Kaken Pharmaceutical Company, Ltd.

Molecular Research Institute

Uchida, Katsuhiro

Mimura, Mitsuo

Matsumura, Misako

Okumura, Makoto

Tohno, Masao

Masumoto, Shozo

Mitsuo Mimura

Makoto Okumura

Katsuhiro Uchida

Masao Tohno

Shozo Masumoto

Nobuo Ishiyama

Kiyonoshin Ichikawa

Misako Matsumura

Ping Huang

Satoru Ikegami

Michiko Nagahara

Kiyoshi Inoguchi

Keigo Hanada

Yoshitaka Ohishi

Mitsuo Hayashida

Masahito Watanabe

Tadashi Okuno

Takuya Yamada

Kiyoharu Ukai

Makoto Tamura

Yoshiyuki Hiyama

Chikara Ieda

Hirohide Ishige

Kiyoshi Nomiyama

Takao Awa

Takeshi Kiyofuji

Shinji Tauchi

Linda J Maki, Legal Representative

Soichiro Sato

An object is to provide a process for producing the compound of formula 1 in higher yield by the ring-opening addition reaction of epoxytriazole with amine under mild conditions without using a large excess of 4-methylenepiperidine. The process for producing (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol or an acid addition salt thereof comprises reacting (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane with an acid addition salt of 4-methylenepiperidine in a reaction solvent in the presence of a hydroxide of an alkali metal or an alkaline earth metal selected from the group consisting of lithium, sodium, calcium, and strontium, or a hydrate thereof.

Process for producing 1-triazole-2-butanol derivatives

Disclosed are the novel compounds as growth hormone secretagogues represented by structural Formula (I), wherein Ris, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amino, X is &#x2014;CO&#x2014; or &#x2014;SO&#x2014;, Y is Formula (II), wherein n is an integer from 0&#x2013;4, Ris hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, Rand Rare independently selected from hydrogen, substituted or unsubstituted alkyl, or Rand Ror Rand Rare taken together to form substituted or unsubstituted alkylene, Ris hydrogen, or substituted or unsubstituted alkyl, Ris substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, D is substituted or unsubstituted amino, substituted or unsubstituted alkoxy, or substituted or unsubstituted alkylthio, * represents an asymmetric center, and pharmaceutically acceptable salts and individual isomers thereof, which have growth hormone releasing activity in humans or animals.

Amide derivatives as growth hormone secretagogues

A bisphosphonic acid derivative of the formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein A is ##STR2## each of R.sup.3 and R.sup.4, which may be the same or different, is (i) a hydrogen atom, (ii) a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a C.sub.1-6 alkyl-carbonyl group, a C.sub.2-6 alkenyl-carbonyl group, a C.sub.2-6 alkynyl-carbonyl group R.sup.5 and R.sup.6, which may be the same or different, is a hydrogen atom, a hydroxyl group, a halogen atom, a cyano group, a carbamoyl group, an aralkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted amino group, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group;

Bisphosphonic acid derivatives, as bone resorption inhibitors

Biphenylylpropionic acid derivatives of the formula: ##STR1## wherein R is an alkylcarbonyloxyalkyl group or an alkenylcarbonyloxyalkyl group having the formula: ##STR2## wherein R.sup.1 is a lower alkyl group having 1 to 5 carbon atoms and R.sup.2 is an alkyl group having 1 to 15 carbon atoms or an alkenyl group having 2 to 8 carbon atoms, or a lactone having the formula: ##STR3## wherein R.sup.3 and R.sup.4 are hydrogen atom or a lower alkyl group having 1 to 2 carbon atoms, and n is an integer of 1 or 2. The compounds have excellent anti-inflammatory, analgesic and antipyretic activities. Moreover, the compounds have no irritation, rapid and long-acting, and high safety margin.

Biphenylylpropionic acid derivative, process for preparing the same and

An azaazulene derivative having the general formula (I): ##STR1## wherein R.sup.1 is hydrogen atom or isopropyl group; the bond C N between C at the 2-position and N at the 1-position is single bond or double bond; when the bond C N is single bond, R.sup.2 is 5-tetrazolyl group, R.sup.3 is taken together with carbon atom to form carbonyl group at the 2-position, and R.sup.4 is hydrogen atom, an alkyl group having 1 to 18 carbon atoms, a lower alkenyl group, a lower alkyl group having oxygen atom or sulfur atom in carbon chain, a lower alkyl group having a halogen atom or cyano group, a lower alkyl group having heteroaromatic ring, a diphenyl lower alkyl group, or a lower alkyl group having hydrocarbon-aromatic ring with the general formula: ##STR2## in which W is single bond or carbonyl group, oxygen atom, sulfur atom or --CH.dbd.CH--, n is an integer of 1 to 6, and R.sup.1', R.sup.2' and R.sup.3' are the same or different and each is hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxyl group, trifluoromethyl group, hydroxyl group, a lower alkoxycarbonyl group, carboxyl group, acetyl group or cyano group; when the bond C N is double bond, N at the 1-position has no substituent R.sup.4, R.sup.2 is cyano group, and R.sup.3 is amino group or a salt thereof, azido group, a diphenyl lower alkyl amino group, a substituted phenyl amino group, a substituted piperazinyl group, a substituted homopiperazinyl group, an amino acid residue bonded by N terminal group in which C terminal group is carboxyl group or a lower alkyl ester thereof, or a lower alkyl amino group which may have an alkyl amino group that may be cyclic one, or a salt thereof, which is useful as an active ingredient of an antiallergic agent and an antiinflammatory agent and has also an inhibitory activity against histamine release, 5-lipoxygenase inhibiting activity, relaxing activity of smooth musculus trachealis and inhibitory activity against carrageenin edema, and further, is useful as medicine for prevention and treatment of bronchial asthma, allergic coryza, allergic conjunctivitis, urticaria, atopic dermatitis, other inflammatory diseases or the like.

Azaazulene compounds which are useful as antiallergic and

Biphenylylpropionic acid derivative and pharmaceutical composition

Biphenylylpropionic acid derivatives of the formula: ##STR1## wherein R is an alkylcarbonyloxyalkyl group or an alkenylcarbonyloxyalkyl group having the formula: ##STR2## wherein R.sup.1 is an alkyl group having 1 to 15 carbon atoms or an alkenyl group having 2 to 8 carbon atoms and m is 0 or an integer of 1. The compounds have excellent anti-inflammatory, analgesic and antipyretic activities. Moreover, the compounds have no irritation, rapid and long-acting, and high safety margin.

A novel anti-inflammatory drug, which exhibits rapidly a pharmacological activity, maintains the activity for a long time, and is free from a side effect such as a gastrointestinal disorder or a central nervous disturbance is disclosed. The drug comprises a compound of an alkylcarbonyloxyalkylester or alkenylcarbonyloxyalkylester derivative of indolylacetic acid or anilinophenylacetic acid. The compound is prepared by an esterification reaction.

Ester substituted alkyl-2-(2,6-dichloroanilino)phenyl acetates

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Fujieda, Japan

Mitsuo Mimura