Pfizer Corporation

Warner-lambert Company

Pfizer Pharmaceuticals, Inc.

Takafumi Ikeda

Rodney W Stevens

Yoshiyuki Okumura

Mitsuhiro Kawamura

Masami Nakane

Yuji Shishido

Akiyoshi Kawai

Hiroaki Wakabayashi

Takashi Mano

Noriaki Murase

Seiji Nukui

Kazuo Ando

Tomoki Kato

Makoto Kawai

Yasuhiro Katsu

Yoko Hoshino

Makato Kawai

Yu-Ting Ge

1,4-dihydropyridine compounds as bradykinin antagonists

5-membered heteroaryl substituted 1,4-dihydropyridine compounds as bradykinin antagonists

Certain novel hydroxamic acid derivatives having the structure

Hydroxamic acid and N-hydroxyurea derivatives and their use

This invention provides a compound of the formula (I): ##STR1## and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo; R.sup.1 and R.sup.2 are independently C.sub.1-4 alkyl; R.sup.3 is substituted or unsubstituted, phenyl or naphthyl; Y is heterocyclic group selected from C.sub.5-10 azacycloalkyl, C.sub.6-10 diazacycloalkyl, C.sub.7-10 azabicycloalkyl and the like; and R.sup.4 is selected from (a) substituted or unsubstituted C.sub.1-8 alkyll; (b) substituted or unsubstituted amino; (c) substituted or unsubstituted C.sub.2-6 alkanoyl; (d) substituted or unsubstituted C.sub.3-8 cycloalkyl or C.sub.7-14 bicycloalkyl; (e) substituted or unsubstituted C.sub.5-10 azacycloalkyl or C.sub.6-10 diazacycloalkyl, and (f) substituted or unsubstituted C.sub.7-14 mono- or di-azabicycloalkyl. These compounds are useful for the treatment of medical conditions caused by bradykinin such as inflammation, cardiovascular disease, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound, and intermediates of the above compounds.

Optically active 1,4-dihydropyridine compounds as bradykinin antagonists

A compound of the formula: ##STR1## and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo or H; X.sup.1 is CH.sub.2, CO, SO or SO.sub.2 ; X.sup.2 is CH.sub.2 or CO; Y is piperazinyl-(CH.sub.2).sub.n --, 2,3,4,5,6,7-hexahydro-1H-1,4-diazepinyl-(CH.sub.2).sub.n --or --N(R.sup.5)--(CH.sub.2).sub.n -- wherein R.sup.5 is H or C.sub.1-4 alkyl, and n is 0, 1, 2, 3, or 4; R.sup.1 is selected from the following: (a) N-morpholino-C.sub.1-4 alkylphenyl, C.sub.1-4 alkoxycarbonyl, C.sub.2-5 acyl, dihydroimidazolyl, formamidino, guanidino or dihydroimidazolylamino, etc.; (b) hydrogen, C.sub.1-4 alkyl, etc.; (c) piperidinyl; (d) C.sub.5-14 cycloalkyl, bicycloalkyl or tricycloalkyl; (e) C.sub.7-14 azacyclo-, azabicyclo- or azatricyclo-alkyl; and (f) C.sub.7-10 bicycloalkenyl, benzo C.sub.5-7 cycloalkyl or heterocyclic, etc., with proviso that when Y is piperazinyl, at least one of A.sup.1 and A.sup.2 is H; X.sup.2 is CH.sub.2 ; and/or R.sup.1 is a group selected from group (a); R.sup.2 is hydrogen, C.sub.1-4 alkyl, optionally substituted phenyl, or heterocyclic; and R.sup.3 and R.sup.4 are each C.sub.1-5 alkyl. The novel dihydropyridine compounds of this invention have excellent bradykinin antagonistic activity and are thus useful for the treatment of inflammation, cardiovascular disease, pain, common cold, allergies, asthma, pancreatitis, burns, virus infection, head injury, multiple trauma or the like in mammalian, especially humans.

1,4-dihydropyridine compounds

Indolinyl N-hydroxyurea and N-hydroxamic acid derivatives as

Cyclopropyl N-hydroxyurea and N-hydroxyacetamides which inhibit

Tetrahydrobenzazepine derivatives which inhibit lipoxygenase

Compounds of the formula ##STR1## wherein X is --CH.sub.2 --, --O-- or --S--, m is 1 to 3, n is 1 or 2 and R.sub.1 is hydrogen, C.sub.1 to C.sub.4 alkyl, aryl or aryl substituted with one or more substituents selected independently from the group consisting of halogen, nitro, cyano, C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 halosubstituted alkyl, C.sub.1 to C.sub.6 alkoxy, alkoxycarbonyl having from one to ten carbon atoms in the alkoxy moiety, aminocarbonyl, alkylaminocarbonyl having from one to ten carbon atoms in the alkyl moiety and dialkylaminocarbonyl having from one to ten carbon atoms in each of the alkyl moieties, and the pharmaceutically acceptable salts thereof, inhibit the enzyme lipoxygenase and are useful in treating allergy and inflammatory and cardiovascular conditions for which the action of lipoxygenase has been implicated. These compounds form the active ingredient in pharmaceutical compositions for treating such conditions.

N-hydroxyurea derivatives which inhibit lipoxygenase

Compounds having the structure ##STR1## wherein X is nitrogen, oxygen, sulfur or a bond and Z is oxygen or sulfur have been synthesized. These compounds are lipoxygenase inhibitors and are useful as the active agent in pharmaceutical compositions for treating inflammatory conditions in humans and other mammals for which lipoxygenase activity has been implicated.

Antiinflammatory hydroxamic acids and N-hydroxyureas

A series of 2-amino-5,6-dimethyl-1,4-benzoquinone derivatives, inhibitors of cyclooxygenase and lipoxygenase and useful as antiallergic and antiinflammatory agents.

Benzoquinone antiallergy and antinflammatory agents

Growing community of inventors

Handa, Japan

Takafumi Ikeda