thereof and novel pharmacological effects of the glucocorticoid receptor agonists. In the formula (1), Rrepresents formula (2a), (3a), (4a) or (5a); R2 represents &#x2014;(CO)&#x2014;R8, &#x2014;(CO)O&#x2014;R9, or the like; R&#x2014;O&#x2014; is substituted at the 4- or -5-position of benzene ring A; Rrepresents a lower alkyl group; R, R, Ror Rrepresents a halogen atom, a lower alkyl group which may have a substituent, or the like; m, n, p or q represents 0, 1 or the like; R, Ror the like represents a lower alkyl group which may have a substituent, a lower alkenyl group, or the like. 

Glucocorticoid receptor agonist comprising 2,2,4-trimethyl-6-phenyl-1,2-dihydroquinoline derivatives having substituted oxy group

A method of preventing or treating a glucocorticoid receptor-related disease involving administering a therapeutically effective amount of a 1,2-dihydroquinoline compound or a pharmaceutically acceptable salt thereof.

Method for preventing or treating a glucocorticoid receptor-related disease

The compounds represented in general formula (1) or a salt thereof are useful for glucocorticoid receptor modulators. In the formula, Rrepresents a lower alkyl group, a lower cycloalkyl group, an aryl group and the like; Rrepresents a hydrogen atom, a lower alkyl group and the like; Rrepresents a hydrogen atom, a lower alkyl group and the like; Rand Rrepresent a hydrogen atom, a lower alkyl group and the like; Rrepresents a hydrogen atom, a lower alkyl group and the like; Rrepresents a hydrogen atom, a lower alkyl group, a lower alkenyl group and the like; W represents an oxygen atom, a sulfur atom, NRand the like; Rrepresents a hydrogen atom, a lower alkyl group and the like; X represents an oxygen atom or a sulfur atom; Y represents a lower alkylene group and the like; Z represents an oxygen atom, a sulfur atom, NR, OCO or OSO; Rrepresents a hydrogen atom, a lower alkyl group and the like respectively. 

1,2,3,4-tetrahydroquinoxaline compound with a phenyl group substituent having a sulfonic acid ester structure or a sulfonic acid amide structure introduced therein and having glucocorticoid receptor-binding activity

An object of the present invention is to study synthesis of a novel 1,2-dihydroquinoline derivative and to find a pharmacological action of the derivative. A compound represented by the general formula (1) or a salt thereof is effective in the treatment of a glucocorticoid receptor-related disease. In the formula, the ring X represents a benzene ring or a pyridine ring; Rrepresents a halogen atom, an alkyl group, a hydroxy group, an alkoxy group, an amino group or the like; p represents an integer of 0 to 5; Rrepresents a halogen atom, an alkyl group, a hydroxy group or the like; q represents an integer of 0 to 2; Rrepresents a hydrogen atom, an alkyl group, an alkenyl group or the like; Rand Rrepresent a hydrogen atom or the like; Rrepresents a hydrogen atom or the like; A represents an alkylene group or the like; and Rrepresents OR, NRR, SR, S(O)Ror S(O)R, wherein Rrepresents an aryl group, a heterocyclic group or the like and Rrepresents a hydrogen atom or the like. 

1-2-dihydroquinoline derivative having glucocorticoid receptor binding activity

The compounds represented in general formula (1) and a salt thereof are useful for glucocorticoid receptor modulator. The Rrepresents a hydrogen atom or a lower alkyl group; Rrepresents a hydrogen atom or a lower alkyl group; Rand Rmay be the same or different and represent a hydrogen atom or a lower alkyl group; Rrepresents a hydrogen atom or a lower alkyl group; Rrepresents a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group, a nitro group or a cyano group; X represents &#x2014;C(O)&#x2014;, &#x2014;C(O)NR&#x2014;, &#x2014;S(O)&#x2014; and the like; Rand/or Rmay be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, a lower alkoxy group which may have a substituent and the like; Y represents a lower alkylene group; Z represents a benzene ring or a heterocyclic ring; and P represents 0, 1, 2 or 3.

1,2-dihydroquinoline derivative having (substituted phenyl or substituted heterocyclic) carbonyloxy lower alkyl group and ester-introduced phenyl group as substituents

The compounds represented in general formula (1) and a salt thereof are useful for glucocorticoid receptor modulator. The Rrepresents a hydrogen atom or a lower alkyl group; Rrepresents a hydrogen atom or a lower alkyl group; Rand Rmay be the same or different and represents a hydrogen atom or a lower alkyl group; Rrepresents a hydrogen atom or a lower alkyl group; Rrepresents a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group, a nitro group or a cyano group; X represents &#x2014;C(O)&#x2014;, &#x2014;C(O)NR&#x2014;, &#x2014;S(O)&#x2014; and the like; Rand/or Rmay be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, a lower alkoxy group which may have a substituent and the like; Y represents a lower alkylene group; and P represents 0, 1, 2 or 3.

1,2-dihydroquinoline derivative having substituted phenylamino lower alkyl group and ester-introduced phenyl group as substituents

The compounds represented in general formula (1) and a salt thereof are useful for glucocorticoid receptor modulator. The Rrepresents a hydrogen atom or a lower alkyl group; Rrepresents a hydrogen atom or a lower alkyl group; Rand Rmay be the same or different and represent a hydrogen atom or a lower alkyl group; Rrepresents a hydrogen atom or a lower alkyl group; Rrepresents a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group or a nitro group; X represents &#x2014;C(O)&#x2014;, &#x2014;C(O)NR&#x2014;, &#x2014;S(O)&#x2014; and the like; Rand/or Rmay be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, a lower alkoxy group which may have a substituent and the like; Y represents a lower alkylene group; Z represents a chalcogen atom; and P represents 0, 1, 2 or 3.

1,2-dihydroquinoline derivative having substituted phenylchalcogeno lower alkyl group and ester-introduced phenyl group as substituents

An object of the present invention is to find further new pharmacological actions of useful mercaptoacylcysteine derivatives. The present invention relates to therapeutic agents for osteoarthritis comprising compounds represented by the following general formula &lsqb;I&rsqb; or salts thereof as active ingredients. In the formula, &ldquo;A&rdquo; is lower alkylene. The lower alkylene is exemplified by straight-chain or branched alkylene having one to six carbon atoms such as methylene, ethylene, (dimethyl)methylene or (diethyl)methylene.

Growing community of inventors

Ikoma, Japan

Miwa Takai