Sumitomo Chemical Company, Limited

Sumitomo Pharmaceuticals Company Limited

Other

Dainippon Sumitomo Pharma Co., Ltd.

Dianippon Sumitomo Pharma Co., Ltd.

Hajime Kawakami

Junki Katsube

Keiichi Ono

Hitoshi Fujita

Norio Fujiwara

Fujio Antoku

Akihiko Sugie

Ayumu Kurimoto

Toshinari Sugasawa

Tetsuhiro Ogino

Yoshiaki Isobe

Atsuyuki Kojima

Haruhisa Ogita

Masanori Tobe

Haruo Takaku

Shunsuke Sami

Kiyotaka Iwai

Hiroshi Tanaka

Yutaka Ueda

Jun Hidaka

Fumiyo Hirota

Shinobu Murata

Hideo Nagata

This invention relates to an adenine derivative, a tautomer thereof, or a pharmaceutically acceptable salt thereof represented by general formula (I): wherein X represents NR(wherein Rrepresents a hydrogen atom or Calkyl) or the like; Rrepresents substituted or unsubstituted alkyl or the like; Rrepresents hydroxyl or the like; and Y represents a substituted or unsubstituted aromatic hetero ring or the like. Also, the present invention relates to pharmaceuticals such as an interferon inducer, antiviral agent, anticancer agent, type 2 helper T cell selective immune response inhibitor, antiallergic agent, and immune response modulator comprising the above derivative as an active ingredient.

Adenine derivatives

A 5-membered cyclic compound of the formula: wherein X is oxygen or sulfur, Ris hydrogen, substituted or unsubstituted alkyl, etc., Ris hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, etc., Yis a direct bond, substituted or unsubstituted alkylene, &#x2014;CO(CH)&#x2014;, etc., the wavy line means (E)-configuration or (Z)-configuration, Ris substituted or unsubstituted aryl, etc., Yis substituted or unsubstituted alkylene, etc., Ris hydrogen, substituted or unsubstituted alkanoyl, substituted or unsubstituted alkyl, etc., Ris hydrogen, etc., or a salt thereof, these compound being able to inhibit infiltration of leukocytes such as eosinophils and lymphocytes, by which being useful for the treatment of various kinds of inflammation.

Five-membered cyclic compounds

1. A pyrimidine derivative of the formula (1) or a salt thereof;has an inhibitory activity of production of Th2 type cytokines such as IL-4, IL-5, etc., and is useful as an therapeutic agent for allergic diseases, autoimmune diseases such as systemic lupus erythemathosus, etc., and acquired immunodeficiecy syndrome (AIDS) and so on.

Bicyclic pyrimidine compounds and therapeutic use thereof

A 5-membered cyclic compound of the formula:wherein X is oxygen or sulfur, Ris hydrogen, substituted or unsubstituted alkyl, etc., Ris hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, etc., Yis a direct bond, substituted or unsubstituted alkylene, &#x2014;CO(CH)&#x2014;, etc., the wavy line means (E)-configuration or (Z)-configuration, Ris substituted or unsubstituted aryl, etc., Yis substituted or unsubstituted alkylene, etc., Ris hydrogen, substituted or unsubstituted alkanoyl, substituted or unsubstituted alkyl, etc., Ris hydrogen, etc., or a salt thereof, these compound being able to inhibit infiltration of leukocytes such as eosinophils and lymphocytes, by which being useful for the treatment of various kinds of inflammation.

Five-membered-ring compound

Transformed cells designed to express a recombinant human SMBP at an elevated level to the extent that its ligand-binding activity can be measured, and cellular membrane fractions thereof; recombinant human SMBPs isolated from the transformed cells or the cellular membrane fractions thereof; a screening system for human SMBP agonists/antagonists characterized by utilizing the transformed cells, the cellular membrane fractions thereof or the isolated recombinant human SMBPs; and human SMBP agonists or antagonists obtainable by the screening system, are provided by deleting the polythymidine sequence from the base sequence of the 3&prime;-untranslated region.

Recombinant human SM-11044-binding receptor proteins exhibiting ligand-binding activities, and their use

The present invention relates to a heterocyclic compound of the following general formula (I):

Heterocyclic compounds

A compound of formula (1) ##STR1## wherein X.sup.1 is amino or hydroxyl, X.sup.2 is carbonyl and the like R.sup.1 is an alkyl, an aryl and the like, R.sup.2 is hydrogen and the like, and R.sup.3 is an alkyl and the like, or a pharmaceutical acceptable salt thereof is effective for inibiting the production and/or secretion of tumor necrosis factor in a patient in need of such inhibition.

Piperidinylpyrimidine derivatives

Leukotriene B.sub.4 antagonists of the formula: ##STR1## wherein each symbol is as defined in the specification, processes for producing them, and pharmaceutical compositions containing them. The compounds of the present invention are very useful as the drugs for the treatment of allergic and inflammatory diseases.

Pyridine compounds which are useful as leukotriene B4 antagonist

Diphenylalkanoether and diphenylalkanone oximeether derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each independently an aryl group optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, di(C.sub.1 -C.sub.4)alkylamino, amino, benzyloxy, hydroxyl, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, C.sub.1 -C.sub.4 alkanoylamino, C.sub.1 -C.sub.4 alkylamino and N-(C.sub.1 -C.sub.4 )alkyl-N-(C.sub.1 -C.sub.4)alkanoylamino, Z.sup.1 is a group of the formula: ##STR2## (wherein R.sup.3 and R.sup.4 are each independently a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or an ar(C.sub.1 -C.sub.4)alkyl group or, when taken together with the adjacent nitrogen atom to which they are attached, represent a nitrogen-containing 5 to 7-membered saturated heterocyclic group optionally having an oxygen atom or an additional nitrogen atom as the hetero atom in addition to the said nitrogen atom and, in case of having the additional nitrogen atom, bearing a hydrogen atom, a C.sub.1 - C.sub.4 alkyl group, an ar(C.sub.1 -C.sub.4)alkyl group or a phenyl group thereon), ##STR3## is a group of the formula: ##STR4## or the formula: ##STR5## A.sup.1 is a C.sub.2 -C.sub.6 alkylene group and A.sup.2 is a C.sub.2 -C.sub.4 alkylene group, and non-toxic, pharmaceutically acceptable acid addition salts thereof, which have cerebral vasodilating activity and antihypoxic activity.

Diphenylalkanoether and diphenylalkanone oximeether derivatives

A compound of the formula ##STR1## wherein X.sup.1 is a free or esterified carboxyl group, a hydroxymethyl group, a cyano group, a group of the formula: ##STR2## (R.sup.a and R.sup.b are each independently a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, a C.sub.3 -C.sub.7 cycloalkyl group, a benzyl group, a phenyl group, a phenyl group substituted with a halogen atom or a C.sub.1 -C.sub.4 alkyl group, or, when taken together with the adjacent nitrogen atom to which they are attached, they represent a 5 to 7-membered saturated heterocyclic group) or a group of the formula: ##STR3## (R.sup.a and R.sup.b are each as defined above), Y is an ethylene group or a vinylene group, R.sup.1 is a hydrogen atom, a hydroxyl group or a protected hydroxyl group, R.sup.2 is a hydrogen atom or R.sub.1 and R.sub.2, when taken together, means a single linkage to form a double bond between the carbon atoms which they are linked, R.sup.3 is a hydroxyl group or a protected hydroxyl group, R.sup.4 is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group, R.sup.5 is a hydrogen atom, a C.sub.3 -C.sub.8 alkenyl group, a C.sub.3 -C.sub.8 alkynyl group, a C.sub.1 -C.sub.8 alkyl group, a C.sub.3 -C.sub.7 cycloalkyl group or a group of the formula: --(CH.sub.2).sub.n --B (n is 1 or 2 and B is a C.sub.1 -C.sub.4 alkoxyl group, a C.sub.3 -C.sub.7 cycloalkyl group, or a phenyl or phenoxy group optionally substituted with a halogen atom, a C.sub.1 -C.sub.4 alkyl group, a trifluoromethyl group or a C.sub.1 -C.sub.4 alkoxyl group), A is a group of either one of the formulae: ##STR4## (R.sup.6 and R.sup.7 are each independently a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group) and ##STR5## m.sub.1 is 1 or 2 and m.sub.2 is 0, 1 or 2, and the non-toxic pharmaceutically acceptable salts threreof. Said compounds have strong anti-ulcerogenic activity and are useful in treatment of gastraintestinal ulcer.

Bicyclooctane derivatives

Diphenylalkanoether and diphenylalkanone oximeether derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each independently an aryl group optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, di(C.sub.1 -C.sub.4) alkylamino, amino, benzyloxy, hydroxyl, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, C.sub.1 -C.sub.4 alkanoylamino, C.sub.1 -C.sub.4 alkylamino and N-(C.sub.1 -C.sub.4)alkyl-N-(C.sub.1 -C.sub.4)alkanoylamino, Z.sup.1 is a group of the formula: ##STR2## (wherein R.sup.3 and R.sup.4 are each independently a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or an ar(C.sub.1 -C.sub.4) alkyl group or, when taken together with the adjacent nitrogen atom to which they are attached, represent a nitrogen-containing 5 to 7-membered saturated heterocyclic group optionally having an oxygen atom or an additional nitrogen atom as the hetero atom in addition to the said nitrogen atom and, in case of having the additional nitrogen atom, bearing a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, and ar(C.sub.1 -C.sub.4)alkyl group or a phenyl group thereon), ##STR3## is a group of the formula: ##STR4## or the formula: ##STR5## A.sup.1 is a C.sub.2 -C.sub.6 alkylene group and A.sup.2 is a C.sub.2 -C.sub.4 alkylene group, and non-toxic, pharmaceutically acceptable acid addition salts thereof, which have cerebral vasodilating activity and antihypoxic activity.

Diphenylalkanoether and diphenylalkanone oximeether derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each independently an aryl group optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, di(C.sub.1 -C.sub.4)alkylamino, amino, benzyloxy, hydroxyl, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkysulfonyl, C.sub.1 -C.sub.4 alkanoylamino, C.sub.1 -C.sub.4 alkylmino and N-(C.sub.1 -C.sub.4)alkyl-N-(C.sub.1 -C.sub.4)alkanoylamino, Z.sup.1 is a group of the formula: ##STR2## (wherein R.sup.3 and R.sup.4 are each independently a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or an ar(C.sub.1 -C.sub.4)alkyl group or, when taken together with the adjacent nitrogen atom to which they are attached, represent a nitrogen-containing 5 to 7-membered saturated heterocyclic group optionally having an oxygen atom or an additional nitrogen atom as the hetero atom in additon to the said nitrogen atom and, in case of having the additional nitrogen atom, bearing a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, an ar(C.sub.1 -C.sub.4)alkyl group or a phenyl group thereon), ##STR3## is a group of the formula: ##STR4## or the formula: ##STR5## A.sup.1 is a C.sub.2 -C.sub.6 alkylene group and A.sup.2 is a C.sub.2 -C.sub.4 alkylene group, and non-toxic, pharmaceutically acceptable acid addition salts thereof, which have cerebral vasodilating activity and antihypoxic activity.

Diphenylalkanoether derivatives

Diphenylalkanoether and diphenylalkanone oximeether derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each independently an aryl group optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, di(C.sub.1 -C.sub.4)alkylamino, amino, benzyloxy, hydroxyl, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, C.sub.1 -C.sub.4 alkanoylamino, C.sub.1 -C.sub.4 alkylamino and N-(C.sub.1 -C.sub.4)alkyl-N-(C.sub.1 -C.sub.4)alkanoylamino, Z.sup.1 is a group of the formula: ##STR2## (wherein R.sup.3 and R.sup.4 are each independently a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or an ar(C.sub.1 -C.sub.4)alkyl group or, when taken together with the adjacent nitrogen atom to which they are attached, represent a nitrogen-containing 5 to 7-membered saturated heterocyclic group optionally having an oxygen atom or an additional nitrogen atom as the hetero atom in addition to the said nitrogen atom and, in case of having the additional nitrogen atom, bearing a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, an ar(C.sub.1 -C.sub.4)alkyl group or a phenyl group thereon, ##STR3## A.sup.1 is a C.sub.2 -C.sub.6 alkylene group and A.sup.2 is a C.sub.2 -C.sub.4 alkylene group, and non-toxic, pharmaceutically acceptable acid addition salts thereof, which have cerebral vasodilating activity and antihypoxic activity.

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Takarazuka, Japan

Hajime Kawakami