CA2202058C

CA2202058C - Cyclic hexapeptides having antibiotic activity

Info

Publication number: CA2202058C
Application number: CA002202058A
Authority: CA
Inventors: Hidenori Ohki; Masaki Tomishima; Hisashi Takasugi; Akira Yamada
Original assignee: Astellas Pharma Inc
Current assignee: Astellas Pharma Inc
Priority date: 1994-10-07
Filing date: 1995-09-29
Publication date: 2007-11-06
Anticipated expiration: 2015-09-29
Also published as: HU228151B1; JPH10507174A; JP3518665B2; ATE229541T1; AU696949B2; AU3578095A; FI119988B; RU2165423C2; HK1004136A1; BR9504791A; BR9504791B1; LU91452I2; CN1203089C; IL115484A0; IL115484A; ES2187575T3; US6107458A; CN1168675A; CA2202058A1; MX9702531A

Abstract

This invention relates to new polypeptide compounds repre-sented by formula (I), wherein R1 is as defined in the description and pharmaceutically acceptable salt thereof which have antimicro-bial activities (especially, antifungal activities), inhibitory activity on .beta.-1,3-glucan synthase, to process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for the prophylactic and/or therapeutic treatment of infectious dis-eases including Pneumocystis carinii infection (e.g. Pneumocystis carinii pneumonia) in a human being or an animal.

Description

DESCP.-TPTION
Cyclic hexapeptides having antibiotic activity TFCHNIC_ FIE=D
The ~resent invention re,ates to new polypepticie compound and a pharmaceut=cal?v acceptable salt thereof which are useful a3z a meciicamenz.

ln U.S. Pat. No. 5, 376, 0'34, there are disc~osed t'r:e aolypeptid-- co*npound and a ph.:rmaceutical=y acceptable salt therecf, W: 1c."1 have ant~T:ilcroblal act'vltles (especi?llv antifungal activitv).
i5 DyJCLOSURE OF IN"VENTION
The present invention relates tc new poiypeptide compound and a pharmaceutically acceptabie salt -~:hereof.
More particularly, it relates to new po~vpeptide coTpound and a pharmaceutically acceptable salt thereof, which have antimicrobial activities respecially, antifungal activities, in which tl:e fungi may include Aspergilius, Cryptococcus, Candida, Mucor, Actinomyces, Histoplasma, Dermatophyte, Malassezia, Fusarium. and the l=ke. ), inhibitory activi ty o-n G-1, 3-glucar. synthase, and further which are excected t: be usefu-i for the prophylactic and/or therapeutic t.reatment of Pneumocvstis carinii _nfection (e.g. Pneumccyst'_s carinii pneumonia) in a h;ur:an bei ng or an animal, to a process for preparation therecf, to a pharzmaceutical composition comprising the same, and to alrethod for the prophylactic and/or therapeutic treatment of infectious diseases including Pneumocystis carinii infection (e. g. Pneu-mocy ti s,.arinii pneu.*nonia> in a human being cr an animai.

The object polypeptide compound used in the present invention are new and can be represented by t~:e following general formula [I]

HO OH

NH
H3C NH-Ri HO -0 HN O::

NH
C CH3 [I~
H2N 0-/ N, HC NH
OH

i ~ HO-II-O

HO
wherein R1 is lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s);
lower alkanoyl substituted with 1,2,3,4-tetrahydroisoquinoline which may have one or more suitable substituent(s);
lower alkanovl substituted with unsaturated condensed heterocyclic group containing at least one oxygen atom which may have one or more suitable 30 substituent(s);

lower alkanovl substituted with unsaturated condensed heterocyclic group containing 1 to 3 sulfur atom(s) which may have one or more suitable substituent(s);
lower alkanoyl substituted with unsaturated condensed heterocyclic group containing 2 or more nitrogen atom(s) which may have one or more suitable substituent(s);
lower alkanoyl substituted with saturated 3 to 8 membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s);
ar(lower)alkenovl substituted with aryl which may have one or more suitabie substituent(s);
naphthyl(lower)alkenoyl which may have one or more higher alkoxy;
lower alkynoyl which may have one or more suitable substituent(s);
(C2-C6)alkanoyl substituted with naphthyl having higher alkoxy;
ar(C2-C6)alkanoyl substituted with aryl having one or more suitable substituent(s), in which ar(C2-C6)alkanoyl may have one or more suitable substituent(s);
aroyl substituted with heterocyclic group which may have one or more suitable substituent(s), in which aroyl may have one or more suitable substituent(s);
aroyl substituted with aryl having heterocyclic(higher)alkoxy, in which heterocyclic group may have one or more suitable substituent(s);
aroyl substituted with aryl having lower alkoxy(higher)alkoxy;
aroyl substituted with aryl having lower alkenyl (lower) alkoxy;
aroyl substituted with 2 lower alkoxy;

G

aroyl substituted witn aryl having lower alkyl;
aroyl substituted wi Th aryl having higher alkyl;
~ aryloxy(lower)alkanoyl which may have one ~.~
or more suitable substituent(s);
ar(lower)alkoxy(lower)alkanoyl which may have one or more suitable substituent(s);
arylamino(lower)alkanoyl which may have one or more suitable substituent(s);
lower alkanoy'_ substituteu with pyrazolyl which has lower alkyl and aryl having higher alkoxy;
lower alkoxy(higher)alkarioyl, in whicr~-higher alkanoyl may have one or more suitable substituent(s);
aroyl substituted with aryl having heterocyclicoxy, in which heterocyclicoxy may have one or more suitable substituent(s);
aroyl substituted with cyclo(lower)alkyl having lower alkyl;
indolylcarbonyl having higher alkyl;
naphthoyl having lower alkyl;
naphthoyl having higher alkyl;
naphthoyl having lower alkoxy(higher)alkoxy;
aroyl substituted with aryl having lower alkoxy(lower)alkoxy(higher)alkoxy; 30 aroyl substituted with aryl having lower alkoxy(lower)alkoxy;
aroyl substituted with aryl which has aryl having lower alkoxy;
aroyl substituted with aryl which has aryl having lower alk_oxy(lower)alkoxy;

aroyl substituted with aryl having heterocyclicoxy (higher) alkoxy;
aroyl substituted with aryl having aryloxy (lower) alkoxy;

aroyl substituted with aryl having heterocycliccarbonyl (higher) alkoxy;
lower alkanoyl substituted with oxazolyl which has aryl having higher alkoxy;
lower alkanoyl substituted with furyl which has aryl substituted with aryl having lower alkoxy;
lower alkanoyl substituted with triazolyl which has oxo and aryl having higher alkyl;
higher alkanoyl having hydroxy;
higher alkanoyl having ar(lower)alkyl and hydroxy;
3-methyl-tridecenoyl; or (C2-C6) alkanoyl substituted with aryl having higher alkoxy, in which (C2-C6) alkanoyl may have amino or protected amino.

In one aspect, the present invention provides a polypeptide compound or a pharmaceutically acceptable salt thereof of the following general formula HO OH

y HO HN OH

x H2N a o c OH
O H YZ
HO-+O ~ /
AO

-5a-wherein R' is naphthyl (C1.-C6) alkoxy (Cl-C6) alkanoyl which may have 1 to 3 substituent(s) selected from the group consisting of (C1-C6) alkoxy, (C7-C20) alkoxy, (Cl-C6) alkyl, (C7-C20) alkyl, (C7-C20) alkoxy (Cl-C6) alkyl, phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, naphthyl having (Cl-C6) alkoxy, naphthyl having (C7-C20) alkoxy, phenyl having (Cl-C6) alkyl, phenyl having (C7-C20) alkyl, naphthoyl having (C7-C20) alkoxy, phenyl substituted with phenyl having (C1-C6) alkyl, and oxo;
(Cl -C6) alkanoyl substituted with pyrazolyl which has (C1.-C6) alkyl and phenyl having (C7-C20) alkoxy;

(Cl-C6) alkoxy (C7-C20) alkanoyl, in which (C7-C20) alkanoyl may have amino or protected amino;

benzoyl substituted with cyclo (C3-C6) alkyl having (Cl-C6) alkyl;

indolylcarbonyl having (C7-C20) alkyl;
naphthoyl having (C1-C6) alkyl;
naphthoyl having (C7-C20) alkyl;

benzoyl substituted with phenyl having (Cl-C6) alkoxy (Cl-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (Cl-C6) alkoxy (Cl-C6) alkoxy;

benzoyl substituted with phenyl which has phenyl having (C1-C6) alkoxy (C1-C6) alkoxy;

benzoyl substituted with phenyl having tetrahydropyranyloxy (C-7-C20) alkoxy;

benzoyl substituted with phenyl having phenoxy (C1-C6) alkoxy;

-5b-(C1-C6) alkanoyl substituted with oxazolyl which has phenyl having (C7-C20) alkoxy;

(C7-C20) alkanoyl having hydroxy;

(C7-C20) alkanoyl having benzyl and hydroxy;
3-methyl-tridecenoyl;

(C1-C6) alkanoyl substituted with pyridyl or pyridazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkoxy, (C7-C20) alkoxy (Cl-C6) alkyl, phenyl having (C7-C20) alkoxy, phenyl substituted with phenyl having (C1-C6) alkoxy, piperazinyl substituted with phenyl having (C7-C20) alkoxy, piperazinyl substituted with phenyl having (Cl-C6) alkoxy (C7-C20) alkoxy, and piperazinyl substituted with phenyl having (C1-C6) alkoxy;

(C1-C6) alkanoyl substituted with benzothiophenyl which may have 1 to 3 (C7-C20) alkoxy;

(C1-C6) alkanoyl substituted with benzo [b] furanyl which may have 1 to 3 substitutent(s) selected from the group consisting of (C7-C20) alkoxy and (Cl-C6) alkyl;

(C1-C6) alkanoyl substituted with benzooxazolyl which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl substituted with phenyl having (Cl-C6) alkyl, and pyridyl having (C7-C20) alkoxy;

(C1-C6) alkanoyl substituted with piperidyl or piperazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C7-C20) alkoxy, and naphthoyl having (C7-C20) alkoxy;

phenyl (C3-C6) alkenoyl substituted with phenyl which may have 1 to 3 substituent(s) selected from the group consisting of -5c-(Cl-C6) alkoxy, (Cl-C6) alkyl, (C7-C20) alkyl, (Cl-C6) alkoxy (Cl-C6) alkyl, halo (Cl-C6) alkoxy, (C2-C6) alkenyloxy, halo (C7-C20) alkoxy, and (Cl-C6) alkoxy (C7-C20) alkoxy;

naphthyl (C3-C6) alkenoyl which may have 1 to 3(C7-CZO) alkoxy;

2-propynoyl, (2- or 3-) butynoyl, (2- or 3- or 4-) pentynoyl, or (2- or 3- or 4- or 5-) hexynoyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of naphthyl having (C7-C20) alkoxy, and phenyl substituted with phenyl having (Cl-C6) alkyl;

phenyl (C2-C6) alkanoyl substituted with phenyl which has 1 to 3 substituent(s) selected from the group consisting of (C1-C6) alkoxy, (C7-C20) alkoxy, (Cl-C6) alkyl, (C7-C20) alkyl, and phenyl having (Cl-C6) alkoxy (Cl-C6) alkyl, in which phenyl (C2-C6) alkanoyl may have hydroxy, oxo, protected amino or amino; or (C2-C6) alkanoyl substituted with naphthyl having (C7-C20) alkoxy;

benzoyl substituted with pyrrolidinyl, imidazolidinyl, piperidyl, or piperazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (Cl-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkyl, phenyl having (Cl-C6) alkoxy (C7-C20) alkoxy, phenyl having (C7-C20) alkenyloxy, piperidyl substituted with phenyl having (C1-C6) alkoxy, piperidyl, cyclo (C3-C6) alkyl having phenyl, phenyl having cyclo (C3-C6) alkyl, and phenyl substituted with triazolyl having oxo and (C1.-C6) alkyl, in which benzoyl may have halogen;

benzoyl substituted with oxazolyl, isoxazolyl, or oxadiazolyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl, phenyl having (Cl-C6) -5d-alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (Cl-C6) alkoxy (C7-C20) alkoxy, and phenyl substituted with phenyl having (Cl-C6) alkoxy;

benzoyl substituted with pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl, or tetrazolyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl and phenyl having (Cl-C6) alkoxy;

benzoyl substituted with thiazolyl, isothiazolyl, thiadiazolyl, or dihydrothiazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (Cl-C6) alkoxy, phenyl having (C7-C20) alkoxy, cyclo (C3-C6) alkyl having (C1-C6) alkyl, phenyl substituted with phenyl having (Cl-C6) alkoxy, phenyl having cyclo (C3-C6) alkyl, phenyl having piperidine, and phenyl having (Cl-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (Cl-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (C1-C6) alkyl; or benzoyl substituted with phenyl having (C7-C20) alkyl.

The new polypeptide compound [2] and a pharmaceutically acceptable salt thereof can be prepared by the process as illustrated in the following reaction scheme or can be prepared by elimination reaction of amino protective group in Rl .

process 1 HO OH
HO 0 R1-OH [III]
NH
H3C NH or its reactiye derivative ? at the carboxy group 0 or a salt thereof HO -O HN OH
O

HO NH N
OH

1 !
HO-S-O
O
HO [II]
or its reactive derivative at the amino group 1 5 or a salt thereof HO OH

NH

NH-P.
O
HO O HN OH
O

HO NH
OH
li OH O
HO-I-O
O
HO [I]
or a salt thereof - % -wherein Rl is as defined above.

Suitable pharmaceuticallv acceptable salts of the object polypeptide compound [I] are conventional non-toxic salts and may include a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt;
a salt with an organic base, for example, an organic amine salt (e.g., triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.);
an organic carboxylic sulfonic acid addition salt (e.g., formate, acetate, trifluoroacetate, maleate, tartrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); a salt with a basic or acidic amino acid (e.g., arginine, asnartic acid, glutamic acid, etc. ) .

In the above and subsequent descriptions of the present specification, suitable examples and illustration of the various definitions which the present invention intends to include within the scope thereof are explained in detail as follows.
The term "lower" is used to intend a group having 1 to 6 carbon atom(s), unless otherwise provided.
The term "higher" is used to intend a group having 7 to 20 carbon atoms, unless otherwise provided.
Suitable example of "one or more" may be the number of 1 to 6, in which the preferred one may be the number of 1 to 3.
Suitable example of "lower alkanoyl" may include - g -straight or branched one such as formyl, acetyl, 2-methylacetyl, 2,2-uimethylacetyl, propionyl, butyrvl, isobutyrvl, pen-.anoy-~, 2,2-dimethylpropionyl, hexanoyl, and the like.
Suitable example of "suitable substituent(s)" in the groups such as "lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)", "lower alkanoyl substituted with 1,2,3,4-tetrahydroisoauinoline which may have one or more suitable substituent(s)", etc. may include lower alkoxv as mentioned below, higher alkoxy as mentioned below, lower alkvi as mentioned below, higher alkvl as mentioned below, higher alkoxy(lower)alkyl, lower alkoxycarbonyl, oxo, aryl which may have one or more lower alkoxy, aryl which may have one or more higher alkoxy, aryl which may have one or more lower alkyl, aryl which may have one or more higher alkyl, aryl substituted with aryl which may have one or more lower alkoxy, aryl substituted with aryl which may have one or more higher alkoxy, aryl substituted with aryl which may have one or more lower alkyl, aryl substituted with aryl which may have one or more higher alkyl, aroyl which may have one or more lower alkoxy, aroyl which may have one or more higher alkoxy, aroyl which may have one or more lower alkvl, aroyl which may have one or more higher alkyl, heterocyclic group which may have one or more lower alkoxy, heterocyclic group which may have one or more higher alkoxy, arvl having heterocyclic(higher)alkoxy, heterocyclic group which may have aryl having higher alkoxy, heterocyclic group which may have aryl having lower alkoxy(higher)alkoxy, heterocyclic group which may have aryl having lower alkoxy, lower alkoxy(lower)alkyl, halo(lower)alkoxy, lower aikenyloxy, halo (higher) alkoxy, lower aikoxy(higher)alkoxy, aryl which mav have one or more lower alkoxy(lower)alkoxy, heterocyclic group, aryl which may have one or more lower alkoxy(higher)alkoxy, aryl which may have one or more higher alkenyloxy, cyclo(lower)alkyl which may have aryl, arvl substituted with heterocyclic group which may have lower alkyl and oxo, cyclo(lower)alkyl which may have one or more lower alkyl-, aryl which mav have cyclo(lower)alkyl, aryl which may have heterocyclic group, and the like.
Suitable example of "lower alkoxy" mav include straight or branched one such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentvloxy, neo-pentyloxy, hexyloxy, isohexyloxy and the iike, in which the preferred one mav be methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy and isohexyloxy.
Suitable example of "higher alkoxy" may inciude straight or branched one such as heptyloxy, octyloxy, 3,5-dimethyloctyloxy, 3,7-dimethyloctyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, hexadecyloxy, heptadecyloxy, octadecvloxy, nonadecyloxy, icosyloxy, and the like, in which the preferred one may be (C7-C14)alkoxy, and the more preferred one may be heptyloxv and octyloxy.
Suitable example of "lower alkyl" may include straight or branched one having 1 to 6 carbon atom(s), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-pentyl, neo-pentyl, hexyl, isohexyl and the like, in which the preferred one mav be methyl, pentyl, hexyl and isohexyl.
Suitable example of "higher alkyl" may include straight or branched one having 7 to 20 carbon atoms, such as heptyl, octyl, 3,5-dimethyloctyl, 3,7-dimethyloctyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecvl, heptadecyl, octadecyl, nonadecyl, icosvl, and the like, in which the preferred one may be (C7-Ci4')alk_yi, and the more preferred one may be heptyl, octyl, nonyl and ciecvl.
Suitable example of "aryl" and "ar" moiety may include phenyl which may have lower alkyl (e.g., phenyl, mesityl, tolyl, etc.), naphthyl, anthryl, and the like, in which the preferred one may be phenvl and naphthyl.
Suitabie example of "arovl" may include benzoyl, toiuoyi, naphthoyl, anthrylcarbonyl, and the like, in which the preferred one mav be benzovl and naphthoyl.
Suitable example of "heterocvciic group" and "heterocyclic" moietv may include unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocvclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolvl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, nyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., 1H-tetrazolyl, 2H-tetrazolyl, etc.), etc ;
saturated 3 to 8-membered (more preferably 5 or 6-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, etc.;
unsaturated condensed heterocyclic group containing 1 to 4 nitrogen atom(s), for example, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolvl, auinolyl, isoquinolyl, indazolyl, benzotriazolyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.), etc.;

saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, morpholinyl, sydnonyl, etc.;
unsaturated condensed heterocyclic group containing 1 to 2 oxygen atom(s) and 1 to -3 nitrogen atom(s), for examule, benzoxazolyl, benzoxadiazolyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolyl, isothiazolyl, thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2, 5-thiadiazolyl, etc.), dihydrothiazinyl, etc.;
saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic grou, containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s), for example, thienyl, dihydrodithiinyl, dihydrodithionyl, etc.;
unsaturated condensed heterocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzothiadiazolyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonc-yclic group containing an oxygen atom, for example, furyl, etc.;
saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing an oxygen atom, for example, tetrahydrofuran, tetrahydropyran, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing an oxygen atom and 1 to 2 sulfur atom(s), for example, dihydrooxathiinyl, etc.;
unsaturated condensed heterocyclic group containing 1 - '2 -~ 2 sulrur ato*n(s), ior example, benzc--hienyl, -Enzodithiinyl, etc.;

unsaturated condensed _I-:ererocvclic group cor_tai ning an oxvgen a tom and 1 to 2 sulfur atcm ( s), for example, benzox_athiiny=, etc.; and the like.

cui tab i e e?:amDle cf nhalc" mav 1n clude =lll.orc, chloro, bromo and iocio.
Suitabie example of "lower alkenyloxy" may include vinyioxy, 1- (or 2-) propenyloxy, _- (or 2- ,)r _~- ) butenyloxy, _-(or 2- or 3- or 4-)entenyloxy, --(or %- or 3- or 4- or 5-. .~exenvicxy, and -t:c li ke, --- W~"?-c ~ tr.e ~~"eferred one "=y be i~--C(i alkenylOXv, anci z!.e ?P.OS= preferred one ?laV
tie 5-hexenyloxy.
Suitable example of "higher alkenyloxy" mav include 'C7-C20)aikenyloxy, in which the prererred one may be 6-heptenyloxv and ?-octenyloxv.
Suitable example of "cyclo(lower)alkyl" mav include cvclopropyl, cyclobutyl, cvcio-per.tvl, cycichexyl, ar:d the like, in which the preferred one may be cyclo (;.;-C6) alkyl, and the most preferred one mav be cyclohexyl.
Suitable example of "higher alkanoyl" may include he-ctanoyl, octanoyl, r.onanoyl, decanoyl, undecanoyl, lauroyl, tridecanoyl, tetradecanoyl, per.tadecanoyl, hexadecanovl, heptadecanoyl, octadecanoyl, nonadecanoyl, icosanoyl, and the like, in which the preferred one may be ;C-7-Cq0)alkanovl, and the most -oreferred one mav be ",exadecanoyl.

Suitable example of "aY' '1owe'_") alkv2_";lay include benzyl, phenethyl, phenylpropyl, phenylbutyl, phenvipentyl, phenylhexyl, naphthylmethyl, naphthylethvl, naphthylpropyl, naphthylbutyl, r-aphthylpentyl, naphthylhexyl, and the like, in which the preferred one may be phenyl;C;-Cz)alkyl, and the most nreferred one mav be benzvl.

Suitable example of "protected amino" may include iower or higher alkoxycarbonvlamino (e.g., methoxvcarbonylamino, ethoxycarbonyiamino, t-butoxycarbonylamino, t-pentyloxycarbonylamino, heptyloxycarbonylamino, etc.), ar(lower)alkoxycarbonylamino [e.g.,, phenvl(lower)alkoxycarbonylamino (e.g., benzyloxycarbonylamino, etc.), etc.], an amino group substituted with a conventional protecting group such as ar(lower)alkyl which may have suitable substituent(s) (e.g., benzvl, trityl, etc.) and the like, in which the preferred one may be phenyl(lower)alkoxycarbonylamino, and the most preferred one may be benzyloxycarbonylamino.

Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)"
can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (C1-C4)alkanoyl, and the more preferred one may be formyl.
Suitable example of "unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom" in the term of "lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)" may include pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl (e.g., 4H-1,2,4-triazinyl, 1H-1,2,3-triazinyl, etc.), tetrazinyl (e.g., 1,2,4,5-tetrazinyl, 1,2,3,4-tetrazinyl, etc.), and the like, in which the preferred one may be unsaturated 6-membered heteromonocyclic group containing 1 to 3 nitrogen atom(s), and the most preferred one mav be pyridyl and pyridazinyl.
Suitable example of "suitable substituent(s)" in the term of "lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic groups containing at least one nitrogen atom which may have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one mav be higher alkoxy, higher alkoxv(lower)alkyl, heterocyclic group which may have aryl having higher alkoxy, aryl which may have one or more higher alkoxy, aryl substituted with aryl which may have lower alkoxy, heterocyclic group which may have aryl having lower alkoxy(higher)alkoxy, and heterocyclic group which may have aryl having lower alkoxy, and the more preferred one may be (C7-C14)alkoxy, (C7-C14)alkoxy-(Ci-C4)alkyl, 3 to 8-membered saturated heteromonocyclic group containing at least one r_itrogen atom which may have phenyl having 1 to 3(C7-C14)alkoxy, phenyl which may have 1 to 3(C7-C14)alkoxy, phenyl substituted with phenyl which may have 1 to 3 (C3-C6)alkoxy, 3 to 8-membered saturated heteromonocyclic group containing at least one nitrogen atom which may have phenyl having (C1-C4)-alkoxy(C7-C14)alkoxy, and 3 to 8-membered saturated heteromonocyclic group containing at least one nitrogen atom which may have phenyl having 1 to 3 (C3-C6)alkoxy, and the most preferred one may be octyloxy, octyloxymethyl, piperazinyl which has phenyl having heptyloxy or octyloxy, phenyl having heptyloxy, phenyl substituted with phenyl having butoxy, piperazinyl which has phenyl having methoxyoctvloxy, and piperazinyl which has phenyl having hexyloxy.
Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with 1,2,3,4-tetra-hydroisoquinoline which may have one or more suitable substituent(s)" can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (C1-C4)-alkanovi., and the more preferred one may be formvl.
Suitable examcle of "suitable substituent(s)" in the term of "lower alkanovl substituted with 1,2,3,4-tetrahydroisoauinoline which may have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one may be lower alkoxy, higher alkoxy, lower alkyl, higher alkyl and lower alkoxycarbonyl, and the more preferred one may be (C7-C14)alkoxy and (C,-Cq)alkoxycarbonyl, and the most preferred one mav be octvlox.v and tert-butoxvcarbonyl.

Suitable example of "lower alkanoyl" in the term of "lower alkanoy.11- substituted with unsaturated condensed heterocyclic group containing at least one oxygen atom which may have one or more suitable substituent(s)" can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (Cl-Ca)alkanoyl, and the more preferred one may be formyl.
Suitable example of "unsaturated condensed heterocvclic group containing at least one oxygen atom" in the term of "lower alkanoyl substituted with unsaturated condensed heterocvclic group containing at least one oxygen atom which may have one or more suitable substituent(s)" may include unsaturated condensed heterocyclic group containing one or more oxygen atom(s) and, optionally, another hetero atom(s) except oxygen atom, in which the preferred one may be unsaturated condensed heterocyclic group containing 1 to 3 oxygen atom(s), unsaturated condensed heterocyclic group containing 1 to 2 oxygen atom(s) and 1 to 2 sulfur atom(s) and unsaturated condensed heterocyclic group 1 to 3 oxvgen atom(s) and 1 to 3 nitrogen atom(s), and the more preferred one may be benzo[b]furanyl, isobenzofuranyl, chromenyl, xanthenyl, benzoxazolyl, benzoxadiazolyi, dihydrooxathiinyl, phenoxathiinyl, and the like, and the most preferred one may be benzo[b]furanyl, chromenyl and benzoxazolyl.
Suitable example of "suitable substituent(s)" in the term of "lower alkanoyl substituted with unsaturated condensed heterocvclic group containing at least one oxvgen atom which mav have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one may be lower alkoxy, higher alkoxy, lower alkyl, higher alkyl, oxo, arvl which may have one or more lower alkoxy, heterocyclic group which may have one or more higher alkoxy, and aryl substituted with arvl which mav have one or more lower alkyl, and the more preferred one may be (C7-C14)alkoxy, (Ci-C4)alkyl, (C7-C14)alkyl, oxo, phenyl which may have 1 to 3 (C3-C6)alkoxy, unsaturated 6-membered heteromonochclic group containing at least one nitrogen atom which may have 1 to 3(C7-C14)alkoxy, and phenyl substituted with phenyl which mav have 1 to 3(C3-C6)alkyl, and the most preferred one may be octyloxy, methyl, nonyl, oxo, phenyl having hexyloxy, pyridyl having octvloxy, and phenyl substituted with phenvl having hexyl.
Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with unsaturated condensed heterocyclic group containing 1 to 3 sulfur atom(s) which may have one or more suitable substituent(s)" can be referred to aforementioned "lower alkanovl", in which the preferred one may be (C1-C4)alkanoyl, and the more preferred one may be formyl.
Suitable example of "unsaturated condensed heterocyclic group containing 1 to 3 sulfur atom(s)" in the term of "lower alkanoyl substituted with unsaturated condensed heterocyclic group containing 1 to 3 sulf-r atom(s) which may have one or more suitable substituent(s)" may include unsaturated condensed heterocyclic group containing only 1 to 3 sulfur atom(s), in which the preferred one may be benzothienyl and benzodithiinvi-, and the most preferred one may be benzothienyl.
Suitable example of "suitable substituent(s)" in the term cf "lower alkanovl substituted with unsaturated condensed heterocyclic group containing 1 to 3 sulfur atom(s) which mav have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one mav be lower alkoxy, higher alkoxy, lower alkyl and higher alkyl, and more preferred one mav be (C7-Cl4)alkoxy, and the most preferred one may be octyloxy.

Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with unsaturated condensed heterocvclic group containing 2 or more nitrogen atom(s) which may have one or more suitable substituent(s)" can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (C1-C4)alkanoyl, and the most preferred one may be formyl.
Suitable example of "unsaturated condensed heterocyclic group containing 2 or more nitrogen atom(s)"
in the term of "lower alkanoyl substituted with unsaturated condensed heterocyclic group co aining 2 or more nitrogen atom(s) which may have one or ...Dre suitable substituent(s)" may include 1H-indazolyl, purinyl, phthalazinyl, benzoimidazolyl; naphthyridinyl, quinoxalinvl, quinazolyl, cinnolinyl, peteridinyl, and the like, in which the most preferred one may be benzoimidazolyl.

WO 96/11210 PC1'/JP95/01983 Suitable example of "suitable substituent(s)" in the term of "lower alkanovl substituted with unsaturated condensed heterocvclic group containing 2 or more nitrogen atom(s) which may have one or more suitable ~ substituent(s)" can be referred to aforementioned "suitabie substituent(s)", in which the preferred one mav be lower alkoxy, higher alkoxy, lower alkvl, higher alkvl, aryl which may have one or more lower alkoxy and aryl which may have one cr more higher alkoxy, and the more preferred one may be (C7-C14)alkyl and phenyl which may have 1 to 3(Cl-CE)alkoxv, and the most preferred one mav be nonyl and phenvl which mav have hexyloxy.

Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with saturated 3 to 8-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)"
can be referred to aforementioned "lower alkanoyl", in which the preferred one mav be (Ci-C4)alkanoyl, and the more preferred one may be formvl.
Suitable example of "saturated 3 to 8-membered heteromonocyclic group containing at least one nitrogen atom" in the term of "lower alkanoyl substituted with saturated 3 to 8-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)" mav include pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, pyrazolidinyl, morpholinyl, thiomorpholinyl, and the like, in which the preferred one may be piperidyl and piperazinyl.
Suitable example of "suitable substituent(s)" in the term of "lower alkanovl substituted with saturated 3 to 8-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)" mav include lower alkoxv, higher alkoxy, higher alkoxy(lower)alkyl, lower alkyl, higher alkyl, oxo, aryl which may have one or more lower alkoxy, aryl which may have one or more higher alkoxy, aryl which may have one or more lower alkyl, aryl which mav have one or more higher alkvl, arovl which may have one or more lower alkoxy, arovl which may have one or more higher alkoxy, aroyl which may have one or more lower alkvl, arovl which may have one or more higher alkyl, and the like, in which the preferred on=_ mav be aryl which mav have one or more lower alkoxy, arvi which may have one or more higher alkoxy, aroyl which mav have one or more lower alkoxy and aroyl which may have one or more higher alkoxy, and the more preferred one may be aryl which may have 1 to 3 higher alkoxy and aroyl which may have 1 to 3 higher alkoxy, and the much more preferred one may be phenyl which may have 1 to 3(C7-C14)alkoxy and naphthoyl which may have 1 to 3(C7-Ci4)alkoxy, and the most preferred one may be phenyl which mav have octyloxy and naphthoyl which may have heptvloxy.

Suitable example of "ar(lower)alkenoyl" in the term of "ar(lower)alkenoyl substituted with arvl which may have one or more suitable substituent(s)" may include phenvl(lower)alkenoyl (e.g., 3-phenvlacryloyl, (2- or 3-or 4-)phenyl-(2- or 3-)butenoyl, 3-phenvlmethacryloyl, (2- or 3- or 4- or 5-)phenyl-(2- or 3- cr 4-)pentanoyl, (2- or 3- or 4- or 5- or 6-)phenyl-(2- or 3- or 4- or 5-)-hexanoyl, etc.), naphthyl(lower)alkenoyl (e.g., 3-naphthylacryloyl, (2- or 3- or 4-)naphthyl-(2- or 3-)butenoyl, (2- or 3- or 4- or 5-)naphthyl-(2- or 3- or 4-)pentanoyl, (2- or 3- or 4- or 5- or 6-)naphthyl-(2- or 3- or 4- or 5-)hexanoyl, etc.), and the like, in which the preferred one mav be 3-phenylacryloyl and 3-methvl-3-phenylacrvloyl.
Suitable example of "suitable substituent(s)" in the term of "ar(lower)alkenoyl substituted with aryl which may have one or more suitable substituent(s)" can be referred to aforementioned "suitable subst-ituent(s)", in which the preferred one may be lower alkoxy, lower alkyl, higher alkyl, lower alkoxy(lower)alkyl, halo(lower)alkoxy, lower alkenvloxy, halo(higher)alkoxy, and lower alkoxy(higher)alkoxv and the much more preferred one may be (C1-CE)alkoxy, (C1-C6)alkyl, (C7-C14)alkyl, (C1-C4 ) alkoxy (C3-C6) alkyl, halo (C3-C6) alkoxy, (C3-C6)alkenyloxy, halo(C7-C1d)alkoxy, and (CI-C4)alkoxy(C-7-Ci4)alkoxy and the most preferred one may be pentyloxy, heptvi, pentyl, methoxyhexyl, fluorohexyloxy, isohexyloxy, 5-hexenyloxy, haloheptyloxy, methoxyheptyloxy, methoxvoctyloxy, and butyloxy.

Suitable example of "naphthyl(lower)alkenoyl" in the term of "naphthyl(lower)alkenoyl which may have one or more higher alkoxy" may include 3-naphthylacryloyl, (2- or 3- or 4-)naphthyl-(2- or 3-)butenovi, (2- or 3- or 4- or 5-)naphthyl-(2- or 3- or 4-)pentanoyl, (2- or 3- or 4- or 5- or 6-)naphthyl-(2- or 3- or 4- or 5-)hexanoyl, and the like, in which the preferred one mav be 3-naphthylacryloyl.
Suitable example of "lower alkvnoyl" in the term of "lower alkynoyl which may have one or more suitable substituent(s)" may include 2-propynoyl, (2- or 3-)butynoyl, (2- or 3- or 4-)pentynoyl, (2- or 3- or 4- or 5-)hexynovl, and the like, in which the preferred one may be 2-propynoyl.
Suitable example of "suitable substituent(s)" in the - ~1 -term of "lower alkynoyl which may have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one mav be aryl which may have one or more lower alkoxy, aryl which may have one or more higher alkoxy, arvl substituted with aryl which may have one or more lower alkvl and aryl substituted with aryl which may have one or more higher alkvl, and the more preferred one may be arvl substituted with aryl which may have 1 to 3 lower alkyl and aryl which mav have 1 to 3 higher alkoxy, and the much more preferred one mav be phenvl substituted with phenyl which may have 1 to 3(Cl-C6)alkvl and phenyl which may have 1 to 3 (C7-C14)alkoxy, and the most preferred one may be phenyl substituted with phenyl which may have pentyl and naphthyl which may have heptyloxy.

Suitable example of "ar(C9-C6)alkanoyl" in the term of "ar(C2-C6)alkanoyl substituted with arvl having one or more suitable substituent(s), in which ar(Cg-C6)alkanoyl may have one or more suitable substituent(s)" may include phenyl(Cq-C6)alkanoyl [e.g., phenvlacetyl, (2- or 3-)-phenylpropanoyl, (2- or 3- or 4-)phenylbutanoyl, (2- or 3-or 4- or 5-)phenylpentanoyl, (2- or 3- or 4- or 5- or 6-)-phenylhexanoyl, etc.], naphthyl(C2-C6)alkanoyl [e.g.
naphthylacetyl, (2- or 3-)naphthylpropanoyl, (2- or 3- or 4-)naphthylbutanoyl, (2- or 3- or 4- or 5-)-naphthylpentanoyl, (2- or 3- or 4- or 5- or 6-)-naphthylhexanoyl, etc.], and the like, in which the preferred one may be 2-phenylacetyl and 3-phenylpropanoyl.
Suitable example of "suitable substituent(s)" in the term of "ar(C2-C6)alkanoyl substituted with arvl having one or more suitable substituent(s), in which ar(C2-C6)-alkanoyl may have one or more suitable substituent(s)" may include lower alkoxy, higher alkoxv, lower alkyl, higher alkyl, higher a-'kcxy(lower)alkyl, oxo, aryl having one or more lower a_t:ox,-, aryl having one or more higher alkoxy, aryl havir.g one or more lower alkvl, aryl having one or more higher aikvl, aryl substituted with aryl having one or more lower alkoxy, aryl substituted with aryl having one or more higher alkoxy, aryl substituted with aryl having one or more lower alk_yi, aryl substituted with aryl having one or more higher alkvi, arvl having one or more lower alkoxv(lower)alkoxy and the like, in which the preferred one mav be lower alkoxy, higher alkoxy, lower alkyl, higher alkyl, and phenyl having 1 to 3 lower alkoxy(lower)alkoxv and the much more preferreci one may be (Cl-Cn)alkoxy, (Cl-C6)alkvl, (C7-C14)alkyl and phenyl having (Cl-C4)alkoxy(C3-C6)alkoxy and the most preferred one may be pentvloxv, pentyl, heptyl and phenyl having methoxypentyloxy.
Suitable example of "suitable substituent(s)" in the term of "in which ar(C2-C6)alkanoyi may have one or more suitable substituent(s)" may be hydroxy, oxo, amino and a=orementioned "protected amino".

Suitable example of "(C2-C6)alkanoyl" in the term of "(C'?-CE)alkanoyl substituted with naphthyl having higher alkoxv" may include acetyl, propanoyl, butanoyl, pentanovl, hexanoyl, and the like, in which the preferred one may be propanoyl.
Suitable example of "higher alkoxy" in the term of ";C-~-C6)alkanoyl substituted with naphthyl having higher alkoxv" can be referred to aforementioned "higher alkoxy", in which the preferred one ma_v be (C7-C14)alkoxy, and the most preferred one may be heptvloxy.

Suitable example of "aroyl" in the term of "aroyl substituted with heterocyclic group which may have one or more suitable substituent(s), in which arovl may have one or more suitable substituent(s)" may include benzoyl, toluoyl, naphthoyl, and the like, in which the preferred one may be benzovl.
Suitable example of "heterocyclic group" in the term of "arovl substituted with heterocyclic group which may have one or more suitable substituent(s), in which arovl may have one or more suitabie substituent(s)" may include unsaturated 3 to 8-membered (more preferably 5 or 6-m embered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pvrroiyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., 1H-tetrazolyl, 2H-tetrazolyl, etc.), etc.;

saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, etc.;
unsaturated condensed heterocyclic group containing 1 to 4 nitrogen atom(s), for example, indolyl, isoindolvl, indolinyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-meir.bered) heteromonocyclic group containing 1 to 2 oxvgen atom(s) and 1 to 3 nitrogen atom(s), for example, oxazolyi, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.), etc.;
saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, morpholinyl, svdnonyl, etc.;

unsaturated condensed heterocvclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for examnle, thiazolyl, isothiazolvl, thiadiazcivl (e.g., 1,2,3-thiaciiazoiyl, 1,2,4-thiaciiazolvl, 1,3,4-thiadiazolyl, 1,2,5-thiaciiazolyi, etc.), dihydrothiazinyl, etc.;
saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s), for example, thienyl, dihydrodithiinyl, dihydrodithionyl, etc.;
unsaturated condensed heterocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzothiadiazolvl, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing an oxygen atom, for example, furyl, etc.;
saturated 3 to 8-membered (more preferablv 5 or 6-membered) heteromonocyclic group containing an oxygen atom, for example, tetrahydrofuran, tetrahydropyran, etc.;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing an oxygen atom and 1 to 2 sulfur atom(s), for example, dihydrooxathiinyl, etc.;
unsaturated condensed heterocyclic group containing 1 to 2 sulfur atom(s), for example, benzothienyl, benzodithiinyl, etc.;
unsaturated condensed heterocyclic group containing oxvgen atcm and 1 tc 2 sulfur arom(s), for examnle, benzoxat~iinvl, etc.; and the like, ir.~ which the preferred one mav be saturate: 3 to 8-.nemberea heteromonocyclic group containi~g 1 to 4 nitrogen atom ( s ), unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom's) , unsaturateci 3 to 8-membered 'neteromor_ocvclic group containing 1 to 4 nitrogen atom(s), and unsaturated 3 to 8-membered heteromonocvclic group contai ning 1 to 2 sulfur atom (s) and 1 to 3 riitrogen arom(s;, and the most preferred one mav he niperaziny~, isCxazolvl, oxadiazolyl, t7iadiazolvl, pvrazolvl, piperidyl, oxazolyl and pyrimidyl.
i~
Suitable example of "suitable substituent(s)" ir. the term of "aroyl substituted with heterocvclic group which mav have one or more suitable substituent(s), in which arov' may have one or more suitable substituent(s)", car:
be referred to aforementioned "suitable substituent(s)", in which the preferred one may be arvl which mav have I
to 3 higher alkoxv, aryl which *aav have 1 to 3 lower alkoxy, higher alkyl, heterocyclic group, aryl which mav have 1 to 3 lower alkoxy(higher)alkoxy, aryl which mav have higher alkenyloxy, heterocvclic group which may have arvl having.lower alkoxy, cyclo(lower)alkvl which may have aryl, aryl which may have 1 to 3 lower alkyl, aryl which may have cvclo (lower) alkyl, arvl which mav have hi gher alkenvloxv, arvi substi:uted with heterocyclic group which :nay have lower alkvl and oxo, cvcle(lower)alkyl which mav have lower alkvl, aryl substituted with arvi whic~ may have 1 tc 3 lower alkoxy, and arvl which may have heterocvclic group, and the more preferred one may be phenyi which may have 'L to 3(C7-C14)alkoxy, phenvl which 3-5 may have 1 t.; 3 (C3-C6)alkoxv, (C -/-C; /,) alkyl, saturated 3 - ir -to 8-membered heteromonocVclic grou te n~ - rO~eP. dLOIP. ( s ), Dhenyl wt'iic.- ?A~y 1c vc ~ tC

~ i d, KGXy (C~-C, 4i aikoXV, pnenV-' wlh_c =. .i':aV :LaT'c'' C--C,,~)alkenyloxy, saturated 3 to 3-membered hetercmonocyc_ic 7- group containi n:. I t0 4 nitroQc~:: atGIIt s! s'õ'Dstitl::ted wi --h phenyl having ,C-~-CF) alkox.v, cyc_o (C--C6al 'k.vl r~~ay t:ave phenyl, phenvl wnich may r:a ,.Te ? tG 3(C J-CG ) alky1, pher.yl which may have cyclo;C3-CGialkvl, phenyl which may have ;C~-C1/I ) dll>enyloxy, phenvl substi-t:teci with 1 '3 heterocyclic group which may have (C-,-Cc; ~14_yl and oxc, CyCiv (C3-C6) diky_ wril~_ maV have (CJ-CC; -Ky-- :!:enVi substituted with phenvl whi c:i ~:a%, have 1-o 3'C, -~
C4;alkoxy, and phenyl which may havE > to 8-me:roered ~eteromonocvclic group centaininc _ tc 4 =.irrogen ato~:;s;, and the most preferred one mav be pher~v; having cctyloxy, phenvl having pentyloxy, phenvl hav_c hexvioxv, her)tvl, piperidyl, phenyi having isohexyloxy, chenvl :having heptyloxy, phenyl having methoxvheptvloxv, phenyl havine methoxvoctvloxy, phenvi havina 6-heptenvloxy, piperidyl 2C substituted wit~ phenyl having hexyloxy, cyclchexvi having p,henyl, phenyl having hexyl, phenJl naving cyclohexvi, ohenyl having 7-octenyloxv, phenv-i substituted with tr=azolyl having lower alkyl and oxc, --vclohexyl having per_tyl, phenvl having methoxyoctyloxv, nonyl, phenyl 25 substituted with phenyl having propoxy, and phenvl having oineridine.
Suitable eXample of "suitable subst'_tuent(s)" in the term of "in which aroyl may have one or more suitable substituent(s)" mav be halogen, in which the Nreferred one 30 mav be fluorc and chloro.

Suitable example oT "aroyl" in the term of "aroyl substituted with aryl having heterocyc'i-c(hicher)alkoxy, in which heterocyclic group mav have one or more suitable 35 substituent(s)" may include benzovi, toluoyl, naphthovl, - % i --ar--hrvlcarbonv: and the like, -n which the nre*P_rred one Il1a_J be hcnzoy- .

Su? tabie example o- "heterocvc' ic" ?Ttoiet'y' ' i tI e ~er??1 of "aroyl substituted with arvi havir.a heterocvclic(higher)alkoxy, in whicr :-~eterocvc_ic group may have one or more suitable substituent(s)" can be Yeferred to the ones as exemtilifieci hefore for "heterocyciic group" in the term of "aro'J1 subst? -_utea with heterocyclic group which may have one or more i0 suitable substituent(s)", in which the zreferred one may ..~e unsaturated 3 to 8-:nembered heteromonocyclic group co=a,i ni'_7q 1. to 4?litrpqen atom,s) and saturated 3 to 8-membered i?eteromonocvcl_c yroup containing 1 zo 2 oxyger- atom(s) and 1 to 3 nitrogen atom(s), and the most preferred one may be triazolvl, tet.razoly' and morpholinvl.
Suitable example of "(higher)alkoxy" moietv ir: the term of "aroyl substituted with ary~ having nererocyclic(higher)alkoxy, in which heterocyclic group ~ay have one or more suitable substituent(s)" can be referred to aforementioned "higher alk-oxy", in which the preferred one may be (C7-Ci4) aikox_v, and the most preferred one may be octvloxy.
Su?table example of "a=vl" in the term of "arovl substituted with aryl having heterocyclic(higher)alkoxv, ir. which heterocyclic group mav have one or more suitable sL'bstituent (s) " can be referred to afcreme-~.tione' "arvl", in which the preferred one mav be phenvi.
Suitable example of "suitable substituent(s)" in the term of "in which heterocyciic group may have one or more suitable substituent(s)" mav be lower alkyl, in which the preferred one may be methyl.

Suitable example of "arovi" ir. the term of "aroyl substituted with aryl having lower alkoxv(hicher)aikoxy"

may include benzoyl, toluoyl, naphthoyl, anthrylcarbonv' and the like, in which the preferred one may be benzoyl.
Suitable example of "arvl" in the term of "aroyl substituted with arvl having lower alkoxy(higher)alkoxv"
can be referred to aforementioned "aryl", in which the preferred one mav be phenyl.
Suitable example of "lower alkoxy(higher)alkoxy" in the term of "arovi substituted with aryl having lower alkoxy(higher)alkoxy" may be methoxyheptvloxy, methoxvoctyloxv, methoxynonyloxv, methoxydecyloxy, ethoxvheptvloxv, ethoxvoctyloxy, ethoxvnonyloxy, ethoxvdecvloxv, ethoxyundecyloxy, propoxyundecyloxy, butoxydodecyloxv, pentyloxytridecyloxy, hexyloxytetradecyloxy, propoxyheptyloxy, propoxyoctyloxy, propoxynonvloxy, butoxydecyloxy, or the like, in which the preferred one may be (C1-CE)alkoxy(C7-C14)alkoxy, and the more preferred one may be methoxyoctyloxv.

Suitable example of "arovl" in the term of "aroyl substituted with aryl having lower alkenvl(lower)alkoxy"
may include benzovl, toluoyl, naphthovl, anthryicarbonvl and the like, in which the preferred one may be benzoyl.
Suitable example of "aryl" in the term of "aroyl substituted with aryl having lower alkenyl(lower)alkoxy"
can be referred to aforementioned "aryl", in which the preferred one may be phenyl.
Suitable example of "lower alkenyl(lower)alkoxy" in the term of "aroyl substituted with ar_vl having lower alkenyl(lower)alkoxv" may be vinylmethoxy, vinylethoxy, vinylpropoxy, vinylbutoxy, vinylpentvloxy, vinylhexyloxy, 1-(or 2-)propenylmethoxy, 1-(or 2-)propenylethoxy, 1-(or 2-)propenvlpropoxy, 1-(or 2-)propenylbutoxy, 1-(or 2-)-propenylpentyloxy, 1-(or 2-)propenylhexyloxy, 1-(or 2- or 3-)butenylbutoxy, 1-(or 2- or 3-)butenylhexvloxy, 1-(or 2-or 3- or 4-)pentenylpentyloxy, 1-(or 2- or 3- cr 4-)-pentenvlhexvloxy, ;-(or 2- or 3- or 4- or 5-)-hexenylbutoxy, 1-(or 2- or 3- or 4- or 5-)hexenylhexyloxv, ~ or the like, Jn which the preferred one may be (C2-C6)alkenyl(Cj-C6)alkoxy, and the more preferred one may be vinvihexyloxy.

Suitable example of "arovl substituted with 2 lower alkoxy" may include benzoyl substituted with 2 iower alkoxy and naphthovl substituted with 2 lower alkoxy, in whic'.: the preferred one may be benzovl substituted with 2(C1-C6)alkoxy, and the most preferred one may be benzoyl substituted with 2 pentyloxy.

Suitable example of "aroyl substituted with aryl having lower alkyl" may include benzoyl substituted with phenyl having lower alkyl, benzoyl substituted with naphthyl having lower alkyl, naphthoyl substituted with phenyl having lower alkyl, naphthoyl substituted with naphthyl having lower alkyl, and the like, in which the preferred one may be benzoyl substituted with phenyl having (C1-C6)alkyl, and the most preferred one may be benzoyl substituted with phenyl having hexvl and benzovl substituted with phenyl having pentyl.

Suitable example of "arovl substituted with aryl having higher alkyl" may inciude benzoyl substituted with phenyl having higher alkyl, benzoyl substituted with naphthyl having higher alkyl, naphthoyl substituted with phenyl having higher alkyl, naphthoyl substituted with naphthyl having higher alkyl, and the like, in which the preferred one may be benzoyl substituted with phenyl having (C7-C14)alkyl, and the most preferred _ 30 -one mav be benzoyl substituted with phenyl having heptyl.
Suitable example of "arvioxy" moiety in the term of "aryloxy(lower)alkanovl which may have one or more suitable substituent(s)" may include phenoxy, mesitvloxy, toivloxy, naphthyloxy, anthryloxy, and the like, in which the preferred one mav be phenoxv.
Suitable example of "lower alkanoyl" moiety in the term of "aryloxy(lower)alkanoyl which mav have one or more suitable substituent(s)" can be referred to aforementioned "lower aikanoyl", in which the preferred one mav be formvi, acetvl, 2,2-dimethylacetyl, propionvl, butveyl, isobutyryl and pentanovl, hexanoyl, and the more preferred one may be (C1-C6)alkanoyl, and the much more preferred one mav be formyl, acetyl, propionyl and 2,2-dimethylacetyi.
Suitable example of "suitable substituent(s)" in the term of "aryloxy(lower)alkanovl which mav have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one mav be (C7-C14)alkoxy, and the more preferred one may be octyloxy.

Suitable example of "ar(lower)alkoxy" moiety in the term of "ar(lower)alkoxv(lower)alkanoyl which may have one or more suitable substituent(s)" may include phenyl(lower)alkox_v [e.g., phenvlmethoxy, (1- or 2-)-phenylethoxy, phenyipropoxy, 2-phenyl-l-methylpropoxy, 3-phenvl-2,2-dimethylpropoxy, (1- or 2- or 3- or 4-)phenylbutoxy, (1- or 2- or 3- or 4-or 5-)phenylpentyloxy, (1- or 2- or 3- or 4- or 5- or 6-phenvlhexyloxy, etc.], naphthvl(iower)alkoxy [e.g.
naphthylmethoxy, (1- or 2-)napthylethoxy, 1-naphthylpropoxy, 2-naphthvl-l-methylpropoxy, 3-naphthvl-2,2-dimetylpropoxy, (1- or 2- or 3- or 4-)naphthylbutoxy, i?- or 2- or 3- or 4- or 5-)naphthylpentyloxy, (?- or 2-or 3- or 4- or 5- or 6-)naphthvlhexvloxy, etc.], and the like, in which the preferred one may be naphthyl(C1-C4)alkoxy, and the more preferred one may be naphthylmethoxy.
Suitable example of "(lower)alkanoyl" moietv in the term of "ar(lower)alkoxv(lower)alkanoyi which may have one or more suitable substituent(s)" can be referred to aforementioned "lower alkanovl", -10 in which the preferred one may be (Cl-C4)alkanoyl, and the more nreferred one may be formvl.
Suitable example of "suitable substituent(s)" in the term of "ar (lower) alkoxy (lower) alkanoyl which may have one or more suitable substituent(s)" can be referred to aforementioned "suitable substituent(s)", in which the preferred one may be lower alkoxy, higher alkoxy, lower alkyl and higher alkyl, and the more preferred one may be higher alkoxv, and the much more preferred one may be (C7-Ci4)alkox1-, and the most preferred one may be heptyloxy.

Suitable ;-amnle of "aryiamino" moiety in the term of "arvlamino(lowe-)alkanoyl which may have one or more suitabie substituent(s)" r:,av include phenylamino, mesitvlamino, tolylamino, naphthylamino, anthrylamino and the like, in which the preferred one mav be phenylamino and naphthylamino.
Suitable example of "lower alkanoyl" moiety ir: --he term of "arylamino(lower)alkanoyl which may have on,::- or more suitable substituent(s)" can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (C1-C4)alkanoyl, and the more preferred one may be formvl.
Suitable example of "suitable substituent(s)" in the term of "arylamino(lower)alkanovl which may have one or more suitable substituent(s)" can be referred to a*orementioned "suitable substituent(s)", in which the preferred one may be lower alkoxy, higher alkoxy, lower alkyl, higher alkyl, aryl which may have i to 3 lower alkoxv and aryl which may have 1 to 3 higher alkoxy, and the more preferred one may be (C7-C14)alkoxy, and phenyl which may have 1 to 3 (C7-C14)alkoxy, and the most preferred one may be heptyloxy and phenvl which mav have heptyloxy.
Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with pyrazolyl which has lower alkyl and arvl having higher alkoxy" can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (Ci-C4)alkanoyl, and the most preferred one may be formyl.
Suitable example of "lower alkyl" in the term of "lower alkanoyl substituted with pyrazolyl which has lower alkvl and aryl having higher alkoxy" can be referred to aforementioned "lower alkyl", in which the preferred one may be (Ci-C4)alkyl, and the most preferred one may be methyl.
Suitable example of "aryl" in the term of "lower alkanoyl substituted with pyrazolyl which has lower alkyl and aryl having higher alkoxy" can be referred to aforementioned "aryl", in which the preferred one may be phenyl.
Suitable example of "higher alkoxy" in the term of "lower alkanoyl substituted with pyrazolyl which has lower alkyl and aryl having higher alkoxy" can be referred to aforementioned "higher alkoxy", in which the preferred one may be (C7-C14)alkoxy, and the most preferred one may be octvloxy.

Suitable example of "lower alkoxy(higher)alkanoyl" in the term of "iower alkoxv(higher)alkanoyl, in which higher alkanoyl may have one or more suitable substituent(s)" may be (Ci-C4)alkoxv(C-7-C2G)alkanoyl, in which the preferred one may be methoxyoctadecanovl.
Suitable example of "suitable substituent(s)" in the term of "lower alkoxv(higher)alkanoyi, in which higher alkanoyl mav have one or more suitable substituent(s)" mav be amino and aforementioned "protected amino", in which the preferred one may be amino and ar(lower)alkoxycarbonylamino, and the most preferred one may be amino and benzvloxvcarbonviamino.

Suitable example of "arovl" in the term of "aroyl substituted with arvl having heterocyclicoxv, in which i5 heterocyclicoxy may have one or more suitable substituent(s)" can be referred'to aforementioned "aroyl", in which the preferred one may be benzoyl.
Suitable example of "aryl" in the term of "aroyl substituted with aryl having heterocyclicoxy, in which heterocyclicoxy mav have one or more suitable substituent(s)" can be referred to aforementioned "aryl", in which the preferred one may be phenyl.
Suitable example of "heterocyclic" moiety in the term of "aroyl substituted with aryl having heterocyclicoxy, in which heterocvclicoxy may have one or more suitable substituent(s)" can be referred to aforementioned "heterocyclic" moiety, in which the preferred one may be unsaturated 3 to 8-membered heteromonocyc..c group containing 1 to 4 nitrogen atom(s), and t::<- most preferred one may be pyridazinyl.
Suitable example of "suitable substituent(s)" in the term of "aroyl subE'ituted with aryl having heterocvclicoxy, in which heterocyclicoxy may have one or more suitable subst-ituent(s)" may be aryl, in which the preferred one may be phenyl.

- 3~ -fr SuiLabie exampile of rrarov_ _-he +,_.erm c= rraroy__ 5u-stfr::teCt w'_ zh Cyci C(7owe") ai.Kyi ;-~aving _ower a-kv-" ca:-_ be referred --o azoreme::ti017ed "arGV l", in wP=c.: the preferred one may be benzoyl.

Suitable exa?Aple of "cyclo ('lower) aik_yl" i'_7 the teY'm Or "arovl substituted with cVclo( l ower) alkVl -~aving lower a-lkvl" can be referred to afore_~.:er:tioned "cvc i o(lower) alky_I", in whi cr the preferred cr_e rLay be cvclohexyl .
Suitable example of "lower alkyl" -n the term of "arovl substituted with cvclo;lower~alkvi havina lower alkvi" can be referred :o arore"1e.~_t_o:leC "lower alky_", jr wh=ch the preferred one may be pentv'_.

Suitable example of "higher aiky" -n the -cerm o-r "_ndo'_ylcarbonyl having higher aikvi" can be referred to aforementioned "higher alkyl", _*: wt:iCP the prefzrred one may be decyl.

Suitable example of "lower a_kv?" in the zerm of "nalJhLhCvl having lower alkyl" can be referred to afcremenLioned "lower alkyl", I_1 whLc:l the preferred o:]e may be hexyl.

Suitable example of "higher alkyl" in the term of "naphthoyl having higher alkv!" can be referred to aforementloned "higher alkvl", -'~ which, the preferred one may be heptyl.

Suitable example of "lower alkoxv(h=gher)alkoxy"
L!le term of "naphthoyl having lower alkoxy(hiaher)alkoxy"
mav be (Cj-CL)alkoxV(C7-C1..4)alkoxy, i-1i which the preferred cne may be methoxyoctyloxy.

Suitable exam-oie o' "arov_" ir_ the term of "arov=

substituted with aryl having lower alkoxy(lower)alkoxy(higher)alkoxy", "aroyl substituted with aryl having lower alkoxy(lower)alkoxy", "aroyl substituted with aryl which has arvl having lower alkoxy", "aroyl substituted with aryl which has aryl having lower alkoxy(lower)alkoxy", "aroyl substituted with aryl having heterocyclicoxy(higher)alkox_v", "aroyl substitued with aryl having aryloxy(lower)alkoxy" and "aroyl substituted with. aryl having heterocvcliccarbonyl(higher)alkoxy" can be referred to aforementioned "aroyl", in which the preferred one may be benzoyl.
Suitable example of "ar_yl" in abovementioned terms can be referred to aforementioned "aryl", in which the preferred one may be phenyl.
Suitable example of "lower alkoxy(lower)alkoxy-(hiaher)alkoxy" in the term of "arovi substituted with aryl having lower alkoxy(lower)=alkoxy(higher)alkoxy" may be (C1-C4)alkoxy(C1-C4)alkoxy(C7-Ci4)alkoxy, in which the preferred one may be ethoxyethoxyoctyloxy.

Suitable example of "lower alkoxy(lower)alkoxy" in the term of "aroyl substituted with arv'- having lower alkoxy(lower)alkoxv" mav be (C1-C4)alkoxy(C3-C6)alkoxy, in which the preferred one may be propoxyhexyloxy.
Suitable example of "lower alkoxy" in the term of "aroyl substituted with aryl which has phenyl having lower alkoxy" may be (C3-C6)alkoxy, in which the preferred one may be butoxy.

Suitable example of "lower alkoxy(lower)alkoxy" in the term of "aroyl substituted with aryl which has phenyl having lower alkoxy(lower)alkoxv" may be (C1-C4)alkoxy-(C3-C6)alkoxy, in which the preferred one may.be r:ethoxypentyloxy and methoxyhex.ylox_y.

Suitable examDie cf "!:eterocycllc" moiety in the term cf "aroyl suDszinuteQ with aryl having ., heterocyclicoxv;higher)alkoxy" can be referred to afoYementlcne'..: "heterocvclic" moietv. in which the preferred Gne may be satL'rated 3 to 6-membered heteromonocyclic group containing an oxygen atom, and the most preferred one may be tetrahydropyranv'.

iv Suitable example of "higher alkoxv" mci etv in the term of "arGyl substituted with arv_ having =_eterocvc iico3SV (hlgher) a'-' kox:'n may ie 2--C, L i a_t:cXV, =~
which the preferred one may be octyloxv.

15 Suitable example of "aryloxy(lower)alkoxy" _., the term of "aroyl substituted with aryl having aryloxy ( lower ) al'xoxy" may be phenoxy, ( C3-Valkox-y, in which the preferred one may be phencxypentyloxy.

20 Suitable example of "heterocyclic" moiety in the term of "aroyl substituted with aryl having heterocycliccarbonyl(higher)alkoxy" can be referred to aforementioned "heterocyclic" moiety, in which the preferred one may be saturated 3 to 8-:nembered 25 heteromonocyclic group containing 1 to 4 nitrog2:: atom(s), and the most preferred one may be piperidyl.
Suitable example of "higher alkoxy" moiety in the term of "aroyl substituted with aryl having heterocycliccarbonyl(higher)alkoxy" can be referred to 30 aforementioned "higher alkoxy", in which the preferred one may be (O-C!4)alkoxy, and the most preferred one may be heptyloxy.

Suitable examnle of "lower alkanoyl" in the term of 35 "lower alkanoyl substituted with oxazolyl which has aryl having higher alkoxy" can be referred --c aforementioned "lower alkanovl", in which the preferred one may be (Cl-C4)alkanoyl, and the most preferred one mav be formvi.
Suitable example of "aryl" in the term of "lower alkanoyl substituted with oxazolvl which has aryl having higher alkoxy" can be referred to aforementioned "aryl", in which the preferred one mav he phenyl.
Suitable example of "higher alkoxy" in the term f "lower alkanovl substituted with oxazolyl which has ;l having higher alkoxv" can be referred to aforementioned "higher aikoxy", in which the preferred one may be (C7-C14)alkoxy, and the most preferred one may be octyloxv.

Suitable example of "lower a- <:.noyl" --_ the term of "lower alkanoyl substituted with _jl which has aryl substituted with aryl having lower alkoxy" can be referred to aforementioned "lower alkanoyl", in which the preferred one may be (C1-C4)alkanoyl, and the most preferred one may be formyl.
Suitable example of "aryl" in the term of "lower alkanoyl substituted with furyl which has aryl substituted with aryl having lower alkoxy" can be referred to aforementioned "aryl", in which the preferred one may be phenyl.
Suitable example of "lower alkoxy" in the term of "lower alkanoyl substituted with furyl which has aryl substituted with aryl having lower alkoxy" can be referred to aforementioned "lower alkoxy", in which the preferred one mav be (Ci-CL)alkoxy, and the most preferred one may be butoxv.

Suitable example of "lower alkanoyl" in the term of "lower alkanoyl substituted with triazolvl which has oxo and aryl having higher alkyl" can be referred to a:or2Iite?.tioned "lower alkanov1". ir: --r.e -cre=erred one mav be (C,-C,~;alkanoyl, anci the most pre-f-'e=red or.e may be =crmyl.
Suitable example of "higher alky'-" in the term o=
"lower alkanoyl substltuteQ Witr: tr? ?ZOlvl which has cxc and arvl havir_g higher alky_" can he referred to ~fereme=ioned "r'-gher aikv''', wh-,c__ tne :?'eferred or_e m av be (C7-C14ialkyl, and the most preTerred one may be octyl.

~ G S i;.able cxample o~ "arv_""-' zc="m of "lower _-kancyl substituLed with tr;azoi',1~ WhiCr: has oxo and arv,.
nvirQ ~1 gher a~kyl " can ~'Je reTer'_"'eC L: afcreII'ie_lt=onc:.
"arvl", in which the preferrea one mGv be pher.yl.

i5 Suitable ex_arr.ple cf "higher alkanovl " ir_ the ter:-; c_ "~ia'r:er alkanovl having hydrox.y" can be referred to c.forementioned "higher aikanov-, ", in whi ch the nreferred one Tav be (C7-C20)alkanov?, and the most preferred one may be hexadecanoyl.

Suitable example of "higher aiKanov?" in tne term of "= igher alkanovi :aving ar (lower)alkvi and hvdrOXv" can beE
re_erred to aforemer_tioned "higher alkanoyl", in which the :,referred one may be (C7-C20)a'lkanov', and the most preferred one may be hexadecanoyl.
Suitable example of "ar(iower)aikyl" in the term of ":igher alkanoyl having ar(lower)alkyl and hydrox_y" can be referred to aforementioned "ar (lower) alk_yl", in which the preferred one may be phenyl(CI-CQ)alkyl, and the most r-referred one mav be benzvl.

Suitable example of "(C2-C6)aikar.oyi" in the terms of 2-C6)a_kanoy2. substituted with aryl havinr higher al.koxy, in whi c'r. (C2-C6) alkanov, mav have amiro or protected amino" mav incl-ude acetyl, prcpanov'_, butar.oyl, pentanoyl, hexanoyl, and the like, in which the preferred one may be acetvl and propanoyl.
Suitable example of "aryl" in the term of "(C2-C6)alkanoyl substituted with aryl having higher alkoxy, in which (C2-C6)alkanoyl may have amino or protected amino"
can be referred to aforementioned "aryl", in which the preferred one may be phenvl.
Suitable example of "higher alkoxv" in the term of "(C2-C6)alkanovl substituted with arvl having higher alkoxy, in which (C2-C6)alkanoyl may have amino or protected amino" can be referred to aforementioned "higher alkoxy", in which the preferred one mav be (C-/-Cl4)alkoxy, and the most preferred one mav be octvloxv.
Suitable example of "protected amino" in the term of "(C2-C6>alkanoyl substituted with aryl having higher alkoxy, in which (C2-C6)alkanoyl may have amino or protected amino" can be referred to aforementioned "protected amino", in which the preferred one may be ar(lower)alkoxycarbonylamino, and the most preferred or may be benzyloxycarbonvlamino.

The process for preparing the object polypeptide compound [I] or a salt thereof of the present invention are explained in detail in the following.
Process The object polyneptide compound [I] or a salt thereof can be prepared by reacting the compound [II] or its reactive derivative at the amino group or a salt thereof with the compound [III] or its reactive derivative at the carboxy group or a salt thereof.
Suitable reactive derivative at the carboxv group of the compound [III] may include an acid halide, an acid anhydride, an activated amide, an activated ester, and the like. Suitable examples of the reactive derivatives may be an acid chioride; an acid azide; a mixed acid anhydride with an acid such as substituted phosphoric acid [e.g., dialkvlphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid, etc.j, dialkylphosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid [e.g., methanesulfonic acid, etc.], aliphatic carboxylic acid [e.g., acetic acid, nropionic acid, butvr=c acid, isobutvric acid, pivaric acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid, trichloroacetic acid, etc.]; or aromatic carboxvlic acid [e.a., benzoic acid, etc.]; a svmmetrical acid anhydride;
an activated amide with imidazole, 4-substituted imidazole, ciimethvipyrazole, triazole, tetrazole or 1-hvdroxv-lH-benzotriazole; or an activated ester [e.g., cvanomethvl ester, methoxymethvl ester, dimethyliminomethyl [(CH3)?N=CH-] ester, vinvl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenvl ester, trichloronhenyl ester, pentachlorophenyl ester, mesvlphenyl ester, phenylazophenyl ester, phenyl thioester, p-nitrophenyl thioester, p-cresyl thioester, carboxymethyl thioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolyl thioester, etc.], or an ester with a N-hydroxy compound [e.g. N,N-dimethylhydroxylamine, 1-hydroxy-2-(1H)-pyridone, N-hvdroxysuccinimide, N-hvdroxvphthalimide, 1-hydroxy-lH-benzotriazole, etc.], and the like. These reactive derivatives can ontionally be selected from them according to the mind of the compound [III] to be used.
Suitable salts of the compound [III] and its reactive derivative can be referred to the ones as exemplified for the object polvpeptide compound [I].
The reaction is usually carried out in a conventional solvent such as water, alcohol [e.g., methanol, ethanol, etc.], acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide, pyridine or any other organic solvent which does not adversely influence the reaction. These conventional solvent may also be used in a mixture with water.
In this reaction, when the compound [III] is used in a free acid form or its salt form, the reaction is preferably carried out in the presence of a conventional condensing agent such as N,N'-dicyclohexylcarbodiimide;
N-cyclohexvl-N'-morpholinoethvicarbodiimide;
N-cyclohexyl-N'-(4-diethvlaminocyclohexvl)carbodiimide;
N,N'-diethylcarbodiimide, N,N'-diisopropvlcarbodiimide;
N-ethyl-N'-(3-dimethvlaminopropyl')carbodiimide, N,N-carbonylbis-(2-methylimidazole);
pentamethvlenek.etene-N-cyclohexvlimine;
diphenylketene-N-cvclohexylimine; ethoxyacetylene;
1-alkoxv-2-chloroethylene; trialkyl phosphite; ethyl polyphosphate; isopropyl polyphosphate; phosphorus oxychloride (phosphoryl chloride); phosphorus trichloride;
thionvl chloride; oxalyl chloride; lower alkyl haloformate [e.g., ethyl chloroformate, isopropvi chloroformate, etc.]; triphenyiphosphine; 2-ethyl-7-hvdroxybenzisoxazolium salt;
2-ethyl-5-(m-sulfophenyl)isoxazolium hydroxide intramolecular salt; 1-(p-chlorobenzenesulfonyloxy)-6-chloro-lH-benzotriazole; so-called Vilsmeier reagent prepared by the reaction of N,N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorous oxychloride, methanesulfonyl chloride, etc.;
or the like.
The reaction may also be carried out in the presence of an inorganic or organic base such as an alkali metal carbonate, alkali metal bicarbonate, tri(lower)alkylamine, pyridine, di;lower)alkylaminopyridine (e.g., - a~ -4-dimethylaminopyridine, etc.), N-(lower)alkylmorpholine, N,N-di(lower)alkylbenzylamine, or the like.
The reaction temperature is not critical, and the reaction is usually carried out under cooling to warming.
The starting compound [II) is a known compound. It can be prepared by fermentation and synthetic processes disclosed in EP 0462531 A2.
A culture of Coleophoma sp. F-11899, which is used in said fermentation process, has been deposited with National Institute of Bioscience and Human-Technology Aaencv of Industrial Science and Technology (former name:
Fermentation Research Institute Agency of Industrial Science and Technology) (1-3, Higashi 1-chome, Tsukuba-shi, IBARAKI 305, JAPAN) on October 26, 1989 under the number of FERM BP-2635.

The compounds obtained by the above Process 1 can be isolated and purified by a conventional method such as pulverizatior., recrystallization, column-chromatography, high-performance liquid chromatography (HPLC), reprecipitation, or the like.

The compounds obtained by the above Process 1 may be obtained as its hydrate, and its hydrate is included with-in the scope of this invention.

It is to be noted that each of the object compound (I) may include one or more stereoisomer such as optical isomer(s) and geometrical isomer(s) due to asymmetric carbon atom(s) and double bond(s) and all such isomers and mixture thereof are included within the scope of this invention.

Biological property of the polypeptide cc~r:rour.d ',I 1 of the present invention In order to show the usefulness of the polypeptide ~ compound [Ij of the present invention, the bioiogical data of the representative compound is explained in the following.

Test 1 (Antimicrobial activity) In vitro antimicrobial activity of the compound of Example 17 disclosed later was determined by the two-fold agar-plate dilution method as ciescribed below.

Test Method One loopful of an overnight culture of each test microorganism in Sabouraud broth containing 2~ Glucose (105 viable cells per ml) was streaked on yeast nitrogen base dextrose agar (YNBDA) containing graded concentrations of the object polypeptide compound [I], and the minimal inhibitory concentration (MIC) was expressed in terms of pg/ml after incubation at 30 C for 24 hours.
Test Result MIC (}ig/ml) Test compound The compound of Test organism Examr)le 17 candida albicans FP-633 0.2 From the test result, it is realized that the object polypeptide compound [I] of the present invention has an antimicrobial activity (especially, antifungal activity).
The pharmaceutical composition of the present invention can be used in the form of a pharmaceutical preparation, for example, in solid, semisolid or liquid from, which contains the object polypeptide compound (I) or a pharmaceutically acceptable salt thereof, as an active ingredient in admixture with an organic or inorganic carrier or excipient which is suitable for rectal; pulmonarv (nasal or buccal inhalation); ocular;
external (topical); oral administration; parenteral (including subcutaneous, intravenous and intramuscular) administrations; insufflation (including aerosols from metered dose inhalator); nebulizer; or drv powder inhalator.

The active ingredient may be compounded, for example, with the usual non-toxic, pharmaceutically acceptable carriers in a solid form such as granules, tablets, dragees, pellets, troches, capsules, or suppositories;
creams, ointments; aerosols; powders for insufflation;
in a liquid form such as solutions, emulsions, or suspensions for injection; ingestion; eye drops; and any other form suitable for use. And, if necessarv, there mav be included in the above preparation auxiliary substance such as stabilizing, thickening, wetting, emulsifying and coloring agents; perfumes or buffer;'or any other commonly may be used as additives.
The object polypeptide compound [I] or a pharmaceutically acceptable salt thereof is/are included in the pharmaceutical composition in an amount sufficient to produce the desired antimicrobial effect upon the process or condition of diseases.
For applying the composition to human, it is preferable to apply it by intravenous, intramuscular, pulmonary, oral administration, or insufflation. While the dosage of therapeutically effective amount of the object polypeptide compound [I] varies from and also depends upon the age and condition of each individual patient to be treated, in the case of intravenous administration, a dailv dose of 0.01-20 mg of the objec~~
polypeptide compound [I] per kg weiyht of human being in the case of intramuscular administration, a daily dose of 0.1-20 mg of the object polypeptide compound [I] per kg weiQht of human being, in case of oral administration, a daily dose of 0.5-50 mg of the object polvpeptide comnound [I] per kg weight of human being is generally given for treating or preventina infectious diseases.
Especially in case of the treatmer.t of prevention of Pneumocystis carinii infection, the fo~lowings are to be noted.
For admir.istration bv inhalation, the compounds of the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized as powders which may be formulated and the powder compositions may be inhaled with the aid of an insufflation powder inhaler device. The preferred delivery svstem for inhalation is a metered dose inhalation aerosol, which may be formulated as a suspension or solution of compound in suitable propellants such as fluorocarbons or hydrocarbons.
Because of desirability to directly treat lung and bronchi, aerosol administration is a preferred method of administration. Insufflation is also a desirable method, especiallv where infection may have spread to ears and other bodv cavities.
Alternatively, parenteral administration may be emploved using drip intravenous administration.

The following Preparations and Examples are given for the purpose of illustrating the present invention in more detail.

~
Preparation To a suspension of 1-(4-Hydroxyp::enyl)-4-tert-butox_ycarbonvipiperazine (3 g) and potassium carbonate (0.82 g) ir. N,N-dimethylformamide (15 ml) was added octyl bromide (1.87 mi;. The mixture was stirred for 10 hours at 70 C. The reaction mixture was added to a mixture of water and ethyl acetate. The organic la_ver was taken, and dried over magnesium sulfate. The *ragnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure. The residue was subjected to column cnromatographv on silica gel, and eluted with (hexane ethyl acetate = :1). The fractions containing the object ccmpound were combined, and evaporated under reduced pressure to give 1-(4-n-Octyloxvphenyl)-4-tert-butoxvcarbonylpiperazine (2.7' g).
IR (KBr) : 1687, 1513, 1241 cm-1 NMR (CDC13, b) : 0.88 (3H, t, J=6.2Hz), 1.2-1.4 (10H, m), 1.48 (9H, s), 1.65-1.85 (2H, m), 3.00 (4H, t, J=5.2Hz), 3.57 (4H, t, J=5.2Hz), 3.90 (2H, t, J=6.5Hz), 6.83 (2H, dd, J=6.4 and 2.1Hz), 6.89 (2H, dd, J=6.4 and 2.1Hz) preparation 2 A solution of 1-(4-n-Octyloxyphenyl)-4-tert-butoxycarbonylpiperazine (2.61 g) in trifluoroacetic acid (20 ml) was stirred for 4 hours at ambient temperature.
The reaction mixture was evaporated under reduced pressure, and to the residue was added a mixture of iN
NaOH aaueous solution and ethyl acetate. The organic layer was taken, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 1-(4-n-Octyloxyphenyl)piperazine (0.86 g).
IR (KBr) : 2923, 1513, 1259, 831 cm-1 NMR (CDC13, b) . 0.88 (3??, t, J=6.4Hz), 1.2-1.53 (10'ri, m), 1.65-1.85 (2H, m), 3.C3 (4H, s), 3.90, (2H, t, J=6.5Hz), 6.83 (2H, dd, J=6.4 and 2. 9Hz ), 6.90 (2H, dd, J=6 . 4 and 2. 9Hz ) APCI-MASS m/z = 291 (M*+1) preparation 3 Tc a suspension of 1-(4-n-Octylox_yphenyl)piperazine (1 g) and potassium carbonate (0.476 g) in N,N-dimethyl-formamide (1 ml) was added p-fluorobenzonitriie (0.347 g), and stirred for 5 hours at 160 C. The reaction mixture was added to a mixture of water and ethyl acetate. The organic iayer was taken, and dried over magnesium sulfate.
The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-[4-(4-n-Octyloxyphenyi)piperazin-l-yl;benzonitrile (0.93 g).
IR (KBr) : 2848, 2217, 1604, 1511, 1241 cm-1 NMR (CDC13, 5) : 0.89 (3H, t, J=6.8Hz), 1.2-1.53 (10H, m), 1.65-1.85 (2H, m), 3.2G (4H, t, J=5 . 4Hz ), 3.48 (4H, t, J=5 . 4Hz ), 3.91 (2H, t, J=6.5Hz), 6.8-7.0 (6H, m), 7.52 (2H, d, J=8.9Hz) APCI-MASS : m/z = 392 (M++1) Lreparation 4 A mixture of 2,4-Dihydroxybenzaldehyde (5.52 g), potassium carbonate (6.08 g) and octyl bromide (7.73 g) in acetonitrile (55 ml) was stirred for 16 hours at 60 C.
The solvent of reaction mixture was removed under reduced pressure, and the residue was dissolved in ethyl acetate, and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesiu_*rM, sulfate was filtered off, and the filtrate was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with (hexane : ethyl acetate = 9:1) to give 2-Hydroxy-4-octyloxybenzaldehyde (6.73 g).

NMR (CDC13, b) : 0.89 (3H, t, J=8.8Hz), 1.2-1.5 (10H, m) , 1. 8-2. 0 (2H, m) , 4. 0-4.2 (2H, m,; , 6. 42 (1H, s ) , 6.52 (1H, d, J=8 . 7Hz ) , 7.79 ( ? H, d, J=8.7Hz), 10.33 (iH, s) F_PCI-MASS : m/z = 257 (M++1) The following compound was obtained according to a similar manner to that of Preparation 4.

Preparation 5 Methyl 3,4-dipentyloxybenzoate NMR (CDC13, 5) : 0.93 (6H, t, J=6.0 and 9.0Hz), 1.3-2.0 (12H, m), 3.88 (3H, s), 4.04 (4H, m), 6. 8 6(1H, d, J=8 . 4Hz ), 7.53 (1H, d, J=2 . 0Hz ), 7.63 (1H, dd, J=8.4 and 2.0Hz) APCI-MASS : m/z = 309 (M++l) Preparation 6 A mixture of 4-bromo-4'-pentylbiphenyl (5.04 g), trimethylsilylacetylene (2.4 ml), tetrakis(triphenylphosphine)palladium (0.96 g), triphenylphosphine (0.22 g) and cuprous iodide (95 mg) in piperidine (10 ml) was heated for an hour under atmospheric pressure of nitrogen at 90 C. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and adjusted to about pH 1 with 6N hydrochloric acid. The separated organic layer was washed with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give crude 2-[4-(4-pentylphenyl)phenyl)-1-trimethylsilylacetylene, which was used for the next reaction without further purification.
Crude mixture was dissolved in a mixture of ciichloromethane (10 ml) and methanol (10 ml), and to the solution was added potassium carbonate (2.75 g) at 0 C.

The mixture was allowed to warm to ambient temperature, and stirred for ancther 2 hours. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and the resultant precipitate was filtered off. The filtrate was adjusted to about pH 7 with iN hydrochioric acid, and washed with brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude powder, which was subjected to column chromatography on silica gel (300 ml), and eluted with a mixture of (n-hexane : ethyi acetate = 99:1 - 97:3, V/V) to give 4-(4-Pentylpheny=)phenylacetylene (2.09g).
IR (Nu-iol) : 3274, 1490 cm-1 n'gR (CDC13, b) : 0.90 (3H, t, J=6.4Hz), 1.30-1.50 i5 (4H, m), 1.50-1.80 (2H, m), 2.64 (2H, t, J=7.6Hz), 7.20-7.30 (2H, m), 7.45-7.60 (6H, m) APCI-MASS : m/z = 281 (M++l + MeOH) The following compound was obtained according to a similar manner to that of Preparation 6.

Preparation 7 6-Heptyloxynaphthalen-2-yl-acetylene NMR (CDC13, b) : 0.90 (3H, t, J=6.5Hz), 1.20-1.60 (8H, m), 1.70-1.90 (2H, m), 3.10 (1H, s), 4.07 (2H, t, J=6.5Hz), 7.08 (1H, d, J=2.5Hz), 7.15 (1H, dd, J=2 . 5 and 8. 9Hz ), 7.47 (1H, dd, J=1 . 6 and 8. 5Hz ), 7.64 ( iH, d, J=7 . 3Hz ), 7.68 ( iH, d, J=8.5Hz), 7.94 (iH, d, J=1.6Hz) APCI-MASS : m/z = 267 (M++1) Preparation 8 To a solution of 4-(4-Pentylphenyl)phenylacetylene (2.09 g) in tetrahydrofuran (30 ml) was added dropwise a solution of lithium diisobutylamide in a mixture of tetrahydrofuran and n-hexane (1.60 M, 5.6 ml) at -75 C, and the resultant mixture was stirred for an hour at -78 C. To the TM_xtzre was added methyl chloroformate (0.72 ml), and the reaction mixture was allowed to warm to 2 ambient temperature. The solution was diluted with ethyl acetate, and washed in turn with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude product, which was subjected to column chromatography on silica gel (150 ml), and eluted with a mixture of (n-hexane : ethyl acetate =
100:0 - 9:1, V/V) to give Methyl 3-[4-(4-pentylphenyl)phenyl]propionate (2.20 g).
IR (Nujol) : 2225, 1712 cm-1 NMR (CDC13, 6) : 0.90 (3H, z, J=6.5Hz), 1.25-1.50 (4H, m), 1 .52-1 .80 (2H, *_ ;) , 2.64 (2H, t, J=7.6Hz), 3.85 (3H, s), 7.20-7.35 (2H, m), 7.40-7.70 (6H, m) APCI-MASS : m/z = 307 (M++1) The following compound was obtained according to a similar manner to that of Preparation B.

Preparation 9 Methyl 3-(6-heptyloxynaphthalen-2-yl)propionate IR (Nujoi) : 2219, 1704, 1621 cm-1 NMR (CDC13, b) : 0.90 (3H, t, J=6.5Hz), 1.20-1.60 (8H, m), 1.70-2.00 (2H, m), 3.86 (3'r'., s), 4.08 (2H, t, J=6.5Hz), 7.10 (1H, d, J=2.5Hz), 7.17 (1H, dd, J=2 . 5 and 8. 9Hz ), 7.52 (1H, dd, J=1 . 6 and 8.5Hz), 7.68 (1H, d, J=7.3Hz), 7.72 (1H, d, J=8.5Hz), 8.06 (1H, d, J=1.6Hz) APCI-MASS : m/z = 325 (M++1) Preparation 10 P_ mixture of 4-bromo-4'-pentylbiphenyl (5.0 g), methyl acrylate (2.2 mi), palladium acetate (0.11 g) and tris(o-tolyl)phosphine (0.60 g) in triethylamine (16 ml) was refluxed for 15 hours under nitrogen atmosphere. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and adjusted to about pH 1.5 with 6N
hydrochloric acid. The separ =d organic layer was washed in turn with water and brine, :_..d dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude powder, which was subjected to column chromatography on silica gel (200 ml), and eluted with a mixture of (n-hexane : ethyl acetate = 100:0 - 94:6, V/V) to give Methyl 3-[4-(4-pentylphenyl)phenylJacrylate (4.48 g).
IR (Nujol) : 1718, 1637 cm-1 NMR (CDC13, S) : 0.91 (3H, t, J=6.7Hz), 1.20-1.50 (4u, m), 1.50-1.80 (2H, m), 2.65 (2H, t, J=7.4Hz), 3.82 (3H, s), 6.47 (1H, d, J=16. OHz) , 7.20-7.35 (2H, m), 7.45-7.68 (6H, m), 7.73 (1fi, d, j=16.OHz) APCI-MASS : m/z = 309 (M++1) The following compounds (Preparations 11 to 11) were obtained according to a similar manner to that of Prenaration 10.
Preparation 11 Methyl 3-(6-heptyloxynaphthalen-2-yl)acr_late IR (~'ujol) : 1716, 1625, 1459 cm-1 NMR (CDC13, b) : 0.90 (3H, t, J=6.5Hz), 1.20-1.65 (8H, m), 1.76-1.93 (2H, m), 3.82 (3H, s), 4.07 (2H, t, J=6.5Hz), 6.49 (1H, d, =J=16. OHz) , 7.05-7.20 (2H, m), 7.55-7.90 (5H, m) APCI-MS : m/z = 327 (M++1) Preparation 12 Methyl 3- [ 4- ( 4-heptylpner_yl ) phenyl 1 acrylate NMR (CDC13, 5) : 0.88 (3H, t, J=6.5Hz), 1. 15-1 .50 (8H, m), 1. 50-1 . 75 (2H, m), 2.64 (2H, t, ,T=7 . 6Hz ), 3.81 ( 3H, s), 6.46 (1H, d, J=16 . OHz ), 7.26 (2H, d, J=8.2Hz), 7.52 (2H, d, J=8.2Hz), 7.59 (6H, s), 7.73 (1H, d, J=16.OHz) APCI-MP.SS : m/z = 337 (M++1) Prenaration 13 Methyl 3-[4-(4-penty'_oxyphenyi)phenyljacrylate NMR (CDC13, 5) . 0.94 (3H, t, J=7.OHz), 1.30-1.60 (4H, m), 1.70-1.93 (2H, m), 3.82 (3H, s), 4.00 (2H, t, J=6.7Hz), 6.45 (1'r?, d, J=16. OHz) , 6. 90-7.05 (2H, m), 7.48-8.65 (6H, m), 7.72 (1H, d, J=16.OHz) APCI-MASS : m/z = 325 (M++l ) Dreparation 14 A mixture of 6-Heptyloxynaphthaler--2-carboxylic acid (1.00 g) and thionyl chloride (5 ml) was stirredn for 18 hours at ambient temparature, and concentrated under reduced pressure to give crude 6-heptyloxy-2-naphthoyl chloride. To a mixture of ethyl isoriipecotinate (605 mg), triethylamine (425 mg) and N,N-dimethylaminopyridine (i0 mg) in dichloromethane (10 ml) was added crude 6-heptyloxy-2-naphthoyl chloride, and the mixture was stirred for 2 hours at ambient temperature, and diluted with dichloromethane. The mixture was washed with water, 1N hydrochloric acid and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel, and eluted with (n-hexane : ethyl acetate = 3:1) to give 4-Ethoxycarbonyl-l-(6-hept_yloxy-2-naphthoyl)piperidine (1.20 g) NMP, (CDCi3, 5) . 0.90 (3H, t, J=6. 6Hz) , 1.2-2.0 (19H, m) , 2. 5-2 . 7 (1H, m), 3. 0-3 . 2 (2H, m), 4.1-4.3 (4H, m), 7.1-7.2 (2H, m), 7.44 (1H, dd, J=8.4 and 1.7Hz), 7.72 (1H, d, J=3.9Hz), 7.77 (1H, d, J=3.9Hz), 7.82 (1H, s) APCI-MASS : m/z = 426 (M++l) Preparation 15 To a mixture of Methyl 3,4-diaminobenzoate (1.91 g) and triethylamine (0.56 g) in N,N-dimethylformamide (20 mi) was added decanoyl chloride (2.31 g), and the mixture was stirred for an hour at 0 C. The reaction mixture was diluteci with ethvl acetate, and washed with water and brine. The separateci organic laver was dried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure.
The residue was dissolved in methanol (20 ml), and conc.
sulfuric acid (0.05 ml) was added, and the mixture was stirred for 6 hours at 60 C. After cooling, the reaction mixture was evaporated under reduced pressure. The residue was diluted with ethvi acetate, and washed with water and brine. The separated organic layer was ciried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel eluted with (n-hexane : ethyl acetate = 3:1) gave 5-Methoxycarbonyl-2-nonylbenzimidazole (1.40 g).
IR (KBr pelet) : 2923, 1718, 1623, 1544, 1438, 1413, 1288, 1213, 1085, 750 cm-1 NMR (DMSO-d6, 5) : 0.84 (3H, t, J=6.7Hz), 1.1-1.4 (12H, m), 1. 7-1 . 9 (2H, m), 2.83 (2H, t, J=7.4Hz), 7.56 (1H, d, J=8.4Hz), 7.78 (1H, d, J=8.4Hz), 8.07 (1H, s) APCI-MASS m/Z = 303 (M++1) Preparation 16 To a mixture of dimethvlmalonate (4 ml), 2-hydroxv-4-octvloxvbenzalciehyde (2.50 g) and piperidine (0.1 ml) in methanol (10 ml) was added acetic acid (0.01 ml), and the mixture was stirred for 3 hours at 70 C. The solvents were removed under reduced pressure, and the residue was dissolved in ethyl acetate, and washed with 0.5N
hydrochloric acid, water and brine, and ciried over magnesium sulfate. The magnesium sulfate was filtered of=, and filtrate was evaporated under reduced pressure, and the iJL"eclnitate was collected by filtrazion, and washed with n-hexane, and dried to give Methyl 7-octylox-ycoumarin-3-carboxylate (0.94 g).
NMR (DMSO-d6, (5) : 0.86 (3H, m), 1.2-1.6 (10H, m), 1.7-1.8 (2H, m), 3.81 (3H, s), 4.11 (2H, t, J=6.4Hz), 6.9-7.1 (2H, m), 7.83 (iH, d, J=9.OHz), 8.75 (1H, s) APCI-MASS m/z = 333 (M++1) preparation 17 To a mixture of sodium hydride (423 mg) and 4-octylphenol (2.06 g) in tetrahydrofuran (16 ml) was added dropwise ethyl 2-chloroacetoacetate at ambient temoerature. The mixture was stirred for 6 hours at 70 C
under nitrogen atmosphere, and poured into saturated amir,onium chloride aaueous solution. The solution was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure. The residue was added to conc. H?S04 (10 ml) at 0 C, and mixture was stirred for 10 minutes. The reaction mixture was poured into ice-water, and adjusted to pH 7.0 wit:~. iN

- 5~ -NaOH aaueous soiution, and extracted with ethyl acetate.
The organic laver was washed with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure. The residue was subjected to column-chromatography on silica gel, and eluted with (hexane ethvi acetate = 95:5). The fractions containing the object compound were combined, and evaporated under reduced pressure to give Ethvl 3-methvl 5-octvlbenzo[b]furan-2-carboxylate (1.44 g).
IR (Neat) . 2925, 2854, 1712, 1596, 1463, 1292, 1149, 1089 c~:-1 NMR (CDC13, 6) : 0.88 (3H, t, J=6.7Hz), 1.2-1.5 (10H, m), 1.44 (3H, t, J=7.1Hz), 1.6-1.8 (2H, m), 2.58 (3H, s), 2.71 (2H, t, J=B.OHz), 4.45 (2H, t, J=7.1Hz), 7.2-7.5 (3H, m) APCI-MASS : m/z = 317 (M++1) Preparation 18 To a solution of Ethyl 3-amino-4-hydroxybenzoate (1.81 g) and triethvlamine (1.53 ml) in dichloromethane (20 ml) was dropwise added decanovl chloride (2.01 ml) at 0 C. The reaction mixture was stirred for 48 hours at ambient temperature, and washed with water, 0.5N
hydrochloric acid, water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off, and the Tiltrate was evaporated under reduced pressure. To the residue dissolved in xylene (30 ml) was added p-tolune sulfonic acid monohydrate (0.5 g), and the mixture was stirred for 4 hours at 130 C . Ethyl acetate was added to the mixture, and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel elluted with (n-hexane : ethyl acetate = 9:1, V/V) gave Ethyl 2-nonyl benzo[bloxazole-6-carboxylate (2.36 g).
IR (KBr pelet) . 2914, 1722, 1621, 1575, 1470, 1429, 136S, 1290, 1203, 1151, 1115, 1081, 1022 cm-1 NMR (CDCl3, 5) : 0.88 (3H, t, J=6.7Hz), 1.2-1.4 (12H, m), 1.42 (3H, t, J=7.2Hz), 1.90 (2H, m), 2. 95 (2H, t, J=7.4Hz), 4.40 (2H, q, J=7. 0Hz) , 7.50 (1H, d, J=8.5Hz), 8.06 (1H, d, J=8.5Hz), 8.37 (1H, s) APCI-MASS : m/z = 318 !M++l) prebaration 19 A mixture of Methyl 3,4-diaminobenzoate (1.84 g) and 4-hexyloxy benzaldehyde (2.30 g) in nitrobenzene (40 ml) was stirred for 48 hours at 145 C. After cooling, the mixture was evaporated under reduced pressure.
Purification of the residue by column chromatography on silica gel eluted wit:~. (n-hexane : ethyl acetate = 2:1) gave 5-Methoxycarbonyl-2-(4-hexyloxyphenyl)benzimidazole (1.19 g).
NMR (CDC13, b) : 0.90 (3H, t, J=6.4Hz), 1.2-1.9 (8H, m), 3.92 (3H, s), 3. 90-4. 1(2H, m), 6.93 (2H, d, J=8.9Hz), 7.5-7.8 (lu, br), 7.94 (1H, dd, J=8.5 and 1.5Hz), 8.03 (1H, d, J=8.9Hz), 8.2-8.4 (1H, br) APCI-MASS : m/z = 353 (M++1) Preparation 20 A mixture of Methyl 3-[4-(4-pentylphenyl)phenyl]-acrylate (2.0 g) and 10% palladium on carbon (501 wet, 0.2 g) in tetrahydrofuran (20 ml) was stirred for 8 hours under atmospheric pressure of hydrogen at ambient temAarature. The catalyst was filtered off, and the filtrate was evanorated under reduced pressure to give Methyl 3- [ 4- ( 4-centylphenyl ) phenyl ] propionate (1.93 g).
NMR (CDCi3, o) 0.90 (3H, t, J=6. 8Hz) , 1.25-1.50 (4H, m), 1.50-1.75 (2H, m), 2.55-2.75 (4H, m), 2.99 (2H, t, J=B.OHz), 3.68 (3H, s), 7.10-7.30 (4H, m), 7.40-7.60 (4H, m) APCI-MASS m/z = 311 (M'+l ) Preparation 21 A mixture of Methyl 3-[4-(4-pentyloxyphenyl)phenyl]-acrylate (2.70 g) and platinum oxide (0.41 g) in tetrahydrofuran (40 ml) was stirred for 8 hours under 3 atom of hydrogen at ambient temperature. The catalyst was filtered off, and the filtrate was evaporated under reduced pressure to give Methyl 3-[4-(4-pentyloxyphenyl)phenyl]propionate (2.70 g).
NMR (CDC13, b) : 0.94 (3H, t, J=7.OHz), 1.28-1.60 (4H, m), 1.60-1.95 (2H, m), 2.55-2.78 (2H, m), 2.98 (2H, t, J=7.8Hz), 3.98 (2H, t, J=6.5Hz), 6.85-7.05 (2H, m), 7.05-7.30 (2H, m), 7.40-7.55 (4H, m) APCI-MASS : m/z = 327 (M+11) The following compound was obtained according to a similar manner to that of Preparation 21.

Preparation 22 Methyl 3-(6-heptylox_ynaphthalen-2-yl)propionate NMR (CDC13, b) : 0.90 (3H, t, J=6.5Hz), 1.20-1.70 (8H, m), 1.70-1.93 (2H, m), 2.70 (2H, t, J=7 . 7Hz ), 3.07 (2H, t, J=7 . 7Hz ), 3.67 (3H, s), 4.05 (2H, t, J=6.5Hz), 7.02-7.20 (2H, m), 7.20-7.38 (2H, m), 7.55 (1H, s), 7.66 (1H, dd, J=3.0 and 8.5Hz) APCI-NlASS : m/z = 329 (N:++1) Preparation 23 To a mixture of Methyl 3-4-(4-pentylpher_yl)phenyl]-acrylate (0.41 g) in tetrahydrofuran (5 ml ) was added 3N
NaOH aqueous solution (1.3 ml), and the resultant mixture was heated to 85 C for 10 hours. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and adjusted to about pH 2 wi:h 6N hydrochloric acid. The separated organic layer was washed in turn with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 3-'4-(4-Dentyiphenyl)phenyl]acrylic acid (0.41 g).
NMR (DMSO-d6, b) : 0.87 (3H, t, J=7.SHz), 1.15-1.46 (4H, m), 1.48-1.70 (2H, m), 2.61 (2H, t, J=7.4Hz), 6.56 (1H, d, J=16. OHz) , 7.29 (2H, d, J=8.2Hz), 7.60 (2H, d, J=4 . OHz) , 7.66 (2H, d, J=4.OHz), 7.68-7.85 (3H, m) APCI-MASS . m/z = 295 (M++1) The following compounds (Prenarations 24 to 31) were obtained according to a similar manner to that of Lreparation 23.

Prenaration 24 3-[4-(4-Pentyloxyphenyl)phenyl]propionic acid IR (Nujol) : 1697, 1606, 1500 cm-1 NMR (CDC13, b) : 0.94 (3H, t, J=7.lHz), 1.25-1.60 (4H, m), 1.70-1.95 (2H, m), 2.72 (2H, t, J=7.5Hz), 3.00 (2H, t, J=7.5Hz), 3.99 (2H, t, J=6.SHz), 6.95 (2H, dd, J=2.1 and 6.7Hz), 7.25 (2H, d, J=8.2Hz), 7.40-7.60 (4H, m) APCI-MASS : m/z = 313 (M++i) Preparation W
3-[4-(4-Heptylphenyl)phenyl]propionic acid NMR (CDC13, 5) : 0.88 (3H, t, J=6.8Hz), 1.15-1.50 (8H, m) , 1.50-1.78 (2H, m), 2.65 (2H, t, J=7. 6Hz) , 6.48 (1H, d, J=16.OHz), 7.27 (2H, d, J=8.2Hz), 7.53 (2H, d, J=8.2Hz), 7.63 (4H, m), 7.83 (1H, d, J=16.OHz) APCI-?"IASS : r.m/z = 323 (M++1) =
~renaration 26 3-[4-(4-Pentylphenyl)phenyl]propionic acid NMR (CDC13, b) : 0.90 (3H, t, J=6.4Hz), 1.20-1.50 (4H, m), 1.50-1.75 (2H, m), 2.64 (2H, t, J=8.OHz), 2.67 (2H, t, J=9.6Hz), 3.00 (2H, t, J=8.0Hz), 7.15-7.38 (4H, m), 7.38-7.60 (4H, m) APCI-MASS : m/z = 297 (Mt+1) Preparation 27 3-(6-Heptyloxynaphthalen-2-yl)propionic acid NMR (CDC13, d) : 0.90 (3H, t, J=6.5Hz), 1.20-1.65 (8H, m), 1.75-2.00 (2H, m), 2.75 (2H, t, 2C J=7.7Hz), 3.09 (2H, t, J=7.7Hz), 4.06 (2H, t, J=6.5Hz), 7.05-7.15 (2H, m), 7.15-7.3S (2H, m), 7.50-7.73 (2H, m) APCI-MASS : m/z = 315 (M++1) Prenaration 28 3-(6-Heptyloxynaphthalen-2-yl)acrylic acid NMR (CDC13, b) : 0.90 (3H, t, J=6.5Hz), 1.15-1.60 (8H, m), 1.75-1.95 (2H, m), 4.09 (2H, t, J=6.5Hz), 6.51 (1H, d, J=16. OHz) , 7.09-7.30 (2H, m), 7.65-8.00 (5H, m) Preparation 29 3-[4-(4-Pentylphenyl)phenyl]propionic acid NMR (CDC13, b) : 0.91 (3H, t, J=6.5Hz), 1.23-1.50 (4H, m), 1.50-1.80 (2H, m), 2.65 (2H, t, WO 96/11210 PCTlJP95/01983 J=7. 6Hz) , 7.27 (2H, d, J=8.2Hz) , 7. S 1 (2H, d, J=8.2Hz), 7.58-7.80 (4H, m) APCI-MASS m/z = 325 (M*+1 + MeOH) Drenaration 30 3-(6-Heptyloxynaphthalen-2-yi)propionic acid IR (Nujol) : 2645, 2198, 1670, 1627 cm-i NMR (DMSO-d6, 5) : 0.85 (3H, t, J=6.5Hz), 1.10-1.60 (8H, m), 1. 65-1 . 90 (2H, m), 4.10 (2H, t, J=6.5Hz), 7.24 (1H, dd, J=2.4 and 8.9Hz), 7.39 (1H, d, J=2.SHz), 7.55 (iH, dd, J=1.6 and 8. 5Hz ), 7. 8-8 . 0 (2H, m), 8.22 (1H, d, J=1 . 6Hz) APCI-MASS m/z = 343 (M++i + MeOH) Preparation 31 4-[5-(4-Pentyloxyphenyl)isoxazolyl-3-yl]benzoic acid IR (KBr) : 2939, 2867, 1681, 1614, 1429, 1255, 1178, 821 cm-1 NMR (DMSO-d6, b) : 0.91 (3H, t, J=7.iHz), 1.3-1.5 (4H, m), 1. 6-1. 8(2H, m), 4.04 (2H, t, J=6.5Hz), 7.11 (2H, d, J=8.9Hz), 7.54 (1H, s), 7.85 (2H, d, J=8. 9Hz) , 7.98 (2H, d, J=8. 6Hz) , 8.11 (2H, d, J=8.6Hz) APCI-MASS : m/z = 352 (M+H)+
Preparation 32 To a solution of Ethyl 3-methyl-5-octylbenzo[b]furar.-2-carboxylate (1.44 g) in ethanol (20 ml) was added 10 NaOH aqueous solution (2.2 ml), and stirred for 2 hours at ambient temperature, and evaporated under reduced pressure. The residue was adjusted to pH 3.0 with 1N
hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 3-Metnyl-5-octylbenzo[b)furan-2-carboxylic acid ;1.00 g ) .
IR (i:2r pelet) . 2923, 1689, 1664, 1581, 1456, 1319, 1159, 933 cm-1 NTMR (:)MSO-d6, 6) : 0.85 (3H, t, J=6 . 7Hz ), 1.2-1.5 (lOH, m), 1.5-1.8 (2H, m), 2.49 (3H, s), 2.69 (2H, t, J=7.9Hz), 7.32 (1H, dd, J=8.5 and i. 7Hz ), 7.52 (1H, a, J=8 . 5Hz ), 7.54 (1H, d, J=1.7Hz), 13.2-13.5 (1H, br) APCI-MIASS : m/z = 289 (M++l ) The Tcilowing compounds (Prenarations 33 to 39) were obtained according to a similar manner to that of a reparation 32.
Dreiparation 33 3,4-Dipentyloxybenzoic acid NMR (DMSO-d6, 5) : 0.89 (oH, t, J=6.8Hz), _.2-1.5 (8H, m), 1.6-1.8 (4H, m), 3.9-4.1 (4H, m), 7.02 (1H, d, J=8.4Hz), 7.43 (1H, d, J=1.7Hz), 7.53 (iH, dd, J=8.4 and 1.7Hz) APCI-MASS : m/z = 295 (M++1) Prelparation 34 1-(6-'rIeptyloxy-2-naphthoyl)piperidine-4-carboxylic acid NMR (DMSO-d6, 5) : 0.88 (3H, t, J=6.7Hz), 1.2-2.0 (14H, m), 2.5-2.6 (1H, m), 2.9-3.2 (2H, br), 3.25 (2H, s), 4.09 (2H, t, J=6.5Hz), 7.20 (1H, dd, J=8.9 and 2.4Hz), 7.36 (1H, d, J=2.3Hz), 7.43 (1H, dd, J=8.4 and 1.5Hz), 7.8-8.0 (3H, m), 12.30 (1H, br) APCI-MASS : m/z = 398 (M++1) Preparation 35 7-Octyloxvcoumarin-3-carboxyiic acid IR (KBr) . 1748, 1625, 1558, 1467, 1430, 1386, 1360, 1257, 1217, 1120 cm-1 NMR (DMSO-d6, d) : 0.86 (3H, t, J=6.8Hz), 1.2-1.5 (lOH, m), 1.6-1.8 (2H, m), 4.11 (2H, t, J=6.4Hz), 6. 9-7. 1(2H, m), 7.82 (1H, d, J=8.9Hz)',, 8.72 (1H, s), 12. 98 (1H, br) APC?-IMASS : rn/z = 319 (M++l ) ~~eoaration 36 4- (4-Pentvlox.yphenyl) cinnamic acici TR (Nujol) 2923, 1675, 1500, 1290, 1223, 985, 821 cm-1 NI-IR (DMSO-d6, b) : 0.90 (3H, t, J=7.OHz), 1.3-1.5 (4H, m), 1. 6-1 . 8 (2H, m), 4.01 (2H, z:, J=6. 5Hz) , 6.54 (1H, d, J=16 . OHz ), 7.02 (2H, d, J=8 . 8Hz ), 7.5-7.8 (7H, in) APCI-MASS m/z = 311 (MTtl) preparation 37 2-Nonvlber.zoxazole-6-carboxylic acid NMR (DMSO-d6, b) : 0.84 (3H, t, J=6.7Hz), 1.2-1.5 (12H, m), 1.7-1.9 (2H, m), 2.96 (2H, t, J=7.4Hz), 7.76 (1H, d, J=8.4Hz), 7.98 (1H, d, J=8.4Hz), 8.19 (iH, s) APCI-MASS : m/z = 290 (M++1) Pretiaration 38 2-(4-Hexyloxyphenyl)benzimidazole-5-carboxvlic acid NMR (DMSO-d6, b) : 0.8-1.0 (3H, m), 1.3-1.6 (6H, m), 1.7-1.8 (2H, m), 4.06 (2H, t, J=6.4Hz), 7.12 (2H, d, J=8.8Hz), 7.6-7.9 (2H, m), 8.1-8.2 (3H, rn), 13.00 (1H, br) APCI-MASS : m/z = 339 (M+t1) Preparation 39 2-Nonylbenzimidazoie-5-c.arboxylic acid NMR (DMSO-d6, b) : 0.85 (3H, t, J=6.7Hz) , i.l-1.4 (12H, m), 2.7-2.9 (2H, m), 2.96 (2H, t, J=7.6Hz), 3.6-5.2 (1H, br), 7.66 (iH, d, J=8.4Hz), 7.90 (1H, d, J=8.4Hz), 8.15 (1H, s) APCI-MASS : m/z = 289 (M++l) Preparation 40 A solution of 4-[4-(4-Octyloxyphenyl)piperazin-l-yl]benzonitrile (0.5 g) in 20= H2SO4 aqueous solution (30 ml) and acetic acid (20 ml) was refluxed for 9 hours. The reaction mixture was pulverized with water. The precipitate was collected by filtration, and added to a mixture of water, tetrahydrofuran and ethyl acetate, and adjusted to pH 2.5 with 1N NaOH aqueous solution. The organic layer was taken, and dried over magnesium sulfate.
The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-[4-(4-Octyloxyphenyl)piperazin-1-yl]benzoic acid (388 mg).
IR (KBr) : 2929, 1664, 1600, 1510, 1240 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6. 6Hz) , 1.2-1.5 (10H, m), 1.5-1.8 (2H, m), 3.13 (4H, t, J=5.3Hz), 3.44 (4H, t, J=5. 3Hz) , 3.88 (2H, t, J=6. 5Hz) , 6.83 (2H, d, J=9.2Hz), 6.94 (2H, d, J=9.2Hz), 7.02 (2H, d, J=9.OHz), 7.79 (2H, d, J=9.0Hz) APCI-MASS : m/z = 411 (M++1) Preparation 41 To a suspension of sodium hydride (607 suspension in mineral oil) (0.296 g) in N,N-dimethylformamide (14 ml) was added 1,2,4-triazole (0.511 g) and 4-[4-(8-bromooctyloxy)phenyl]benzoic acid (1 g), and was stirred for 5 hours at 120 C. The reaction mixture was added to a mixture of water and ethyl acetate, and adjusted tc pH 2.5 with conc. hydrochloric acid. The organic layer was taken and dried cver ma:,nesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-[4-[8-(1,2,4-Triazol-1-yl)octyloxy]phenyl]benzoic acid (0.81 g).
IR (KBr) : 2940, 1689, 1604, 1297, 1189 cm-1 NMR (DMSO-dc, 5) : 1.1-1.53 (8H, m), 1.6-1.9 (4H, m), 4.00 (2H, t, j=6.3Hz), 4.16 (2H, t, j=7 . OHz ), 7.03 (2H, d, J=8 . 7Hz), 7.67 (2H, d, J=8.7Hz), 7.75 (2H, d, J=8.4Hz), 7.95 (1H, s), 7.99 (2H, d, J=8.4Hz), 8.51 (?H, s), 12.9 (1H, s) APCI-NASS : m/z = 394 (M++1) preparation 42 A mixture of 2-Carbamoyl-5-methoxybenzo[b]thiophene (2.0 g), acetic acid (5 ml) and 48'; hydrobromic acid (20 ml) was stirred for 16 hours at 110 C, and the mixture was poured into the ice-water. The resulting precipitate was collected by filtration, and dried to give 5-Hydroxybenzo[b]thiophene-2-carboxylic acid (1.66 g).
NMR (DMSO-d6, b) : 7.03 (1H, dd, J=8.8 and 0.6Hz), 7.31 (1H, d, J=0 . 6Hz ), 7.81 (1H, d, J=8 . 8Hz ), 7.96 (1H, s), 9.64 (1H, s), 13.32 (1H, s) APCI-MASS : m/z = 195 (M++1) Preparation 43 A solution of (S)-2-Tert-butoxycarbonyl-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (1 g) in a mixture of 10 NaOH aqueous solution (2.73 ml) and dimethylsulfoxide (11 ml) was stirred for half an hour at 80 C. Then, octyi bromide (0.589 ml) was added thereto, and stirred for 4 hours at 60 C. The reaction mixture was added to a mixture of water and ethyl acetate, and - 6~ -adjusted tc pH 2.5 with conc. hydrochloric acid. The organic layer was taken, and dried over magnesium sulfate.
The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give (S)-2-Tert-butoxycarbonyl-1,2,3,4-tetrahydro-7-octyloxyisoauinoline-3-carboxylic acid (1.30 g).
IR (Neat) : 2929, 1743, 1704, 1164 cm-=
NMR (CDC13, b) : 0.89 (3H, t, J=6.lHz), 1.1-1.6 (10H, m), 1.41 + 1.51 (9H, s, cis + trans), 1.75 (2H, quint, j=6.5Hz), 3.10 (2H, m), 3.90 (2H, t, j=3 . 9Hz ), 4.42 (1?I, d, J=16 . 8Hz ), 4.65 (1H, d, X16.8Hz), 4.74 + 5.09 (1H, m, cis + trans), 6.5-6.8 (2H, m), 7.03 (1H, d, J=8.3Hz) APCI-MASS m/z = 306 (M++1-Boc) The following compounds (Preparations 44 to 45) were obtained according to a similar manner to that of ?renaration 43.

Preparation 44 5-Octyloxybenzo[b]thiophene-2-carboxylic acid IR (KBr) 1673, 1666, 1600, 1517, 1409, 1267, 1214, 1153, 865 cm-1 NMR (DMSO-d6, b) 0.86 (3H, t, J=6.7Hz), 1.2-1.5 (lOH, m), 1.7-1.9 (2H, m), 4.02 (2H, t, J=6.4Hz), 7.13 (1H, dd, J=8.9 and 0.6Hz), 7.51 (1H, d, J=0.6Hz), 7.90 (1H, d, J=9.OHz), 7.99 (1H, s) APCI-MASS : m/z = 307 (M++l) Preparation 45 4-[4-(4-Hexyloxyphenyl)piperazin-1-yl)benzoic acid dihydrochloride IR (KBr) : 1668, 1600, 1510, 1228 cm-1 NMR (DMSO-d6, b) : 0.88 (3H, t, J=6.9Hz), 1.2-1.5 (6H, m) , 1. 6-1. 9 (2H, m) , 3. 0-3.2 (4H, m) , 3.3-3.S (4H, m) , 3.88 (2H, t, j=6.3Hz) , 6.83 (2i?, d, J=9Hzi , 6.9-7.1 (4H, m) , 7.79 (2H, d, J=8.8Hz) , 12.32 (1H, s) APCI-MASS m/z = 383 (M+H+) Preparazion 46 Tc a susoension of dimethyl tereohthalate (1.94 g) and potassium t-butoxide (2.24 g) in tetrahydrofuran (3C
ml) was added 4-pentyloxyacetophenone (1.59 g) in tetrahydrofuran (10 ml) at 70 C dropwise. The mixture was refluxed for 30 minutes and poured in.-o iN HC1 (50 ml).
The m;xture was extracted with ethyl acetate (100 ml) and the organic laver was washed with H20 (100 ml), brine (100 mll and evaporated under reduced pressure. The residue was triturated with acetonitrile (20 ml), collected by filtration and dried under reduced pressure to give 1-;4-Methoxvcarbonylphenyl)-3-(4-pentyloxyphenyl)propane-1,3-dione (2.41 g) as yellow solid.
IR (KBr) : 3475, 2956, 2923, 1720, 1606, 1508, 1284, 1176, 1108, 769 cm-1 NMR (CDC13, (5) : 0.95 (3H, t, J=7.OHz), 1.3-1.5 (4H, m), 1.7-2.0 (2H, m), 3.96 (3H, s), 4.04 (2H, t, J=6.5Hz), 6.82 (1H, s), 6.96 (2H, d, J=8. 9Hz) , 8.0-8.1 (4H, m), 8.14 (2H, m, J=8.7Hz), 12-13 (iH, br) APCI-MASS : m/z = 369 (M+H+) Preparation 47 The solution of 1-(4-Methoxycarbonylphenyl)-3-(4-pentvloxyphenyl)propane-1,3-dione (1.00 g) and hydroxylamine hydrochloride (567 ma) in methanol (10 ml) was refluxed for 10 hours. The reaction mixture was diluted with ethvl acetate (50 ml) and washed with water (50 ml x 2), brine (50 ml). The organic layer was dried over magnesium sulfate and the solvents were removed under reduced pressure. The residue was triturated with acetonitrile (10 ml), collected by filtration, and dried under reduced pressure to give Methyl 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoate (0.74 g).
IR (KBr) : 2942, 2873, 1716, 1616, 1508, 1280, 1108 cm-1 NMR (CDC1,, b) : 0.95 (3H, ;., J=6.9Hz), 1.3-1.6 (4H, m), 1.8-2.0 (2H, m), 3.95 (3H, s), 4.02 (2H, t, J=6.5Hz), 6.74 (1H, s), 6.99 (2H, d, J=8.8Hz), 7.76 (2H, d, J=8. 8Hz) , 7.93 (2ri, d, J=8.5Hz), 8.14 (2H, d, J=8.5Hz) APCI-MASS : m/z = 366 (M+H)+
Preparation 48 A solution of 4-[4-(8-Bromooctyloxy)phenyl]benzoic acid (1 g) in a mixture of sodium methylate (28t solution in methanol) (10 ml) and N,N-dimethylformamide (5 ml) was refluxed for 5 hours. The reaction mixture was added to a mixture of water and ethyl acetate and adjusted to pH 2.0 with conc. HCl. The organic layer was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-[4-(8-Methoxyoctyloxy)phenyll-benzoic acid (0.77 g).
IR (KBr) : 2935, 1685, 835, 773 cm-1 I'TMR (CDC13, b) : 1 .27-1 .7 (10H, m), 1 . 7-1 . 95 (2H, m), 3.34 (3H, s), 3.38 (2H, t, J=6.4Hz), 4.01 (2H, t, J=6.5Hz), 6.99 (2H, d, J=8.7Hz), 7.58 (2H, d, J=8.7Hz), 7.66 (2H, d, J=8. 4Hz) , 8.15 (2H, d, J=8.4Hz) APCI-MASS : m/z = 339 (M++H - H20) Prenaration 49 To a suspension of 1-Hydroxybenzotriazole (0.283 g) and 6-octyloxymethyipicolinic acid (0.505 g) i~_ dichloromethane (15 mi) was added 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (WSCD=HC1) (0.473 g), and stirred for 3.hours at ambient temperature.
The reaction mixture was poured into water. The organic layer was taken, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was eva~orated under reduced pressure to give 1-(6-Octyloxymethyipicolinoyl)benzotriazole 3-oxide (737 mg).
IR (Neat) . 1793, 1654, 1591, 1039 cm-1 The following compounds [Prenarations 50 to 66) were obtained according to a similar manner to that of Preparation 49.
Preparation 50 1-[4-(4-Octyloxyphenyl)piperazin-i-yl)benzoyll-benzotriazole 3-oxide IR (KBr) : 1783, 1600, 1511, 1232, 1184 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.6Hz), 1.2-1.65 (1GH, m), 1. 65-1 . 9 (2H, m), 3.24 (4H, t, j=5.3Hz), 3.62 (4H, t, J=5.3Hz), 3.93 (2H, t, J=6.5Hz), 6.8-7.1 (6H, m), 7.35-7.63 (3H, m), 8.0-8.25 (3H, m) preparation 51 !-[4-[4-[8-(1,2,4-Triazol-l-yl)octyloxy]phenyl]-benzoyllbenzotriazole 3-oxide IR (KBr) : 1776, 1600, 1193, 983 cm-1 NMR (CDC13, b) : 1.2-2.0 (12H, m), 4.03 (2H, t, J=6.4Hz), 4.18 (2H, t, J=7.lHz), 7.02 (2H, d, J=8.7Hz), 7.4-7.63 (3H, m), 7.63 (2H, d, J=8 . 7Hz ), 7.79 ( 2"r.', d, J=8 . 3Hz ), 7.95 (1H, s), 8.06 (1H, s), 8.12 (1H, d, J=7.7Hz), 8.32 (2H, d, J=8.3Hz) APCI-MASS : m/z = 511 (M++l) Preparation 52 1-[2-Methyl-2-(4-octyloxyphenoxy)propionyl]-benzotriazole 3-oxide IR (Neat) : 2927, 1810, 1504, 1047 cm-i Preparation 53 i-[2-(4-Octvloxyphenoxy)propionyl]benzotriazole 3-oxide IR (KBr) 2954, 1812, 1513, 1232 cm-1 Preparation 54 1-[(S)-2-tert-Butoxycarbonyi-1,2,3,4-tetrahydro-7-octvioxyisoquinoiin-3-yl-carbonyllbenzotriazole 3-oxide IR (Neat) : 2929, 1816, 1739, 1704, 1392 cm-1 preparation 55 Succinimido 4-(4-n-octyloxyphenvl)piperazine-l-carboxviate iR (KBr) : 2925, 1758, 1743, 1513, 1241 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.8Hz), 1.2-1.5 (10H, m), 1.65-1.85 (2H, m), 2.83 (4H, s), 3.0-3.2 (2H, m), 3.6-3.85 (2H, m), 3.91 (2H, z, J=6.5Hz), 6.84 (2H, dd, J=8.5 and 2.7Hz), 6.90 (2H, dd, J=8 . 5 and 2. 7Hz ) APCI-MASS : m/z = 432 (M++l) Prenaration 56 (6-Heptyloxv-2-naphthyl)methylsuccinimido carbonate IR (KBr) : 1878, 1832, 1787, 1735, 1209 cm-1 NMR (CDC13, 6) : 0.90 (3H, t, J=6 . 2Hz ), 1. 2-1 . 6 ( 8Ii, m), 1.73-2.0 (2H, m), 2.83 (4H, s), 4.07 (2H, t, J=6.5Hz), 5.44 (2H, s), 7.13 (1H, d, J=2.4Hz), 7.17 (1H, dd, J=8.8 and 2.4Hz), 7.44 (1H, dd, J=8.4 and 1.6Hz), 7.67-7.8; (3:, m) Preparation 57 1-(3,4-Dipentvloxybenzoyl)benzotriazole 3-oxide IR (KBr) : 2952, 1774, 1594, 1515, 1430, 1272, 1147, 1089 cm-1 I N M R (CDC13, b ) : 0.9-1.1 (6H, m) ,1.3-1.6 (8 H, m), i.8-2.1 (4H, m), 4.0-4.2 (4:, m), 6.99 (1H, d, J=8.5Hz), 7.4-7.6 (3H, m), 7.68 (l:i, d, J=2.OHz), 7.92 (1H, dd, J=8.5 and 2.0Hz), 8.10 (1H, d, J=8 . 5Hz ) APCI-M_ASS : :n/z = 412 (M++l ) Preparation 58 1-(7-Octvloxvcoumarin-3-vl-carbonyl)benzotriazole 3-oxide IR (KBr) . 2925, 1754, 1716, 1610, 1548, 1282, 1199, 1172, 1139, 1064, 781, 750 cm NN'R (DMSO-d6, b) 0.86 (3H, t, J=7.8Hz), 1.2-1.5 (lOH, m), 1.6-1.8 (2H, m), 4.17 (2H, t, J=6.5Hz), 6.9-7.1 (2H, m) , 7.41 (iH, t, J=7 . 2Hz ), 7.54 (1H, t, J=7 . 2Hz ), 7. 7% ( li:, d, J=8.3Hz), 7.82 (1H, d, J=8.3Hz), 7.99 (1H, d, J=8.3Hz), 8.72 (1H, s) APCI-MASS : m/z = 436 (M++1;
Prebaration 59 1-[4-(4-Pentyloxyphenyl)cinnamoyl]benzotriazole 3-oxide IR (Nujol) : 2854, 1778, 1708, 1620, 1597, 1494, 1459, 1434, 1377, 1350, 1250, 1188, 1138, 1086, 978 cm-1 preparation 60 1-(5-Octyloxybenzo[b]thiophen-2-yl-carbonyl)-benzotriazole 3-oxicie 1R (KBr) 295 1776, 1517, 1342, 1211, 1151 cm I\TY-R (DMSO-ab, c= : 0.86 (3H, t, J=6.7Hz) , 1.2-1.5 (10H, m), i.77-1.9 (2H, m), 4.01 (2H, t, J=6.4Hz), 7.13 (1H, dd, J=8.8 and 2.4Hz), 7.42 (1H, d, J=-/.1Hz), 7.5-7.6 (3H, m), 7.72 (1H, d, J=8.4Hz), 7.89 (1'n, d, J=8.8Hz), 7.9-8. 1(2H, m), APCI-MASS 424 (M++l) Preparation 61 1-(3-Methvl-5-octvlbenzo[b]ruran-2-vi-carbonyl)-benzotriazoie 3-oxide IR (KBr) . 1776, 1575, 1469, 1363, 1324, 1276, 1114, 1027 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.7Hz), 1.2-1.5 (iOH, m), 2.6-2.8 (2::, m), 2.71 (3H, s), 2.76 (2H, t, J=7.4Hz), 7.4-7.6 (o'H, m), 8.12 (1H, s) APCI-MASS : m/z = 406 (M++1) Preparation 62 1-(2-Nonvlbenzoxazol-5-yl-carbonvl)benzotriazole 3-oxide IR (KBr) : 2980, 1783, 1623, 1573, 1276, 1151, 1091, 989 cm-1 NMR (DMSO-d6, b) : C.84 (3H, t, J=6.8Hz), 1.1-1.4 (12H, m), 1.81 (2H, t, J=7.2Hz), 2.96 (3H, t, J=7.4Hz), 7.41 (iH, t, J=7.0Hz), 7.54 (1H, t, J=7. 0Hz) , 7.74 (2'ri, t, J=7.OHz), 7.98 (2H, d, J=7.0Hz), 8.19 (1H, s) APCI-MASS : m/z = 407 (MT+I) preparation 63 1-[2-(4-Hexyloxyphenvl)benzimidazol-5-yl-carbonyl]-benzotriazole 3-oxide IR (KBr) : 3160, 2931, 2863, 1778, 1612, 1502, 1448, 1388, 1294, 1247, 1174, 1097, 1010, 732 c*n-1 NMR (DMSO-d6, 5) : 0.89 (3H, t, J=6.7Hz), 1.2-1.5 (6H, m), 1.7-1.8 (2H, m), 4.08 (2H, t, J=6.4Hz), 7.16 (2H, d, J=8-7Hz), 7.6-8.4 (9H, m), 8.3-8.6 (1H, br) APCI-I~..ASS : m/z = 456 (M++1) PreiDaration 64 i-[4-[4-(8-Methoxyoctvloxy)phenyl]benzovl]-benzotriazole-3-oxide IR (KBr) : 293i, 1793, 1770, 1600 cm-1 NMR (CDC13, (5) 1.2-1.7 (10H, m), 1.7-1.93 (2H, m), 3.34 (3H, s), 3.38 (2H, t, J=6.4Hz), 4.03 (2H, t, J=6.5Hz), 7.03 (2H, d, J=8. 8Hz) , 7.4-7.7 (3H, m), 7.63 (2H, d, J=8.8Hz), 7.79 (2H, d, J=8.6Hz), 8.12 (1H, d, J=8.2Hz), 8.32 (2H, d, J=8.6Hz) Dreparation 65 1-[4-[4-(4-Hexyloxyphenyl)piperazin-l-yllbenzovl]benzotriazole 3-oxide IR (KBr) 1770, 1604, 1510, 1232, 1186 cITI-1 I\TMR (CDC13, b) : 0.91 (3H, t, J=6.6Hz), 1.2-1.6 (6H, m), 1.6-1.9 (2H, m), 3.1-3.3 (4H, m), 3.5-3.7 (4H, m), 3.93 (2H, t, J=6.5Hz), 6.87 (2H, d, J=9.2Hz), 6.96 (2H, d, J=9.2Hz), 7.00 (2H, d, J=9.OHz), 7.3-7.7 (3H, m), 8.10 (1H, d, J=8.2Hz), 8.15 (2H, d, J=9.OHz) APCI-MASS : m/z = 500 (M+HT) Preparation 66 1-[4-[5-(4-Pentyloxyphenyi)isoxazol-3-yl]benzoyl]-benzotriazole 3-oxide IR (KBr) : 2950, 2837, 1774, 1616, 1508, 1452, 1251, 1006 cm-1 NMR (CDC13, b) : 0.95 (3H, t, J=7.1Hz), 1.3-1.-E (4u, m) , ~. 8-2 . 0 (2H, m) , 4. 04 (2H, t, J=6. SHz) , 6. 8~
(1H, s), 7.C-7.1 (3H, m), 7.4-7.6 (3H, m), 7.80 (2H, d, J=8.8Hz) , 8..0-8.2 (3H, m) , 8.40 (2H, d, J=8.4Hz) APCI-MASS : m/z = 469 (M+H)+
Preparation 67 To a suspension of 1-hvdroxybenzotriazole (0.20 g) and 4-(4-pentylphenyl)cinnamic acid (0.40 g) in dichloromethane (12.0 ml) was added 1-ethyl-3-(3'-dimethylaminopropvl)carbodiimide hvdrochloride (0.33 g) (WSCD=HC1), and the mixture was stirred for 12 hours at arbient temperature. The reaction mixture was diluted wit~ ciichioromethane, and washed with brine, and dried over magnesium sulfate. After magnesium sulfate was filtered off, evaporation of the filtrate and trituration with acetonitrile gave 1-[4-(4-Pentvlphenvl)cinnamovl]benzotriazole 3-oxide (0.24 g).
NMR (CDC13, 5) : 0.91 (3H, t, J=6.6Hz), 1.20-1.50 (4H, m), 1.50-1.75 (2H, m), 2.66 (2H, t, J=8.OHz), 7.20-8.25 (11H, m), 8.55 (1H, d, J=8.4Hz) APCI-MASS m/z = 412 (M++l ) The following compounds (Preparations 68 to 73) were obtained according to a similar manner to that of Preparation 67.

Preparation 68 1-[3-[4-(4-Pentyloxyphenyl)phenyl]-2-propanoyl]-benzotriazole 3-oxide NMR (CDC13, 5) : 0.90-1.05 (3H, m), 1.30-1.65 (4H, m), 1.70-1.95 (2H, m), 3.10-3.60 (4H, m), 3.90-4.10 (2H, m), 6.88-7.08 (2H, m), 7.20-8.50 (lOH, m) APCI-MASS : m/7 = 430 (M++!) preparation 69 1-;4-(4-Heptvlphenyl)cinnamovl]benzotriazole 3-oxide NMR (CDC13, b; 0.89 (3H, t, J=6.7Hz), 11.20-1.50 (8H, m), 1.50-1.80 (2H, m), 2.66 (2H, t, J=7.6Hz), 6.70-8.60 (12H, m) APCI-MASS : m/z = 440 (M++l) Preparation 70 1-(3-r4-(4-Pentylphenvl)phenvl]-2-propanoyl]-benzotriazole 3-oxide NMP. (CDC13, 5) : 0.90 (3H, t, J=6.8Hz), 1.20-1.50 (4H, m), 1.50-1.76 (2H, m), 2.63 (2H, t, J=7.4Hz), 3.21 (2H, t, J=7.3Hz), 3.S1 (2H, t, J=7.3Hz), 7.20-7.45 (4H, m), 7.45-7.70 (5H, m), 7.78 (1H, dt, J=1.0 and 7.2Hz), 8.00 (1H, d, J=8.2Hz), 8.42 (iH, d, J=8.4Hz) APCI-MASS : m/z = 414 (M++1) Preparation 71 1-[3-(6-Heptyloxvnaphthalen-2-vl)propanoyl]-benzotriazole 3-oxide NMR (CDC13, (5) 0.80-1.10 ;3H, m), 1.20-1.70 (8H, m), 1.70-2.00 (2H, m), 3.10-3.70 (4H, m), 4.00-4.18 (2H, m), 6.80-8.50 (10H, m) APCI-MASS : m/z = 432 (M++1) Preparation 72 1-[3-(6-Heptyloxvnaphthalen-2-yl)propenoyl]-benzotriazole 3-oxide NMR (CDC13, 5) : 0.90 (3H, t, J=6.5Hz), 1.20-1.65 (8H, m), 1.75-1.95 (2H, m), 4.10 (2H, d, J=6.5Hz), 6.75-8.62 (8H, m) -APCI-MASS m/z = 430 (M++!' Lreparafiion 73 1-(4-Hexylphenylbenzoyl)benzotriazole 3-oxide NMR (CDC13, 5) 0.90 (3H, t, J=4.4Hz), 1.2-1.5 (6 H, m), 1.6-1.8 (2H, m), 2.68 (2H, t, J=8.OHz), 7.32 ;2H, d, J=8.2Hz), 7.4-7. (5H, m), 7.81 (2H, d, J=6. 6Hz) , 8.10 (2H, d, J=B.lHz), 8.32 (2H, d, j=7.6Hz) APCI-MASS : m/z = 400 (M++l ) preparation 74 To a solution of 4-octyloxyphenol (1 g) in dimethylformamide (10 ml) and pyridine (0.364 ml) was added N,N'-disuccinimidylcarbonate (1.16 g). The mixture was stirred for 12 hours at ambient temperature. The reaction mixture was added to a mixture of water and ethyl acetate.
The organic layer was taken, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-Octyloxyphenylsuccinimidyl carbonate (0.59 g).
TR (KBr) : 2927, 1876, 1832, 1735 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.3Hz), 1.2-1.55 (10H, m), 1.67-1.87 (2H, m), 2.87 (4H, s), 3.94 (2H, t, J=6.5Hz), 6.89 (2H, d, J=9.2Hz), 7.17 (2H, d, J=9.2Hz) APCI-MASS : m/z = 364 (M++1) The following compounds (Prenarations 75 to 88) were obtained according to a similar manner to that of Preparatior, ~.

Preparation 75 Methyl 4-(4-(6-phenylpyridazin-3-yl-oxy)phenyl]benzoate IR (KBr) : 1708, 1427, 1280, 1187, 1112 cm-1 NMR (CDC13, b) . 3.95 (3H, s), 7.2-7.7 (10H, m), 7.92 (1H, d, J=9 . 2Hz ), 8. 0-8 . 2 (4H, m) APCI-MASS : m/z = 383 (M+H) preparation 76 Methyl 4-[4-(5-bromopentyloxy)phenyl]benzoate I. (KBr) . 2946, 2871, 1716, 1602, 1294, 1199, 1112, 837 cm-1 NMR (CDC13, 5) : 1.7-2.0 (6H, m), 3.45 (2H, t, J=6.7Hz), 3.93 (3H, s), 4.02 (2H, t, J=6.1Hz), 6.97 (2H, d, J=8 .7Hz) , 7.56 (2H, d, J=8.7Hz), 7.61 (2H, d, J=8.3Hz), 8.07 (2H, d, J=8.3Hz) APCI-MASS : m/z = 378 (M+H)+
Preoaration 77 Methyl 4-[4-(5-phenoxypentyloxy)phenyl]benzoate IR (KBr) : 2944, 2931, 1720, 1600, 1492, 1197, 1110 cm-1 NMR (CDC13, b) : 1.6-1.8 (2H, m), 1.8-2.0 (4H, m), 3.93 (3H, s), 4.00 (2H, t, J=6.3Hz), 4.04 (2H, t, J=6.3Hz), 6.9-7.1 (5H, m), 7.3-7.4 (2H, m), 7.56 (2H, d, J=8.7Hz), 7.62 (2H, d, J=8.3Hz), 8.07 (2H, d, J=8.3Hz) APCI-MASS m/z = 391 (M+H)+
Preparation 78 1-[2-(4-Cyclohexylphenylamino)ethyl]-2-oxazolidone hydrochloride IR (KBr) 2923.6, 2852.2, 1747.2, 1683.6 cm-1 NMR (DMSO-d6, b) : 1.1-1.5 (6H, m), 1.6-1.9 (4H, m), 2.3-2.6 (1H, m), 3.3-3.5 (4H, m), 3.58 (2H, dd, J=9.4 and 7.4Hz), 4.22 (2H, dd, J=9.4 and 7.4Hz), 7.1-7.4 (4H, m) Preparation 79 Methyl 4-[4-(8-hydroxvo~tvlcxy)phenvl]benzoate 7R (KBr) 3250, 2933, 2E56, 1724, 1602, 143, 1292, 1199 cm-=
NTM.R (CDCi3, b) . 1. 3-1 . 9 (12H, m), 3. 6-3. 8(2H, br), 3.93 (3H, s), 4.00 (2H, t, J=o'.7Hz), 4.82 (1H, s), 7.66 (2H, d, J=8.7Hz), 7.56 (2H, d, J=8.7Hz), 7.62 ( 2H, d, J=8 . 3Hz ), 8.07 (2H, d, J=8 . 3Hz ) APCI-MASS : m/z = 357 (M+H+) Prgparation 80 Methyl 4-[4-(6-bromohexyloxv)phenvllbenzoate TR (KR,-; 2937, 2861, 1724, 1602, 1529, 1436, 1292, 1199, 1112 cm-1 NMR (CDC13, b) . 1.5-2.0 (8H, m), 3.43 (2P:, t, =6.8Hz), 3.93 (3H, s), 4.02 (2H, t, J=6.3Hz), 6.98 (2H, d, J=8. 8Hz) , 7.56 (2H, d, J=8. 8Hz) , 7. 62 (2H, d, J=8.4Hz), 8.07 (2H, d, J=8.4Hz) APCI-MASS m/z = 391 (M+H+) Prebaration 81 4-[4-(5-Bromopentyloxy)phenyl]bromobenzene iR (KBr) . 2942, 2867, 1604, 1515, 1477, 1286 NMR (CDC13, b) : 1.5-2.0 (6H, in), 3.44 (2H, t, J=6.7Hz), 3.99 (2H, t, J=6.2Hz), 6.95 (2H, d, J=8.7Hz), 7.3-7.6 (6H, m) APCI-MASS m/z = 399 (M+H+) Preparation 82 8-[4-(4-Methoxycarbonylphenyl)phenoxy]octanoyl piperidine IR (KBr) : 2935, 2852, 1720, 1639, 1604, 1438, 1292 cm-1 NMR (CDCl-~, b).: 1.3-1.9 (16H, m), 2.34 (2H, d, J=7.6Hz), 3.4-3.6 (4H, m), 3.93 (3H, s), 3. (2H, t, J=6.4Hz), 6.97 (2H, d, J=8. 8Hz) , 7.55 ('_: , d, J=8. 8Hz ), 7. 61 (2H, d, J=8. 6Hz ), 8. 07 (2H, J=8.6Hz;

APCI-MASS : m/z = 438 (M+?-i') preparation 83 Methvl 6-~4-(4-n-heptylox.vphenyl)piperazin-"l-v=lnicotinate IR (KBr) . 2933, 2859, 1726, 1608, 1513, 1430, 1280, 1245 cm-=
NMR (CDC13, (5) : 0.89 (3H, -., J=6.7Hz), 1.2-1.8 (lOH, m), 3.17 (4H, t, J=4.9Hz), 3.8-4.0 (9H, m), 6.65 (1H, d, J=9.1Hz), 6.86 (2u, d, 7=9. lHz ), 6.96 (2: , d, J=9. lHz ), 8.05 (1H, dd, J=9 . 1 and 2. 3Hz ), 8. 8%
(1H, d, J=2 . 3Hz ) APCI-MASS : m/z = 412 (M+H+) preoaration 84 Methyl 6-[4-[4-(8-bromooctyloxy)phenyl]piperazin-l-yl]nicotinate IR (KBr) 2933, 2861, 1724, 1608, 1513, 1430, 1280 cm-1 NMR (CDCi-~, 5) . 1.2-2.0 (12H, m), 3.17 (4H, t, J=S.OHz), 3.40 (2H, t, J=6.8Hz), 3.8-4.0 (9H, m), 6.64 (1H, d, J=9.OHz), 6.85 (2H, d, J=9.*1Hz), 6.96 (2H, d, J=9.lHz), 8.05 (1H, dd, J=9.0 and 2.2Hz), 6.82 (1H, d, J=2 . 2Hz ) APCI-MASS 504 (M+u+) Preparation 85 4-[4-(7-Bromoheptyloxy)phenvl]bromobenzene IR (KBr) : 2935.1, 2856.1, 1604.5 cm-1 NMR (CDC13, 5) : 1.18-1.65 (6H, m), 1.70-2.02 (4H, m), 3.41 (2H, t, J=6.8Hz), 3.99 (2H, t, J=6.4Hz), 6.95 (2H, d, J=8. 6Hz) , 7.40 (2H, d, J=8. 6Hz) , 7.46 (2H, d, J=8.6Hz), 7.52 (2H, d, J=8.6Hz) Preparation 86 4-[4-(8-Bromooctyloxy)phenvl]bromobenzene NMR (CDC13, 5) : 1.22-1.65 (8H, m), 1.65-1.95 (4H, m), 3.41 (2H, t, J=6.8Hz), 3.99 (2H, t, J=6.4Hz), 6.95 (2H, d, J=8.6Hz), 7.40 (2H, d, J=8. 6Hz) , 7.46 (21-7, d, J=8 . 6Hz ), 7.52 (2H, d, J=8 . 6Hz ) Dreparation 87 Methvl (E)-3-[4-[4-(5-hexenyi.oxy)phenyl]phenyl]acrvlate NMR (CDC13, 5) : 1 .50-1 .72 (2H, m), 1 .72-1 . 95 (2H, m), 2.05-2.14 (2H, m), 3.82 (3H, s), 4.01 (2H, t, J=6.3Hz), 4.95-5.10 (2H, m), 5.70-5.93 (1H, m), 6.46 (1H, d, J=16Hz ), 6.97 (2H, d, J=8 . 7Hz ), 7.54 (2H, d, J=8 . 7Hz ), 7.58 (4H, s), 7.72 (1H, d, J=16Hz) APCI-MASS : m/z = 337 (M++1) Preparation 88 4-Bromo-4'-(4-methylpentyloxv)biphenyl IR (KBr) : 2956.3, 2871.5, 1606.4 cm-1 NMR (CDC13, b) : 0.93 (6H, d, J=6. 6Hz) , 1.25-1.45 m), 1.62 (1H, sept, J=6.6Hz), 1.72-1.93 (2H, m), 3.98 (2H, t, J=6. 6Hz) , 6.95 (2H, d, J=8. 6Hz) , 7. 30-7 . 60 (6H, m) APCI-MASS : m/z = 332, 334 (M+, M++2) The following compounds (Preparations 89 to 90) were obtained according to a similar manner to that of Prenaration ~-Preparation 89 N- [ 4- [2- ( 4-M,~thylpentvl )-2, 3-dihydro-4?i-1, 2, 4-triazol-3-one-4-yl]phenyl]p._perazine ditrifluoroacetate IR (KBr) : 1668.1, 1519.6, 1203.4, 1176.4, 1130.1 c:r-1 NNnt (DMSO-d6, b) : 0.86 (6H, d, J=6. 6Hz) , 1.1-1.3 (2'r:, m), 1.4-1.8 (3H, m), 3.1-3.3 (4H, m), 3.3-3.5 (4H, 3. 7 C, (2H, t, J=7 . OHz ), 7. 11 (2H, d, J=9 . OHz ) 7.53 (2H, d, J=9.OHz), 8.35 (1H, s), 8.90 (2H, s) Preparation 90 _-(4-Phenylcvclohexyl)piperazine ditrifiuoroacetate 1R (KBr) 1677.8, 1197.6, ii33.9 cm-~
I'TMR (DMSO-d6, (5) : 1.4-1.8 (4H, -~.t) , 1.8-2.25 (4H, in), 2.4-2.7 (1H, m), 3.2-3.7 (9H, m), 4.54 (2H, br s), 7.0-7.4 (5H, :r,) , 9.32 (1H, br s) nPCI-MASS : m/z = 245 (M++H) The following compounds (Preparations 91 to 103) were obtained according to a similar manner to that cf Preparation Preparation 91 Methyl 6-[4-(4-octyloxyphenyl)piperazin-i-yl]nicotinate IR (KBr) : 2923, 1726, 1608, 1515, 1278, 1116 cm-1 NMR (CDC13, 5) : 0.88 (3H, t, J=6.8Hz), 1.2-1.5 (101i, m), 1.7-1.8 (2H, m), 3.1-3.2 (4H, m), 3.8-4.0 (9:, m), 6.64 (1H, d, J=9.OHz), 6.8-7.0 (4H, m), 8.04 (1H, dd, J=9 . 0 and 2. 4Hz ), 8.81 (iH, d, J=2 . 4Hz ) APCI-M.ASS : m/z = 426 (M+H+) preparation 92 4-[4-[4-[2-(4-Methylpentyl)-2,3-dihvdro-4H-1,2,4-triazol-3-one-4-yl]phenyl]piperazin-l-vl]benzoni-trile IR (KBr) : 2217.7, 1685.5 c:n 1 NMR (CDC13, (5) : 0.90 (6H, d, J=6.6Hz), 1.2-1.4 (2H, *_q), 1.5-2.0 (3H, m), 3.3-3.4 (4H, m), 3.4-3.6 (4H, m), 3.83 (2H, t, J=7.4Hz), 6.92 (2'r?, d, J=9. OHz) , 7.01 (2H, d, J=9.OHz), 7.43 (2H, d, J=9.OHz), 7.54 (2H, d, J=9 . OHz ), 7.62 (iH, s) Preparation 93 3-Fluoro-4-[4-(4-methoxyphenyl)piperazin-l-yl]benzonitrile IR (KBr) 2225.5, 1510.0, 1240.0 cm-1 NMR (CDC13, b) : 3.1-3.55 (8H, m), 3.79 (3H, s), 6.7-7.1 (6H, m), 7.3-7.5 (1H, m) Preparation 94 3-Chlcro-4-[4-(4-n-hexyloxyphenyl)piperazir_-l-yl]benzonitrile IR (KBr) : 2223.5, 1592.9, 1510.0, 1490.7, 1236.1 cm-1 NMR (CDC13, 5) : 0.90 (3H, t, J=6.7Hz), 1.3-1.6 (6H, m), 1. 7-1 . 9 (2H, m), 3.2-3. 4( 8H, m), 3.92 (2'r., t, J=6.6Hz), 6.85 (2H, d, J=9.3Hz), 6.94 (2H, d, J=9.3Hz), 7.08 (1H, d, J=8.4Hz), 7.53 (1H, dd, J=8.4 and 1.9Hz), 7.64 (1H, d, J=1.9Hz) APCI-MASS : m/z = 398 (M++H) Preparation 95 Ethyl 3-[4-(4-n-hexyloxyphenyl)piperazin-1-yl]-6-pyridazinecarboxylate IR (KBr) : 1729.8, 1587.1, 1511.9, 1245.8 cm-1 NMR (CDC13, b) : 0.90 (3H, z, J=6.5Hz), 1.2-1.4 (6H, m), 1.44 (3H, t, J=7.1Hz), 1.65-1.85 (2H, m), 3.1-3.25 (4H, m), 3.8-4.0 (6H, m), 4.46 (2H, q, J=7.. 1Hz ), 6. 8-7 . 0 (5H, m), 7.91 (1H, d, J=9 . 6Hz ) APCI-MASS : m/z = 413 (M++H) Preparation 96 4-(4-Piperidinopiperidin-1-yl)be::zonitrile IR (KBr) : 2217.7, 1602.6, 1511.9 cm-1 NMR (CDC13, b) : 1.35-1.75 (8H, m), 1.92 (2H, d, J=12.9Hz), 2.3-2.6 (5H, m), 2.86 (2H, td, J=12.8 and 2. 6Hz ), 3.90 (2H, d, J=12 . 8Hz ), 6.84 (2H, d, J=9. 1Hz) , 7.46 (2H, d, J=9.lHz) APCI-MASS m/z = 270 (M++H) - 8~ -Preparation 97 5-[4-(4-n-Hexyloxyphenyl)piperazin-l-yl]picolir:onitrile IR (KBr) 2223.5, 1575.6, 1511.9, 1241.9 cm-~
NMR (CDC1-~, 5) : 0.90 (3H, t, J=6.5Hz), 1.2-1.55 (6n, m), 1.7-1 . 85 (2H, m), 3.22 (4H, t, J=5.1Hz), 3.5---(4H, t, J=S.lHz), 3.92 (2H, t, J=6.5Hz), 6.86 (2H, d, J=9.4Hz), 6.93 (2H, d, J=9.4Hz), 7. i3 (i~, dd, J=8. 8 and 3. OHz) , 7. 5-3- (lH, d, J=8. 8Hz) , 8.3-'~ (1'r:, d, J=3.OHz) APCI-MASS m/z = 365 (M t+H) Prenaration 98 4-[4-(4-Cyclohexyiphenyl)pipera7 in-l-yl]benzonitrile TR (KBr) 2219.7, 1606.4, 1-513.8, 1238.1 cm-1 i5 h~?~IR (CDC1~, 5) : 1. 1-1 .5 (6H, m) , 1. 65-2. 0(4H, m) , 2.44 (1H, m), 3.30 (4H, t, J=5.1Hz), 3.46 (4H, t, J=5 . 1Hz ), 6.90 (4H, d, J=8 . 9Hz ), 7.14 (2H, d, J=8.9Hz), 7.52 (2H, d, J=8.9Hz) hPCI-N~ASS m/z = 346 (M++H) preparation 99 4-[4-(4-n-Hexylphenyl)piperazin-i-yl]benzonitrile IR (KBr) 2925.5, 2850.3, 2213.9, 1604.5, 1513.8, 1234.2, 944.9 cir.-1 NMR (CDC13, 6) : 0.88 (3H, t, J=6.4Hz), 1.2-1.45 (6H, m), 1.45-1.7 (2H, m), 2.54 (2H, t, J=7.6Hz), 3.2-3. 4(4H, m), 3.4-3. 6(4H, m), 6.89 (2H, d, J=8.5Hz), 6.91 (2H, d, J=8. 9Hz) , 7. 11 (2H, d, J=8.5Hz), 7.52 (2H, d, J=8.9Hz) Preparation 100 1-[2-(4-n-Hexylphenylamino)ethyl]-2-oxazolidone hydrochloride IR (KBr) 2925.5, 2852.2, 1753.0, 1729.8, 1267.0 cm-1 NMR (DMSO-d6, b) . 0.85 (3H, t, J=6.5Hz), 1.1-1.4 (6H, m), 1.45-1.7 (2H, m), 2.56 (2H, t, J=7.6Hz), 3.~-3.53 (4H, m) , 3.57 (2H, t, J=7. 9Hz) , 4.24 (2 :, t, J=7.9Hz), 7.24 (4H, s) APCI-M-P-SS : m/z = 291 (M+ +H) Preparation 101 4-[4-(4-Phenvlcvclohexvl)piperazin-1-yl]benzonitrile IR (KBr) : 2212.0, 1602.6, 1513.8, 1249.6 cm-1 NMR (CDC1-~, 5) : 1.3-1.8 (4H, m), 1.9-2.2 (4H, m), 2.3-2.6 (2H, m), 2.75 (4H, t, J=S.OHz), 3.34 (4H, t, J=S. OHz) , 6.86 (2H, d, J=8.9Hz), 7.1-7.4 (5H, m) , 7.49 (2H, d, J=8.9Hz) APCI-MASS : m/z = 346 (M++H) Preparation 102 Methyl 6-[4-(4-hydroxyphenyl)piperazin-1-yl]nicotinate IR (KBr) : 3411, 1691, 1602, 1510, 1432, 1249, 1147 cm-i NMR (DMSO-d6, b) : 3.0-3.1 (4H, m), 3.7-3.9 (7H, m), 6.67 (2H, d, J=8.8Hz), 6.84 (2H, d, J=8. 8Hz) , 6.93 (1H, d, J=9.lHz), 7.97 (1H, dd, J=2.4 and 9.1Hz), 8.66 (1H, d, J=2.4Hz), 8.88 (1H, s) APCI-MASS : m/z = 314 (M+H)+
Preparation 103 i-n-Decylindole-5-carboxylic acid IR (KBr) : 2921, 2854, 1679, 1612, 1427, 1313, 1199 cm-1 NMR (DMSO-d6, (5) : 0.84 (3H, t, J=6.8Hz), 1.1-1.3 (14H, m), 1. 6-1 .8 (2H, m), 4.19 (2H, t, J=6. 9Hz) , 6.57 (1H, s), 7.4-7.8 (3H, m), 8.23 (1H, s), 12.40 (1H, s) PPCI-MASS : m/z = 302 (M+H+) The following compounds (Preparations 104 to jj_j) were obtained according to a similar manner to that of Preoaration 10.

Preparation 104 (E)-Methvl 4-(4-n-butoxyphenyl)cinnamate IR (KBr) . 2958, 2939, 2873, 1720, 1637, 1498, 1313, 119~, 1170 cm-1 NMR (CDC13, b) : 0.98 (3H, -,-, J=7.3Hz), 1.4-1.8 (4H, m), 3.81 (3H, s), 4.00 (2H, t, J=6.4Hz), 6.45 (1H, d, J=16.OHz), 6.97 (2H, d, J=8.7Hz), 7.5-7.7 (6H, m), 7.72 (1H, d, J=16 . OHz ) APCI-YASS : m/z = 311 (M+HT) Preparation 105 Methyl (E)-3-[4-[4-(4-methvipentvloxy)phenyl]phenyl]-acrvlate IR (KBr) 2956.3, 2873.4, 1720.2, 1635.3, 1600.6 cm-1 NMR (CDC1-~, 5) : 0.93 (6H, d, J=6.5Hz), 1.28-1.50 (2H, m), 1.50-1.95 (3H, m), 3.82 (3H, s), 3.99 (21-1, t, J=6.6Hz), 6.44 (1H, d, J=16.OHz), 6.97 (2H, d, J=8.7Hz), 7.49-7.65 (6H, m), 7.71 (1H, d, J=16Hz) APCI-MASS : m/z = 339 (M++l) Preparation 106 Methyl (E)-3-[4-[4-(6-fluorohexyloxy)phenyl]phenyl]-acrvlate NMR (CDC13, b) : 1.23-2.00 (8H, m), 3.81 (3H, s), 4.01 (2H, t, J=6.4Hz), 4.47 (2H, dt, J=47.4 and 6.0Hz), 6.45 (1H, d, J=16.OHz), 6.96 (2H, d, J=8.8Hz), 7. 45-7 . 63 (6H, m), 7.72 (1H, d, J=16 . OHz ) APCI-MASS : m/z = 357 (MT+1) preuaration 107 Methyl (E)-3-[4-[4-(6-methoxyhexyloxy)phenvl]phenyl]-- 8_ -acrylate APCI-MASS 369 (M+) preparation 108 Methvl (E)-3-[4-1'4-(8-methoxvoctyloxy)phenyl]phenvl]-acrylate IR (KBr; . 2935.1, 2858.0, 1722.1, 1637.3, 1602.6 cm-1 NMR (CDCI3, 5) : 1.30-1.70 (10H, m), 1.70-1.92 (2H, m) , 3.33 (3H, s), 3.37 (2H, t, J=6.5Hz), 3.81 (3H, s', , 4.00 (2'r., t, J=6.5Hz), 6.45 (1H, d, J=16.0Hz), 6. 97 (2:i, u, J=8.8Hz) , 7.46-7.78 (6ri, m) , 7.72 (iH, d, J=16.OHz) APCI-MASS : m/z = 397 (MT+1) Preparation 109 Methvl (E)-3-[4-(4-hvdroxyphenyl)phenyl]acrylate IR (KBr) : 3409.5, 1695.1 cm-i NMR ( DMSO-d6, 5) : 3.73 (3H, s), 6.64 (1H, d, J=16Hz ), 6.85 (2H, d, J=8.6Hz), 7.50-7.83 (5H, m) APCI-MASS : m/z = 255 (M++1) Preparation 110 Methyl (E)-3-[4-[4-(7-methoxyheptvloxy)phenyl]phenvl]-acrylate NMR (CDC13, b) : 1.32-1.70 (8H, m), 1.70-1.92 (2H, m), 3.34 (3"ri, s), 3.38 (2H, t, J=6.4Hz), 3.81 (3H, s), 4.00 (2H, t, J=6.5Hz), 6.45 (iH, d, J=16.0Hz), 6.97 (2H, d, J=8.8Hz), 7.47-7.65 (6H, m), 7.70 (iH, d, J=16Hz) APCI-MASS : m/z = 38: (M++1) Preparatior. 111 Methyl (E)-3-[4-[4-(7-iluorohentvloxy)phenyl]phenyl]-acrylate IR (KBr) . 2937.1, 2861.8, 1722.1, 1637.3, 1600.6 cm-1 The following compound was obtained according to a similar manner tc that of Preparation 20.

prPnaration 112 Methyl 3-f4-(4-heptylphenyl)phenyl]propanoate NMR (CDC13, 5) . 0.88 (3H, t, J=6.5'riz), 1.15-1.50 (8H, m), 1.50-1.77 (2H, m), 2.52-2.73 (4H, m), 2.99 (2H, t, J=7 . 8Hz ), 3.68 (3H, s), 7. 18-7 . 35 (4H, m), 7. 4 0-7.58 (4H, m) APCI-MASS : m/z = 339 (M++l) The following compounds (Preparation 113 to 164) were obtained according to a similar manner to that of Preparation 32.
Preparation 113 4-(4-Octylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one-2-yl-acetic acid IR (KBr) : 2923.6, 1704.8, 1224.6 cm-=
NMR (DMSO-d6, b) : 0.85 (3H, t, J=6.7Hz), 1.1-1.4 (lOH, m), 1.4-1.7 (2H, m), 2.60 (2H, t, J=7.2Hz), 4.38 (2H, s) , 7.32 (2H, d, J=8.5Hz), 7.58 (2H, d, J=8.5Hz), 8.43 (1H, s) Preparation 114 1-Heptyl-4-(4-carboxyphenyl)pyrazole IR (KBr) : 3106, 2917, 1687, 1612, 1425, 1295, 1184, 952, 860, 773 cm-1 NTMR (DMSO-dE, b) : 0. 85 (3H, t, J=o. 8Hz) , 1.1-1.4 (8H, m), 1.7-1.9 (2H, m), 4.11 (2H, t, J=7.OHz), 7.69 (2H, d, J=8 . 5Hz ), 7.91 (2H, d, J=8 . 5Hz ), 7.98 (1H, s ) , 8.32 (1H, s ) , 12 . 82 (1H, br) APCI-MASS : m/z = 287 (M+H+) Preparation 115 6-[4-(4-Octyloxynhenyl)piperazin-1-yl]nicotinic acid TR (KBr pelet) : 2919, 2854, 1697, 1608, 1515, 1429, 1263, 1245, 1228 cm-1 NMR (DMSO-d6, 5) : 0.86 (3H, t, J=6.7Hz), 1.1-1.5 (10H, m), 1. 6-1 .8 (2H, m) , 3.0-3.2 (4H, m), 3.7-3. 9(4P:, m), 3.88 (2H, t, J=6.4Hz), 6.7-7. 0(5H, m), 7.95 (1H, dd, J=9.0 and -.1Hz), 8.64 (1H, d, J=1.1Hz) APCI-IMASS m/z = 412 (M-rHT' preparatior. 116 2-(4-riexv?oxyphenyl)benzoxazole-5-carboxyl~c acid IR (KBr) . 2952, 1689, 1677, 1619, 1500, 1415, 1299, 1172, 1024 cm NMR (DMSO-d6, (5) : 0.89 (3H, t, J=6.7Hz), 1.2-1. 5(6H, m), 1.7-1.9 (2H, m), 4.09 (2H, t, J=6.5Hz), 7.16 (2H, d, J=8.8Hz), 7.84 (1H, d, J=8. SHz) , 8.01 (1H, dd, J=8.5 and 1.5Hz), 8.15 (2H, d, J=8.8Hz), 8.26 (1H, d, J=1 . 5Hz ) APCI-MASS : m/z = 340 (M+H+) Preparation 117 4-[4-(4-n-Butyloxyphenyl)phenyl]benzoic acid IR (KBr) . 2958, 2873, 1689, 1600, 1537, 1396 cm-1 Preparation 118 6-(4-Heptvloxyphenyl)nicotini-c acid IR (KBr) 2858, 1699, 1674, 1589, 1425, 1180, 1016, 781 cm-1 NMR (DMSO-d6, b) : 0.87 (3H, t, J=6.7Hz), 1.2-1.5 (8H, m), 1.6-1.8 (2H, m), 4.04 (2H, t, J=6.4Hz), 7.06 (2H, d, J=8. 9Hz) , 8.03 (1H, d, J=8.2Hz), 8.13 (2H, d, J=8.9Hz), 8.27 (1H, dd, J=8.2 and 2.2Hz), 9.09 (1H, d, J=2.2Hz), 13.31 (1H, br) APCI-MASS : m/z = 314 (M+H+) Preparation 119 5-(4-Octyloxyphenyl)isoxazole-3-carboxyiic acid IR (KBr pelet) . 2923, 2852, 1704, 1612, 1440, 1272, 1178 cm-1 NMR (DMSO-d6, (5) . 0.86 (3H, t, J=6.8Hz), 1.2-1.6 (IOH, m), 1.6-1.9 (2H, m), 4.G3 (2H, t, J=6.5Hz), 7.08 (2H, d, J=8.9Hz), 7.25 (1H, s), 7.86 (2i:, d, J=8.9Hz) APCI-MASS : m/z = 318 (M+'rI+) Preparation 120 2-(2-Octvloxypyridin-5-yl)benzoxazole-5-carboxylic acid IR (KBr) 2954, 2923, 2854, 1697, 1683, 1625, 1488, 1290 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=7.6Hz), 1.2-1.5 (10H, m), 1.7-1.8 (2H, m), 4.36 (2H, t, J=6.6Hz), 7.04 (1H, d, J=8.7Hz), 7.88 (1H, d, J=8.5Hz), 8.04 (1H, dd, J=8 . 5 and 1. 6Hz ), 8.29 (1H, d, J=1 . 6Hz ), 8.43 (1H, dd, J=8.7 and 2.4Hz), 8.99 (1H, d, J=2.4Hz), 13.0-13.2 (1H, br) APCI-MASS m/z = 369 (M+Hr) Preparation 121 2-[4-(4-Hexylphenyl)phenyl)benzoxazole-5-carboxvlic acid IR (KBr) . 2923, 2854, 1683, 1411, 1299, 1054 cm-1 APCI-MASS : m/z = 400 (M+H+) Preparation 122 6-[4-(4-n-Butvloxyphenyl)phenvllnicotinic acid IR (KBr) : 3406, 2958, 1691, 1591, 1394, 1284, j1253 cm-1 NMR (DMSO-d6, b) : 0.94 (3H, t, J=7 . 3Hz ), 1. 4-1 . 8 (4H, m), 4.01 (2H, t, J=6.4Hz), 7.02 (2H, d, J=8.7Hz), 7.57 (2H, d, J=8.7Hz), 7.61 (2H, d, J=8.2Hz). 7.83 (2H, d, J=8.2Hz), 8.05 (1H, d, J=8.5Hz), 8.22 (1H, dd, J=8 . 5 and 1. 6Hz ), 9. 14 (1H, d, J=; . 6Hz', APCI-N.ASS 348 (M+H+) Preparation 123 4-[4-(5-Phenoxypentyloxv)phenyl]benzoic acid NMR (DMSO-d6, 5) . 1.5-i.7 (2H, m), 1.7-1.9 (4H, m), 3.98 (2H, t, J=6.3Hz), 4.05 (2H, t, J=6.1Hz), 6. 8-7. C(3H, m), 7.05 (2H, d, J=8. 6Hz) , 7.25 (2H, t, J=8.2Hz), 7.68 (2H, d, J=8 .SHz; , 7.7-':" (2H, d, J=8.2Hz), 7.98 (2H, d, J=8.2Hz), 12.8-13.0 (1H, br s) APCI-MASS m/ z = 37~ (M-H) -Preparation 124 4-[5-(4-n-Hexvloxyphenvl)-1,3,4-oxadiazol-2-vl]benzoic acid IR (KBr) : 2935, 2854, 1685, 1612, 1495, 1425, 1286, 1251 cm-1 NMR (DMSO-d6, 5) : 0.89 (3H, t, J=6.7Hz), 1.2-1.5 (6H, m), 1.6-1.9 (3H, m), 4.12 (2H, t, J=6.4Hz), 7.19 (2H, d, J=8. 7Hz) , 8.06 (2H, d, J=8.7Hz;, 8.18 (2H, d, J=8 . 4Hz ), 8.24 (2H, d, J=8 . 4Hz ) APCI-MASS m/z = 367 (M+H)+
Preparation 125 4-[5-(4-n-Hexvloxyphenyl)-1,3,4-thiadiazoi-2-yl)benzoic acid IR (KBr) : 2952, 2586, 1699, 1604, 1517, 1432, 1251, 1174 cm-1 NMR (DMSO-d6, b) : 0.89 (3H, t, J=6.7Hz), 1.3-1.9 (8H, m), 4.04 (2H, t, J=6.3Hz), 7.13 (2H, d, J=8.8Hz), 7.97 (2H, d, J=8.8Hz), 8.11 (4h, s) APCI-MASS m/z = 383 (M+H) +
Preparation 126 - a0 -5-(4-Octvioxyphenyl)-1-methvipvrazole-3-carboxylic acic IR (KBr pelet) . 2950, 2923, 1695, 1450, 1282, 1251, 956 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.8Hz), 1.2-1.5 (10H, m), 1. 6-1 . 8 (2H, m), 3.98 (2H, t, J=6.5Hz), 4.10 (3H, s ) , 6 . 95 ( lk, d, J=8 . 8Hz ) , 7.18 (1H, s ) , 7.73 (2H, d, J=8. 8uz) , 13..~ (lH, br) APCI-MASS : m/z = 331 (M+HT;
Prenaration 127 4-r3-(4-n-Pentyloxyphenyi)pvrazo'-5-yilbenzo.4-c acici IR (KBr) . 3224, 2956, 1692, 1614, i506, 1251 cm-1 NMR (DMSO-d6, b) : 0.91 (3H, t, J=6.9Hz), 1.3-1.5 (4Fi, :n) , 1. 6-1 . 8 (2H, m) , 4.00 (2H, t, J=6. SHz) , 7.02 (2H, d, J=8.8Hz), 7.19 (1::, s), 7.75 (2H, d, J=8 . 8Hz) , 7.95 (2H, d, J=8 . 7Hz) , 8.02 (2H, d, J=8.7Hz), 12.8-13.3 (2H, br) APCI-MASS m/z = 351 (M+H+) Preparation 128 5-[4-(4-n-Butoxyphenvl)phenyl]furan-2-carboxylic acid IR (KBr) : 2958, 2873, 1679, 1487, 1253, 1166 cm-1 NMR (DMSO-d6, (5) : 0.95 (3H, t, J=7.3Hz), 1.3-1.8 (4H, m), 4.02 (2H, t, J=6.3Hz), .7.03 (2H, d, J=8.6Hz), 7.17 (1H, d, J=3.6Hz), 7.33 (1H, d, J=3.6Hz), 7.66 (2H, d, J=8.6Hz), 7.74 (2H, d, J=8.4Hz), 7.86 (2H, d, J=8 . 4Hz ), 13.1 ( lr?, br s) APCI-MASS : m/z = 337 (M+H)-Prenaration 129 3-(S)-Hvdroxyhexadecanoic acid IR (KBr) : 1679.7, 1467.6, 1224.6 cm-1 NMR (CDC13, b) : 0.88 (3H, t, J=6.4Hz), 1.1-1.7 (24H, m), 2.35-2.65 (2H, m), 4.03 (1H, m), 5.41 (1H, br s) - 9i -Preparat.ion 130 6-[4-(4-n-Hexyloxyphenyl)piperazin-1-yl]oyridazine-3-carboxylic acid IR (KBr) . 1697.1, 1589.1, 1515.8, 1448.3 cm-i \1TI;R, (HMSGi-d6, 5) . O.F7 (3H, t, .T=6,4Hz) , 1 .2-1.5 (6H, m), 1.6-1.8 (2H, m), 3.0-3.2 (4H, m), 3.7-4.0 (6H, m), 6.83 (2H, d, J=9. OHz) , 6.95 (2H, d, J=9.OHz), 7.36 (1H, d, J=9.6Hz), 7.86 (1H, d, J=9.6Hz), 11.68 (1H, s) Dreparation 131 4-[4-[1-(4-n-Hexyloxyphenyl)piperidir_-4-vi]piperazin-l-yl]benzoic acid hydrochloride IR (KBr) : 1699.C; 1608.3, 1513.8 cm-i NMR (DMSO-d6, 5) : 0.88 (3H, t, J=6.5Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 2.0-2.45 (3H, m), 3.2-3.8 (12H, m), 3.94 (2H, t, J=6.4Hz), 4.03 (2H, d, J=11Hz), 6.95 (2H, d, J=8.7Hz), 7.07 (2H, d, J=8.9Hz), 7.32 (2H, br s), 7.83 (2H, d, J=8.9Hz) APCI-MASS : m/z = 466 (M++H) preparation 132 6-(8-Methoxyoctyloxy)-2-naphthoic acid IR (KBr) : 2937.1, 2854.1, 1677.8, 1211.1 cm-1 NMR (DMSO-d6, b) : 1.2-1.6 (lOH, m), 1.7-1.9 (2H, m), 3.20 (3H, s), 3.29 (2H, t, J=6.5Hz), 4.11 (2H, t, J=6.4Hz), 7.23 (1H, dd, J=9.0 and 2.3Hz), 7.39 (1H, d, J=2.3Hz), 7.85 (iH, d, J=8.7Hz), 7.93 (1H, d, J=8.7Hz), 7.99 (1H, ci J=9.OHz), 8.51 (1H, s), 12.9 (1H, s) Preparation 133 Mixture of (E) and (Z)-3-[4-(4-Heptylphenyl)phenyl]-2-butenoic acid Iv'MR (CDC13, b) 0.88 (3H, t, J=6.6Hz), 1.15-1.50 (BH, 1.52-1.75 (2H, m), 2.63 and 3.62 (total 3H, each s), -.53-2.75 (2H, m), 6.24 and 5.68 (tota~
1H, ea'r s;, 7.19-7.35 (2H, m), 7.47-7.70 (6H, m) APCI-MASS : m/z = 337 (M+i ) , 351 (methyl ester+l ) Preparation 134 3-[4-(4-Heptyiphenyl)phenyl]pronanc~-c acid NMR (CDCi3, 6) : 0.88 (3H, t, J=6.6Hz), 1.13-i.48 (8H, i.48-1.75 (2H, m) , 2.52-2.83 (4H, rr.) , 3.00 (2H, ?0 ~, J=7.8Hz), 7.15-7.35 (4H, m), 7.40-7.60 (4H, m) APCI-MASS : m/z = 323 (M+-1) Dreparation 135 4-(4-n-Heptylphenyl)benzoyl-carboxylic acid 15 NMR (CDC13, 6) : 0.88 (3H, t, J=6.6Hz), 1.13-1.50 (8H, m), 1.50-1.75 (2H, m), 2.66 (2H, t, J=7.7Hz), 7.20-7.40 (2H, m), 7.50-7.66 (2H, m), 7.66-7.84 (2H, m), 8.40-8.60 (2H, m) APCI-MASS : m/z = 323 (M+-1) Preparation 136 6-Hexylnaphthalene-2-carboxylic acid NMR (CDC13, b) : 0.89 (3H, t, J=6.8Hz), 1.15-1.53 (6H, m), 1.55-1.84 (2H, m), 2.80 (2H, t, J=7.6Hz), 7.42 (1H, dd, J=1 . 7 and 8. 4Hz ), 7.67 ( iH, s), 7.84 ( iH, d, J=8 . 6Hz ), 7.90 (1H, d, J=8 . 4Hz ), 8.09 (1H, dd, J=1.7 and 8.6Hz), 8.68 (iH, s) APCI-MASS : m/z = 257 (M++1), 271 (methyl ester++i) Preparation 137 3- (E )-[ 4- [ 4- ( 7-Methoxyheptyloxy) phenyl ] phenyi ] acrylic acid NMR (DMSO-d6, b) : 1.20-1.60 (8H, m), 1.60-1.83 (2H, m), 3.21 (3H, s), 3.25-3.60 (2H, m), 4.01 (2H, t, J=6 . 4Hz ), 6.54 ( iH, d, J=16 . OHz ), 7.02 (2H, d, J=8.8Hz), 7.55-7.80 (7H, m) APCI-MASS m/z = 369 (M+-r1) Preparation 138 3-(:,:)-[4-[4-(8-Methoxyoctyloxy)phenyl]phenyi]acrvlic acid IR (KBr) : 3037.3, 2933.2, 2858.0, 2551.4, 1706.7, 1677.8, 1629.6, 1602.6 cm-1 NMR (DMSO-d6, b) : 1.18-1.55 (lOH, m), 1.65-1.83 (2H, m), 3.18-3.45 (5H, m), 4.01 (2H, t, J=6.5Hz), 6.53 (1H, d, J=16.OHz), 7.02 (2H, d, J=8.8Hz), 7.50-8.80 (7H, r.l) APCI-MASS : m/z = 383 (M+--') Preparation 139 3-(E)-[4-[4-(5-Hexenvloxy)phenyl]phenyl]acrylic acid NTMR (DMSO-d6, b) : 1.42-1.63 (2H, m), 1.63-1.85 (2H, m), 2.00-2.20 (2H, m), 4.03 (2H, t, J=6.3Hz), 4.90-5.15 (2H, m), 5. 68-5. 97 (1H, *n) , 6.54 (1H, d, J=16Hz), 7.02 (2H, d, J=8.7Hz), 7.50-7.80 (7H, m) APCI-MASS : m/z = 323 (M++1) Prez_-ration 140 (E)-[4-[4-(4-Methylpentyloxy)phenyl]phenyl]acrylic acid IR (KBr) : 2956.3, 2869.6, 2713.4, 2599.6, 1689.3, 1627.6, 1602.6 cm-1 NMR (DMSO-d6, S) : 0.89 (6H, d, J=6.5Hz), 1.15-1.43 (2H, m), 1.48-1.90 (3H, m), 4.00 (2H, t, J=6.7Hz), 6.54 (1H, d, J=16Hz), 7.02 (2H, d, J=8.7Hz), 7.50-7.90 (7H, m) APCI-MASS : m/z = 325 (M++1) Preparation 141 3-(E)-[4-[4-(6-Fluorohexyloxy)phenyl]phenyl]acrylic acid NMR (CDCi3, 5) . 1.39-2.00 (8H, m), 4.01 (2H, t, J=6.5Hz), 4.47 (2H, dt, J=47.3 and 6.0Hz), 6.49 (1H, d, J=15. 9Hz) , 6.98 (2H, d, J=8. 7Hz) , 7.40-7.70 (6H, m), 7.81 (1H, d, J=i5.9Hz) APCI-Y.ASS : m/z = 343 (M.+1 ) arPparaticr. 142 3- (E )-[ 4- [ 4- ( 6-Methoxyhexyloxv) phenyl ] pher.yl ] acrylic acid NMR (DMSO-d6, 5) : 1.22-1.63 (6H, m), 1.63-1.88 (2H, :r) , 3.21 (3H, s), 3.22-3.40 (2H, m), 4. 00 (2H, t, J= C,. 5Hz ), 6.54 ( iH, d, J=15 . 8Hz ), 7. G 2 (2H, d, J=8.7Hz), 7.50-7.84 (7H, m) APCI-MASS : m/z = 369 (methvl ester, M++?;
Preparation 143 4-[4-[8-('!etrahydropyran-2-yl-oxy)octyloxy]phenyl]benzoic acici Ik (KBr) : 2935, 1697, 1-683, 1604, 1303, 1290, 1197 cm-1 ATMR (DMSO-d6, b) : 1. 2-1 . 8 (18H, m) , 3. 3-3 . 9 (4H, m), 4.01 (2H, t, J=6.3Hz), 4.5-4.6 (1H, m), 7.03 (2H, J=8.7Hz), 7.67 (2H, d, J=8.7Hz), 7.74 (2H, d, J=8.3Hz), 7.98 (2H, d, J=8.3Hz) APCI-MASS : m/z = 425 (M-u+) Preparatio:. 144 4-[3-(4-n-Hexvloxyphenyl)pyrazol-5-vl]benzoic acid IR (KBr) : 2956, 2935, 1693, 1614, 1508, 1432, 1251, 1178 cm-1 NMR (DMSO-d6, b) : 0.89 (3H, t, J=6.4Hz), 1.2-1.5 (6H, m) , 1. 6-i . 8 (2H, m) , 4.00 (2H, t, J=6. 4Hz) , 7.02 (_~H, d, J=8.7Hz), 7.12 (1H, s), 7.74 (2H, d, J=8.7Hz), 7.95 (2H, d, J=8.8Hz), 8.01 (2H, d, J=8.8Hz), 13.17 (1H, s) APCI-MASS : m/z = 365 (M+H+) Preparaticn 145 4-[4-[4-(6-Methoxvhexvloxy)phenyl]phenyl]benzcic acid IR (KBr) : 2939, 2861, 1685, 1602, 1430, 1286, 1128 cm-1 NMR (DMSO-d6, 5) 1.3-1.8 (8H, m), 3.21 (3H, s), 3. 3-3. 4(2H, m), 4.01 (2H, t, J=6. 5Hz) , 7.04 (2H, d, J=8. 6Hz) , 7.66 (2H, d, J=8. 6Hz) , 7.7-7. 9(6H, m), 8.03 (2H, d, J=8.2Hz) APCI-N',ASS m/z = 405 (M+H+) Preparation 146 4-[5-[4-(8-Methoxyoctyloxy)phenyl]-1,3,4-thiadiazol-2-yl]benzoic acid IR (KBr) : 2931, 2854, 1691, 1602, 1251 cm-1 NMR (DMSO-d6, b) : 1.2-2.0 (12H, m), 3.20 (3H, s), 3.29 (2H, t, J=6.4Hz), 4.04 (2H, t, J=6.4Hz), 7.13 (2H, t, J=8.8Hz), 7.9-8.2 (6H, m), 13.95 (1H, br) APCI-MASS : m/z = 441 (M+H+) Preparation 147 4-(4-n-Butoxyphenyi)cinnamic acid IR (KBr) : 2958, 2871, 1695, 1625, 1498, 1249 cm-1 NMR (DMSO-d6, 5) : 0.94 (3H, t, J=7.3Hz), 1.44 (2H, tq, J=7.0 and 7.3Hz), 1.71 (2H, tt, J=7.0 and 6. 4Hz ), 4.01 (2H, t, J=6 . 4Hz ), 6.54 (1H, d, J=16.0Hz), 7.02 (2H, d, J=8.7Hz), 7.6-7.9 (7H, m) APCI-MASS : m/z = 297 (M+H+) pretiaration 148 4-[5-(4-Cyclohexylphenyl)-1,3,4-thiadiazol-2-yllbenzoic acid IR (KBr) : 2925, 2850, 1683, 1429, 1292 cm 1 TTMR (DMSO-d6, b) : 1.1-1.5 (5H, m), 1.6-2.0 (5H, m), 2.4-2.6 (iH, m), 7.45 (2H, d, J=8.3Hz), 7.96 (2H, d, J=8.3Hz) , 8.13 (4H, s) APCI-M-ASS m/z = 365 (M+H) 1 Preparation 149 4-[5-[4-(Pi-peridin-l-v~)phenyl]-1,3,4-thiadiazol-2-yl]-benzcic acid Irc (KBr) 2931, 2854, 1685, 1604, 1415, 1238 cm-1 h'MR (DMSO-d6, 6) : 1 .61 (6'r:, s), 3.31 (4H, s), 7.05 (2H, d, J=9.OHz), 7.83 (2H, d, J=9.OHz), 8.10 (4H, s) _T-.SS . m/z = 366 (M+H) +
APCI-M

Preparation 150 4-[5-[4-[4-n-Propyloxyphenyl)phenyl]-1,3,4-oxadiazol-2-vl]benzoic acid IR (KBr) : 2939, 1689, 1606, 1488, 1429, 1290 cm-1 NMR (DMSO-d6, 5) : 1.00 (3H, t, J=7 . 3Hz ), 1.76 (2H, ta, J=6.5 and 7.3Hz), 4.00 (2H, t, J=6.5Hz), 7.07 (2H, d, J=8. 8Hz) , 7.70 (2H, d, J=8. 5Hz) , 7.78 (2H, d, J=8.8Hz), 7.90 (2H, d, J=8.5Hz), 8.0-8.4 (4H, m) APCI-MASS : m/z = 401 (M1H)-"

Dreparation 151 4-(5-n-Nonyl-1,3,4-oxadiazol-2-yl)benzoic acid IR (KBr) : 2919, 2852, 1685, 1565, 1430, 1284 cm-1 NMR (DMSO-d6, (5) : 0.84 (3H, t, J=6.5Hz), 1.2-1.5 (12H, m), 1.7-1.9 (2H, m), 2.94 (2H, t, J=7.4Hz), 8.0-8.2 (4H, m), 13.35 (1H, s) PPCI-MASS m/z = 317 (M+H+) preparation 152 4-[3-(4-n-Hexyloxyphenyl)-1,2,4-oxadiazol-5-yl]benzoic acid IR (KBr) 2942, 2869, 1695, 1421, 1251 cm-1 NMr 'DMSO-d6, b ) . 0 . 89 (3H, t , J=6.8Hz) , 1. 2-1. 8(8H , m) , 4.06 (2H, t, J=6.5Hz), 7.13 (2H, d, J=8. 9Hz) , 8.03 (2H, d, J=8. 9Hz) , 8.17 (2H, d, J=8. SHz) , 8.28 (2H, d, J=8.5Hz) APCI-MASS : m/z = 367 (M+H)t Preparation 153 4-[4-[4-(5-Methoxvpentvloxy)phenyllphenyl]phenylacetic acid IR (KBr) 2939, 2861, 1699, 1253, 1182, 1124 cm-NMR (DMSO-d6, b) : 1. 4-1 . 9 (6H, m), 3.22 (3H, s), 3.39 (2H, t, J=6.2Hz), 3.61 (2H, s), 4.01 (2H, t, J=6 . 4Hz ), 7.02 (2H, d, J=8 . 8Hz ), 7.35 (2H, d, J=8.2Hz), 7.6-7.8 (8H, m) APCI-MASS : m/z = 405 (M+H+) Preparation 154 4-[5-(4-n-Octyloxyphenyl)-1,3,4-thiadiazol-2-yl]benzoic acid IR (KBr) . 2921, 2856, 1691, 1432, 1251 cm-1 NI-IR (DMSO-d6, b) : 0.87 (3H, t, J=6.7Hz), 1.2-1.5 (10H, m), 1.7-1.9 (2H, m), 4.07 (2H, t, J=6.5Hz), 7.13 (2H, d, J=8.9Hz), 7.97 (2H, d, J=8. 9Hz) , 8.12 (4H, s) APCI-MASS : m/z = 411 (M+H+) Preparation 155 4-[5-(4-Trans-n-pentylcvclohexyl)-1,3,4-thiadiazol-2-yi]benzoic acid IR (KBr) : 2919, 2848, 1677, 1430, 1294 cm-1 NMR (DMSO-d6, (5) . 0.87 (3H, t, J=6.9Hz), 1.0-1.4 (11H, m), 1.5-1.6 (2H, m), 1.8-2.0 (2H, m), 2.1-2.3 (2H, m), 3.1-3.3 (1H, m), 8.07 (4H, s) APCI-MASS rr./z = 359 (M+H+) Preparation 156 4-~3-(4-n-Pentvloxypher_yl)isoxazoi-5-yl;benzoic acid IK (KBr) . 2925, 2869, 1699, 1687, 1612, 1432, 1251, 1178 cm-1 NMR (DMSO-d6, a) 0.91 (3H, t, J=6. 9Hz ), (4H, n) , 1. 7-1 . 9 (2H, m), 4.04 (2H, t, J=6. 5Hz) , 7. 09 (2H, d, J=8.8Hz), 7.69 (1H, s), 7.8-E 1\2H, d, J=8. 8Hz) , 8.01 (2H, d, J=8.5Hz), 8.11 (2H, d, J=8.5Hz) APCI-MASS : r,:/z = 352 (M+Ht) Preparation 157 4-[5-[4-(8-Methoxvoctvioxy)phenyl]-i,3,4-oxadi-azoi-2-yl]benzcic acid IR (KBr) : 2967, 2937, 2877, 1687, 1290 cm-i NMR (DMSO-d6, b) . 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3.20 (3H, s), 3.29 (2H, t, J=6.4Hz), 4.08 (2H, t, J=6.5Hz), 7.17 (2H, d, J=8.9Hz), 8.07 (2H, d, J=8.9Hz), 8.15 (2H, d, J=8.6Hz), 8.24 (2H, d, J=8.6Hz) APCI-'-lASS : m/z = 425 (M+H) +
Preparation 158 4-[4-(6-Phenylpyridazin-3-yl-oxy)phenyl]benzoic acid IR (KBr) : 1700, 1687, 1608, 1427, 1284, 1186 cm-1 NM-t (DMSO-d6, b) : 7.40 (2H, d, J=8.6Hz), 7.5-7.7 (4H, T), 7.7-7.9 (4H, m), 7.9-8.1 (4H, m), 8.35 (1H, d, J=9.2Hz), 12.99 (1H, br s) APCI-MASS : m/z = 369 (M+H)+
Preparation 159 4-[5-(4-n-Octyloxyphenyl)-1,3,4-oxadiazol-2-vl]benzoic acid IR (KBr) : 2921, 2852, 1685, 1612, 1496, 1425, 1288, 1251 cm 1 NMR (DMSO-d6, 6) : 0.87 (3H, t, J=6.7Hz)', 1.2-1.5 ( 10H, r.) , 1. 7-1 . 9 (2H, m), 4.08 (2H, t, J=6. 4Hz) , 7.11 d, J=8.7Hz), 8.07 (2H, d, J=8.7Hz), 8.15 (2H, d, J=8.5Hz), 8.24 (2H, d, J=8.5Hz), 13.36 (1H, br) APCI-Y-,ASS m/z = 395 (M+H+) Drepararion 160 4-[2-(4-n-Hex.vloxyphenyl)pyrimidin-6-yijbenzoic acid _R (KBr) . 2944, 2863, 1697, 1585, 1415, 1386, 1253 cm-1 :\TMR (DMSO-d6, b) . 0.89 (3H, t, J-=6.7Hz), 1.2-1.6 (6H, m) , 1.7-1. 9(2H, m) , 4.07 (2H, t, j=6. 6Hz) , 7.10 (2H, d, J=8.9Hz), 8.00 (1H, d, ',=5.2Hz), 8.13 (2H, d, J=8.4Hz), 8.44 (2H, d, J=5.9Hz), 8.47 (2H, d, J=5.9Hz), 8.95 (1H, d, J=5.2Hz) APCI-MASS : m/z = 377 (M+H+) pYeparation 161 4-[4-(7-Piperidinocarbonylheptyloxy)phenyl]benzoic acid IR (Kzr) 2933, 2858, 1697, 1677, 1637, 1604, 1429, 1249 cm-1 NTY.R (DMSO-d6, b) 1.2-1 . 8 (16H, m), 2.26 (2H, t, J=7.5Hz), 3.2-3.5 (4H, m), 4.01 (2H, t, J=6.4Hz), 7.03 (2H, d, J=8. 8Hz) , 7.67 (2H, d, J=8. 8Hz) , 7.74 (2H, d, J=8.4Hz), 7.98 (2H, d, J=8.4Hz) APCI-MASS : m/z = 424 (M+H+) PYeoaration 162 6-[4-(4-n-Heptyloxyphenvl)piperazin-l-vl]nicotinic acid IR (KBr) 2929, 2854, 1695, 1673, 1606, 1577, 1515, 1421, 1245 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.7Hz), 1.2-1.5 (8H, m), 1.6-1.8 (2H, m), 3.0-3.2 (4H, m), 3.6-3.8 (4H, m), 3.87 (2H, t, J=6. 5Hz) , 6.8-7.2 (5H, m), 7.95 (1ri, dd, J=8 . 9 and 2. 3Hz ), 8.62 (i:?, d, J=2 . 3Hz ) APCI-MASS m/z = 398 (M+H+) Preparation 163 6-[4-[4-(8-Methoxyoctyloxy)phenvl]piperazir.-l-yl]-nicotinic acid IR (KBr) : 2933, 2856, 1697, 1672, 1605, 1511, 1421, 1245 cm-1 NMR (DMSO-d6, b) : 1.2-1.8 (12H, m), 3.08 (4H, t, J=S. 0'riz) , 3.20 (3H, s), 3.28 (2H, t, J=6.5Hz), 3.78 (4H, t, J=4.6Hz), 3.87 (2H, t, J=6.4Hz), 6.8-7.0 (5H, m), 7.95 (1H, dd, J=9.0 and 2.2Hz), 8.65 (1h, d, J=2 . 2Hz ), 12 . 54 (IH, s) APCI-MASS m/z = 442 (M+H+) Preparation 164 4-[5-[4-(4-n-Propyloxyphenyl)phenyl]-1,3,4-thiadiazol-2-yl]benzoic acid IR (KBr) : 1685, 1537, 1423, 817 cm-1 NMR (DMSO-d6, b) : 1.00 (3H, t, J=6.7Hz), 1.6-1.8 (2H, m), 4.00 (2H, t, J=6. 6Hz) , 7.0-7.2 (2H, d, J=8.6Hz), 7.6-8.1 (10H, m) APCI-MASS m/z = 417 (M+H)+
Preparation 165 To a solution of Ethyl 4-[5-(4-n-pentyloxyphenyl)-isoxazol-3-yl]benzoate (6.33 g) in ethanol (60 ml) and tetrahydrofuran (90 ml) was added 2N sodium hydroxide aqueous solution (12.5 ml) at 80 C. The mixture was refluxed for 1 hour and poured into ice-water. The suspension was adjusted to pH 2.0 with iN HC1. The precipitate was collected by filtration, washed with water and dried to give 4-[5-(4-n-pentyloxyphenyl)isoxazol-3-yl]benzoic acid (5.80 g).
IR (KBr) : 2939, 2867, 1681, 1614, 1429, 1255, 1178, 821 cm-1 NMR (DMSO-d6, b) : 0.91 (3H, t, J=7.1Hz), 1.3-1.5 (4H, m), 1.6-1.8 (2H, m), 4.04 (2H, t, J=6.5Hz), 7.11 (2r, d, J=8.9Hz), 7.54 (1H, s) , 7.85 (2H, d, J=8.9Hz), 7.98 (2H, d, J=8. 6Hz) , 8.11 (2H, d, J=8.6Hz) APCI-MASS : m/z = 352 (M+H)+

The following compounds (Preparations 166 to 170) were obtained according to a similar manner to that of Prenaration 40.

preparation 166 5-[4-(4-n-Hexvloxyphenvl)piperazin-i-yi]picolic acid trihydrochioride IR (KBr) : 1689.3, 1577.5, 1511.9, 1241.9 cm-1 NMR (DMSO-d6, 5) : 0.88 (3H, t, J=6.5Hz), 1.15-1.5 (6H, m), 1.6-1.8 (2H, m), 3.1-3.25 (4H, m), 3.45-3. 6(4H, m), 3.89 (2H, t, J=6.4Hz), 6.84 (2H, d, J=9.lHz), 6.97 (2H, d, J=9.1Hz), 7.43 (1H, dd, J=8.8 and 3.0Hz), 7.90 (1H, dd, J=8.8 and 0.7Hz), 8.41 (1H, dd, J=3 . 0 and 0. 7Hz ) APCI-MASS : m/z = 384 (M++H) Preparation 167 4-[4-(4-Phenylcyclohexyl)piperazin-1-yl]benzoic acid di4hydrochloride IR (KBr) :1700.9, 1606.4, 1220.7, 1180.2 cm-i NMR (DMSO-d6, b) : 1.4-1.85 (4H, m), 1.9-2.05 (2H, m), 2.2-2.4 (2H, m), -.1-3.5 (6H, m), 3.5-3.7 (21-1, m), 3.9-4.2 (2H, m), .06 (2H, d, J=8.8Hz), 7.1-7.4 (5H, m), 7.83 (2H, d, J=8.8Hz) APCI-MASS : m/z = 365 (M++H) Preparation 168 4-(4-Trans-n-pentylcyclohexyl)benzoic acid IR (KBr) . 1681.6, 1423.2, 1290.1 cm-1 ~.'-MR (CDC13, 5) : 0.90 (3H, t, J=6. 6Hz) , 1.0-1. 6(13H, r,), 1.89 (4H, d, J=10Hz), 2.54 (1H, t, J=12Hz), 7.30 (2H, d, J=8.3Hz), 8.03 (2H, d, J=8.3Hz) APCI-M-ASS m/z = 274 (M++H) Pre;paration 169 4-(4-Piperidinopiperidin-l-yl)benzcic acid IR (KBr) : 1710.6, 1403.9 cm NMR (DMSO-d6, 5) : i.6-2.1 (8H, m), 2.17 (2H, d, J=12iIz), 2.7-3.05 (4H, m), 3.2-3.5 (1H, m), 3.35 (2H, d, J=12Hz) , 4. 05 (2H, d, J=13Hz) , 7.01 (2H, d, J=8.9Hz), 7.77 (2H, d, J=8.9Hz), 10.84 (1H, s) APCI-NASS m/z = 289 (M++H) Preparation 170 3-Chloro-4-[4-(4-n-hexyloxyphenyl)piperazin-l-yllbenzoic acid dihydrochloride IR (KBr) : 1712.5, 1598.7, 1513.8, 1251.6 cm-1 NMR- (DMSO-d6, b) : 0.88 (3H, t, J=6.6Hz), 1.2-1.5 (6H, m), 1. 6-1 . 8 (2H, m), 3. 4-3. 6(8H, m), 3.98 (2H, t, J=6.4Hz), 7.02 (2H, d, J=9.OHz), 7.32 (1H, d, J=8.lHz), 7.60 (2H, d, J=9.OHz), 7.89 (1H, d, J=8 . 1Hz ), 8.02 (1H, s) APCI-MASS : m/z = 417 (M++H:) The following compounds (Preparations 171 to 175) were obtained according to a similar manner to that of Preparation 41.
Preparation 171 Ethyl [4-(4-octylphenyl)-2,3-dihydro-4H-1,2,4-triazole-3-one-2-yl]acetate IR (KBr) : 2921.6, 1764.5, 1715, 1197.6 cm-1 NMR (CDC13, 5) : 0.88 (3H, t, J=6.7Hz), 1.30 (3H, t, J=7.1Hz), 1.2-1.4 (10H, m), (%H, m), 2.63 (2H, t, J=7. 9Hz) , 4.26 (2H, q, J=7. 1Hz) , 4.64 (2H, s), 7.28 (2H, d, J=8 . 4Hz ), 7.44 (2H, d, J=8 . 4Hz) , 7.71 (1H, s) preparation 172 4-[4-(4-tert-Butoxycarbonylpiperazin-l-yl)phenyl]-2-(4-methylpentyl)-2,3-dihydro-4H-1,2,4-triazol-3-one i0 IR (KBr) : 1687.4 cm-1 hTMR (CDC13, 5) . 0.90 (614, d, J=6. 5Hz ), _. 1-1 . 4 (2H, m), 1.49 (9H, s), 1.4-1.9 (3H, m), 3.16 (4H, t, J=4 . 9Hz) , 3.59 (4H, t, J=4 . 9Hz) , 3.82 (2H, t, J=7 . 3Hz ), 6. 98 (2H, d, J=9 . OHz ), 7.41 (2H, d, J=9.OHz), 7.61 (1H, s) Preparation 173 Methyl 6-(8-bromooctyloxy)-2-naphthoate IR (KBr) . 2933.2, 2856.1, 1720.2, 1294, 1209.1 cm-1 NMR (CDC13, 5) : 1.3-1.6 (8H, m), 1.75-2.0 (4H, m), 3.42 (2H, t, J=6.8Hz), 3.96 (3H, s), 4.09 (2H, t, J=6.5Hz), 7.14 (1H, d, J=1.7Hz), 7.19 (1H, dd, J=8.9 and 1.7Hz), 7.73 (1H, d, J=8.7Hz), 7.83 (1H, d, J=8.9Hz), 8.01 (1H, dd, J=8.7 and 1.7Hz), 8.51 (1H, d, J=1 . 7Hz ) APCI-MASS m/z = 393 (M++H) Preparation 174 4-[4-(6-n-Propyloxyhexyloxy)phenyl]benzoic acid IR (KBr) : 2937, 2858, 1695, 1683, 1604, 1430, 1290, 1247, 1195 cm-1 NMR. (DMSO-d6, 5) : 0.85 (3H, t, J=7.4Hz), 1.3-1.9 (10H, m) , 3. 2-3 . 4 (4H, m), 4.01 (2H, t, J=6 . 3Hz ), 7.04 (2H, d, J=8.7Hz), 7.67 (2H, d, J=8.7Hz), 7.74 (2H, d, J=8.3Hz), 7.98 (2H, d, J=8.3Hz), 12.9 (1Fi, -s) APCI-MASS 357 (M+:;+) Preparation 175 4-[4-(6-Bromohexvloxy)phenyl]bromobenzene NMR (CDC13, 5) . 1.40-1. 65 (4H, m), 1.70-2.00 (4H, m), 3.43 (2H, t, J=6.7Hz), 4.00 (2H, t, J=6.4Hz), 6.95 (2H, d, J=8.8Hz), 7.30-7.60 (6H, m) The following compounds (Preparations 176 to jj0) were obtained according to a similar manner to that of Preparation 43.

prenaration 176 4-[4-(4-n-Pentyloxyphenyl)piperazin-1-yl]benzoic acid dihydrochloride IR. (KBr) : 1668.1, 1602.6, 1510.0, 1228.4 cm-1 NMR (DMSO-d6, d) : 0.89 (3H, t, J=6.9Hz), 1.2-1.5 (5H, m), 1.6-1.9 (2H, m), 3.0-3.2 (4H, m), 3.4-3.6 (4H, m), 3.88 (2H, t, J=6.4Hz), 6.83 (2H, d, J=9Hz), 6.9-7.1 (4H, m), 7.79 (2H, d, J=8.8Hz), 12.32 (1H, s) APCI-MASS m/z = 369 (M+H+) Preparation 177 4-[4-(4-n-Heptyloxyphenyl)piperazin-1-yl]benzoic acid dihydrochioride IR (KBr) : 1666.2, 1600.6, 1511.9 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6. 9Hz) , 1.2-2.0 (10H, m), 3.1-3.3 (4H, m), 3.4-3.6 (4H, m), 3.92 (2H, t, J=6 . 4Hz ), 6. 8-7 .1 ( 6H, m), 8.00 (2H, d, J=8 . 8Hz ) Preparation 178 4-[4-[4-(4-Methylpentyloxy)phenyl]piperazin-1-yl]benzoic ~0.
acid dihydrochloride IR (KBr) 1668.1, 1602.6, 1510.0, 1236.1 cm Iv-MR (DMSO-d6, b) : 0.89 ( 6H, d, J=6. 5Hz ), 1. 2-1 . 4 (2H, m), 1.4-1.8 (3H, r.i), 3.0-3.2 (4H, m), 3.3-3.5 (4H, m) , 3.87 (2H, t, J=6.3Hz), 6.63 (2H, d, J=9. OHz) , 6.9-7.1 (4H, m), 7.79 (2H, d, J=8. 8Hz) , 12.33 (1H, s) AnCI-MASS : m/z = 383 (M+H+) Preparation 179 4-[4-[4-(8-Bromooctyloxy)phenyl]piperazir.-1-yl]benzoic acid dihycirochloride IR (KBr) : 1670.1, 1602.6, 1511.9, 1234.2 cm-1 NMR (DMSO-d6, bj' : 1.2-1.5 (8H, m), 1.6-1.9 (4H, m), 3.0-3.2 (4H, m), 3.2-3.5 (4H, m), 3.52 (2H, t, J=6.7Hz), 3.88 (2H, t, J=6.4Hz), 6.83 (2H, d, J=9.lHz), 6.94 (2H, d, J=9.lHz), 7.02 (2H, d, J=8.9Hz), 7.79 (2H, d, J=8.9Hz) Preparation 180 3-Fluoro-4-[4-(4-n-hexyloxyphenyl)piperazin-1-vl]benzoic acid dihydrochloride IR (KBr) 1673.9, 1511.9, 1240.0 cri ~
NMR (DMSO-d6, b) : 0.88 (3H, t, J=6.5Hz), 1.2-1.5 (6H, m), 1.6-1.8 (2H, m), 3.0-3.5 (8H, m), 3.88 (2H, t, J=6.4Hz), 6.7-7.2 (5H, m), 7.4-7.8 (2H, m), 12.82 (1H, s) APCI-MASS : m/z = 401 (M+H) The following compound was obtained according to a similar manner to that of Preparation 46.

Preparation 181 1-(4-Methoxycarbonylphenyl)-3-(4-n-hexyloxyphenyl)-propan-1,3-dione IR. (KBr) : 2956, 2927, 2856, 1722, 1511, '284, 1108 cm-1 -%LMR (CDC1Z , b) : 0.92 (3H, t, J=6.4Hz), 1 .2-2. 0 (8H, m), 3.96 (3H, s), 4.04 (2H, t, J=6.5Hz), 6.82 (1H, s), 6.97 (2H, d, J=8.7Hz), 7.9-8.1 (4H:, m), 8.14 ( 2F-i, d, J=8 . 3Hz ) APCI-M.ASS . m/z = 383 (M+H*) The following compounds (Dreparations 182 to 185) were obtained according to a similar manner to that cf Preparation 47.

Prebaration 182 Methvl 5-(4-octyioxyphenvl)-1-methylpvrazole-3-carboxylate IR (KBr pelet) : 2923, 1724, 1616, 1513, 1446, 1251, 1120 cm-1 NMR (CDC13, (5) : 0.89 (3H, t, J=6.8Hz), 1.2-1.5 (lOH, *n) , 1. 7-1 . 9 (2H, m), 3.90 (3H, s), 3.98 (2H, t, J=6.6Hz), 4.20 (3H, s), 6.92 (2H, d, J=8.9Hz), 7.04 (1H, s), 7.89 (2H, d, J=8. 9Hz) APCI-MASS m/z = 345 (M+H.) Preuaration 183 Methyl 4-[5-(4-n-pentyioxyphenyl)pyrazol-3-yl]benzoate IR (KBr) 3236, 2952, 2873, 1716, 1616, 1508, 1276, 1174, 1106 cm-1 ?~rMR (CDC13, b) : 0.94 (3H, t, J=7 . OHz ), 1. 3-1 . 5 (4H, m), 1.7-1.9 (2H, m), 3.92 (3H, s), 3.96 (2H, t, J=6.7Hz), 6.78 (1H, s), 6.88 (2H, d, J=8.7Hz), 7.55 (2H, d, J=8 . 7Hz ), 7.79 (2H, d, J=8 . 4Hz ), 8.02 (2H, d, J=8.4Hz) APCI-MASS : m/z = 365 (M+H+) Preparation 184 Methyl 5-(4-octvioxvphenvl)isoxazole-3-carboxvlate IR (KEr pelet) : 2950, 2921, 1724, 1614, 1510, 1446, 1257, 1178, 1143, 1009 cm-I
hTMR (CDC13, b) : 0.89 (3H, t, J=6.8Hz), 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 4.0-4.1 (5H, m), 6.80 (1H, s), 6.98 (2H, dd, J=6.9 and 2.1Hz), 7.73 (2H, dd, J=6. 9 and 2.1Hz) APCI-M.ASS : m/z = 332 (M+H+) Preparation 185 Methvl 4-[3-(4-n-hexyloxyphenyl)pyrazol-5-vl]benzoate IR (KBr) . 2952, 1716, 1616, 1508, 1276, 1106 cm-1 NMR (CDC13, b) : 0.91 (3H, t, J=6.3Hz), 1.2-1.6 (6H, m), 1.7-1.9 (2H, m), 3.8-4.0 (5H, m), 6.76 (1H, s), 6.86 (2H, d, J=8.8Hz), 7.54 (2'rI, d, J=8.8Hz), 7.77 (2H, d, J=8.4Hz), 8.00 (2H, d, J=8.4Hz) APCI-MASS : m/z = 379 (M+H+) preparation 186 A suspension of 1-(4-n-Pentyloxyphenyl)-3-(4-ethoxvcarbonylphenyl)-1-buten-3-one (74.43 g) and hvdroxyamine hydrochloride (28.23 g) and potassium carbonate (56.11 g) in ethanol (400 ml) was refluxed for 4 hours. The mixture was diluted with ethvl acetate, washed with water (x 2), brine and dried over magnesium sulfate. The solvents were removed under reduced pressure to give crude oxime. To a solution of crude oxime in dichloroethane (500 ml) was added activated-manganese(IV) oxide (200 g). The reaction rmixture was refluxed for 2 hours and filtered. The residue was washed with dichloromethane. The solvents were removed under reduced pressure and the residue was triturated with acetonitrile. The solid was collected by filtration and dried to give ethyl 4-[5-(4-n-Pentyloxyphenyl)isoxazol-3-yl]benzoate (21.07 g).
iR (KBr) : 2945, 2872, 1717, 1615, 1508, 1280, _1 11,08 cm NMR (CDC-1 3, b) . 0. 95 (3H, t, J=6.9Hz) , i. 3-1. 9 (9H, m) , 4. 01 (2H, t, J=6.5Hz) , 4.41 (2H, q, J=7. 1Hz) , 6.74 (1H, s) , 6.99 (2H, d, J=8. 8Hz) , 7.76 (2H, d, J=8 . 8Hz ), 7. 93 (2H, d, J=8. 4Hz ), 8. 15 (2H, d, J=8 . 4Hz ) APCI-MIASS : m/z = 380 (M+H+) The following compounds (Dreuarations 187 to 190) were obtained according to a similar manner to that of PrQparation 48.

Prenaration 187 Methyl 6-[4-[4-(8-Methoxyoctyioxy)phenyl]piperazin-l-yl]nicotinate IR (KBr) : 2933, 2858, 1722, 1608, 1513, 1432, 1405, 1278, 1245 cm-1 NMR (CDC13, 5) . 1.3-1.9 (12H, m), 3.16 (4H, t, J=S.OHz), 3.33 (3H, s), 3.36 (2H, t, J=6.5Hz), 3.8-4.0 (9H, m), 6.64 (1H, d, J=9.lHz), 6.85 (2H, d, J=9 . 2Hz ), 6.93 (2H, d, J=9 . 2Hz ), 8.04 ( iH, dd, J=9.1 and 2.2Hz), 8.81 (1H, d, J=2.2Hz) APCI-MASS : m/z = 456 (M+H+) PrQparation 188 4-[4-(5-Methoxypentyloxy)phenyl]bromober.zene IR (KBr) : 2940, 2856, 1604, 1479, 1286, 1255, 1124 cm-1 N~2R (CDC1-~, b) : 1.5-1.9 (6H, m), 3.34 (3H, s), 3.41 (2H, t, J=6.1Hz), 3.99 (2H, t, J=6.4Hz), 6.95 (2H, d, J=8.7Hz), 7.4-7.6 (6H, m) APCI-MASS : m/z = 349 (M+H+) Preparation 189 Methyl 6-(8-methoxyoctyloxy)-2-naphthoate - ;U9 -NMR (DMSO-d6, b) : 1.2-1.6 (lOH, m), 1.7-1.9 (2H, m), 3.20 (3H, s), 3.29 (2H, t, J=6.4Hz), 3.89 (3H, s), 4.11 (2H, t, J=6.4Hz), 7.24 (in, dd, J=9.0 and 2. 4Hz ), 7.40 (1H, d, J=2 . 4Hz ), 7.88 (1H, d, J=8 . 7Hz ), 7.94 (1H, dd, J=8 . 7 and 1. 5Hz ), 8.03 (1:i, d, J=9 . OHz ), 8.55 (1H, d, J=1 . 5Hz ) Drenaration 190 4-[4-[4-(8-Methoxyoctyloxy)phenyl]piperazin-1-yi]ber.zoic acici dihydrochloride IR (KBr) . 1668.1, 1602.6, 1511.9, 1236.1 cm-1 NMR (DMSO-d6, b) . 1.2-1.8 ;12H, m), 3.05-3.2 (4H, m), 3.29 (2H, t, J=7.lHz), 3.33 (3H, s), 3.4-3.55 (4H, m), 3.88 (2H, t, J=6.4Hz), 6.82 (2H, d, J=9. OHz) , 6.94 (2H, d, J=9. OHz) , 7.02 (2H, d, J=8. 8Hz) , 7.79 (2H, d, J=8.8Hz), 12.31 (1H, s) The following compounds (Preparations 191 to 254) were obtained according to a similar manner to that of Preparation 49.

Preparation 191 ?-[4-[4-[4-[2-(4-Methvlpentyl)-2,3-dihydro-4H-1,2,4-triazol-3-one-4-yl]phenyl]piperazin-1=y1]benzoyl]-benzotriazole 3-oxide IR (KBr) : 1766.5, 1693.2, 1600.6, 1519.6 cm 1 pre-oaration 192 1-[4-(4-Octvlphenyl)-2,3-dihydro-4H-1,2,4-triazol-3-one-2-yl-acetyl]benzotriazole 3-oxide IR (KBr) : 2921.6, 1753.0, 1720.0, 1423.2 cm-1 nTA?R (CDC13, (5) . 0.88 (3H, t, J=6.7Hz), 1.2-1.4 (IOH, m), 1.5-1.8 (2H, m), 2.65 (2H, t, J=7.5Hz), 5.46 (2H, s), 7.30 (2H, d, J=8.5Hz), 7.48 (2H, d, J=8.5Hz), 7.62 (1H, t, J=8.3Hz), 7.80 (1H, s), 7.82 (i:~, " J=8.3~?z) , 8. G5 (~H, d, J=8.3uz), 8.37 (lt, d, J=8.3Hz) preparation 193 1-f4-[4-[4-(7-Methoxyheptvioxy)phenyl]piperazin-l-yl]benzoyl]benzotriazole 3-oxi.de IR (KBr) : 1783.8, 1600.6, 151- 1.9, 1232.3, 1184.1 cm-NMR (CDC13, 5) : 1.3-1.9 (i0u, m), 3.2-3.3 (4H, m), 3.34 (3H, s), 3.38 (2H, :., J=6.4Hz), 3.5-3.7 (4H, i 0 m) , 3.92 (2H, t, J=6.5Hz), 6.87 (2H, d, J=9.2Hz), 6.93 (2H, d, J=9.2Hz), 7.00 (2H, d, J=9. 0uz) , 7.3-7. 6(3H, m), 8.09 (iH, d, J=S.2riz), 8.15 (2:1, ci, J=9.OHz) Preparation 194 i- [4- [4- (4-r.-Heptyloxyphenyl ) piperazin-l-yl]benzoyl]benzotriazole 3-oxide IR (KBr) : 1783.8, 1600.6, 1511.9, 1230.4, 1184.1 c:r.-1 NMR (CDC13, b) : 0.90 (3H, t, J=6.3Hz), 1.2-1.6 (8H, m), 1.7-1.9 (2H, m), 3.2-3.3 (4H, m), 3.5-3.7 (4H, m), 3.93 (2H, t, J=6. 5Hz ), 6.87 (2H, ci, J=9. 2H) , 6. 95- (2H, d, J=9.2Hz), 7.00 (2H, d, J=9. OHz) , 7.3-7.7 (3H, m), 8.09 (1H, d, J=8.2Hz), 8.15 (2H, d, J=9.0Hz) Preparation 195 1-[4-[4-[4-(4-Methylpentyloxy)phenvl)piperazin-1-yl]-benzoyl]benzotriazole 3-oxide NMR (CDC13, b) : 0.92 (6H, d, J=6. 6Hz) , 1.2-1.4 (2H, m), 1.5-1.9 (3H, m), 3.1-3.3 (4H, m), 3.5-3.7 (4H, rn), 3.92 (2H, t, J=6. 6Hz) , 6.87 (2H, d, J=9. 3Hz) , 6.96 (2H, d, J=9.3Hz), 7.01, (2H, d, J=9.OHz), 7.4-7.6 (3H, m), 8.10 (1H, d, J=8.2Hz), 8.15 (2H, d, J=9.OHz) Preparation 196 1- f 4- r 4- (4-r.-?entyloxvphenyl ) piperazir_-1-v,_;her.zovllberzotrlazole 3-oxide IR (KBr) : 1787.7, 1600.6, 1511.9, 1232.3, 1184.1 cm-1 NI!R (CDC1-~, b) . 0.93 (3H, t, J=6.9Hz), 1.3-1.6 (4H, m), 1.7-1.9 (2H, m), 3.1-3.4 (4H, m), 3.5-3.8 (4H, m), 3.93 (2H, t, J=6. 6Hz) , 6.87 (2H, d, J=9.2Hz), 6.92 (2H, d, J=9.2Hz), 7.01 (2H, d, J=9. lHz) , 7.4-7.6 (3H, m), 8.10 (1H, d, J=8.2Hz), 8.15 (2H, d, J=9.1Hz) p*-eparation 197 _-[4-[4-[8-(1H-Tetrazol-'_-yl)octyloxy]phenyl]benzovl]-benzotrl.azole 3-oxide and 1-[4-[4-[8-(2H-tetrazol-2-yl)octyloxy]phenyl]benzoyl]-benzotriazole 3-oxide IR (KBr) : 1778.0, 1602.6, 1189.9, 981.6 cm-1 NMR (CDC13, 5) : 1.2-1 . 6 (8H, m), 1.7-1 . 9 (2H, :n) , 1.9-2.2 (2H, m), 4.02 (2H, t, J=6.4Hz), 4.44 and 4.66 (2H, t, J=7.1Hz), 7.02 (2H, d, J=8.8Hz), 7.4-7.6 (3H, m), 7.63 (2H, d, J=8.8Hz), 7.79 (2H, d, J=8 . 6Hz ), 8.12 (1H, d, J=8 . 2Hz ), 8.32 (2H, d, J=8.6Hz), 8.51 and 8.60 (1H, s) Preparation 198 1-[4-[4-[8-(2,6-Dimethylmorpholin-4-yl)octyloxy]-phenyl]benzoyl]benzotriazole 3-oxide IR (KBr) : 1778.0, 1600.6, 977.7 cm-1 (CDC13, (5) : 1.18 (6H, d, J=6.3Hz), 1.2-1.7 (1OH, m), 1.7-2.0 (4H, m), 2.4-2.6 (2H, m), 2.9-3.2 (2H, m), 3.7-3. 9(2H, ir.) , 4.01 (2H, t, J=6.5Hz), 7.02 (2H, d, J=8.8Hz), 7.4-7.7 (3H, m), 7.63 (2H, d, J=8. 8Hz ), 7. 79 (2H, d, J=8. 5Hz ), B. 12 (1H, d, J=8 . 1Hz ), 8. 32 (2H, d, J=8 . 5Hz ) Preparation 199 1-[6-[4-(4-Octyloxyphenyl)piperazin-1-yl]nicotinoyl]-benzotriazole 3-oxide IR (KBr pelet) : 2922, 2854, 1766, 1602, 1513, 1417, 1234, 1025, 950, 813 cm-i -NMR (CDC13, b) 0.89 (3H, t, J=6.8Hz), 1.2-1.5 (10H, m), 1.7-1.9 (2H, m), 3.1-3.3 (4H, m), 3.9-4.1 (6H, m), 6.75 (1H, d, J=9 . 2Hz ), 6.87 (2H, d, J=9 . 2Hz ), 6.95 (2H, d, J=9.2Hz), 7.4-7.6 (3H, m), 8.10 (11-1, d, J=8 . 1Hz ), 8.19 (1H, dd, J=9 . 2 and 2. 4Hz ), 9. 04 (1H, d, J=2 . 4Hz ) i5 APCI-MASS : m/z = 529 (M+H+) preparation 200 1-[2-(4-Hexyloxyphenyl)benzoxazol-5-yl-carbonyl]-benzotriazole 3-oxide IR (KBr) 2950, 1774, 1623, 1504, 1265, 1176 c:r-1 NMR (CDCi3, b) : 0.93 (3H, t, J=6.9Hz), 1.3-1.6 (6H, m), 1.8-2.0 (2H, m), 4.07 (2H, t, J=6.5Hz), 7.06 (2H, d, J=8.9Hz), 7.4-7.6 (3H, m), 7.75 (1H, d, J=8.6Hz), 8.13 (1H, d, J=8.2Hz), 8.2-8.4 (3H, m), 8.67 (1H, d, J=1.6Hz) APCI-MASS : m/z = 457 (M+H+) Dreparation 201 1-[4-[4-(4-n-Butyloxyphenyl)phenyl]benzoyl]-benzotriazole 3-oxide IR (KBr) : 2958, 2871, 1776, 1600, 1398, 1255, 1211, 1037 cm 1 NMR (CDC13, 5) : 1.00 ( 3H, t, J=7 . 2Hz ), 1. 4-1. 9( 4ii, m) , 4.03 (2H, t, J=6. 4Hz) , 7.01 (2H, d, J=8 . tH.z) , 7. 4-7 . 8 (9H, m), 7.87 (2H, d, J=8 .1Hz ), 8.1~ ,1H, - ~;~ -d, J=8.4Hz), 8.36 (2H, d, J=-' 9Hz) APCI-N.ASS m/z = 464 (??+H)+
rreparation 202 1-[2-(4-heptvloxyphenyl)pyridin-5-yl-carbonyl]benzotriazole 3-oxide IR (KBr) 2944, 2867, 1793, 1770, 1589, 1471, 1321, 1093 cm-1 NMR (CDC13, 5) : 0.91 (3H, t, J=6.7Hz) , 1.2-1.6 (8H, m), 1.7-1.9 (2H, m), 4.0= (2H, t, J=6.5Hz), 7.04 (2H, d, J=8 . OHz ), 7. 4-7 . 6 ; 3i:, m) , 7.91 (1H, d, J=8.5Hz), 8.1-8. 2(3H, m), 0.51 (1H, dd, J=8.5 and 2.3Hz) , 9.47 (1H, d, J=2.3Hz) APCI-MASS m/- z = 431 (M+H+) Preparation 203 1-[2-(2-Octvloxypyridin-5-yl)benzoxazol-5-yl-carbonyl)benzotriazole 3-oxide IR (KBr pelet) : 2925, 2854, 1787, 1623, 1479, 1263, 989 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.8Hz), 1.2-1.5 (10H, m), 1. 8-1 . 9 (2H, rr,), 4.42 (2H, t, J=6.7Hz), 6.91 (1H, d, J=8.7Hz), 6.4-6.6 (3H, m), 7.79 (1H, d, J=8.6Hz), 8.13 (1H, d, J=8.2Nz), 8.32 (1H, dd, J=8.6 and 1.7Hz), 8.41 (1H, dd, J=8.7 and 2.4Hz), 8.70 (1H, d, J=1.4Hz), 9.07 (1H, d, J=1.9Hz) APCI-M-ASS : m/z = 486 (M+H+) Preparation 204 1-[2-[4-(4-Hexylphenyl)phenyl}benzoxazol-5-yl-carbor_yl)benzotriazole 3-oxide IR (KBr) : 2927, 2854, 1785, 1621, 1490, 1261, 1166, 1052 cm-1 NMR (CDC13, 5) : 0.90 (3H, t, J=6.5Hz), 1.2-1.8 (8H, m), 2.68 (2H, t, J=7.9Hz), 7.31 (2H, d, J=8.2Hz), -7.4-7.7 (5H, m) , 7.79-7.81 (3H, m), 8.13 (1H, d, J=8 . 3Hz ), 8. 3-8 . 4 (3H, rt;; , 8.73 ( iH, c:, J=1 . 3Hz ) APCI-?KP_SS m/z = 517 (M+HT) Preparation 205 1-[2-[4-(4-n-Butyloxvphenyl)phenyl;p_vridin-5-yl-carbonvl]benzotriazole 3-oxide IR (KBr) . 2956, 2933, 2871, 1774, 1650, 1591, 1471, 1251 cm-1 NMR (CDC13, b) : 1.00 (3H, t, J=7.2Hz), 1.5-1.9 (4H, TM:) , 4.03 (2H, t, J=6.4Hz), 7.02 (2H, d, J=8. 6Hz) , 7.4-7. c(3H, m), 7.54 (2H, d, J=7.3Hz), 7.62 (2:., d, J=8.5Hz), 8.02 (1H, d, J=8.3Hz), 8.13 (1H, d, J=8.2Hz), 8.21 (2H, d, J=7.9Hz), 8.57 (iH, dd, J=8.3 and 2.0Hz), 9.54 (iH, d, J=2.OHz) APCI-MASS : m/z = 465 (M+H)t Preparation 206 1-[4-[4-(5-Phenoxypentylox_y)phenyl]benzoyli-benzotriazole 3-oxide IR (KBr) : 2944, 2869, 1770, 1600, 1494, 1249, 1189 cm-1 NMR (CDC13, (5) : 1.6-1.8 (2H, m), 1.8-2.0 (4H, m), 4.01 (2H, t, J=6. 3Hz) , 4.07 (2H, t, J=6.2Hz), 6. 91 (2H, d, J=8. 9Hz) , 7.04 (2H, d, J=8. 7Hz) , 7.3-7.6 (4H, m), 7.63 (2H, d, J=8. 6Hz) , 7.78 (2H, d, J=8 . 4Hz ), 8.12 (1H, d, J=8 . iHz ), 8.32 (2H, d, J=8.4Hz) APCI-M-ASS : m/z = 494 (M+H) +
Preparation 207 1-[4-[5-(4-Hexyloxyphenyl)-1,3,4-oxadiazol-2-yl]benzoyl)benzotriazole 3-oxide IR (KBr) : 2956, 2921, 2856, 1778, 1612, 1496, 1261, 1232, 1025 cm-1 NMR (CDC13, 5) : 0.92 (3H, t, J=6.7Hz), 1.3-1.6 (6H, m), 1.8-2.0 (2H, m), 4.05 (2H, t, U-=6.5Hz), 7.05 (2"ri, d, J=8.7Hz), 7.4-7. 6(3H, m), 8.10 (2H, d, J=8 . 7Hz ), 8.13 (iH, d, J=7 . 4Hz ), 8. 37 (2H, d, J=8.5Hz), 8.45 (2H, d, J=8.5Hz) APCI-M.ASS : m/z = 484 (M+H) T
preparation 208 ?-[4-[5-(4-n-Hexyloxyphenyl)-1,3,4-thiadiazol-2-yl;benzoyl]benzotriazole 3-oxide IR (KBr) 2952, 2873, 1774, 1602, 1261, 1230, 1176 cm_1 NMR (CDC13, 5) : 0.93 (3'rI, t, J=6.8Hz), 1.3-2. 0(8H, m), 4.04 (2H, t, J=6 . 5Hz ), 7.02 (2H, d, J=8 . 7Hz ), 7.4-7.7 (3H, m), 7.98 (2H, d, J=8.7Hz), 8.13 (1H, d, J=8.7Hz), 8.25 (2H, d, J=8.3Hz), 8.41 (2H, d, J=8.3Hz) APCI-MASS : m/z = 500 (A?+H)+
Prenaration 209 1-[5-(4-Octyloxyphenvl)-1-methvlpyrazol-3-yl-carbonyljbenzotriazole 3-oxide IR (KBr pelet) : 2939, 2852, 1776, 1687, 1612, 1448, 1249, 995 cm-1 NMR (CDCi3, b) : 0.89 (3H, t, J=6.7Hz), 1.3-1.5 (iOH, m), 1.7-1.9 (2H, m), 4.01 (2H, t, J=6.5Hz), 4.25 (3H, s), 6.97 (2H, d, J=6.8Hz), 7.4-7.7 (4H, m), 7.78 (2H, d, J=6. 8Hz) , 8.14 (ZH, d, J=8.OHz) APCI-~+~lASS : m/z = 448 (M+H+) Preparation 210 1-[4-_f5-(4-n-Pentvloxyphenvl)pyrazol-3-yllbenzoyl]benzotriazole 3-oxide IR (KBr) : 3251, 2956, 2869, 1780, 1612, 1506, 1232, 985 crn-1 'JIMR (CDC13, b) : 0.95 (3H, t, j=6.9Hz; , 1 .3- ~ .6 (4H, *r) , 1. 7-2. 0(2H, m), 4.01 (2H, t, J=6. 6Hz) , 6.90 7z) , .4-7.6 (5H, rn), (1'ri, s) , 6.99 (2H, d, J=8.H
8.0-8.2 (3H, m) , 8.33 (2H, d, J=8.4Hz) APCI-MASS m/z = 468 (M+H+) Preparation 211 1-[5-[4-(4-n-Butoxyphenyl)phenyl]furan-2-yl-carbonyl;benzotri.azole 3-oxide IR (KBr) : 2958, 2871, 1781, 1678, 1603, 1535, 1479, 1265 cm-1 NMR (CDCi3, b) : 1.00 (3H, t, j=7.3Hz), 1.4-1.9 (4:i, m), 4.02 (2H, t, J=6.4Hz), 6.9-7.1 (3H, m), 7.4-8.2 (11H, m) :
APCI-MASS : m/z = 351 ( Methyl ester) Preparation 212 1-(3-(S)-Hvdroxy-2-benzvlhexadecar.oyl)benzotriazole 3-oxide IR (Neat) : 2854.1, 1814.7, 1459.8, 742.5 cm-1 preparation 213 1-(3-(R)-Benzyloxycarboxylamino-18-methoxyoctadecanoyl)-benzotriazole 3-oxide IR (KBr) : 1805.0, 1729.8, 1695.1 cri 1 NMR (DMSO-d6, b) : 1.1-1.65 (30H, m), 3.20 (3H, s), 3.28 (2H, t, J=6. 5Hz) , 4.01 (1H, m), 5.06 (2H, s), 7.32 (5H , m), 7. 4-7 . 8 (3H, m), 8.12 (1H, d, J=7Hz) Preparation 214 1-(3-(S)-Hydroxyhexadecanoyl)benzotriazole 3-oxide IR (KBr) : 1710.6, 1498.4, 1429.0, 771.4 cm-1 NM_R (CDC13, b) : 0.88 (3H, t, J=6.4Hz), 1.2-1.7 (24H, m), 2.00 (1H, s), 3.1-3.5 (2H, m), 4.30 (1H, m), 7.59 (1H, t, J=7.8Hz), 7.81 (1H, t, J=7.8Hz), 8.02 WO 96/11210 PCT/dP95/01983 (1H, d, J=8 . 3Hz ), 8. 42 1(1H, d, J=8 . 3Hz ) Preparation 215 1-(3-Methyl-2-tridecenovl)benzotriazole 3-oxide IR (KBr) 2927.4, 1791.5, 1633.4, 1081.9 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.3Hz), i.1-1.7 (20H, m), 2.25 (3H, s), 6.08 (1H, s), 7.3-7.6 (3H, m), 8.06 (1H, d, J=8 . 2Hz ) Preparation 216 1-[4-[4-[4-(8-Methoxvoctvloxy)phenyl)piperazin-l-yllbenzovllbenzotriazole 3-oxide IR (KBr) : 1780.0, 1600.6, 1511.9, 1234.2, 1184.1 cm-1 NMR (CDC13, 5) : 1.3-1.9 (12H, m), 3.24 (4H, t, J=5.OHz), 3.33 (3H, s), 3.37 (2H, t, J=6.8Hz), 3.62 (4H, t, J=5.OHz), 3.92 (2H, t, J=6.5Hz), 6.8-7.1 (6H, m), 7.35-7.65 (3H, m), 8.09 (1H, d, J=8.2Hz), 8.15 (2H, d, J=9.OHz) Preparation 217 1-[3-Fluoro-4-[4-(4-n-hexyloxyphenvl)piperazin-l-yl]benzoyllbenzotriazole 3-oxide IR (KBr) : 1778.0 cm-1 Preparation 218 1-[3-Chloro-4-[4-(4-n-hexvloxyphenyl)piperazin-l-yl]benzoyllbenzotriazole 3-oxide IR (KBr) : 1778.0, 1594.8, 1511.9, 1218.8 cm-1 I\TMR (CDC13, 3) : 0.91 (3H, t, J=6.5Hz), 1.2-1.6 (6H, m), 1.6-1.9 (2H, m), 3.29 (4H, t, J=3.6Hz), 3.44 .(4H, t, J=3.6Hz), 3.93 (2H, t, J=6.5Hz), 6.87 (2H, d, J=9.2Hz), 6.97 (2H, d, J=9.2Hz), 7.19 (1H, d, J=8.6Hz), 7.4-7.7 (3h, m), 8.10 (1H, d, J=6.4Hz), 8.14 (IH, dd, J=8.6 and 2.1Hz), 8.27 (1H, d, J=2.lHz) APCI-MFSS : m/z = 534 (M++H) Preparatior 219 1-[4-(4-Piperidinopiperidir_-1-v1)benzoyl]benzotriazole 3-oxide IR. (KBr) 1758.8, 1602.6, 1186.0 cm-1 KMR (CDC13, 5) : 1.35-1.8 (SH, m), 1.96 (2H, d, J=13'riz), 2.45-2.7 (5H, m), 2.97 (2H, td, u=12.8 and 2. 6Hz) , 4.04 (2H, d, J=13Hz), 6.93 (2H, d, J=9.2Hz), 7.35-7.6 (3H, m), 8.1-8.4 (3H, m) Preparation 220 !-[3-[4-(4-n-Hexyloxyphenyl)piperazin-1-yl]pyridazin-6-yl-carbonyl]benzotriazole 3-oxide !R (KBr) . 1787.7, 1585.2, 1511.9, 1240.0 cm-1 Preparation 221 1-[5-[4-(4-n-Hexyloxyphenyl)piperazin-1-yl]picolinoyl]-benzotriazole 3-oxide IR (KBr) : 1766.5, 1575.6, 1511.9, 1232.3 cm-1 NMR (CDC13, 5) : 0.91 (3H, t, J=6.5Hz), 1.2-1.6 (6H, m), 1.65-1.9 (2H, m), 3.27 (4H, t, J=5.1Hz), 3.66 (4H, t, J=5.1Hz), 3.93 (2H, t, J=6.5Hz), 6.88 (2H, d, J=9 . 2Hz ), 6.95 (2H, d, J=9 . 2Hz ), 7.25 (1H, dd, J=7.6 and 2.9Hz), 7.35-7.6 (3H, m), 8.09 (1H, d, J=8 . 2Hz ), 8.18 (1H, d, J=8 . 9Hz ), 8.52 ( iH, d, J=2.9Hz) APCI-MASS : m/z = 501 (MT+H) Preparation 222 1-[4-[4-(4-Cyclohexylphenyl)piperazin-1-yl]benzoyl]-benzotriazole 3-oxide IR (KBr) : 1770.3, 1602.6, 1515.8, 1232.3, 1186.0 cm-1 NMLt (CDC13, b) : 1.15-1 . 5 (6H, *_n) , 1. 65-2 . 0 (4H, m), 2.45 (1H, m), 3.33 (4H, t, J=S.iHz), 3.62 (4H, t, - 11a -J=5.1Hz), 6.92 (2H, ci, J=8.7Hz,' , 6.99 (2H, d, J=9.2Hz), 7.16 (2H, d, J=8.7Hz), 7.35-7.65 (3H, m), 8.09 (1H, d, J=8.2Hz) , 8.15 (2H, d, J=9.2Hz) preparation 223 1-[4-[4-(4-r_-Hexylphenyl)piperazin-1-yl]benzoyl]-benzotriazole 3-oxide TR (KBr) : 1768.4, 1602.6, 1515.8, 1230.4, 1184.1 cm-1 NMR (CDC13, 5) : 0.89 1,3H, t, J=6.5Hz), 1.2-1.45 (6H;
rn), 1.5-1.7 (2H, m), 2.55 (2H, t, J=7.6Hz), 3.2-3.4 (4H, m) , 3. 5-3 . 7 (4H, m) , 6.91 (2H, d, J=8 . 6Hz ), 7.00 (2H, d, J=9.lHz) , 7.13 (2H, d, J=8.5Hz), 7. 35-7. 6 (3H, m), 8.09 (1H, d, J=8 . 2Hz ), 8.15 (2H, d, J=9.1Hz) PreDaration 224 1- [4- [4- (4-Phenylcyclohexyl) piperazin-l-yl]benzoyl]benzotriazole 3-oxide IR (KBr) . 1780.0, 1762.6, 1602.6, 1234.2, 1182.2 cm-1 NMR (CDC13, b) : 1.3-1.7 (4H, m), 1.95-2.15 (4H, m), 2.35-2.6 (2H, m), 2.79 (4H, t, J=5.OHz), 3.49 (4H, t, J=5.OHz), 6.95 (2H, d, J=9.OHz), 7.1-7.35 (5H, m), 7.35-7.6 (3H, m), 8.08 (1H, d, J=7.1Hz), 8.12 (2H, d, J=9.OHz) Preparation 225 1- [ 4- [ 4- [ 1- ( 4-n-Hex_yloxyphenyl ) piperidin-4-_vl ] piperazin-1-yl]benzoyl]benzotriazole 3-oxide =R (KBr) : 1768.4, 1602.6, 1511.9, 1234.2 cm-1 NMR (CDC13, 5) : 0.90 (3H, t, J=6.5Hz), 1.2-1.55 (6H, m), 1.6-1.9 (4H, m), 1.96 (2H, d, J=llHz), 2.44 (1H, m), 2.64 (2H, d, J=1 .1Hz) , 2.77 (4H, t, J=5.OHz), 3.48 (4H, t, J=5.OHz), 3.59 (2H, d, J=llHz), 3.91 (2H, t, J=6.5Hz), 6.7-7.05 (6H, m), 7.35-7.6 (3H, m), 8.08 (1H, d, J=6.9Hz), 8.12 (2H, , - 1''0 -d, J=7 . 7Hz ) Preparation 226 1-[4-(4-Trans-n-pentylcyclohexyl)benzoyl]benzotriazole 3-oxide IR (KBr) : 1799.3, 1778.0, 1608.3, 1228.4, 977.7 cm-1 NMR (CDC1-~, 5) : 0.91 (3H, t, J=6. 6Hz) , 1.0-1.7 (13H, m), 1.93 (4H, d, J=9 . 3Hz ), 2.62 (1H, t, J=12Hz ), 7.35-7.6 (5H, in), 8.09 (1H, d, J=7.9Hz), 8.19 (2H, u, J=8 . 4Hz ) PYeparation 227 1-[6-(8-Methoxyoctyloxy)-2-naphthoyl]benzotriazole 3-oxide IR (KBr) 2856.1, 1778.0, 1623.8 cm-i Preparation 228 1- (E) - [ 3- [ 4- [ 4- (7-Fluoroheptyloxy) phenyl ] phenyl ] -acryloyl]benzotriazole 3-oxide IR (KBr) : 3070.1, 2935.1, 2859.9, 1700.9, 1619.9, 1596.8 cm 1 NMR (CDC13, b) : 1.30-2.00 (lOH, m), 4.02 (2H, t, J=6. 4Hz ), 4.45 (2H, dt, J=47 . 5 and 6. 2Hz ), 6.70-8.65 (14H, m) Preparation 229 ?-(6-Heptylnaphthalene-2-carbonyl)benzotriazcle 3-oxide NMR (DMSO-d6, 5) : 0.75-0.93 (3H, m), 1.10-1.45 (8H, m), 1.55-1.80 (2H, m), 2.68-2.90 (2H, m), 7.35-9.06 (lOH, m) APCI-MASS : m/z = 388 (M++1) Preparation 230 1-(E)-[3-[4-[4-(8-Methoxyoctyloxy)phenyl]phenyl]-acrylcyl]benzotriazole 3-oxide Preparation 231 1-(E)-[3-[4-[4-(5-Hexenyloxy)phenyl]phenyl]acryloyl]-benzotriazoie 3-oxide IR (KBr) : 3072.0, 3033.5, 2939.0, 2865.7, 1780.0, 1693.2, 1619.9, 1596.8 cm-1 ?~TMR (DMSO-d6, 5) . 1.43-1 . 66 (2H, m), 1. 66-1. 90 (2H, m), 2.02-2.23 (2H, m), 3.90-4.16 (2H, m), 4.90-5.13 (2H, m), 5.72-6.00 (1H, m), 6.93-8.30 (14H, m) APCT--MASS : m/z = 337 (Methyl ester, M++l) Preparation 232 1- (E ) - [ 3- [ 4- [ 4- ( 4-Methylpentylox.y) phenyl ] phenyl ] -acryloyljbenzotriazole 3-oxide IR (KBr) 3072.0, 3033.5, 2952.5, 2869.6, 1780.0, 1693.2, 1618.0, 1598.7 cm-1 INMR (DMSO-d6, 5) : 0.90 (6H, d, J=6.5Hz), 1.20-1.40 (2H, m), 1.50-1.90 (3H, m), 3.90-4.10 (2H, m), 6.40-8.30 (14H, m) APCI-MASS : m/z = 442 (M++1) Preparation 233 1-(E)-[3-[4-[4-(6-Fluorohexyloxy)phenyl]phenyl]-acryloyl]benzotriazole 3-oxide IR (KBr) 3074.0, 3033.5, 2939.0, 2865.7, 1780.0, 1697.1, 1598.7 cm-1 NMR (DMSO-d6, d) : 1.25-1.83 (6H, m), 4.04 (2H, t, J=6.5Hz), 4.45 (2H, dt, J=47.5 and 6.5Hz), 6.9-8.3 (14H, m) APCI-MASS : m/z = 460 (M++1) prenaration 234 1-(E)-[3-[4-[4-(6-Methoxyhexyloxy)phenyl]phenyl]-acryloyl]benzotriazole 3-oxide NMR (DMSO-d6, 5) : 1.30-1.65 (6H, m), 1.65-1.90 (2H, m), 3.22 (3H, s), 3.22-3.40 (2H, m), 4.02 (2H, t, - _ ~ L -j=6. SHz; , 6. 5-8 . 3 (14H, m) Preuaratior 235 1-[4-[3-(4-n-Hexyloxyphenyl)pyrazol-5-yl]benzovl]benzotriazole 3-oxide IR (KBr) : 2935, 1780, 1610, 1506 1249, 1232, 1178, 1087 cm-1 NMR (CDC=-~, 5) . 0.91 (3H, d, J=6.4Hz), 1.2-1. 6(6H, T), 1.7-1.9 (2H, m), 3.98 (2H, t, J=6.5Hz), 6.8-7.0 (3H, m), 7.4-7.6 (5H, m), 8.00 (2H, d, J=8.4Hz), 8.10 (1'ri, d, J=8 . IHz ), 8.28 (1H, d, J=8 . 4Hz ) APCI-MASS : m/z = 482 (M+H+) Preparation 236 1-[4-[4-[4-(6-Methoxyhexvloxy)phenyl]phenyl]benzovl]-benzotriazole 3-oxide IR (KBr) : 2935, 2858, 11774, 1600, 1490, 1257, 1211 cm-1 NMR (CDC13, 6) : 1.4-1.9 (8H, m), 3.35 (3H, s), 3.40 (2H, t, J=6.3Hz), 4.02 (21H, t, J=6.4Hz), 7.00 (2H, d, J=8. 7Hz) , 7. 4-7. 8(7i:, m) , 7.87 (2H, d, J=8.4Hz), 8.12 (1H, d, J=8 .2Hz) , 8.36 (2H, d, J=8.4Hz) APCI-MASS : m/z = 522 (M+H+) Preparation 237 1- [ 4- [ 5- f 4- ( 8-Methoxyoctylox-y) phenyl ]-1, 3, 4-thi adiazol-2-yl]benzovl]benzotriazole 3-oxide IR (KBr) : 2929, 2854, 1776, 1602, 1469, 1255 c:
ATMR (CDC13, b) : 1.2-1. 6(10H, m), 1.7-1 . 9 (2H, '..), 3.33 (3H, s), 3.37 (2H, d, J=6.4Hz), 4.03 (2H, d, J=6.5Hz), 7.00 (2H, d, J=8.9Hz), 7.4-7.6 (3H, m), 7.97 (2H, d, J=8 . 9Hz ), 8.12 (1H, d, J=8 . 2Hz ), 8.23 (2H, d, J=8 . 7Hz ), 8.39 (2H, d, J=8 . 7Hz ) APCI-M-ASS m/z = 558 (M+H+) preparation 238 1-[4-(4-n-Butoxyphenyl)cinnamovl]benzotriazole 3-oxide IR (KBr) . 2952, 2867, 1778, 1598, 1496, 1249, 1186 cm-1 NMR (CDC13, 5) 0.99 (3H, t, J=7.3Hz), 1.55 (2H, ta, J=7.0 and 7.3Hz), 1.78 (2H, tt, J=7.0 and 6.4Hz), 4.02 (2H, t, J=6.4Hz), 6.75 (1H, d, J=16. 0Hz) , 7.00 (2H, d, J=8.7Hz), 7.4-8.2 (9H, m) APCI-MIASS m/z = 414 (rf+H+) Pre-oaration 239 1-[4-[5-(4-Cvclohex_ylpheny')-1,3,4-thiadiazol-2-yi]benzovl]benzotriazoie 3-oxide IR (KBr) 2925, 2850, 1778, 1230, 989 cm-1 NMR (CDC13, 5) . 1.2-1.6 (5H, m), 1.7-2.0 (SH, m), 2.5-2.7 (1H, m), 7.37 (2H, d, J=8.3Hz), 7.4-7.6 (3H, m), 7.97 (2H, d, J=8.3Hz), 8.13 (iH, d, J=8.2Hz), 8.26 (2H, d, J=8. 6Hz) , 8.42 (2H, d, J=8.6Hz) APCI-MASS : m/z = 482 (M+H)t Dreparation 240 1-[4-[5-[4-(4-n-Propyloxyphenyl)phenyl]-1,3,4-oxadiazol-2-yl]benzoyl]benzotriazole 3-oxide IR (KBr) . 1778, 1604, 1488, 1249, 1232, 998 cm-1 NMR (CDC13, 5) : 1.07 (3H, t, J=7.4Hz), 1.85 (2H, ta, J=6.5 and 7.4Hz), 7.02 (2H, d, J=8.8Hz), 7.4-7.7 (3H, m), 7.61 (2H, d, J=8.8Hz), 7.75 (2H, d, J=8 . 5Hz ), 8.14 ( iH, d, J=8 . 2Hz ), 8.22 (2H, d, J=8.5Hz), 8.40 (2H, d, J=8.8Hz), 8.48 (2H, d, J=8.8Hz) APCI-MASS : m/z = 518 (M+H)+
Preparation 241 1-[4-(5-n-Nonyl-1,3,4-oxadiazol-2-yl)benzoyl]-benzotriazole 3-oxide IR (KBr) : 2919, 2850, 1780, 1565, 1415, 1251 cm-1 NMR (CDC13, b) : 0.89 (3H, t, J=6.7Hz), 1.2-1.6 (12H, m), 1.8-2.0 (2H, m), 2.98 (2H, t, J=7.7Hz), 7.4-7.6 (3H, m), 8.12 (1H, d, J=9. 0Hz) , 8.28 (2H, d, J=8 . 7Hz ), 8.42 (2H, d, J=8 . 7Hz ) APCI-MASS m/z = 434 (M+H+) Preparation 242 i-r4-[3-(4-n-Hexyloxyphenvl)-1,2,4-oxadiazol-5-yl]-benzovl]benzotriazole 3-oxide IR (KBr) : 2946, 2869, 1780, 1251, 1230, 1001 cm-1 NMR (CDC13, b) : 0.92 ( 3H, t, J=6 . 8Hz ), 1. 3-1 . 6 (6H, m), 1.8-1.9 (2H, m), 4.04 (2H, t, J=6.5Hz), 7.03 (2H, d, J=8.9Hz), 7.4-7.6 (3H, m), 8.0-8.2 (3H, m), 8.46 (4H, s) APCI-MASS : m/z = 484 (M+H+) Preparation 243 1-[4-[5-(4-n-Octyloxyphenyl)-1,3,4-thiadiazol-2-yl]-benzoyl]benzotriazole 3-oxide IR (KBr) : 2925, 2856, 1774, 1602, 1259, 1232, 989 cm-1 NMR (CDC13, b) : 0.90 (3H, t, J=6.7Hz), 1.1-1.6 (lOH, m), 1.7-1.9 (2H, m), 4.04 (2H, t, J=6.5Hz), 7.01 (2H, d, J=8.9Hz), 7.4-7.6 (3H, m), 7.97 (2H, d, J=8. 8Hz) , 8.12 (1H, d, J=8.2Hz), 8.24 (2H, d, J=8.6Hz), 8.40 (2H, d, J=8.6Hz) APCI-MASS : m/z = 528 (M+H+) Preparation 244 1-[4-[5-(4-Trans-n-pentylcyclohexyl)-1,3,4-thiadiazol-2-yl]benzoyl]benzotriazole 3-oxide IR (KBr) : 2952, 2919, 2848, 1785, 1444, 1226, 991 cm-1 NMR (CDC13, b) : 0.90 (3H, t, J=6.9Hz), 1.0-1.7 (13H, m), 1.94 (2H, d, J=12. OHz) , 2.27 (2H, d, J=12. OHz) , 3.19 (1H, tt, J=12.0 and 3.6Hz), 7.4-7.6 (3H, m), 8.12 (1-:, d, J=8.OHz) , 8.19 (2H, d, J=8. 6Hz) , 8.38 (2H, d, J1=8.6Hz) APCI-MASS m/z = 476.(M+H+) preparation 245 1- [4- [3- (4-~-Per-tvloxvphen_vl) isoxazol-5-yl]benzoyl]benzotriazole 3-oxide IR (KBr) : 2948, 2867, 1776, 1610, 1436, 1253, 1002 cm-1 i,T_MR (CDC13, (5) : 0.95 (3H, t, J=7.lHz), 1.2-1. 6(4H, m), 1.7-1.9 (2H, m), 4.02 (2H, t, J=6.5Hz), (3H, m), 7. 4-7. 6(3H, m) , 7.81 (2H, d, J=8. 8Hz) , 8.06 (2H, d, J=8. 6Hz) , 8.12 (1H, d, J=8.OHz), 8.39 (2H, d, J=8 : 6Hz ) APCI-MASS : m/z = 469 (M+H+) Preparation 246 1-[4-[5-[4-(8-Methoxyoctyloxy)phenyl]-1,3,4-oxadiazol-2-yl]benzoyl]benzotriazole 3-oxiae IR (KBr) 2923, 2854, 1787, 1608, 1494, 1255, 1228, 993 crr.-1 NMR (CDC13, b) : 1.2-1.6 (10H, m), 1.7-1.9 (2H, m), 3.34 (3H, s), 3.38 (2H, t, J=6.4Hz), 4.05 (2H, t, J=6.5Hz), 7.04 (2H, d, J=8.8Hz), 7.4-7.6 (3H, s), 8.1-8.2 (3H, s), 8.36 (2H, d, J=8. 7Hz) , 8.45 (2H, d, J=8.7Hz) APCI-MASS : m/z = 542 (M+H+) Preparation 247 1-[4-[4-(6-Phenylpyridazin-3-yl-oxy]phenyl]benzoyi]-benzotriazole 3-oxide IR (KBr) 1783, 1604, 1423, 1284, 985 cm-1 NMR (CDC13, 5) : 7.2-8.2 (15H, m), 8.12 (2H, d, J=8.3Hz), 8.36 (2H, d, J=8.4Hz) APCI-MASS m/z = 486 (M++1) - 12c -Preparation 248 1- [ 4- [~--- ( 4-r-Octvioxvpher.y~ )-1, 3, 4-oxadiazol-2-yl]benzcyl]benzc7:riazole 3-oxide IR (KBr) : 2925, 2854, 1780, 1610, 1496, 1257, 1228, 1180 cm-1 ?~T??R (CDC13, 5) . 0.89 J=6.8Hz), _.2-2.0 (12H, m), 4.05 (2H, t, J=6.5Hz), 7.05 (2H, d, J=8.7Hz), 7.4-7.6 (3H, m), 8.0-8'.2 (3H, ma), 8.3 7(2H, d, J=8. 6H--7) , 8.45 (2H, d, J=8.6Hz) APCT-MASS : m/z = 512 (M-H
Preparation 249 1-[4-[2-(4-n-Hexyloxyphenyl)pyrimidin-6-yl]benzoyl]-benzotriazole 3-oxide IR (KBr) : 2948, 2861, 1780, 1552, 1413, 1378, 987 cm-1 NMR (CDC~3, 6) : 0.92 (3H, t, J=6.8Hz), 1.2-1.6 (6H, m), 1 . 8-2. 0 ( 2 H , ?a) , 4. 06 (2H, t, J=6.5Hz), 7.04 (2H, d, J=9.OHz),7.4-7.6 (3H, m), 7.64 (1H, d, J=5.2Hz), 8.13 (1H, d, J=8.2Hz), 8.44 (4H, s), 8.55 (2H, d, J=9. OHz) , 8.90 (1H, d, J=5.2Hz) APCI-MASS : m/z = 494 (M+H+) preparation 250 1-[4-[4-[8-(2-Ethoxyethoxy)octyloxy]phenyl]benzoyl]-benzotriazole 3-oxide IR (KBr) 2933, 2861, 1778, 1598, 1247, 1186, 977 cm-1 NMR (CDC13, 5) : 1.22 (3H, t, J=7.OHz), 1.3-2.0 (14H, m), 3. 4-3. 6(6H, in), 4.02 (2H, t, J=6. 5Hz) , 7.02 (2H, d, J=8.8Hz), 7.4-7.6 (3H, m), 7.62 (2H, d, J=8.8Hz), 7.78 (2H, d, J=8.6Hz), 8.10 (1H, d, J=8.9Hz), 8.31 (2H, d, J=8.6Hz) APCI-MASS : m/z = 532 (M+H+) Preparation 251 1-[4-[4-[7-(Piperidin-1-yl-carbonyl)heptyloxy]phenyl]-WO 96/11210 PCTlJP95/01983 benzoyl]benzotriazole 3-oxide iR (KBr) . 2935, 2856, 1774, 1631, 1598, 1255, 1191 cm-1 NMR (CDC13, c) : 1.3-2.0 (16H, m), 2.37 (2H, t, J=7.6Hz), 3.48 (4H, s;, 4.02 (2H, t, J=6.4Hz), 7.02 (2H, d, J=8.6Hz), 7.4-7.6 (3H, m), 7.63 (2H, d, J=8. 6Hz) , 7.78 (2H, d, J=8.3Hz), 8. 11 (1H, d, J=8 . 1Hz ), 8.31 (2H, d, J=8 . 3Hz ) APCI-MASS : m/z = 541 (M+H
Preoaraticr_ 252 '-f6-[4-(4-n-Heptyloxyn'r~enyl)piperazin-'-v']nicotincyl;-benzotriazole 3-oxide IR (KBr) : 2929, 2856, 1762, 1604, 1510, 1240 cm-1 NMR (CDC13, 5) : 0.89 (3H, t, J=6.7Hz), 1.2-1.9 (10:, m), 3.20 (4H, t, J=5.OHz), 3.8-4.0 (6H, m), 6.75 (iH, d, J=9.5Hz), 6.86 (2H, d, J=9. 3Hz) , 6.95 (2H, d, J=9.3Hz), 7.3-7.6 (3H, m), 8.10 (1H, d, J=8 . 2Hz ), 8.19 (1H, dd, J=9 . 2 and 2. 3Hz ), 9.05 (1H, d, J=2.3Hz) APCI-M.ASS m/z = 515 (M+H+) Preparation 253 i- [ 6- [ 4- [ 4- ( 8-Methoxyoct_vloxy) phenyl ] piperazin-l-ylJnicotinoyl]benzotriazole 3-oxide IR (KBr) : 2929, 2854, 1766, 1602, 1510, 1419, 1234 cm-1 NMR (CDC13, b) : 1.3-1.9 (12H, m), 3.2-3.3 (4H, :n), 3.33 (3H, s), 3.36 (2H, t, J=6 . 4Hz ), 3.92 (2H, t, J=6.5Hz), 4.0-4.2 (4H, m), 6.75 (1H, d, J=9.lHz), 6.87 (2H, d, J=8.9Hz), 7.0-7.2 (2H, m), 7.4-7.6 (3H, m), 8.09 (1H, d, J=8. iHz) , 8.20 (1H, dd, J=9.1 and 2. 3Hz ), 9.05 (1H, d, J=2 . 3Hz ) APCI-MASS : m/z = 559 (M+H+) Preparation 254 1-[4-[5-[4-(4-n-Propyloxvphenyl)phenyl;-1,3,4-thiadiazol-2-vl]benzcyl]benzotriazoie 3-oxide IR (KBr) : 1774, 1600., 1234, 985 cm-1 NMR (CDC1-~, 5) . 1.07 (3H, t, J=7.3Hz), 1.85 (2H, tq, J=6.5 and 7.3Hz), 3.99 (2H, t, J=6.5Hz), 7.01 (2H, d, J=8.7Hz), 7.4-7.7 (5H, m) , 7.72 (2H, d, J=8.7Hz), 8.1-8.2 (2H, r.-L), 8.28 (2H, d, J=8. 6Hz) , 8.44 (2H, d, J=8.6Hz) APCI-N1ASS : m/z = 534 (M+H) T

The following compounds (Preparations 255 to 256) were obtained according to a similar manner to that of preparation 32.
Preoaration 255 6-Heptylnaphthalene-2-carboxylic acid NMR (CDC13, 5) : 0.88 (3H, t, J=6.6Hz), 1.15-1.53 (8H, m), 1.58-1.88 (2H, m), 2.80 (2H, t, J=7.6Hz), 7.42 (1H, dd, J=1 . 7 and 8. 4Hz ), 7.67 (1H, s), 7.84 (1H, d, J=8 . 6Hz), 7.90 (1H, d, J=8 . 4Hz ), 8.09 (iH, dd, J=1.7 and 8.6Hz), 8.68 (1H, s) APCI-MASS : *.n/z = 271 (M++1), 285 (methyl ester*-1) Preparation 256 3- (E )-[ 4- [ 4- ( 7-Fluoroheptyloxy) phenyl ] phenyl ] acrvlic acid IR (KBr) . 3037.3, 2935.1, 2861.8, 1679.7, 1633.4, 1600.6 cm 1 NMR (DMSO-d6, b) : 1.30-1.85 (10H, m), 4.01 (2H, t, J=6.4Hz), 4.44 (2H, dt, J=47.6 and 6.1Hz), 6.54 (1H, d, J=15.9Hz), 7.02 (2H, d, J=8.7Hz), 7.53-7.80 (7H, m) Pregaration 257 To a solution of 4-metnv'_pentanol (3.0 ml) in pyridine (20 ml) were added in turn with p-toluenesulfor_vl chloride (4.6 g) and 4-N,N-dimethyiaminopyridine (1.5 g) at ambient temperature. After stirring at ambient temperature, the reaction mixture was taken up into a mixture of ethyl acetate (100 ml) and water (100 ml). The separated organic layer was washed in turn with hydrochloric acid(1N), water, aqueous sodium hydrogencarbonate, and brine, and dried over magnesium sulfate. Evaporation gave 1-p-Toluenesuifonyloxy-4-methylpentane (5.30 g).
NNR (CDC13, 5) . 0.83 (6H, d, J=6.6Hz), 1.48 (1H, sept, J=6.6Hz), 1.50-1.70 (2H, m), 2.4S (3H, s), 4.00 (2H, t, J=6.6Hz), 7.34 (2H, d, J=8.1Hz), 7.79 (2H, d, J=8.lHz) APCI-MASS m/z = 257 (M++1) preparation 258 To a solution of 4-bromo-4'-n-butyloxybiphenyl (3.05 g) in tetrahydrofuran (60 ml) was added 1.55M n-butyllithium in n-hexane (7.74 ml) at -60 C over a period of 10 minutes. The solution was stirred at -30 C for 1.5 hours and cooled to -60 C. To the solution was added triisopropylborate (3.46 ml) over a period of 5 minutes, and the mixture was stirred for 1.5 hours without cooling. To the solution was added iN
hydrochloric acid (20 ml) and the solution was stirred for 30 minutes and extracted with ethyl acetate. The organic layer was separated and washed with water, brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with n-hexane. The solid was collected by filtration and dried under reduced pressure to give 4-(4-n-Butyloxyphenyi)phenylboronic acid (2.31 g).
IR (KBr) : 3398, 2956, 2919, 2871, 1604, 1531, 1392, 1257 cm-1 NMR (DMSO-d6, b) : 0.94 (3H, t, J=7.3Hz), 1.4-1.8 (4H, m), 4.01 (2H, t, J=6.3Hz), 7.01 (2H, d, J=8.7Hz), 7.58 (2H, d, J=7. 9Hz) , 7.62 (2H, d, J=8. 7Hz) , 7.84 (2H, d, J=7.9Hz), 8.03 (2H, s) The following compounds (Preparations 259 to 260) were cbtained accordina to a similar manner to that of Preparation Preparation 259 4-[4-(6-Methoxyhexyloxy)phenyl]phenylboronic acid TR (KBr) 3448, 3392, 2937, 2861, 1606, 1529, 1346, 1288 cm-1 NMR (DMSO-d6, b) : 1.3-1.8 (8H, m), 3.21 (3H, s), 3.31 (2H, t, J=6.3Hz), 3.99 (2H, t, J=6.4Hz), 7.00 (2H, d, J=8.7Hz), 7.5-7.7 (4H, m), 7.84 (2H, d, J=8.lHz), 8.03 (2H, s) APCI-MASS : m/z = 329 (M+Hr) Preparation 260 4-[4-(5-Methoxypentyloxy)phenyl]phenylboronic acid IR (KBr) 3473, 3369, 3330, 2935, 2863, 1604,.1531, 1338, 1251 cm 1 NMR (DMSO-d6, b) : 1.4-1.8 (6H, m), 3.22 (3H, s), 3.3-3.4 (2H, m), 3.99 (2H, t, J=6.4Hz), 7.00 (2H, d, J=8. 7Hz) , 7.58 (2H, d, J=8. OHz) , 7.61 (2H, d, J=8.7Hz), 7.84 (2H, d, J=8.OHz), 8.04 (2H, s) APCI-MASS : m/z = 315 (M+H+) Drenaration 261 To a suspension of 4-Methoxycarbonylphenyl boronic acid (648 mg) and 4-iodo-l-heptylpyrazole (876 mg) and Pd(PPh3)4 (173 mg) in 1,2-dimethoxyethane (10 ml) was added 2M Na2CO3 aq. (3.6 ml). The reaction mixture was stirred at 80 C for 2 hours under N2 atmosphere, and poured into ice-water and extracted with ethvl acetate. The organic layer was washed with brine, and dried over MgSO4. The solvent was removed under pressure. The residue was subjecLed to column-chromatography on silica gel 60 (Merk) and eluted with n-hexane/ethyl acetate (80:20). The fractions containing the object compound were combined and evaporated under reduced pressure to give 1-heptyl-4-(4-methoxycarbonylphenyl)pyrazole (0.20 g).
IR (KBr pelet) : 2952, 2920, 2848, 1712, 1610, 1288, 1114, 769 cm-1 NMR (DMSO-d6, 5) . 0.85 (3H, t, J=6.7Hz), 1.1-1.4 (8H, m), 1.7-1.9 (2H, m), 3.85 (3H, s), 4.11 (2H, t, J=7.OHz), 7.72 (2H, d, J=8.5Hz), 7.93 (2H, d, J=8.5Hz), 7.99 (1H, s), 8.34 (1H, s) APCI-MASS : m/z = 301 (M+H+) The following compounds (Preparations 262 to 268) were obtained according to a similar manner to that of Preparation Zli=

Preparation 262 Ethyl 4-[4-(4-n-butyloxyphenyl)phenyl)benzoate IR (KBr) : 2958, 2935, 2871, 1714, 1602, 1396, 1280, 1108 cm-1 N'MR (CDC13, 5) : 0.99 (3H, t, J=7.3Hz), 1.4-2.0 (7H, m), 4.02 (2H, t, J=6. 4Hz) , 4.40 (2H, q, J=7. 1Hz) , 6.98 (2H, d, J=6.8Hz), 7.56 (2H, d, J=6.8Hz), 7.66 (4H, s), 7.68 (2H, d, J=8. 4Hz) , 8.12 (2H, d, M.4Hz) APCI-MASS : m/z = 375 (M+H) +
Preparation 263 Methyl 6-(4-heptyloxyphenyl)nicotinate IR (KBr) : 2954, 2859, 1724, 1597, 1288, 1251, 1116, 783 cm-1 NMR (CDC13, 5) : 0.90 (3H, t, J=6.6Hz), 1.2-1.5 (8H, m), 1.7-1.9 (2H, m), 3.96 (3H, s) 4.03 (2H, t, J=6.5Hz', ?.00 (2H, d, J=8.8Hz), 7.75 (1H, d, J=5 . 4H~ 8. 02 (1:?, d, J=8. 8Hz ), 8. 30 (1H, dd, J=8.4 and 2.2Hz), 9.23 (1H, d, J=2.2Hz) APCI-NLz1SS : m/z = 328 (N+'rI+) preparation 264 Methvl 6-[4-(4-n-butyloxyphenyl)phenyl]nicotinate IP. (KBr) 2956, 2933, 2871, 1724, 1598, 1282, 1118 cm-1 NMR (CDC13, 5) . 1.00 (3H, t, J=7.3Hzi , 1.4-1.9 (4H, m), 3.98 (3H, s), 4.02 (2H, t, J=6.4Hz), 7.00 (2H, d, J=8.8Hz), 7.59 (2H, d, J=8.8Hz), 7.70 (21-1, d, ,7=8 . 5Hz ), 7. 8 6 (1H, d, J=8 . 8Hz ), 03.13 (2H, d, i5 J=8.5Hz), 8.37 (1H, dd, J=8.8 and 1.6Hz), 9.30 (1H, d, J=1.61-. Z ) APCI-MASS : m/z = 362 (M+Ht) Preparation 265 Methyl 5-[4-(4-n-butvloxyphenyl)phenyl]furan 2-carboxylate IR (KBr) : 2958, 2933, 2873, 1716, 1483, 1303, 1139 cm-1 NMR (CDC13, 5) : 0.99 (3H, t, J=7.3Hz), 1.5-1.9 (4H, m), 3.93 (3H, s), 4.01 (2H, t, J=6 . 4Hz ), 6.75 (1H, d, J=3 . 6Hz ), 6.98 (2H, d, J=8 . 7Hz ), 7.26 (1H, d, J=3.6Hz), 7.56 (2H, d, J=8.4Hz), 7.61 (2H, d, J=8.7Hz), 7.83 (2H, d, J=8.4Hz) APCI-MASS : m/z = 351 (M+H)+
Preparation 266 Ethyl 4- [ 4- [ 4- ( 6-methoxyhex.vloxy) phenyl ]z:~::enyl ] benzoate IR (KBr) : 2937, 2863, 1712, 1602, 1396, 1278, 1108 cm-1 3-5 NMR (CDC13, 5) : 1.4-2.0 (11H, m), 3.34 (3H, s), 3.39 (2H, t, J=6.4Hz) , 4.01- (2H, t, J=6.4Hz) , 4.4i (2H, q, J=7.iHz) , 6.98 (2H, d, J=8.7Hz) , 7.5e (2'ri, d, J=8.7Hz), 7.6-7.8 (6H, m), 8.12 (2H, d, J=8.4Hz) APCI-MASS : m/z = 433 (M+H+) Preparation 267 4-[4-[4-(5-Methoxypentvloxv)phenyl]phenyllbenzoic acid IR (KBr) 2939, 2859, 1679, 1587, 1396, 1321, 1292, 1126 cm-1 NMR (DMSO-d6, b) . 1.3-1 . 8 (6H, m), 3.21 (3H, s), 3.2-3.4 (2H, m), 4.01 (2H, t, J=6.5Hz), 7.04 (2H, d, J=8.6Hz), 7.66 (2H, ci, J=8. 6Hz) , 7.7-7.9 (6H, m), 8.03 (2H, d, J=8.2Hz) APCI-MASS : m/z = 391 (M+H+) Preparation 268 Methyl 4-[4-[4-(5-methoxypentyloxy)phenyl]phenyl]phenvl acetate IR (KBr) : 2937, 2863, 1739, 1604, 1492, 1255 cm-1 NMR (CDC13, b) : 1.5-2.0 (6H, m), 3.34 (3H, s), 3.42 (2H, t, J=6.3Hz), 3.68 (2H, s), 3.72 (3H, s), 4.02 (2H, t, J=6.4Hz), 6.97 (2H, d, J=8.7Hz), 7.36 (2H, d, J=8.2Hz), 7.5-7.7 (8H, m) APCI-MASS m/z = 419 (M+Hr) Preparation 269 A solution of 3-[2-(4-Hexvlphenylamino)ethyl]-2-oxo-oxazolidine hydrochloride (2.131 g) in 250C hydrobromic acid in acetic acid (13.04 ml) was stirred for 96 hours at ambient temperature. The reaction mixture was pulverizeci wi-th diisonropyl ether. The precipitate was collected bv filtration and added to ethanol (15 ml). The solution was refluxed for 5 hours and pulverized with diisopropyl ether.
The precipitate was collected by filtration to give 1-(4-n-Hexylphenvl)piperazine dihydrobromide (2.413 g).

IR (KBr) : 2921.6, 2711.4, 2485.8, 1452.1, 1012.4 cm-1 NMR (DMSO-d6, b) 0.85 (3H, t, J=6.6Hz), 1.1-1.4 (6H, m), 1.4-1.6 (2H, m), 2.49 (2H, t, J=8.4Hz3.1-3.4 (8H, m), 6.54 (2H, s), 6.90 (2H, d, J=8.7Hz), 7.08 (2H, d, J=8.7Hz), 8.78 (1H, s) 7~PCI-MIASS : m/z = 247 (M+~H) The fcllowing compounds (Preparations 270 to 274) were obtained according to a similar manner tc that of preparation 269.

preparation 270 4-[4-(4-r.-Hexylphenyl)piperazin-l-yl]benzoic acid dihvdrobromide IR (KBr) : 2956.3, 1691.3, 1664.3, 1602.6, 1232.3 cr.:-1 NMR (DMSO-d6, b) : 0.85 (3H, t, J=6. SHz) , 1.2-1.4 (10H, m), 1.4-1.6 (2H, m), 2.51 (2H, t, J=7.4Hz), 3.2-3.6 (8H, m), 7.0-7.2 (6H, m), 7.81 (2H, d, J=8.8Hz) APCI-MASS : m/z = 367 (M++H) Preparation 271 1-(4-Cyclohexylphenyl)piperazine dihvdrobrcmide IR (KBr) : 2927.4, 1510.0, 1452.1 cm-1 NMR (DMSO-d6, 5) : (6H, *_n) , 1 . 6-1 . 9 (4H, m), 2.41 (1H, m), 3.1-3.4 (8H, m), 6.91 (2H, d, J=8.7Hz), 7.11 (2H, d, J=8.7Hz), 8.78 (1H, s) APCI-MASS : m/z = 245 (M++H) Preparation 272 4-[4-(4-Cyclohexvlphenvl)piperazir.-1-yl]benzoic acid dihydrobromide IR (KBr) . 1668.1, 1602.6, 1230.4, 1189.9 cm-1 APCI-MASS : m/z = 365 (M++H) preparation 273 3-Fluoro-4-[4-(4-hydroxyphenyl)piperazin-1-yl]benzoic acid dihydrobromide IR (KBr) . 1708.6, 1610.3 cm-1 NMR. (DMSO-d6, 5) : 3.2-3. 6(8H, m), 6.81 (2H, d, J=8.6Hz), 7.0-7.4 (3H, m), 7.4-7.8 (2H, m) APCI-MASS : m/z = 317 (M++H) Preparation 274 4-[4-(4-Hydroxyphenyl)piperazin-1-yl]benzoic acid dihvdrobromide IR (KBr) : 1670.1, 1604.5, 1226.5, 775.2 cm-1 NMR (DMSO-d6, 5) . 3.0-3.2 (4H, m), 3.3-3.5 (4H, m), 6.68 (2H, d, J=8. 8Hz) , 6.85 (2H, d, J=8. 8Hz) , 7.02 (2H, d, J=8.8Hz), 7.79 (2H, d, J=8.8Hz), 8.86 (1H, s), 12.29 (1H:, s) APCI-MASS : m/z = 299 (M+H+) Preparation 275 A mixture of 4-n-hexyloxyaniline (10 g), ethyl acrylate (56.1 ml), glacial acetic acid (19.25 ml), and cuprous chloride (1.02 g) was heated under reflux with stirring under nitrogen for 26 hours. A solution of the cold product in ether was shaken with water and then with aqueous ammonia.
The organic layer was taken and dried over magnesium sulfate.
The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with hexane - ethyl acetate (9:1). The fractions containing the object compound were combined and evaporated under reduced pressure to give Ethyl 3-[N-(2-ethoxycarbonylethyl)-N-(4-hexyloxyphenyl)amino]propionate (15.756 g).
IR (Neat) : 1733.7, 1513.8, 1241.9, 1182.2 cm-1 NMR (CDC13, b) :, 0.90 (3H, t, J=6.5Hz), 1.2-1.55 (6H, m), 1.24 (6H, t, J=7.1Hz), 1. 65-1 . 85 (2H, m), 2.51 (4H, t, J=7.2Hz), 3.53 (4H, t, J=7.2Hz), 3.89 (2H, t, J=6 . 5Hz ), 4. 12 ( 4H, q, J=7 . lHz ), E. 72 (2H, d, J-9.3Hz) , 6.53 (2H, d, J=9.3Hz) APCI-MASS m/z = 394 (M++H) Drenaration 276 A suspension of methyl 4-formylbenzoate (4.92 g), hyciroxylamine hydrochloride (5.21 g) and sodium acetate (6.15 g) in ethanol (50 ml) was refluxed for 2 hours. The mixture was poured into water and extracted with ethyl acetate and the separated organic layer was washed with brine and dried over magnesium sulfate. The soivents were removed under reduced pressure to give 4-methoxycarbonyl-benzaldehyde oxime (1.28 g).
I: (KBr) : 3291, 1727, 1438, 1284, 1112 cm-1 NMR (CDC- q, 5) : 3.93 (3H, s), 7.65 (2H, d, J=8.3Hz), 8.10 (2H, d, J=8.3Hz), 8.18 (iH, s), 8.27 (1H, s) APCI-MASS : m/z = 180 The following compound was obtained according to a similar manner to that of Preparation 276.

Prenaration 277 N-Hydroxy-4-n-hexyloxvbenzamidine 1R (KBr) . 3446, 3349, 2937, 2865, 1650, 1610, 1519, 1392, 1253 cm-'-NMR (DMSO-d6, b) : 0.88 (3H, t, J=6.4Hz), 1.2-1.8 (8H, m), 3.97 (2H, t, J=6.5Hz), 5.70 (2H, s), 6.90 (2H, d, J=8 . 4Hz ) , 7.58 (2H, d, J=8 . 4Hz ) , 9.43 (1H, :. ) APCI-MASS : m/z = 237 (M+H)+
Preparation 278 To a solution of 4-methoxycarbonylbenzaldehyde oxime (896 mg) in N,N-dimethylformamide (10 ml) was added 4N-hydrochloride acid in 1,4-dioxane (1.38 ml) and oxone R(1.69 g). The suspension was stirred at ambient temperature for 16 hours and poured into ice-water. The object compound was extracted with ethyl acetate and the organic iayer was washed with brine, dried over magnesium sulfate. The solvents were removed under reduced pressure to give 4-Methoxvcarbonvlbenzaldehyde oxime chloride (1.05 g).
IR (KBr) : 3390, 1710, 1436, 1405, 1284, 1232, 1116, i016 cm-1 NMR (CDC13, b) : 3.95 (3H, s), 8.93 (2H, d, J=8.3Hz), 8.10 (2H, d, J=8.7Hz), 8.39 (1H, s) APCI-MASS : m/z = 176 (M-H+-HC1) Prenaration 279 A solution of Ethyl 4-oxo-1-(4-n-hexyloxyphenyl)piperidine-3-carboxylate (1.437 g) in 20;
hydrochloric acid (7.2 ml) was refluxed for 2 hours, cooled, basified with 60 ; aqueous sodium hydroxide, and extracted with ethyl acetate. The organic layer was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure to give !-(4-n-Hexyloxyphenyl)-4-piperidone (0.959 g).
, IR (Neat) : 2931.3, 1716.3, 1511.9, 1243.9, 825.4 cm-' NMR ( CDC13, b) : 0.90 (3H, t, J=6 . 5Hz ), 1. 2-1 . 6 (6H, m), 1.65-1.85 (2H, m), 2.57 (4H, t, J=6.lHz), 3.46 (4H, t, J=6.1Hz), 3.92 (2H, t, J=6.5Hz), 6.85 (2H, d, J=9.3Hz), 6.95 (2H, d, J=9.3Hz) APCI-MASS : m/z = 276 (M++H) PYeparalion 280 A solution of 4-[4-(7-Bromoheptyloxy)phenyl]bromobenzene (0.25 g) in a solution of tetra n-butylammonium fluoride (tetrahydrofuran solution, 1M, 2.9 ml) was heated to 50 C for 2 hours. After cooling to ambient temperature, the solution was taken up into a mixture of ethyl acetate (20 ml) and water (20 ml). The separated organic layer was washed with water, brine, and dried over magnesium sulfate. Evaporatior:
gave a residue which was chromatographed on silica gel (30 ml) eluting with a mixture of n-hexane and ethyl acetate (100:0-97:3, V/V). The fractions which contained the objective compound were collected and evaporated a residue which was triturated with n-hexane to give 4-[4-(7-Fluoroheptyloxy)phenyl]bromobenzene (104 mg).
IR (KBr) : 2937.1, 2859.9, 1606.4 cm-1 NMR (CDC13, (5) : 1.20-1. 90 (10H, m) , 3.99 (2H, t, J=6.4Hz), 4.45 (2H, dt, J=47.3 and 6.1Hz), 6.95 (2H, d, J=6.7Hz), 7.40 (2H, d, J=6.7Hz), 7.47 (2H, d, J=6 . 7Hz ), 7.52 ( 2E, d, j=6 . 7Hz ) The following compound was obtained according to a similar manner to that of Preparation 280.

Dreparation 281 4-[4-(6-Fluorohexyloxy)phenyi]bromobenzene NMR (CDC13, b) : 1.40-1.95 (8H, m), 4.01 (2H, t, J=6.4Hz), 4.47 (2H, dt, J=47.5 and 6.0Hz), 6.95 (2H, d, J=8.6Hz), 7.35-7.59 (6H, m) Preparation 282 A solution of 4-[4-(8-Bromooctyloxy)phenyl]bromobenzene (3.7 g) in a mixture of sodium methoxide (4.9M in methanol, 17 ml), N,N-dimethylformamide (20 ml) and tetrahvdrofuran (8 ml) was heated to 80 C for 3 hours. The reaction mixture was taken up into a mixture of ethyl acetate (200 ml) and water (100 ml). The separated organic laver was washed in turn with water, brine, dried over magnesium sulfate. Evaporation gave a residue which was subjected to column chromatography (silica gel, 100 ml) eluting with n-hexane to give 4-[4-(8-Methoxyoctyloxy)phenyl]bromobenzene (2.73 g).
IR (KBr) : 2935.1, 2858.0, 1604.5 cm-1 NMR (CDC13, b) : 1.25-1.70 (10H, r.~), 1.70-1.95 (2H, m) , 3.33 (3H, s) , 3.37 (2H, t, J=6,5Hz) , 3.99 (2H, o, J=G. SHz), 6.95 (2H, d, J=8.8Hz), 7.35-7.66 (6H, m) APCI-MASS : m/z = 391 (M+) The following compounds (Preparations 283 to 284) were obtained according ;.o a similar manner to that cf Preparation 282.

Preparation 283 4-[4-(6-Methoxyhex-yloxy)phenyllbromobenzene NMR (CDC13, o) : 1.50-1.70 (6H, m), 1.70-1.95 (2H, :n), 3.34 (3H, s), 3.40 (2H, t, J=6.2Hz), 3.99 (2H, :, J=6. 5Hz ), 6. 95 (2H, d, J=8 . 7Hz ), 7. 30-7 . 60 (6H, m) APCI-MASS : m/z = 365 (M++2) Preparation 284 4-[4-(7-Methoxyheptyloxy)phenyl]bromobenzene IR (KBr) : 2935.1, 2854.1, 1604.5 cm-1 2C NMR (CDC13, 5) : 1.25-1.70 (8H, m), 1.70.1.95 (2H, m), 3.33 (3H, s), 3.37 (2H, t, J=6.4Hz), 3.98 (2H, t, J=6.5Hz), 6.95 (2H, d, J=8.8Hz), 7.35-7.56 (6H, m) APCI-MASS : m/z = 379 (M++2) Preparation 285 N-(4-octylphenyl)-N'-aminourea, Formamidine acetate (12.76 g) and N-carbazoyl-4-octylaniline (6.458 g) in N,N-dimethylformamide (19.4 ml) were stirred at 150 C for 6 hours. The reaction mixture was pulverized with water. The precipitate was collected by filtration and washed with water to give 4-(4-Octylphenyl)-2,3-dihydro-4H-1,2,4-triazol-3-one (4.27 g).
IR (KBr) . 3214.8, 3085.5, 1704.8 cm-1 NMR (CDC13, 5) : 0.88 (3H, t, J=6.7Hz), 1.2-1.5 (10H, m), 1.5-1.8 (2H, m), 2.64 (2H, t, J=7.9Hz), 7.29 (2H, d, J=8.5Hz), 7.43 (2H, d, J=o~.SHz), 7.67 (1'ri, d, J=1.3Hz), 10.31 (1H, s) APCI-MASS : m/z = 274 (M+H+) The following compound (Preparation 286) was obtained according to a similar manner tc that of Preparation 285.
Preparation 286 4-[4-(4-tert-Butoxycarbonylpiperazir_-1-yl)phenyl]-2,3-dihyciro-4H-1,2,4-triazol-3-one IR (KBr) : 320C, 1699.0, 918.0 cm NMR (CDC13, 5) : 1.49 (9H, s), 3.17 (4H, z, J=4.9Hz), 3.60 (4H, t, J=4.9Hz), 7.00 (2H, d, J=9.0Hz), 7.40 (2H, d, J=9 . OHz ), 7.63 (1H, s), 10.4 (1H, s) APCI-MASS : m/z = 346 (M+H+) Preparation 287 A mixture of Methyl 6-(1-heptynyl)naphthalene-2-carboxylate (4.51 g) and platinum oxide (0.4 g) in tetrahydrofuran was stirred under 3.5 atm pressure of hydrogen for 5 hours. The catalyst was filtered off and the filtlate was evaporated to give Methyl 6-heptylnaphthalene-2-carboxylate (4.40 g).
NMR (CDC13, b) : 0.88 (3'rI, t, J=6.6Hz), 1.16-1.50 (~oH, m), 1.50-1.80 (2H, m), 2.78 (2H, t, J=7.6Hz), 3.97 (3H, s), 7.39 (1H, dd, J=17 and 8. 4Hz ), 7.64 (1H, s), 7.79 (1H, d, J=8.6Hz), 7.86 (1H, d, J=8.4Hz), 8.02 (1H, dd, J=1 . 7 and 8. 6Hz ), 8.57 (1H, s) APCI-MASS m/z = 285 (M++1) The following compound (Preparation 288) was obtained according to a similar manner to that of Preparation 287.
Preparation 288 Methyl 6-hexylnaphthalene-2-carboxylate - l~, -NMR (CDC13, b) . 0.88 (3H, t, J=6.8Hz), 1.17-1.53 (6H, m), 1.60-1.82 (2H, m), 2.79 (2H, t, J=7.7Hz), 3.97 (3H, s), 7.39 (1H, dd, J=1.7 and 8.4Hz), 7.64 (1H, s), 7.80 (1H, d, J=8.6Hz), 7.86 (1H, d, J=8.4Hz), 8.03 (1H, dd, J=1 . 7 and 8. 6Hz ), 8.57 (1H, s) APCI-MASS : m/z = 271 (M+1) Preoaration 289 To a stirred solution of Methyl 6-hydroxynaphthalene-2-carboxvlate (3.0 g) in dichloromethane (40 ml) were added in turn ciiisopropylethylamine (3.9 ml) and triflic anhydride (3.0 ml) at -40 C. After stirring at -40 C for 20 minutes, the mixture was taken up into a mixture of ethyl acetate and cold water. The organic layer was separated, washed with brine, dried over magnesium sulfate, and dried in vacuo. The residue was taken up into piperidine (20 ml) and to the solution were added 1-heptyne (4.0 ml) and tetrakis(triphenylphosphine)palladium(0) (0.5 g). After heating to 85 C for 1 hour under nitrogen atmosphere, the reaction mixture was evaporated in vacuo. The residue was diiuted with ethyl acetate, and the solution was washed in turn with hydrochloric acid and brine, dried over magnesiuT
sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (200 ml) eluting with a mixture of n-hexane and ethyl acetate (9:1, V/V) to give Methyl 6-(1-heptynyl)naphthalene-2-carboxylate (4.01 g).
NMR (CDC13, b) . 0.94 (3H, t, J=7.lHz), 1 .30-1 .70 (6H, m), 2.46 (2H, t, J=7.OHz), 3.97 (3H, s), 7.50 (1H, dd, J=1.7 and 8. 6Hz) , 7.80 (1H, cd, J=8. 6Hz) , 7.86 (1H, d, J=8 . 6Hz ), 8.04 (1H, dd, J=1 . 7 and 8. 6Hz ), 8.55 (1H, s) APCI-MASS : m/z = 281 (M++1) The following compound was obtained according to a similar manner to that of Preparation 289.

-Preparation 290 Methyl 6-(i-hexynyl)naphthalene-2-carboxylate NMR (CDC13, 5) . 0.97 (3H, t, J=7.1Hz), 1.40-1.71 (4H, m), 2.47 (2H, t, J=6.8Hz), 3.98.(3H, s), 7.50 (1H, dd, J=1.5 and B.SHz), 7.79 (1H, d, J=8.6Hz), 7.85 (1H, d, J=8.5hz), 7.92 (1H, s), 8.04 (1H, dd, J=1.7 and 8.6Hz), 8.55 (1H, s) APCI-MASS m/z = 267 (W+1) Prenaration 291 To a solution of 4-octylar.iline (5 ml) in a mixture of pyridine (12.5 r.a ) and chloroform (40 ml) was added phenyi chioroformate (2.95 ml) and stirred for 1.5 hours at ambient temperature. The reaction mixture was added to a mixture of water and ethyl acetate. The organic layer was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to giv=_ 4-Octyl-N-phenoxycarbonylaniline (4.51 g) IR (KBr) : 3318.9, 1714.4, 1234.2 cm-1 NMR (CDC13, b) : 0.88 (3H, t, J=6.2Hz), 1.2-1.4 (10H, m), 1.5-1.7 (2H, m), 2.57 (2H, t, J=7.3Hz), 6.88 (1H, s), 7.1-7.5 (9H, m) The following compounds (Preparations 292 to 299) were obtained according to a similar manner to that of Preparation Preparation 292 4-(4-tert-Butoxycarbonylpiperazin-1-yl)-N-phenoxycarbonylaniline IR (KBr) 3309.2, 1743.3, 1658.5, 1197.6 cm-1 NMR (CDC13, b) : 1.48 (9H, s), 3.08 (4H, t, J=5. 3Hz) , 3.58 (4H, t, J=5 . 3Hz ), 6.87 (1H, s), 6.91 (2H, d, J=9Hz), 7.1-7.5 (7H, m) APCI-MASS : m/z = 398 (M+H+) preparation 293 1-(4-Cyclohexvlber.zoyl)-2-(4-methoxycarbonvlbenzoyl)-hydrazine IR (KBr) 3236, 2925,. 2852, 17206, 1679, 1637, 1278, 1110 cm-1 NMR (DMSO-d6, 5) (5H, m', 1.6-2.0 (SH, m), 2.60 (1H, m), 3.90 (3H, s), 7.37 (2H, d, J=8.OHz), 7.85 (2H, d, J=8.0Hz), 8.0-8.2 (4H, m), 10.48 (1H, s), 10.68 (1H, s) APCI-MASS : m/z = 381 (M+H)' preparation 294 l-[4-(Piperidin-1-yl)benzoyll-2-(4-methoxycarbonylbenzoyl]hydrazine IR (KBr) : 3500, 3286, 2941, 2854, 1712, 1689, 1650, 1606, 1286, 1242 cm-1 NMR (DMSO-d6, (5) 1.59 (6H, s), 3.33 (4H, s), 3.90 (3H, s), 6.97 (2H, d, J=8.8Hz), 7.79 (2H, d, J=8.8Hz), 8.02 (2H, d, J=8.4Hz), 8.09 (2H, d, J=8.4Hz), 10.23 (1H, s), 10.57 (iH, s) APCI-MASS m/z = 382 (M+H)+
Preparation 295 1-[4-(4-n-Propvloxyphenyl)benzoyl]-2-(4-methoxycarbonylbenzoyl]hydrazine IR (KBr) : 3230, 1724, 1679, 1654, 1280, 1108 cm-1 NM-R (DMSO-d6, b) : 1.00 3H, d, J=7.5Hz), 1.76 (2H, tq, J=6.5 and 7.5Hz), 3.91 (3H, s), 7.05 (2H, d, J=8.7Hz), 7.71 (2H, d, J=8.7Hz), 7.79 (2H, d, J=8.5Hz), 8.00 (2H, d, J=8.5Hz), 8.05 (2H, d, J=8.6Hz), 8.11 (2H, d, J=8.6Hz), 10.60 (1H, s), 10.72 (1H, s) APCI-MASS : m/z = 433 (M+H)-PreParation 296 1-(4-Methoxycarbonylbenzoyl)-2-decanoylhydrazine IR (KBr) : 3220, 2919, 2850, 1724, 1643, 1600, 1567, 1479, 1284 cm 1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.8Hz), 1.2-1.7 (14H, m), 2.18 (2H, t, J=7.4Hz), 3.89 (3H, s), 7.97 (2H, d, J=8.5Hz), 8.06 (2H, d, J=8.5Hz), 9.15 (1L, s), 10.49 (1H, s) APCI-MASS : m/z = 349 (M+H+) Preparatio*_-i 297 1-(4-Methoxycarbonylbenzoyl)-2-(trans-4-n-pentvlcvclohexvlcarbonvl)hvdrazine IR (KBr) . 3201, 2923, 2852, 1727, 1600, 1567, 1479, 1282 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6. 9Hz) , 0. 9-1 .0 (2H, *n), 1.1-1.5 (11H, m), 1.7-1.9 (4H, m), 2.20 (1H, m), 3.88 (3H, s), 7.97 (2H, d, J=8. 6Hz) , 8.06 (2:i, d, J=8.6Hz), 9.85 (1H, s), 10.46 (1H, s) APCI-MASS m/z = 375 (M+H+) preparation 298 1-[4-(8-Methoxyoctyloxy)benzoyl)-2-(4-methoxycarbonylbenzoyl)hydrazine IR (KBr) 3213, 2935, 2856, 1718, 1600, 1567, 1465, 1282 cm-1 NMR (DMSO-d6, b) : 1. 2-1 . 8 (12H, m), 3.21 (3H, s), 3.29 (25, t, J=6.4Hz), 3.90 (3H, s), 4.04 (2H, u, J=6.5Hz), 7.04 (2H, d, J=8.8Hz), 7.90 (2H, d, J=8. 8Hz) , 8.04 (2-rI, d, J=8.7Hz), 6.10 (2H, d, J=8.7Hz), 10.41 (1H, s), 10.64 (1H, s) APCI-MASS : m/z = 457 (M+H+) Preparation 299 1-(4-Octyloxybenzoyi)-2-(4-methoxycarbonylber.zoyl)-hydrazine IR (KBr) : 3224, 2923, 2854, 1724, 1681, 1643, 15C2, 1434, 1282, 1253, 1106 cm-1 NMR (DMSO-d6, 5) : 0.86 (3H, " J=6.8Hz), 1.2-1.5 (10H, m), 1.6-1.8. (2H, m), 3.89.(3H, s), 4.04 (2H, t, J=6.3Hz), 7.04 (2H, d, J=8.7Hz), 7.90 (2H, d, J=8.7Hz), 8.03 (2H, d, J=8.6Hz), 8.10 (2H, d, J=8.6Hz), 10.42 (1H, s), 10.64 (1H, s) APCI-MASS : m/z = 427 (M+ii+) Preparation 300 A solution of Methyl 4-n-hexyloxybenzoate (2.00 g) and hydrazine hydrate (4.24 g) in ethancl (10 ml) was refluxed for 6 hours. After cooling, the reaction mixture was poured into water. The pretipitate was collected by filtration, washed with water and dried over P205.under reduced pressure to give N-(4-n-hexyloxybenzoyl)hydrazine (1.96 g).
IR (KBr) : 3311, 2954, 2869, 1623, 1253 cm-1 NMR (DMSO-d6, 5) : 0.87 (3H, t, J=6 . 8Hz ), 1. 2-1 . 5 (6H, *_r.) , 1. 6-1 . 8 (2H, m), 4.00 (2H, t, J=6.5Hz), 4.40 (2H, s), 6.95 (2H, d, J=B. 6Hz) , 7.77 (2H, d, J=8.6Hz), 9.59 (1H, s) APCI-MASS : m/z = 237 (M+H) +

The following compounds (Preparations 301 to 308) were obtained according to a similar manner to that of Preparation 300.

Preparation 301 N-(4-Octylphenyl)-N'-aminourea IR (KBr) : 3309.2, 1683.6, 1554.3 cm-1 NMR (DMSO-d6, b) : 0.85 (3H, t, J=6.7Hz), 1.1-1.4 (lOH, m), 1.4-1.6 (2H, m), 2.48 (2H, t, J=8.9Hz), 4.32 (2H, s), 7.03 (2H, d, J=B. 4Hz) , 7.32 (1H, s), 7.38 (2H, d, J=8.4Hz), 8.50 (1H, s) - 1a6 -prenaration 302 N-f4-(4---e---R;:tcxycarbonylpiperazin-1-yl)phenvl;-Nl-aminourea IR (KBr) . 3237.9, 1695.1, 1670.1, 1540.8, 1230.4 cm-1 NMR (DMSO-d6, b 1.. 42 ( 9H, s), 2. 97 (4H, t, J=4.9Hz), 3.44 (4H, t, 7=4.9Hz), 4.30 (2H, s), 6.8-E.
(2H, d, J=9. 0uz) , 7.26 (iI:, s), 7.36 (2H, d, J=9.OHz), 8.41 (1H, s) Preparatior, 303 4-Cvclohexvlbenzovlhvcirazine IR (KBr) . 3318, 2925, 2852, 1625, 1606, 1527, 1326 cm-1 NMR (DMSO-d6, (5)' : 1.1-1.5 (5H, m), 1.6-2.0 (5H, m), 2.4-2. 6(1H, m), 4.44 (2H, s), 7.27 (2H, d, J=8.2Hz), 7.73 (2H, d, J=8.2Hz), 9.66 (1H, s) APCI-MASS : m/z = 219 (M+H) +
Preparation 304 4-(Piperidin-l-yl)benzoylhydrazine IR (KBr) : 3263, 2852, 1612, 1504, 1245, 1124 cm-1 NMR (DMSO-d6, b) : 1.57 (6H, s), 3.25 (4H, s), 4.35 (2H, s), 6.90 (2H, d, J=9.OHz), 7.68 (2H, d, J=9.0Hz), 9.44 (1H, s) APCI-MASS : m/z = 220 (M+;;) +
Preparation 305 4-(4-n-Propyloxyphenyl)benzoylhydrazine IR (KBr) : 3350, 3276, 1610, 1494, 1288, 978 cm-1 NMR (DMSO-d3, b) : 0.99 (3H, t, J=7.5Hz), 1.75 (2H, tq, J=6.5 and 7.5Hz), 3.98 (2H, t, J=6.5Hz), 4.50 (2H, s), 7.03 (2H, d, J=8.8Hz), 7.65 (2H, d, J=8.8Hz), 7.69 (2H, d, J=8.4Hz), 7.88 (2H, d, J=8.4Hz), 9.79 (1H, s) AIPCI-MASS : m/z = 271 (M+H+) Preparation 306 4-Methoxycarbonylbenzoylhydrazine IR (KBr) , 3322, 3250, 3018, 1727, 1658, 1621, 1565, 1432, 1280, 1110 cm-1 i~MR (DMSO-d6, b) 3.87 (3H, s) , 4.58 (2:?, s) , 7.93 (2H, dd, j=8 . 6 and 3. 1Hz ), 7.02 (2H, dd, J=8 . 6 and 3.1Hz), 9.97 (iE, s) APCI-MASS m/z = 195 (M+HT) Preparation 307 Trans-4-n-pentylcyclohexylcarbonylhydrazine IR (KBr) . 3303, 3199, 2954, 2925, 2850, 1639, 1619, 1533, 1457 cm-1 NMR (DMSO-ci6, 5) : 0. 8-1 .0 (6'ri, m), 1.1-1.5 (10H, m), 1.6-2.2 (5'ri, m), 4.10 (2H, s), 8.85 (1H, s) APCI-MASS : m/z = 213 (M+H+) Preparation 308 4-(8-Methox-yoctyloxy)benzoylhydrazine IR (KBr) : 3309, 2937, 2852, 1606, 1494, 1253 cm-1 NMR (DMSO-d6, b) : 1.2-1.9 (12H, m), 3.20 (3H, s), 3.25 (2H, t, J=6.5Hz), 3.99 (2H, z, J=6.5Hz), 4.39 (2H, s), 6.95 (2H, d, J=8. 8Hz) , 7.77 (2H, d, J=8.8Hz), 9.58 (1H, s) APCI-MASS : m/z = 295 (M+H)+
prenaration 309 To a stirred solution of 4-bromo-4'-n-heptylbiphenyl (2.71 g) in tetrahydrofuran (100 ml) was added dropwise a solution of n-butyllithium in a mixture of diethyl ether and n-hexane (1.6M, 5.1 ml) at -78 C. After stirring at -78 C
for 30 minutes, the resultant mixture was added to a solution of diethyl oxalate (3.4 ml) in tetrahydrofuran (50 ml) at -78 C. The resultant mixture was allowed to warm to 0 C for about 1 hour, and to the mixture was added acetic acid (0.5 ml). Evaporation gave a residue which was taken up into a mixture of water and ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium suifate.
Evaporation gave a residue which was chromatographed on silica gel (200 ml) eluting with a mixture of n-hexane and ethyl acetate (10:0-95:5, V/V) to give 1-Ethyl-2-(4-n heptyibhenyl)ethanedione (2.23 g).
NMR (CDC13, b) : 0.88 (3H, t, J=6.6Hz), 1.10-i.SC (8H, m), 1.44 (3H, t, J=7.lHz), i.50-1.80 (2:i, m), 2.66 (2H, t, J=7.7Hz), 4.47 (2H, q, J=7.lHz), 7.20-7.40 (2H, m), 7. 50-7. 64 (2H, m), 7. 64-7. 85 (2H, m), 8.00-8.20 (2H, m) APCI-MASS : m/z = 353 (M++l) Preparation 310 To a suspension of sodium hydride (60: in oil, 0.37 g) in tetrahydrofuran (40 ml) was added by portions 4-acetyl-4'-n-heptylbiphenyl (2.50 g) at ambient temperature. After stirring at ambient temperature for 1 hour, to the solution was added triethyl phosphonoacetate (1.9 ml) and the mixture was heated to reflux for 5 hours. After cooling to ambient temperature, to the mixture was added acetic acid (0.53 T:1) and evaporated. The residue was taken up into a mixture of water and ethyl acetate. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue was chromatographed on silica gel (200 mi) eluting with mixture of n-hexane and diisopropyl ether (99: 1-20: 1, V/V) to give Ethyl (E) -3- [4- (4-heptvlphenyl)phenvlj-2-butenoate (2.19 g).
NMR (CDC13, b) : 0.88 (3H, t, J=6.6Hz), 1.13-1.48 (8H, m), 1.48-1.78 (2H, m), 2.61 (3H, s), 2.65 (2H, t, J=7 . 4Hz ), 4.22 ( 2'ri, q, J=7 .1Hz ), 6.20 (1H, t, J=2.7Hz), 7.23-7.28 (2'r?, m), 7.50-7.63 (6H, m) APCI-MASS : m/z = 365 (M++1) Preparation 311 To a solution of 4-bromo-4'-n-heptylbiphenyl (5.1 g) in tetrahydrofuran (60 ml) was added a solution of n-butyllithium in a mixture of n-hexane anddiethyl ether (1.6M, 9.7 ml) at -60 C. After stirring at -60 C fcr 30 minutes, to the mixture was added N,N-ciimethylacetamide (4.3 :rl) and the reaction mixture was allowed to warm to 0 C. The reaction mixture was taken up into a mixture of cold water and ethyl acetate, and the pH was adjusted to around 1 with 1N hydrochloric acid. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated. The residue was chromatographed on silica gel (150 ml) eluting with a mixture of n-hexane and ethyl acetate (20:1, V/V) to give 4-Acetyl-4'-n-heptylbiphenyl (1.60 g).
hTMR (CDC13, b) : 0.89 (3H, t, J=6.6Hz), 1.05-1.48 (8H, m), 1.48-1.75 (2H, m), 2.65 (2H, t, J=7.6Hz), 2.63 (3H, s), 7.20-7.31 (2H, m), 7.52-7.58 (2H, m), 7.65-7.70 (2H, m), 7.97-8.05 (2H, m) APCI-MASS : m/z = 295 (M+1) Preparation 312 To a solution of Methyl 4-[4-(8-hydroxyoctyloxy)phenyl?-benzoate (500 mg) and dihydropyrane (141 mg) in dichloromethane (15 ml) was added p-toluenesulfonic acid (5 ml). The mixture was stirred at ambient temperature for 10 minutes and diluted with dichloromethane and washed with water and brine. The separated organic layer was dried over magnesium sulfate and evaporated under reduced pressure to give Methyl 4-[4-(8-tetrahydropyran-2-yl-oxyoctyloxy)pher.yl;-benzoate (616 mg).
IR (KBr) . 2935, 2856, 1722, 1602, 1438, 1290, 1199 cm-1 h'MR (CDC13, b) : 1.3-2.0 (18H, m), 3.3-3.9 (4H, m), 3.93 (3H, s), 4.00 (2H, t, J=6.5Hz), 4.5-4.6 (1H, m), 6.98 (2H, d, J=8.7Hz), 7.56 (2H, d, J=8.7Hz), 7.62 (2H, d, J=8.3Hz), 8.07 (2H, d, J=8.3Hz) Prenararion 313 To a solution of titaniu.m ( IV) chloride (11.6 g) in dichloromethane (100 ml) was added 4-n-Pen}yloxyacetophencne (10.3 g) and Methyl 4-formylbenzoaLe (8.21 g) in dichloromethane (50 mi) dropwise at 0 C. To the mixture was added triethvlamine (11.15 ml) in dichloromethane (30 ml).
The mixture was stirred at 0 C for 30 minutes and diluted with n-hexane. The organic layer was washed with water (four times), brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with iso-propyl ether. The solid was collected by filtration and dried to give 1-(4-Methoxycarbonylphenyl)-3-(4-n-pentyloxyphenyl)-1-proper--3-one (4.02 g).
IR (KBr) . 2950, 2910, 2863, 1718, 1654, 1606, 1274, 1176 cm-1 NMR (CDC13, b) : 0.94 (3H, t, J=6.9Hz), 1.3-1.6 (4H, m), 1.8-2.0 (2H, m), 3.93 (3H, s), 4.04 (2H, t, J=6.5Hz), E.97 (2H, d, J=8.8Hz), 7.60 (1H, d, J=15.7Hz), 7.68 (2H, d, J=8.4Hz), 7.80 (1H, d, J=15.7Hz), 8.0-8.2 (4H, m) APCI-MASS : m/z = 353 (M+H+) Prenaration 314 To a solution of titanium(IV) chloride (13.88 g) in dichloromethane (100 ml) was added Ethyl 4-acetylbenzoate (11.53 g) and 4-n-pentyloxybenzaldehyde (12.69 g) in dichloromethane (50 ml) was added dropwise at 0 C. Tc the mixture was added triethylamine (12.44 ml) in dichloromethane (30 ml). The mixture was stirred at 0 C for 30 minutes and diluted with ethyl acetate. The organic layer was washed with water (four times) and brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with n-hexane. The solid was collected by filtration and dried to give '-(4-n-Pentyloxyphenyl)-3-(4-ethoxycarbonylphenyl)-1-propen-3-one (13.45 g).
IR (KBr) : 2956, 2929, 2861, 1718, 1656, 1594, 1510, 1272 cm-1 NMR (CDC13, 5) . 0.94 (3H, t, J=7.1Hz), 1.3-1.9 (9H, m), 4.01 (2H, t, J=6 . 5Hz ), 4.42 (2H, q, J=7 . iHz ), 6.93 (1H, d, J=8.7Hz), 7.37 (iH, d, J=15.6Hz), 7.60 (2H, d, J=8 . 7Hz ), 7.81 (1H, d, J=15 . 6Hz ), 8.03 (2H, i0 d, J=8.5Hz), 8.16 (2H, d, J=8.5Hz) APCI-MASS : m/z = 367 (M+HT) The following compound was obtained according to a similar manner to that of Preparation 314.
Preparation 315 Ethyl 4-oxo-1-(4-n-hexyloxyphenyl)piperidine-3-carboxylate IR (Neat) : 1664.3, 1511.9, 1243.9, 1216.9 cm-1 NMR (CDC13, 5) : 0.90 (3H, t, J=6.5Hz), 1.2-1.5 (6H, m), 1.32 (3H, t, J=7.lHz), 1.65-1.85 (2H, m), 2.51 (2H, t, J=5.8Hz), 3.31 (2H, t, J=5.8Hz), 3.76 (2H, s), 3.91 (2H, t, J=6.5Hz),4.26 (2H, q, J=7. 1Hz) , 6.84 (2H, d, J=9.2Hz), 6.94 (2H, d, J=9.2Hz), 12.06 (1H, s) APCI-MASS : m/z = 348 (M++H) Preparation 316 To a solution of 4-n-Hexyloxybenzoylhydrazine (1.96 g) and pyridine (0.74 ml) in tetrahydrofuran (20 ml) was added a solution of terephthalic acid monomethyl ester chloride (1.56 g) in tetrahydrofuran (15 ml) dropwise at 0 C. The reaction mixture was stirred at room temperature for 2 hours, and poured into water. The precipitate was collected by filtration and washed with acetonitrile. The residue was dried under reduced pressure to give 1-(4-r_-Hexyloxybenzoyi)-2-(4-methoxycarbonyibenzoyl)hydrazine (2.99 g).
IR (KBr) . 3230, 3023, 2954, 2858, 1724, 1681, 1643, 1280, 1251, 1105 cm-, NMR (DMSO-d6, 5) : 0.88 (3H, t, J=6. 6Hz) , 1.2-1.5 (6h, m), 1.6-1.8 (2H, m), 3.90 (3H, s), 4.04 (2H, t, J=6.4Hz), 7.04 (2H, d, J=8.7Hz) , 7.90 (2H, d, J=8.7Hz), 8.03 (2H, d, J=8.4Hz), 8.10 (2H, d, J=8.4Hz), 10.42 (iH, s), 10.65 (1H, s) APCI-MASS m/z = 399 (M+H) Preparation 3i7 A mixture of 1-(4-n-Hexyloxyphenyl)-4-piperidone (0.823 g), 1-(4-Ethoxycarboriylphenyl)piperazine (0.7 g), and titanium(IV) isopropoxide (1.11 m') was stirred at room temperature. After 1 hour, the IR spectrum of the mixture showed no ketone band, and the viscous solution was diluted with absolute ethanol (3 ml). Sodium cyanoborohydride (0.121 g) was added, and the solution was stirred for 3 hours.
Water (3 ml) was added with stirring, and the resulting in organic precipitate was filzereci and washed with ethanol.
The fiitrate was extracted with ethyl acetate. The organic layer was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure to give Ethyl 4-[4-[1-;4-n-hexyloxyphenyl)piperidin-4-yl]piperazin-1-vi]benzoate (331 mg ) .

I? (KBr) : 1708.6, 1606.4, 1511.9, 1284.4, 1236.1 c:r.-' Nr-_ ;CDC13, 5) : 0.90 (3H, t, J=6.5Hz), 1.2-1.55 (6H, m), 1.37 (3H, t, J=7.1Hz), 1.6-1.85 (4H, m), 1.95 (2H, d, J=12Hz), 2.41 (iH, m), 2.62 (2H, d, J=11Hz), 2.75 (4H, t, J=5.OHz), 3.35 (4H, t, J=5. OHz ),; 3.58 (2H, d, J=llHz), 3.90 (2H, t, J=6.5Hz), 4.32 (2H, q, J=7.lHz), 6.7-7.0 (6H, m), 7.92 (2H, d, J=9 . OHz ) APCI-MASS : m/z = 494 (M++H) The fcllowirg ccmpound was obtained according to a similar manner to that of Preparation 317.
Preparatior_ 318 1-tert-Butoxycarbonyl-4-(4-phenylcyclohexyl)piperazine IR (KBr) : 1697.1, 1245.8, 1170.6, 1124.3, 700 cm-1 NMR (CDC1,, b) : 1.2-1.65 (17H, m), 1.9-2.1 (4H, m), 2. 3-2 . c' (2H, m), 2.55 (4H, t, J=5 . OHz ), 3.44 ( 4?i, t, J=5 . OHz ), 7. 1-7 . 4 ( 5H, m) APCI-MASS . m/z = 345 (M *+H) Prenaration 319 To a suspension of 1-(N,N-dimethylamino)-2-(4-ethoxycarbonylbenzoyl)ethylene (0.742 g) and 4-n-hexyloxybenzamidine hydrochloride (0.847 g) in methanol (10 ml) was added 281 sodium methoxide in methanol (0.64 ml).
The suspension was refluxed for 6 hours, and partitioned with ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with acetonitrile, collected by filtration and dried under reduced pressure to give Methyl 4-[2-(4-n-hexyloxyphenyl)pyrimidin-6-yl]benzoate (0.61 g).
IR (KBr) : 2931, 2861, 1722, 1606, 1558, 1251 cm-1 NMR (CDC13, 5) : 0.95 (3H, t, J=6.7Hz), 1.2-1.6 (6H, m), 1.8-2.0 (2H, m), 3.97 (3H, s), 4.05 (2tI, t, J=6.5Hz), 7.02 (2H, d, J=B. 8Hz) , 7.56 (1H, d, J=5.2Hz), 8.18 (2H, d, J=8. 6Hz) , 8.28 (2P:, d, J=B. 6Hz) , 8.52 (2H, d, J=8.8Hz), 8.83 (1'ri, d, J=5.2Hz) APCI-MASS m/z = 391 (M+H+) Preparation 320 A solution of 1-(4-Methoxvcarbonvlphenvl)-3-(4-n-pentvloxyphenyi)-1-propen-3-one (4.0 g) and hydroxvamine hydrochloride (3.93 g) in ethanol (40 ml) was refluxed for 4 hours. The mixture was diluted with ethvl acetate, ar_d the organic layer was washed with water (x 2), brine and dried over magnesium sulfate. The solvents were removed under reduced pressure to give crude oxime. To a solution of crude oxime in 1,2-dichloroethane (20 ml) was added activated-manganese(IV) oxide (10.0 g). The reaction mixture was refluxed for 2 hours and filtered. The residue was washed with dichloromethane. The solvents were removed under reduced pressure and the residue was zriturated with acetonitrile. The solid was collected bv filtration and dried to give Methvl 4-[3-(4-n-pentvloxyphenyl)isoxazol-5-ylJbenzoate (0.98 g).

IR (KBr) : 2940, 2871, 1720, 1612, 1278, 1249, 1178, 1108 cm-1 NMR (DMSO-d6, S) : 0.94 (3H, t, J=7.2Hz), 1.2-1.6 (4H, m), 1.7-1.9 (2H, m), 3.95 (3H, s), 4.01 (2H, t, J=6.5Hz), 6.87 (1H, s), 6.98 (2H, d, J=8.9Hz), 7.79 (2H, d, J=8.9Hz), 7.89 (2H, d, J=8.6Hz), 8.15 (2H, d, J=8.6Hz) APCI-MASS : m/z = 366 (M+H+) Preparation 321 To a solution of 4-Methoxycarbonylphenylhydroxvimine-methyl chloride (16.98 g) ar.d 4-n-pentyloxyphenylacetylene (18.96 g) in tetrahydrofuran (170 mi) was added triethylamine (14.4 ml) in tetrahydrofuran (140 ml) over a period of 2 hours at 40 C and the mixture.was stirred at 40 C for 30 minutes. The mixture was diluted with dichloromethane and washed with water and brine. The separated organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with acetonitrile. The precipitate was collected bv filtration and dried to give Methyl 4-[E-(4-n-pentyioxyphenyl)isoxazol-3-yl]benzoate (24.56 g).
1R (KBr) : 2942, 2873, 1716, 1616, 1508, 1280, 1108 cm-1 NMR (CDC13, 6) : 0.95 (3H, t, J=6.9Hz), 1.3-1. 6 (4H, m), 1. 8-2 . 0 (2H, m), 3.95 (3H, s), 4.02 (2H, t, J=6.5Hz), 6.74 (ln, s), 6.99 (2H, d, J=8.8Hz), 7.76 (2H, d, J=8.8Hz), 7.93 (2H, d, J=8.5Hz), 8.14 (2H, d, J=8 . 5Hz ) APCI-MASS : m/z = 366 (M+Ht =reparation 322 To a solution of N-Hydroxy-4-octyloxybenzamidine 11.89 g) in pyridine (10 ml) was added terephthalic acid monomethyl ester chloride (1.67 g) in tetrahydrofuran (15 ml) dropwise at 0 C. The mixture was stirred at room temperature for 15 minutes, and poured into water. The precipitate was collected by filtration, dried and dissolved in pyridine (10 ml). The solution was refluxed for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with 1N
HCI, water and brine. The separated organic layer was dried over magnesium sulfate and the solvents were removed under reduced pressure. The residue was triturated with acetonitrile and collected by filtration. The solid was dried to give Methyl 4-f3-(4-n-hexyloxyphenyl)-1,2,4-oxadiazol-5-yl]benzoate (2.27 g).
IR (KBr) : 2950, 2925, 2863, 1720, 1280, 1255 cm-1 N'MR (CDC13, 5) : 0.92 (3H, t, J=6 . 6Hz ), 1. 2-1 . 9 (8H, m), 3.97 (3H, s), 4.03 (2H, d, J=6.5Hz), 7.00 (2ri, d, J=B. 9Hz) , 8.09 (2H, d, J=8.9Hz), 8.20 (2H, d, J=6. 6Hz) , 8.28 (2H, d, J=6. 6Hz) APCT_-MASS : m/z = 381 (M+H) +
Preparation 323 A suspension of 1-(4-n-Hexyloxybenzoyl)-2-(4-methoxycarbonylbenzoyl)hydrazine (1.00 g) in phosphorus oxychloride (5 mi) was refluxed for 1 hour. After cooling, the solution was concentrated under reduced pressure. The residue was poured into ice-water and extracted with dichioromethane. The organic layer was washed with water, brine and dried over magnesium sulfate. The solvents were removed under reduced pressure. The residue was triturated with acetonitrile, collected by filtration and dried under reduced pressure to give Methyl 4-[5-(4-n-hexyloxyphenyl)-1,3,4-oxadiazole-2-yl]benzoate (761 mg).
IR (KBr) : 2954, 2854, 1724, 1612, 1494, 1280, 1249 cm-1 NMR (CDC13, b) . 0.91 (3H, t, J=6.6Hz), 1.3-1.6 (6H, m), 1.7-1.9 (2H, m), 3.96 (3H, s), 4.04 (2H, t, J=6.5Hz), 7.02 (2H, d, J=8. 6Hz) , 8.07 (2H, d, J=8.6Hz), 8.19 (4H, m) APCI-MASS : m/z = 381 (M+H)+

The following compounds (Preparations 324 to 117) were obtained according to a similar manner to that of Preparation Preparation 324 Methyl 4-[5-[4-(4-n-propyloxyphenyl)phenyl]-1,3,4-ox.adiazol-2-yl]benzoate IR (KBr) : 1720, 1614, 1496, 1280, 1103 c:r.-1 NMR (CDC13, b) : 1.07 (3H, d, J=7.5Hz), 1.84 (2H, tq, J=6.5 and 7.5Hz), 3.98 (3H, s), 3.99 (2H, t, J=6.5Hz), 7.01 (2H, d, J=8. 8Hz) , 7.60 (2H, d, J=B. 8Hz) , 7.73 (2H, d, J=8. 5Hz) , 8.19 (2H, d, J=8.5Hz), 8.22 (4H, s) APCI-MASS : m/z = 415 (M+HT) grenaration 325 Methyl 4-[5-(n-nonyl)-1,3,4-oxadiazol-2-yl]benzoate IR (KBr) . 2915, 2848, 1724, 1569, 1436, 1413, 1278 cm-1 NMR (CDCi3, b) : 0.88 (3H, t, J=6.4Hz), 1.2-1.6 (12H, m), 1.8-2.0 (2H, m), 2.94 (2H, t, J=7.6Hz), 3.96 (3H, s), 8.11 (2H, d, J=8.8Hz), 8.17 (2H, d, J=8.8Hz) APC=-MASS m/z = 33= (M+H'y Dreparation 326 Methyl 4- [ 5- [ 4- ( 8-methoxvoctyloxy) phenvi. ]-1, 3, 4-oxadiazol-2-vl)benzoate IR (KBr) . 2925, 2858, 1722, 1614, 1280, 1259 cm-1 NMR (CDC13, (5) . 1.3-1.9 (12H, *n) , 3.36 (3H, s), 3.37 (2H, t, J=6.4Hz), 3.97 (3H, s), 4.04 (2H, t, J=6. SHz) , 7.02 (2H, d, J=8. 9Hz) , 8.07 (2H, d, J=8.9Hz), 8.20 (4H, s) APCI-MASS : m/z = 439 (M+H+) Pregaration 327 Methyl 4-[5-(4-n-octyloxypnenyl)-1,3,4-oxadiazol-2-vl';benzoate IR (KEr) 2923, 2856, 1722, 1614, 1496, 1282, 1103 cm 1 NMR (CDC13, 5) : 0.89 (3H, t, J=6.8Hz), 1.2-1.6 (10'ri, m), 1.7-1.9 (2H, m), 3.97 (3H, s), 4.04 (2H, t, J=6.5Hz), 7.03 (2H, d, J=8.7Hz), 8.07 (2H, d, J=8.7Hz), 8.19 (4H, m) APCI-MASS : m/z = 409 (M+H+) Preparation 328 A suspension of 1-(4-Hexvloxybenzoyl)-2-(4-methoxvcarbonylbenzoyl)hydrazine (1.0 g) and di-phosphorus pentasulfide (1.28 g) in tetrahydrofuran (15 ml) was stirred at room temperature for 3 hours. The mixture was diluted with water (30 ml), stirred for 30 minutes and extracted with WO 96/11210 PC'1'/JP95/01983 dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with acetonitrile. The solid was collected by -L"iltration and dried under reduced pressure to give Methyl 4- [ 5- ( 4-n-hexvloxyphenvl )-i, 3, 4-thiadiazol-2-yl]benzoate (816 mg).
IR (KBr; . 2925, 2871, 1722, 1608, 1436, 1276, 1106 cm-1 NMR (CDC13, b) : 0.92 (3H, t, J=6.6Hz), 1.3-2.0 (8H, m), 3.96 (3H, s), 4.03 (2H, t, J=6.5Hz), 6.99 (2H, d, J=8 . 6Hz ), 7.95 (2H, d, J=8 . 4Hz ), 8.16 (2H, d, J=8.4Hz) APCI-MASS : m/z = 397 (M+H)+

The 'foliowing compounds (Preparations 329 to 334) were obtained according to a similar manner to that of Preparation Preparation 329 Methyl 4- [ 5- [ 4- ( 8-methoxyoctyloxy) pheny] -i, 3, 4-thiadiazol-2-vl]benzoate IR (KBr) 3210, 2935, 2856, 1718, 1600, 1465, 1280, 1110 cm-1 NMR (CDC13, b) : 1.3-1.6 (10H, m), 1.7-1.9 (2H, m), 3.33 (3H, s), 3.37 (2-H, d, J=6.4Hz), 3.96 (3H, s), 4.03 (2H, t, J=6 . 5Hz ), 160.99 (2H, d, J=8 . 9Hz ), 7.94 (2H, d, J=8.9Hz), 8.07 (2H, d, J=8.6Hz), 8.16 (2H, d, J=8.6Hz) APCI-MASS m/z = 455 (M+HT) Preparation 330 Methyl 4-j5-(4-cyclohexylphenyl)-1,3,4-thiadiazol-2-yl]benzoate IR (KBr) : 2925, 2850, 1716, 1432, 1274, 1108, 997 cm i NMR (CDC13, b) : 1.2-1.6 (5H, m), 1.7-2.0 (SH, m), 2.58 (1H, m) , 3.96 (3H, s) , 7.34 (2H, d, J=8.2'rIz) , 7. 93 (2H, d, J=8. 2Hz ), 8. 0-7 (2H, , d, J=8. 6Hz ), 8. 16 (2H, d, J=8.6Hz) APCI-MASS : m/z = 379 (M+H+) Preparation 331 Methyl 4-[5-[4-(piperidin-l-yl)phenvi]-1,3,4-thiadiazol-2-yl;benzoate IR (KBr) : 2940, 2848, 1720, 1602, 1436, 1415, 1276, 1108 cm-1 NMR (CDC13, b) : 1.68 (6H, br), 3.34 (4H, br), 3.96 (3H, s), 6.95 (2H, d, J=8 . 7Hz ), 7.88 (2H, d, J=8.7Hz), 8.05 (2H, d, J=8.6Hz), 8.16 (2H, d, J=8.6Hz) APCI-MASS : m/z = 380 (M+H+) Preparation 332 Methyl 4-[5-(4-r.-octyloxvphenyl)-1,3,4-thiadiazol-2-yl]benzoate IR (KBr) : 2927, 2858, 1720, 1606, 1434, 1276, 1106 cm-1 NMR (CDC1-~, 5) : 0.89 (3H, t, J=6.8Hz), 1.2-1.6 (lOr:, m), 1.7-1.9 (2H, m), 3.96 (3H, s), 4.03 (2H, t, J=6.5Hz), 7.00 (2H, d, J=8.9Hz), 7.95 (2H, d, J=8.9Hz), 8.06 (2H, d, J=8.4Hz), 8.16 (2H, d, J=8.4Hz) APCI-MASS : m/z = 425 (M+H+) Preparation 333 Methvl 4-[5-(4-trans-n-nentylcyclohexyl)-1,3,4-thiadiazol-2-vl]benzoate IR (KBr) : 2923, 2850, 1722, 1440, 1276, 1110 cm 1 NMR (CDC13, b) : 0.89 (3H, t, J=6.9Hz), 1.0-1.8 (13H, m), 1.92 (2H, d, J=13.4Hz), 2.24 (2H, d, J=12.2Hz), 3.15 (1H, tt, J=12.2 and 3.5Hz), 3.95 (3H, s), 8.01 (2H, dd, J=8. 6 and 2. 0Hz) , 8.13 (2H, dd, J=B. ar.d APCI-MASS : m/7 = 373 (M+Ht) Preparation 334 Methvl 4-[S-[4-(4-n-propvloxyphenvl)phenyl]-1,3,4-thiadiazol-2-vl]benzoate IR (KBr) : 1720, 1540, 1508, 1282 cm-1 NMR (CDC13, b) : 1.07 (3H, t, J=7.5Hz), 1.85 (2H, m), 3.9-4.1 (5H, m), 7.01 (2H, d, J=8.8Hz), 7.59 (2H, d, J=8. 8Hz) , 7.70 (2H, d, J=8.4Hz), 8.07 (2H, d, J=8. 4Hz ), B. 1-8 . 2 ( 4H, m) APCI-MASS : m/z = 431 (M+H)+
Preparation 335 To a suspension of 4-hexyloxybenzoic acid in oxalvl chloride (10 ml) and dichloromethane (10 ml) was added N,N-dimethylformamide (0.1 ml). The mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure to give crude 4-hexyloxybenzoyl chloride.
To a suspension of Ethyl 3-amino-4-hydroxybenzoate (733 mg) and triethyiamine (1.38 ml) and 4-dimethylaminopyridine (DMAP, 10 mg) in methylene chloride (10 ml) was added the solution of 4-hexyloxvbenzoyl chloride obtained above in dichloromethane (5 ml) dropwise at 10 C. The reaction mixture was stirred at 10 C for 1.5 hours and diluted with dichloromethane (20 ml). The solution was washed with HnO
(20 mi), 1N HCl aa. (20 ml x 2), H20 (20 mi) and brine (20 ml) successively. The organic layer was ciried over MgSO4 and the solvent was removed under reduced pressure. To the residue was added toluene (15 ml) and p-toluenesulfonic acid (10 mg). The mixture was refluxed for 6 hours and the solvent was removed under reduced pressure. The residue was triturated with acetonitrile, and precipitate was collected with filtration and dried over PO5 to give 2-(4-Hexyloxyphenyl)-5-ethoxycarbonylbenzoxazole (0.60 g).
IR (KBr) : 2952, 2871, 1712, 1623, 1500, 1294, 1255 cm-1 NMR (CDC13, 5) 0.92 (3H, t, J=6 . 6Hz ), 1. 3-1 . 6 (9H, m), 1.7-1.9 (2H, m), 4.05 (2H, t, J=6.5Hz), 4.42 (2H, q, J=7.lHz), 7.03 (2H, d, J=6.9Hz), 7.57 (1H, d, J=8 . 6Hz ), 8.08 (1fi, dd, J=8 . 6 and 1. 7Hz ), 8.18 (2H, d, J=6 . 9Hz ), 8.43 (1H, d, J=1 . 7Hz ) APCI-MASS : m/z = 368 (M+H+) The following compounds (Preparations 336 to 337) were obtained according to a similar manner to that of Preparation 335.

Preparation 336 5-Ethoxycarbonyl-2-(2-octyloxypyridin-5-yl)benzoxazole IR (KBr) 2933, 2858, 1716, 1623, 1604, 1577, 1467, 1290, 1213, 1083 cm-1 Nr?R (CDC13, b) : 0.89 (3H, t, J=6.7Hz), 1.2-1.5 (10H, m), 1.43 (3H, t, J=7.lHz), 1.7-1.9 (2H, m), 4.3-4.5 (4H, m), 6.87 (1H, d, J=8 . 7Hz ), 7.60 ( iH, d, J=8.6Hz), 8.11 (iH, dd, J=8.6 and 1.6Hz), 8.37 (1H, dd, J=8.8 and 2.4Hz), 8.45 (1H, d, J=1.6Hz), 9.03 (1H, d, J=2 . 4Hz ) APCI-MASS : m/z = 397 (M+H+) preparation 337 2-[4-(4-Hexylphenyi)phenyli-5-ethoxycarbonylbenzoxazole IR (KBr) . 2952, 2871, 1712, 1623, 1500, 1294, 1255, 1024 cm-1 A?KR (CDC13, b) . 0.90 (3H, t, J=6.6Hz), 1.2-1.5 (6H, m), 1.44 (3H, t, J=7.1Hz), 1. 6-1. 8(2H, m), 2.67 (2H, t, J=7.3Hz), 4.43 (2H, q, J=7.lHz), 7.27 (1H, d, J=3.7Hz), 7.32 (1H, s), 7.5-7.7 (3H, m), 7.77 (2H, d, J=8 . 6Hz ), 8.12 (1H, dd, J=8 . 6 and 1. 7Hz ), 8. 32 (2H, d, J=8. 5Hz ), 8. 4 8 (1H, d, J=1 . 2Hz ) APCI-MASS m/z = 428 (M+H+) Preparation 338 A suspension of 4-[4-(8-bromooctyloxy)phenvl]benzoyc acid 11 g) in 2,6-dimethylmorpholine (3.06 m_) was refluxed for 30 minutes. The reaction mixture was added to a Tixture of water and ethyl acetate and adjusteci to pH 2.0 with conc.
HCI. The organic iaver was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the -'-'trate was evaporated under reduced nressure to give 4- 4-8-(2,6-dimethvlmorpholin-4-yi)cctyloxy]phenyljbenzoic acid hvdrochloride (0.95 g).
IR (KBr) : 2939.0, 1704.8, 1606.4, 1189.9 cm-i NMR (DMSO-d6, b) : 1.12 (6H, d, J=6.3Hz), 1.2-1.6 (10H, m), 1.6-1.9 (4H, m), 2.4-2.7 (2H, m), 2.9-3.1 (2H, m), 3.8-4.0 (2H, m), 4.02 (2H, t, J=6.3Hz), 7.04 (2H, d, J=8.8Hz), 7.68 (2H, d, J=8.8Hz), 7.75 (2H, d, J=8 . 4Hz ), 7.99 (2H, d, J=8 . 4Hz ) APC I-TML; S : m/ z= 440 (M+H+ ) prenaration 339 Sodium hydride (60'r- suspension in mineral oil, 108 mg) was added to ethoxvethanol (10 ml), and the solution was stirred at 60 C for 20 minutes. To the solution was added Methyl 4-[4-(8-bromooctyloxy)phenvl]benzoate (1.26 g), and the reaction mixture was stirred at 70 C for 2 hours. To the reaction mixture was added 10'<: sodium hydroxide aaueous solution (2.4 ml), and the solution was s'. ==red at 70 C for 1 hour. After cooling, the solution was ad-,-..ted to pH 2.C
with iN hydrochloric acid. The precipitate was collected bv filtratior., and dried to give 4-[4-[8-(2-Ethoxvethoxy)octvioxy]phenyl]benzoic acid (1.13 g).
IR (KBr) : 2933, 2858, 1685, 1604, 1434, 1294, 1132 cm 1 -NMR (DMSO-d6, b) . 1.09 (3H, t, J=7.OHz), 1.2-1.0-(14H, m), 3.2-3.6 (6H, m), 4.01 (2H, d, J=6.3Hz), 7.04 (2H, d, J=8.8Hz), 7.67 (2H, d, J=8.8Hz), 7.74 (2H, d, J=8.5Hz) , 7.98 (2H, d, J=8.5Hz) APC=-MASS : m/z = 415 (M+H

The fcllowina compound was obtained according to a similar manner to that of Preiparation 300.

Preparation 340 4-n-Pentvloxybenzoylhydrazine IR (KBr) 3182, 2937, 2869, 1645, 1618, 1571, 1251 cm-i NMR (DMSO-d6, b) , : 0.89 ( 3H, d, J=7 . 1Hz ), 1. 2-1 . 8 ( 6::, m) , 4.00 (2H, t, J=6.5Hz), 4.41 (2H, s; , 6.96 (2H, d, J=8.8Hz), 7.78 (2H, d, J=8.8Hz), 9.59 (1H, s) APCI-MASS : m/z = 223 (M+H+) The followina compound was obtained according to a similar manner to that of Preparation 291.

Preparation 341 1-(4-Methoxvcarbonylbenzoyl)-2-(4-n-pentyloxvbenzcyl)-hydrazine IR (KBr) : 3234, 2956, 2931, 1724, 1683, 1643, 1610, 1284, 1253 cm-1 NMR (DMSO-d6, S) : 0.90 (3H, t, J=6.9Hz), 1.2-1.5 (4H, m), 1.6-1.8 (2H, m), 3.90 (3H, s), 4.04 (2H, t, J=6.5Hz), 7.04 (2H, d, J=8.8Hz), 7.90 (2H, d, J=8. 8Hz) , 8.03 (2H, d, J=8.7Hz), 8.10 (2H, d, J=8.7Hz), 10.42 (1H, s), 10.64 (1H, s) APCI-MASS m/z = 385 (M+H+) The following compound was obtained according to a similar manner to that of Preparation 328.

- ;6~ -Preparatior. 342 Methyl 4- r7_ r c-r_-pentyloxvphen_,-_ th_aciazc ~-~-ybenzoate IR (KBr) : 2940, 2871, 1-1720, 1,606, 143c~, 1280 cm =
INTYIR (CDC131 6) 0.95 (3H, -J=7.- Hz), 6 1, 4:i, m;, 1.6-2.0 (2H, m;, ...96) (3H, s;, L.u' (2H, t, J=e. 5Hz) , 6.99 (2H, d, j=8. BHz, , 7.94 (2H, J=8.8Hz) , 8.06 (2H, d, j=8.7Hz, , 8.16 (2H, ci , J=8. 7Hz) 1C APCI-MASS m/z = 383 (M-H+

The LollOWl-~.% comDolinC was Owt :.' neQ ac..C?"uLng tc a si1-:ilar manner to that o-f Preparation 32 15 PreDaratio-~. 343 4-[5-(4-n-Pentyloxyphenv'_)t'r_iadiazol-2-y'=_jbenzoic acid IR (K3r) . 2954, 2867, 1687, 16C2, 1-4132, 1294, i255 cm-1 NMR ; DMSO-d6, b) . 0.91. (3H, t, J=7 . 0Hz ), _. 3-1 . 5 ( 4F:, 20 .~.i) , 1.7-1.9 (2H, m) , 4.07 (2H, t, J=6.7?Iz), 7.,---(2H, d, J=8.8Hz), 7.97 (2H, d, J=8. 8Hz) , 8.07 (4H, s) APC=-MASS . m/z = 369 (Mj~t) 25 The following cempound was obtained according tc a similar manner to that of Preparation 49.

~reparation 344 'L-[4-[5-(4-r.-Pentv'_oxyphenvl)t~iadiazol-2-yl]benzoylj-30 ber.zotriazole 3-oxide 7R (KBr) 2948, 2873, 1770, 1602, 1257, 7-232 c:n-y NMR (CDC1 -,, O) . 0.95 (3ri, -, J=?.1Hz) , 1.3-i.6 (41:, i r . ), 1 . 8-2. 0 ( 2 i : , m) ,4.04 :2H, --, J=E.5Hz), 7.01 (2H, d, J=8.1Hz), 7.4-7. 7(3'r-, mj , 7.97 (2H, d, 35 J=8.iHz), 8.12 (1F:, c, 8.24 (2Fi, d, J=8.OHz), 8.40 (2H, d, J=8.OHz) APCI-MASS . m/z = 486 (M+H+;
Preparation 345 To a solution of 4-bromobenzaldehyde oxime chloride (647 mg) and 4-n-pentyloxy-phenylacetylene (650 mg) in tetranydrofuran (7 ml) was added triethylamine (0.5 ml) in tetrahydrofuran (5 ml) dropwise a: 40 C. The solution was stirred at 40 C for 30 minutes, poured into water and extracted with ethyl acetate. The organic iayer was washed with H20, brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with acetonitrile. The precipitate was collected by filtration and dried to give 4-[5-(4-n-pentyloxyphenyl)isoxazol-3-yl]bromobenzene (0.59 g).
IR (KBr) : 2948, 2867, 1612, 1430, 1255 cm-1 NMR (CDC13, 5) : 0.95 (3H, t, J=6.9Hz), 1.3-1.6 (4H, m), 1.7-1.9 (2H, m), 4.01 (2H, t, J=6.5Hz), 6.66 (1H, s), 6.98 (2H, d, J=8.8Hz), 7.60 (2H, d, J=8.6Hz), 7.7-7.9 (4H, m) APCI-MASS : m/z = 388 (M+H+) Preparation 346 To a suspension of 4-[5-(4-n-pentyloxyphenyl)isoxazol-3-yl]bromobenzene (386 mg) in tetrahydrofuran (5 ml) was added 1.55M n-butyllithium in hexane (0.84 ml) at -40 C under N2 stream and the solution was stirred for 1 hour at -40 C. To the solution was added crushed dryice (1 g) and the suspension was stirred for 1 hour at -40 C. The suspension was diluted with H20, and acidified with iN-hydrochloric acid. The precipitate was collected by filtration and dried to give 4-[5-(4-n-pentyloxyphenyl)isoxazol-3-yl]benzoic acid (312 mg).
IR (KBr) : 2939, 2867, 1681, 1614, 1429, 1255, 1178, 821 cm-1 WO 96/11210 PC'T/JP95/01983 - ~6G -NMR (OMSO-dn, b) . 0.91 (3.H, t, J=-7.1Hz), ~.3-i. (4H, *n) , i . 6-1 . 8 (2H, m) , 4. 04, (2::, ~:, _7=6 . 5Hz ) , 7.
(2H, d, J=8.9Hz), 7.54 (1H, s) , 7. 8-5 (2H, d, J=8.9Hz), 7.98 (2H, d, J=8. 6Hz) , 8.11 (2H, d, J=8.6Hz) m/z = 352 (M~

The Starting Compound in rhe =ciiowing Examnles i tc =17, and The Object Compounds (1) to (122' and (124) in the following Examip es i to 122 and 124 are iliustrated by chemical fCrmulae as beiow.

='~e Startina Comnound ( the same in Examnles 1 to !17) Ho o?i HO o NH '~r N ~C
HO -O HN OH
O

HO NH
OIi ~~ - oH ~
NaO-I-O
C
HO

- 16i -T~e Oi)ject Com-counds (1) to (122) an d(i24;
?i0 C?-:
HG G
N:
'C__~
'TF-R' _N O

HO HN OH
G ~
1 C NF C--~ CH J
Fi2N pJ N
,.\ OF
HO

pu d NaO-.'-O

ln the following Examples, The Object Compound (X) 20 re.g. The Object Compound (1); means the object compou:.d of Example (X) ~e.g. Example (1)].

J

pCT1JP95/01983 Example No. Rl -CO ~
N CH2-0-(CH')-CH3 2 -co / \ N~ o- (CH2 ) 7cH3 - ~..~ -3 -CO 0- ( CH9) 8-N
\ I
NJ
4 -CO 0 0-(CH?)7CH3 5 _ / \ 0- ( CH~ ) CH
CO _ 7 3 --CO _ ~ I
ii~ ~
6 i0-- i O-(CH2)7CH3 ~ -CO-O- 0-(CH2)~CH~

8 -CO-0-CH2 / \ .--- \ / 0-(CH2)6CH3 Example No. R~
0-(CH2),mCH3 -CO 0-(CH2)4CH3 -CO

10 0 0 0-(CH~)7CH3 -CO 0- i Cii~ i~ CH3 0-(CH2)7CH3 -CO
S
0-(CH~)~CH3 13 I \ /
-CO

N
'~Z--(CH2 ) 8CH3 14 - C O / l 0( N\ ra 0- (CH2 ) JCH3 15 u -CO

Example No.
R
0- ( CH,)) 4CH 3 -CO ' -17 Cu;CH

(CH-))_4Ch-~
-CO
- - i 19 -CO (CH,~)4Cu3 20 2) ECH3 21 -C~ - \ 0- (CH 2) ECH3 22 -CO (Cu2)5CH3 23 -C a N 0- ( CH9) 5CH J
~~ - =

major -CO / \ / 0-(CH2)80CH3 product - -Example No. R

minor -CO 0-(CH2)6-CH=CH2 product - -25 -CO 0- (CH2 ) arn' N,,O

~N / \ 0- (CH~ ) 7C=~3 - -27 -cO-CHg-O / \ O-(cH2)7cH3 28 -co rT-C
pI O- (CH2 ) 6CH3 N
~- (CH2) 8C?-i3 29 -CO / \ H

C - N

-CO-C_C

0- (CH2 ) ECH3 Example No. R
-CO-N ILt 32 H
- (CH-, ) 6CH3 33 _CO-H 0-(CH2)ECHJ

-CO-C-C Cn2)4CHJ
- --CO / \ ( CH2 ) 6CH3 36 /--~ I
-co N N / \ N ~T
- ~l - N

37 _ ~ , -co ; N (CH2;7CH3 N~

major -co N \ 0-(CH2),OCH

product - ~ -minor -co N N O
product - ~~ -Example No. Ri -CO N N ~ \ O- (CH?) 6CH3 ~/ -40 -co N N 0 - ~~ -41 -CO N N 0-(CH~)4CH3 N
mixture -CO C~-a 0-(CH?)N N
product N ~~

43 -";~-Cri3 -c0 0-(CH2) 8--N 0 - - ~CH3 44 -CO / \ N ?~ / \ O-(CH9)7CH3 - \-~ --CO <):N
45 \ ~ \ O-(CH2)5CH3 -CO 0-(CH2)3CH3 Example Nc. R

-CO 0- ( C'.L ) 6CH~
-N

N
48 -CO \ / ~
0-(CH~)7CH3 qg -CO
(Cuq-CHq -CO 0-(CH2)3CH3 - N

-CO / aO- ( CH2 ) S-0 ~,T--CO aO-(CH2)vCH3 C

N

-CO o-(CH27JCh3 Exampie No. Ri 54 -CO 0-(CH27CH~
N-N
I

~
5~ -CO 0-(CH2)4CH3 N-N
H

-C0 z~- 0-(CH2)3CH3 NH(Z) 57 -CO / \ / \
G- (CH9) QCH3 NH(Z) 58 -CO / )7CH3 NH(Z) 59 -CO / \
0-(CH2)7CH3' Example No. Ri 60 (CH2 ) 1LCH3 V
OH
NH(Z) 61 =
-CO
OCH-~
-co /~i(CH2) 12CH3 {

C
( ' > ) ,OCH3 63 Z--<
-co CH

major -co O-(CH;)o0CH3 nroduct - ~~

minor -co N N 0 product - ~J

F

65 -CO / N ~N 0-(CHo)JCH3 - ~ l -co / N N O-(CH2)5CH3 \~/

Example No. Rl 67 -CO / \ N N

68 C O N N O 0- ( CH2 ) JCH3 N-N ~ -69 -CO N N 0-(CH?)5CH3 -CO / \ N\ NT ' ~
- ~/ -71 -CO N N (CH2)5CH3 - \ / -- ~

-CO N N N / \ O-(CH2)5CH3 - ~-~

74 -CO c) .....,,. (CHG) 4 CH3 Example No. Ri 75 _ ,. O
J y \- ~
0-(CH9)80CH3 76 (CH2)ECHJ
--CO (CH2)ECH-~
--CO~~

79 -CO O-c (CH2)6CH3 I
OH
80 -CO / \ (CH9)ECH3 _ Example No. R

_ \
(CH2)6CH3 -CO / \
82 - \ (CHq)5CH3 CO

84 -CO~~ 0 F

Example No. Rl 87 (CH2)60CH3 88 0-(CH2)SCH3 - - ~

89 -CO-'(~ 0-(CH?)EOCH3 N-N
90 -CO 0-(CH2)80CH3 91 -CO 0-(CH915CH3 N-N

-CO

N
-CO _(CH2))2CH3 - i8, -Example No.

N
94 -co CH2)ECH3 0-(CH2)5CH3 - - -96 -co / a0- ( CH2 ) 7CH5 -co ...... .( CH2)4 CH3 98 -co 0-(CH2)4CH3 99 25 -co 0- (CH2 ) 8OC'ri3 100 -co " ~

- N=N
101 - ~ ~ 0- CH CH
-co ( 2)~ 3 Example No. ki -CO I
N aO-(Cu?)5CH3 -CO aO- (CH2) 80~~0"~

-C0 0-(CH2)7-C-N
ls _ ( CH2 ) 6CH3 105 -CO N N a 106 -CO / \ N N / \ O- (CH2 ) 80C~i3 -N ~~ --, 07 -CO O- (CH2 ) 2CH3 108 -CO O ~ N- ( CH2 ) 6CH3 _ Example No. R1 109 -CO 0-(CH2)7CH3 110 -CO ~ ~ (CH2)4CH3 -G- (CHL ) ;OCH3 -CO

112 -CO 0-(CH2)80 -CO

N
(&2)gCH3 114 -CO 0- ( CH2)60 30 115 -CO c 0- ( CH2 ) 50Ci-:3 Example No. Rl 116 s -CO
N--CO 0-(CH2)50CH3 -CO--~~(CH2)1JOCH3 -COac O-(CH ) CH

~H2 C O- (CH2 ) 7CH3 -CO C~-O- (CH2) 7CH3 Example No. R1 122 -CO 0-(CH2)4CH3 Example No. Ri 123 / \ ~NS---CO ~ ~ ~ 0-(CH2)4CH3 Example 1 To a solution of The Starting Compound (1 g) and 1-(6-octyl-oxymethylpicolinoyl)benzot=iazole 3-oxide (0.399 g) in N,N-dimethylformamide (10 mi) was added 4-(N,N-dimethylamino)pyridine (0.140 g), and stirred for 12 hours at ambient temperature. The reaction nixture was pulverizeci with ethyl acetate. The precipitate was collected by filtration, and dried under reduced pressure.
The powder was dissolved in water, and subjected to column chromatography on ion exchange resin (DOWEX-50WX4 (Trademark : prepared by Dow Chemical)) eluting with water. The fractions containing the object compound were combined, and subjected zo column chromatoarap=y or. ODE
(YMC-gel=ODS-A.M=S-50) ;Trademark : prepared by Yamamura Chemical Lab.) eluting with 50:: methanol aqueous solution.
The fractions containing the object compound were combined, and evaporated under reduced pressure to remove methanol. The residue was lyophilized to give The Object Compound (1).
IR (KBr) 3347, 1664, 1629, 1517 cm-1 NMR (DMSO-d6, b) : 0.86 ( 3H, z, J=6 . 7Hz ), 0.98 ( 3H, d, J=6.7Hz), 1.09 (3H, d, J=6.OHz), 1.2-1.47 (10ri, m), 1.47-1.67 (2H, m), 1. 67-2. 06 (3H, m), 2.06-2.5 (4H, m), 3.19 (1H, m), 3.53 (2H, t, J=6.4Hz), 3.5-3.85 (2-r', m), 3.85-4.7 (13H, m), 5.35 (11H, m), 5.56 (1H, d, J=5.7Hz), 6.73 (1H, d, J=8.3Hz), 6.83 (1H, d, J=8.3Hz), 6.89 (1H, s), 7.05 (1H, s), 7.11 (1H, s), 7.32 (1H, m), 7.43 (1H, d, J=8.5Hz), 7.63 (1H, d, J=7.3Hz), 7.85-8.13 (4H, m), 8.66 (1N:, d, J=7.8Hz), 8.84 (1H, s) FAB-MASS : m/z = 1228 (M++Na) Elemental Analysis Calcd. for C50H72N9O22SNa=6H2O
C Q.49, H 6.44, N 9.59 Found . C 45.89, H 6.52, N 9.69 - i87 -The Object Compounds (2) tc (25; -were ob::ained according to a simiiar manner to that o-I Examrie i.
Example 2 1R (KBr) 3353, 1666, 1510, 1236 cm-1 \TMR (DMSO-d6, b) . 0.86 (3H, L, J=6.7Hz) , 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, U-,=5.8Hz), 1.2-1.5 (10H, m), 1.55-2.05 (5H, m), 2.11-2.7 (4H, m), 3.0-3.3 (5H, m), 3.3-3.5 (4H, m), 3.6-4.5 (15H, rr), 4.6-5.6 (12H, m), 0.6-7.2 (10H, m), 7.2-7.5 (3H, *n) , 7.81 (2H, d, .1=8 . 8Hz ), 8. 05 (1H, d, J=8.7Hz), 8.28 (1H, d, J=8.7Hz), 8.41 (iH, d, J=6.7?Iz) , 8.84 (1H, s) FAR-MASS : m/z = 1373 (M++Na) Elemental Analysis Calcd. for C6OH83N10O22SNa=4H-)0 C 50.63, H 6.44, N 9.84 Found : C 50.59, H 6.59, N 9.79 Example 3 IR (KBr) : 3350, 1664, 1627, 1047 cm-1 Iv'MR (DMSO-d6, b) : 0.96 (3H, d, j=6.6Hz), 1.08 (3H, d, J=5 . 7Hz ) , 1.15-1 . 53 ( 8'ri, *:i) , 1 . 55-2 . _ ( 9H, m), 2.1-2.45 (3H, r.~~), 2.5-2.7 (1H, m), 3.i8 (1H, m), 3.6-3.83 (2H, m), 3.83-4.6 (17H, m), 4.7-5.4 (11H, m), 5.51 (1H, d, J=5 . 9Hz ), 6.73 (1H, d, J=8.2Hz), 6.83 (1H, d, J=8.2Hz), 6.85 (1H, s), 7.03 (2H, d, J=8.4Hz), 7.05 (1H, s), 7.30 (1H, s), 7.2-7.5 (2H, m), 7.67 (2"rI, d, J=8.4Hz), 7.71 (2H, d, J=7 . 4Hz ), 7.94 (1ii, s), 7.96 (2H, d, J=7.4Hz), 8.06 (1H, d, J=8.OHz), 8.25 (1H, d, J=6.7Hz), 8.50 (1H, s), 8.74 (1H, d, J=6.7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1356 (MY+Na) Elemental Analvsis Calcd. for C58H76N11022SNa=4H2O
C 49.53, H 6.02, N 10.95 Found C 49.26, H 6.22, IN 10.77 Example 4 IR (KBr) . 3350, 1660, 1631, 1047 NMR (DMSO-d6, G) . 0.86 (3H, --, J=6.9Hz), 0.97 (3-H, u, J=c. 0Hz) , 1.09 (3H, d, J-5.3Hz) ,_.2-1.5 (10u, m , 1 . 37 (6H, s ) , 1. 55-2 . 0 ( 5H, :: ) , 2 . 1-2.6 (4 :, r:) , 3.16 (1?:, mi , 3.73 (2H, m! , 3.89 (2'ri, " J=6.3Hz), 3.95-4.49 (11H, r-i), 4.68-5.21 (10H, m) , 5.25 ('_H, d, J= ~_ . 1Hz ), 5.53 (1H, d, J=5.7Hz; , 6.73 (iH, d, J=8.2Hz;, 6. 7/5-6.85 (4H, m) , 6. 9- (1H, d, J=8 . 2Hz ), 7. 05 (1: , s), 7. 15 (iH, s), 7.3-7.5 (2H, m), 7.9-8.2 ;3h, 8.84 (1H, s) FAB-MASS m/z = 1271 (Mt+Na) Elemental P.nalysis Calcd. For C53H77NQ023SNa=4H2O
C 48.18, H 6.48, N 8.48 Found : C 48.04, _'E 6.51, N 8.38 Example 5 IR (KBr) : 1666, 1629, 1222 cm-1 NMR (DMSO-d6, b) . 0.85 (3H, " J=6. 6Hz) , 0. 9-1. 12 ( 6H, 1 . 12-1 . 52 (13'r., r:) , 1. 52-1 . 93 :n) , 2. 08-2. 55 (4H, m), 3. 1.6 (1H, ?n) , 3.6-5.3 (26H, m), 5.49 + 5.54 (1H, d, J=5.8Hz, mixture of diastereomer), 6.60-7.1 (7H, m), 7.04 (1H, s), 7. 1(1H, m), 7.2-7. 5(2H, *_n) , 7.9-8.43 (3H, m) , 8.83 (1H, s) FAB-MASS : m/z = 1257 (M''+Na) Elementa_ Anaiysis Calcd. for C52H75N8023SNa=3H2O
C 48.44, H 6.33, N 8.69 Found : C 48.16, H 6.51, N 8.53 Example 6 IR (KBr) : 3349, 1666, 1629, 1259 cm-1 NNR (DMSO-d6, 5 ) . 0.86 (3H, t , J=6.7Hz), 0. 9(3H, d, J=5.7Hz), 0.96 (3H, d, J=6.7Hz), 1.1-1.55 (19H, m), 1.55-2.0 (5-ri, m), 2.0-2.47 (4H, m), 2.65-3.25 (3H, m), 3.5-5.13 (27H, m) , 5.17 (1'r., d, J=3 . 2Hz ), 5.24 (11a, d, J= ~-_ . 5Hz ), 5.38 ( iH, d, J=5 . 9Hz ), 6. 5-6 . 9 ( 5:?, m), 6. 9-7 . l (3H, ?~ ), 7. 2-7.46 (2:i, m) , (3a, m), 8.83 (1H, s) FAB-MASS : m/z = 1368 (M++Na) Elemental Analysis Caicd. for :.58H84N9024SNa=5H2O
C 48.50, N 6.60, N 8.78 Found : C 48.47, H. 6.83, N 8.78 ExamDle 7 TR (KBr. 3350, 1666, 1502, 1199 cm-i NMR (DMSO-d6, b) : 0.86 (3H, --, j=6.6Hz), 0.97 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.7Hz), 1.2-1.5 (10H, m), 1.55-2.0_(5H, m), 2.1-2.6 (4H, m), 3.17 (1H, m), 3.7-4.5 (15H, m), 4.7-5.22 (10H, m), 5.24 (1H, d, J=4.4Hz), 5.60 (1H, d, J=5.9Hz), 6.68-7.03 (8H, m), 7.04 (iH, s), 7.2-7.42 (2H, m), 7.85-8.1- (3H, m), 8.83 (1H, s) FAB-Y-z.SS : m/z = 1229 ;MT+Na) Elemental Analysis Calcd. for C50H71N8023SNa=5H2O
C 46.29, H 6.29, N 8.64 Found : C 46.39, H 6.05, N 8.72 Example 8 IR (KBr) 335C, 1666, 1631, 1513 cm-=
N?m-R (DMSO-d6, b) : 0.88 (3H, -., J= 6. 2Hz ), 0.97 (3H, d, J=6.7Hz), 1.04 (3H, d, J=5.7Hz), 1.2-1.58 (8H, m), 1.58-2.0 (5H, m), 2.0-2.6 (4H, m), 3.17 (1H, m), 3.6-4.5 (i5H, m), 4.63-5.33 (13H, m), 5.53 (1H, d, J=5 . 9Hz ), 6.73 (1H, d, J=8 . 2Hz ), 6.82 (1H, d, J=8 . 2Hz ), 6.84 (1H, s), 6. 95-7 . 52 (7H, m), 7.66 (1H, d, J=7.6Hz), 7.7-7.9 (3H, m), 8.05 (1H, d, J=9.1HZ;, 8.15 (1H, d, j=7.6Hz), 8.85 (1H, s) EAR-MASS : m/ z= 1279 (M++Na ) Elemental Analysis Calcd. for C54H73N8023SNa=5H2O
C 48.14, H 6.21, N 8.'L
~
J
_ound : C 48.43, :i 6.28, N 8.30 Example 9 IR (KBr) . 3347, 2956, 1664, 1633, 1508, 1444, 1268, 1047 cm-1 ?''Y, R (DMSO-d6, b) . 0.9-1. 1 (9H, m), i.06 (3H, d, J=5. 9Hz ) , 1 . 3-1 . 5 ( 8H, *.r.), 1 . 6-2 . 0 ( 7 H, :rõ , _ . _-2.4 (3H, m), 2.5-2.6 (lH ,;*t) , 3.1-3.3 (1"r., *.r.) , 3.6-4.4 (17H, m), 4.7-5.0 (8H, m), 5.09 (1H, d, J=5.5Hz), 5.16 (1H, d, J=3.1Hz), 5.24 (1H, d, J=4.5Hz), 6.73 (1H, d, J=8.2Hz), 6.8-6.9 (2H, m), 6.98 (1H, d, J=8.3Hz), 7.05 (1H, d, J=1 . 7Hz ), 7. 3-7 . 6 ( 5i3, r':? , 8.08 (1'r', d, J=8 . 9Hz ), 8.25 (1H, d, J=8 . 4Hz ), 8.54 (1=-, d, J=7.5Hz), 8.83 (1H, s) FAB-MASS m/z = 1257 (M'+Na) Eleme_~.tal Analvsis Caicd. for C52H75N802 <SNa=uHqO
C 47.78, H 6.40, N 8.57 Found : C 47.88, H 6.71, N 8.53 Example 10 IR (KBr) . 3350, 2931, 1664, 1625, 1529, 1440, 1276, 1226, 1047 cm-~ W
?~~MIR (DMSO-d6, 5) . 0.86 (3H, t, J=6.8Hz), 0.97 (3H, d, J=6.7Hz), 1.12 (3H, d, J=5.9Hz), 1.2-1.5 (lOH, r.:) , 1. 6-2.1 (5H, m), 2.1-2.4 (4ii, m), 3. _-3.3 (1H, m), 3.5-4.6 (15H, m), 4.7-5.0 (3H, m), 5. 0-5 . 2 (7H, m), 5.27 ( iH, d, J=4 . 4Hz ), 5. 55 (iH, d, J=5.7Hz), 6.73 (1H, d, J=8.2Hz), 6.8-7.0 (2H, m), 7.0-7.2 (4H, m), 7. 3-7. 6(2::, rr.) , 7.90 (2H, (1 H, d, J=8.8Hz), 8.0-8.~ (2H, ~;t) , 8.8-8.9 m) , 9.06 (1"ri, d, J=7 . 2Hz ) FP.B-M-ASS m/z = 1281 (M++Na) Elemental Analysis Calcd. for C53u71N8024SNa=5H2O
C 47.18, H 6.05, N 8.3C
Found C 46.97, H 6.27, N 8.2%
Exar,lnle 11 NMZ (DMSO-ci6, 0.87-1.05~ (6H, m), 1.1G (3H, d, J=5.7uz) , 1.3-1.5 (4-mj ,_.6-1.9 (5H, m) , 2.2-2.5 (3H, m), 2.6 (1H, m), 3. 1- -3.2 ;1H, ~-:) , 3.7-4.~ (15H, m), 4.8-3.1 (8H, m), 5.09 (1H, d, J=5.64Hz), 5.16 (1H, d, J=3.2Hz), 5.26 (1H, d, J=4.2Hz), 5.52 (1H, d, J=6.OHz), 6.73 (2H, d, J=8.4Hz), 6.8-6.9 (2H, m), 7.0-7.1 (3H, m), 7.2-7.4 (4H, m), 7.6-7.8 (6H, m), 8.11 (1H, d, J=8 . 4Hz ), 8.29 (1H, d, J=8 . 4Hz ), 8.51 (1H, d, J=7 . 7Hz ), 8.85 (1H, s) FAB-MASS : m/z = 1273 (M+1Na) Elemental Analysis Calcd. for C55H71N8022SNa=4Hq0 C 49.92, H 6.02, N 8.47 Found : C 49.79, H 6.14, N 8.45 Example 12 IR (KBr) 3330, 2929, 1670, 1629, 1533, 1440, 1280,.' 1226, 1045, 804 cm-1 NMR ( DMSO-d6, S) : 0.86 (3H, t, J=6 . 7Hz ), 0.97 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.9Hz), 1.2-1.6 (10H, m), 1.6-2.0 (5H, m), 2.1-2.5 (4H, m), 3.1-3.3 (_Y, m), 3. 6-4 . 5 (15H, m), 4. 8-5 . 1 (9H, m), 5.17 (iH, d, J=3.0Hz), 5.25 (1H, d, J=4.5Hz), 5.56 (1H, d, J=5.6Hz), 6.73 (1H, d, J=8.2Hz), 6.83 (1H, d, J=6 . 8Hz ), 7. 1-7 . 2 (3H, m), 7. 3-7 . 5 (3H, m), 7.85 (1H, d, J=8. 8Hz) , 8.0-8.2 (3H, m), 8.84 (1H, s), 8.96 (1H, d, J=7.2Hz) : :B-MP,SS : m/z = 1269 (Mt1Na) Elemental Analysis Calcd. for C52H71N8022S2Na4H2O
C 47.34, H 6.04, N 8.49 Found C 47.21, H 5.96, N 8.41 Example 13 IR. (KBr) . 3345, 2927, 1664, 1629, 1515, 1442, 1274, 1047 cm-1 NMR (DMSO-d6, b) : 0.85 (3'ri, t, J=6.7Hz), 0.97 (3H, d, J=6.7Hz), 1.10 (3H, d, J=5.9Hz), 1.2-1.4 (10H, m), 1.5-2.5 (8H, m), 2.46 (3H, s), 2.69 (2H, t, J=7.7Hz), 3.1-3.4 (2H, m), 3.6-4.5 (17H, m), 4. 8-5. 2( 8H, m), 6. 7-7 . 0 (3H, m), 7. 05 (iH, c:. J=1.7Hz), 7.14 (iK, s), 7.3-7.6 !5H, m), 8.0-8.2 (2H, m), 8.47 (1H, d, J=7.OHz), 8.84 (1H, s) FAB-MASS : m/z = 1251 (M++Na) Elemental Analysis Calcd. for CE3H73N8022SNa=3H2O
C 49.61, H 6.21, N 8.73 Found : C 49.88, H 6.44, N 8.74 Exarmb le 14 IR (KBr) : 3340, 1672, 1627, 1542, 1513, 1440, 1268, 1045 cm-1 NMR (DMSO-d6, b) : 0.84 (3H, t, J=6 . 7Hz ), 0.94 (3H, d, J=6.7Hz), 1.07 (3H, d, J=6. OHz) , 1.2-1.4 (12H, m), 1.6-2.0 (5H, m), 2.1-2.4 (3H, m), 2.6 (1H, m), 2.96 (2H, t, J=7.4Hz), 3.1-3.3 (1H, m), 3.6-4.5 (13H, m), 4.7-5.2 (11H, m), 5.50 (iH, d, J=5.7Hz), 6.73 (1H, d, J=8.2Hz), 6.8-6.9 (2H, m), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.72 (1H, d, J=8.5Hz), 7.91 (1H, d, J=8.4Hz), 8.05 (iH, d, J=8.4Hz), 8.2-8.4 (iH, m), 8.80 (1H, d, J=7.7Hz), 8.83 (1H, s) FAB-MASS : m/z = 1252 (M++Na) Elemental Analysis Calcd. for C52H72N9022SNa=6H2O

C 46.67, H 6.33, N 9.42 Found . C 46.72, H 5.53, N 9.45 Example 15 IR (KBr) . 3350, 2935, 1664, 1627, 151 7, 1446, 125' , 1045 cm-1 NMR (DMSO-d6, 5) : 0.90-1.1 (6H, m), 1.10 (3H, d, J=5.9Hz), 1.2-1.4 (6H, m), 1.6-2.4 (8H, m), 2.6-2.7 (1H, m), 3.1-3.3 (1H, m), 3.7-4.5 (16H, m), 4. 7-5 . 4 (11H, m), 5.51 (1H, d, J=5 . 6Hz ), 6. 7-7 . 0 (3H, m), 7.0-7.6 (7H, m), 7.74 (lH, d, J=8.6Hz), 8.0-8.4 (5H, m), 8.7-8.8 (IH, m), 8.84 (IH, s;
FA3-MASS m/z = 1301 W+Na) Elemental Analysis Calcd. for C55H7,N,0022SNa=6HO0 C 47.62, H 6.03, N 10.01 Found : C 47.65, H 6.03, N 10.03 Example 16 iR (Nujol) : 3353, 1668, 1627, 1540, 1515, 1500 cm-1 NMR (DMSO-d6, b) : 0.80-1.00 (6H, m), 1.06 (3H, d, J=5.9Hz), 1.20-1.53 (4H, m), 1. 60-1 . 95 (5H, :n) , 2. 00-2. 65 (8H, m), 2.80 (2H, t, J= 7.SHz) , 3.05-3.45 (1H, m), 3.50-3.85 12F:, m), 3.90-4.48 (11::, m), 4. 65-5. 38 (11H, m), 5.47 (1H, d, J=6. OHz) , 6.65-6.90 (2H, m), 6.90-7.10 (2H, m), 7.10-7.65 (11H, m), 7. 90-8 .25 (2H, m), 8.30 (1H, d, J=7.8Hz), 8.84 (1H, s) FAB-MASS : m/z = 1275.3 (M++Na) Elemental Analysis Calcd. for C55H73N8022SN03H20 C 50.53, H 6.09, N 8.57 Found : C 50.48, H 6.39, N 8.5i Example 17 TR (Nujol) : 3351, 1656, 1623, 1538, 1515 cm 1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.7Hz), 0.96 (3H, c, J=6.7Hz), 1.08 (3H, d, J=5.8Hz) , - .15-1 .40 (8: , m) , 1.50-2.00 (5r, Tr:; , 2.10-2.48 (4H, m) , 2.52-2.70 (2H, m), 3.05-::.28 (IH, m), 3.60-4.50 (13H, m), 4.70-5.20 (9H, m), 5.25 (1H, d, J=4 . 6Hz ), 5.52 (1H, d, J=6 . OHz ), 6. 68-6 . 92 (4H, m), 7.04 (1H, d, J=1.OHz), 7.22-7.50 (5H, m), 7.55-7.82 (7H, m), 8._4 (iH, d, J=8.4Hz), 8.3_ (1H, d, J=8.4Hz), 8.54 d, J=7.7H7) , 8.84 (1H, 5) FAB-M. S S : m/ z= 12 8 5 (M++Na 1 Ex_amnle 18 iR. (Nujol) . 3351, 1666, 1627, i540, 1515 cm.--NMR (DMSO-d6, 6) : 0.87 (3H, J=6.8Hz), 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.8Hz), 1.17-1.48 (4H, ~:) , 1.50-1.95 (SH, m), 2.05-2.70 (8H, m), 2.70-2.95 (2H, m), 3.05-3.30 (1H, m), 3.60-3.90 (2H, m), 3.90-4.50 (11H, m), 4.65-5.10 (9H, m), 5.15 (iH, d, J=3 . 2Hz ), 5.23 (1H, d, J=4 . 2Hz ), 5.48 (iF, d, J=6.OHz), 6.67-6.90 (3H, m), 7.03 (1H, d, J=1.5Hz), 7.15-7.80 (11H, m), 8.00-8.20 (2H, m), 8.29 (1H, c, J="'.EHz) , 8.84 (1H, s) 7-A.B-MASS : m/z = 1259 (M++Na;
Elemental Analysis Calcd. fo= CJ5H73N8021SNa=6H2O
C 50.30,'H 6.52, N 8.53 Found : C 50.42, H 6.50, N 8.45 Exampie 19 IR (Nujol) . 3351, 1668, 1652, 1623, 1540 cm 1 NMR (DMSJ-d6, 5) . 0.87 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.7Hz), 1.07 (3H, d, J=6.OHz), 1.25-1.45 (4H, m), 1.50-2.00 (5H, m), 2.05-2.48 (4H, m), 2.50-2.75 (2H, m), 3.60-4.50 (13H, m), 4.68-5.25 (10H, m), 5.27 (1H, d, J=4.5Hz), 5.53 (1H, d, J=6.OHz), 6.67-6.98 (4H, m), 7.05 (1H, d, - ~9~ -J=1.OHz) 7.22-7.58 (5H, m), 90 (7H, J=9.0Hz), 8.34 (1:~, d, 7=8.4??7;, c. % '-=-, , J=7.7Hz) , 8.85 FAB-MASS : T~/z = 1258 (M++Na) Elemental A~.aiysis Caicd. for C55H71N8021SNa=5Hq0 C 49.84, H 6.15, N 8.45 Found . C 49.77, H 6.27, N 8.39 Zxample 20 IR (Nujol) . 3353, 1670, 1629, 1540, 1508 cm-'-NMR (DMSO-d6, 5) . 0.88 (3H, t, J=6.5H::) , 0.97 (3H, d, J=6. 8Hz) , 1.04 (3H, d, J=5. 9Hz ), 1.20-1 . 58 ( 8H, :n) , 1. 60-1. 96 (5H, m) , 2. 08-2. 60 (6H, m) , 2.70-3.00'(2H, m), 3.00-3.40 (1H, m), 3.60-3.8'5 (2H, m), 3. 85-4. 50 (13H, m), 4. 50-5. 60 (12H, m), 6.65-6.90 (3H, m), 7.00-7.15 (3H, m), 7.18-7.50 (4H, m), 7.59 (1H, s), 7.62-7.78 (2H, m), 7.95-8.20 (2H, m), 8.30 (1H, d, J=7.7Hz), 8.83 (lii, s) FAB-MASS m/z = 1277 (M++Na) Elemental Analysis Calcd. ror C55H75N8022SNa=4H2C
C 49.77, 'r'- 6.30, N 8.44 .Found : C 49.67, H 6.31, N~0.40 Example 21 IR (Nujol) : 3351, 1654, 1623, 1538, 1515 cm-1 NMR (DMSO-d6, 5) : 0.87 (3H, t, J=6.7Hz), 0.97 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.9Hz), 1.20-1.58 m), (8H, m), 1.66-1.95 (5H, m), 2.10-2.60 (4H, 3. 09-3. 30 (1H, m) , 3. 58-4. 60 (15H, r.m) , 4.69-5.20 (10H, m), 5.24 (1H, d, J=4 . 5Hz ), 5.51 ( iH, cd, J=6 . 0Hz ), 6. 68-6 . 95 (4H, :r.) , 7.04 (1H, d, J=1.0Hz), 7.10-7.73 (7H, ::1), 7.73-7.90 (2H, m), 7.98 (1H, d, J=1.9Hz), 8.10 (iH, d, J=8.4Hz), 8.32 (1H, d, J=8 . 4Hz ), 8.50 ( IH, d, J=7 . 7Hz ), 8.84 (1H, s) TAB-MASS . fii z = 1277 !v,+-N=. ) Flemental Analysis Calcd. 'C= C55H73N8022SNa5H2O
C. 50.38, H 6.38, N 8.55 ~ Found . C 49.98, H 6.37, N 8.41 IR (KBr) - 3340, 2931, 1664, 1627, 1531, 1444, 1-278, 1047 cm-1 NMR ( DMSO-ci6, b) 0. 8 r ( 3:_, t, J=6 . 6Hz ), 0.96 (3H, d, J=6.8Hz), 1.08 (31-, J=5.9Hz), 1=2--.4 (6H, m) i - - --' = 7 ( 2:'., '-- . ? ( 3H, fi.) , 2 . 2-2 . ~
( 3??, m) , 2. 6-2 . 7 (3H, ,:,) , 3. 1-3 . 2 (1H, m) , 3 . 7-4.6 (13H, m), 4.78 d, J=6.OHz), 4.8-5.1 (1H, m) , 5.09 (1H, d, J=5 . 6Hz ), 5.16 (1H, d, J=3 . 2Hz ), 5.24 (1H, d, J=4 . 4Hz ), 5.52 (1H, d, J=6.OHz), 6.73 (1H, d, J=8.2Hz), 6.83 (2H, d, J=8.3Hz), 7.05 (i.H, s), 7.3-7.5 (5H, m), 7.65 (2H, d, J=8.2Hz), 7.74 (2H, d, J=8.4Hz), 7.98 (2H, d, J=8.4Hz), 8.11 (1H, d, J=8.4Hz), 8.31 (iH, d, J=8.4Hz), 8.79 (iH, d, J=7.7Hz), 8.84 (1H, s) FAB-M-ASS : m/z = 1245 (M++Na) Elemental Analysis Calcd. fcr C54H71N8O21SNa=4Hq0 C 50.07, H 6.15, N 8.65 Found : C 50.26, H 6.44, N 8.67 Example 23 NMR (DMSO-d6, b) . 0.91 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6. 8Hz ), 1.05 (3H, d, J=5 . 6Hz ), 1. 2-1. 5( 6:?, m), 1.6-2.1 (5H, m), 2.1-2.7 (4H, m), 3.0-3.5 (9H, m), 3. 6-4 . 5 (15:-?, m), 4. 6-5. 6(11H, rn) , 6.73 (1'rI, d, J=8.2Hz), 6.8-6. 9(4H, m), 6.95 (2H, d, J=8. 6Hz) , 7.02 (2H, d, J=9.2Hz), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.82 (2H, d, J=8.6Hz), 8. 06 (iH, d, J=8Hz) , 8.25 (11-7, d, J=6.7Hz) , 8.43 (1H, d, J=6.7HZ), 8.85 (1H, s) IR (KBr) . 3350, 1668, 1629, 1510 cm-1 7-PB-MASS : m/z = 1345 (M+Na) --lemental A_nalysis Calcd. ior C58H79N10022SNa6H20 C 48.67, H 6.41, N 9.78 Founc C 48.80, H 6.46, N 9.82 Example 24 Major product TR (KBr) . 3350, 1668, 1-631, 1047 cm-1 NI-'R (DMSO-d6, 5) : 0.96 (3H, d, J= 6. 7 H z ), 1. 08 (3 H, d, J=5.7Hz), 1.2-1.6 110H, m,), 1.6-2.4 (8H, m), 2.5-2.7 (IH, m), 3.18 (1H, n~.), 3.21 (3H, s), 3.29 (2H, t, J=6.4Hz), 3.0-3.83 (2H, m), 3.83-4.6 (13H, m), 4.7-5.4 (11H, m), 5.51 (1H, d, J=5.9Hz), 6.73 (1H, d, J=8.2Hz), 6.83 (1H, d, J=8.2Hz), 6.85 (1H, s), 7.04 (2H, d, J=8.4Hz), 7.06 (1H, s), 7.31 (1H, s), 7.2-7.5 (2H, m), 7.67 (2H, d, J=8. 4Hz) , 7.71 (2H, d, J=8. 4Hz) , 7.96 (2H, d, J=8.4Hz), 8.06 (1H, d, J=8Hz), 8.25 (1H, d, J=6.7Hz), 8.74 (1H, d, J=6.7Hz), 8.84 (1H, s) FP.B-MASS m/z = 1319 (M+Na) Elemental Analvsis Calcd. 'for C57H77N8023SNa=4H2O
C 49.99, H 6.26, N 8.18 Found : C 49.74, H 6.27, N 8.06 Minor product IR (KBr) : 3350, 1668, 1631 cm-1 NMR (DMSO-d6, b) : 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.7Hz), 1.2-1.6 (6H, m), 1.6-2.1 (7H, m), 2.1-2.5 (3H, m), 2.5-2.7 (1H, m), 3.18 (1H, m), 3. 6-3. 8(2H, m), 3. 8-4 . 6 (13H, m), 4. 6-5. 2(12H, m), 5.26 (1H, d, J=4 . 6Hz ), 5.53 (1H, d, J=5.8Hz), 5. 6-6.0 (_'r', r.:) , 6.73 (iH, d, J=8.2Hz), 6.83 (1H, d, J=8.3Hz), 6.8-E) (1H, s), 7.04 (2-H, c, J=8.5Hz) , 7.06 (1H, s; , 7.30 (1H, s) , 7.2-7. 5 (2H, m) , 7. 68 (2H,. d, J=8.5F.z) , 7.72 (2H, d, J=8.5Hz), 7.96 (2H, d, J=8.5Hz), 8.06 (1H, d, J=8Hz), 8.25 (?H, d, J=6.7Hz), 8.74 (1H, d, J=6.7Hz) , R.8_5 (1H, s!
FAB-MASS m/z = _87 (M+Na) Elemental Analvsis Calcd. for C3-6H73N~NaC22S=7H2C
C 48.34, H 6.30, N 8.05 Found . C 48.19, H 6.19, N 7.99 Exampie 25 IR (KBr) . 3350, 2935, 2873, 1668, 1629, 1538, 1506, 1438, 1257, 1049 cm-i NMR (DMSO-d6, o) 0.9-1.0 (6'r:, m), 1.08 (3H, d, J=5 . 7Hz ), 1. 2-1 . 6 (4H, *_n) , 1. 6-2 . G ( 5:i, m), 2.1-2.4 (3H, m), 2.5-2. 6(1H, :a) , 3.1-3.2 (1H, m), 3. 6-4 . 6 (15H, zn) , 4. 7-5 . 2 ( l OH, m) , 5.26 (1H, c J=4.5Hz), 5.55 (1H, d, J=5.9Fz), 6.7-6.9 (3H, m), 7.0-7.6 (7H, :n) , 7.85 (2H, d, J=8.6Hz), 7.9-8.2 (4H, m), 8.26 (1H, d, J=7. 7Hz) , 8. 8-9. C(2H, m) FAB-MASS : m/z = 1314.3 (M+Na)~
Elemental Analysis Calcd. fo: C56H70N9C23NaS=7H2O
C 47.42, H 5.97, N 8.89 Found . C 47.33, H 5.85, N 8.73 xamr) e 26 30 T a solution of The Starting Compound (1 g) and succinimido 4-(4-octyloxyphenvl)piperazir.e-l-carboxvlate (0.45 g) in N,N-dimethylformamicie (10 ml) was added 4-dimethylaminopyridine (0.141 g), and stirred for 5 days at 50 C. The reaction mixture was pulverized with ethyl acetate. The precipitate was collected bv filtration, and WO 96/11210 PC'I'/JP95/01983 dried under reduced pressure. The powder was dissolved in water, and subjected to column chromatography on ion exchage resin (DOWEX-50WX4) eluting with water. The fractions containing the object compound were combined, and subjected to column chromatography on ODS (YMC-gel=O1_DS-.WrS-50 ) eluting with 50 : acetonitrile aqueous soluticn. The fractions containing the object compound were combined, and evaporated under reduced pressure to remove acetoni:.riie. The residue was lvoTJP_llized to give crude The Object Compound (23). The powder of crude The Objeco Compound (23) was purified by preparative HPLC
utilizing a C18 u Bondapak resin (Waters Associates, Inc.) which was eluted with a solvent system comprised of 5cetonitrile-pH 3 phosphate buffer = 40:60) at a flow rate of 80 ml/minute using a Shimadzu LC-8A pump. The column was monitored by a UV detector set at 240 um. The fractions containing the object compound were combined, and evaporated under reduced pressure to remove acetonitrile. The residue was subjected to column chromatography on ion exchange resin (DOWEX-50WX4) eluting with water. The fractions containing the object compound were combined, and subjected to coiumn chromatography on ODS (YMC-gel=ODS-AM=S-50) eluting with 50 acetonitrile aqueous solution. The fractions containing the object compound were combined, and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give The Object Compound (23) (60 mg).
IR (KBr) . 3347, 1629, 1511, 1245 crn-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.7Hz), 0.95 (3H, d, J=6.8Hz), 1.06 (3H, d, J=5.9Hz), 1.2-1.5 (10H, m), 1.55-1.92 (5H, *_n), 2.0-2.65 (4H, m), 2.8-3.05 (5H, m), 3.2-4.47 (17H, m), 4.6-5.6 (12H, m), 6. 6-7. 0(7H, m), 7.03 (1H, s), 7.2-7.5 (3H, m), 7.9-8.3 (3H, m), 8.84 (1H, s) FAB-MASS : m/z = 1297 (M1TNa) Elemental Analysis Calcd. for C54H79N10022SNa=6'ri20=CH3CN:
r47.22, H 6.65, N 10.82 Found : C 47.58, H 7.05, N 10.85 Example 27 To a suspension of 1-hydroxybenzotriazole (0.53 g) and 2- (4-octyloxyphenoxy) acetic acid (i g) in dichiormethane (30 ml) was added 1-ethyl-3-(3'-di*_~.ethylaminopropyl ) carbodi i mide hydrochloride (WSCD=HC1) (0.866 g), and stirred for 3 hours at ambient Lemperature.
The reaction mixture was added te water. The organic layer was taken, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 1-[2-(4-octyloxyphenoxy)acetyl]benzotriazole 3-oxide (892 mg). To a solution of The Starting Compound (1.79 g) and 1-[2-(4-octyloxyphenoxy)acetyl]benzotriazoie 3-oxide (892 mg) in N,N-d.imethylformamide (18 ml) was added 4-(N,N-dimethylamino)pyridine (0.297 g), and stirred for 12 hours at ambient temperature. The reaction mixture was pulverized with ethyl acetate. The precipitate was collected by filtration, and dried under reduced pressure.
The powder was added to water, and subjected to ion-exchange column chromatography on DOWEX-50WX4, and eluted with water. The fractions containing the object compound were combined, and subjected to column chromatogranh on ODS (YMC-gel=ODS-AM=S-50 ), and elured with 50 =. methanol aqueous solution. The fractions containing the object compound were combined, and evaporated under reduced pressure to remove methanol. The residue was lyophilized to give The Object Compound (24) (1.75 g).
IR (KBr) : 3350,.1666, 1629, 1228 cm-1 NMR ( DMSO-d6, b) : 0.86 ( 3?i, t, J=6 . 9Hz ), 0.95 ( 3H, d, J=6.7Hz), 1.04 (3H, d, J=5.7Hz), 1.15-1.5 ( l OH, m), 1. 55-2 . 0 (5H, r.t) , 2. 05-2 . 5 (4H, m), 3.16 (1H, m), 3.72 (2H, m) , 3.88 (3H, t, J=6.3Hz), 4.41 (2H, s), 3.93-4.6 (iiH, m), 4.69-5.25 (10H, m), 5.28 (iH, d, J=4.3Hz), 5.57 (1H, d, J=5 . 7Hz ), 6. 73 (1H, d, J=8 . 2Hz ), 6. 8-7 . 0 , (5H, m), 7.04 (1H, s), 7.09 (iH, s), 7.3-7.4 (2H, m), 7 . 92-8 .17 (2H, r.) , 8.29 (1H, d, J=7.5Hz), 8.84 (1H, s) FAB-MASS : m/z = 1243 (M++Na) Eiemental Analysis Calcd. for C51H73N8023SNa=4H2O
C 47.36, H 6.31, N 8.66 Found : C 47.22, H 6.44, N 8.37 The Object Compounds (28) to (31) were obtained according to a similar manner to that of Example 27.
Example 28 IR (KBr) : 3350, 2933, 1664, 1628, 1446, 1205, 1045 cm-1 NMR (DMSO-d6, b) : 0.8-1.1 (9H, m), 1.2-2.0 (19H, m), 2.1-2.3 (3H, m), 3.6-3.8 (4H, m), 3.9-4.4 (13H, m), 4. 6-5 . 0 (8H, m), 5.07 ( iH, d, J=5 . 6Hz ), 5.14 ( iH, d, J=3 . 2Hz ), 5.23 (1H, d, J=4 . 3Hz ), 5.46 (1H, d, J=6.7Hz), 6.7-6.9 (3H, m), 7.04 (iH, s), 7.2-7.5 (6H, m), 7.8-8.0 (3H, m), 8.05 (iH, d, J=8.4Hz), 8.2-8.4 (2H, m), 8.83 (iH, s) FAB-MASS : m/z = 1360 (M*+Na) Elemental Analysis Calcd. for C59H8CN9023SNa=6H2O
C 48.99, H 6.41, N 8.72 Found : C 48.92, H 6.37, N 8.64 Example 29 IR (KBr) 3350, 2927, 1668, 1627, 1535, 1515, 1452, 1440, 1286, 1045 c:n-1 NMR (DMSO-d6, S) : 0.83 (3H, t, J=6.7Hz), 0.95 (3H, d, J=6.7Hz), 1.07 (3H, d, J=5.9Hz), 1.2-1.4 i.6-2.0 (5H, m), 2.1-2.4 (3H, m), 2.6 2 . 82 (2H, t, J=7 . 4Hz ) , 3 . _-3 . 2 (1H, m) , 3.6-4.5 (13H, m), 4.7-5.2 (11H, m), 5.4-5.6 (1H, m), 6.72 (1H, d,. J=8 . 2Hz ), 6.82 (2H, d, J=8.1Hz), 7.03 (1H, s), 7.2-7.4 (3H, m), 7.47 (1H, d, J=8.5Hz), 7.69 (iH, d, J=8.5Hz), 8.1-8.2 (2H, m), 8.23 (1H, d, J=8.4iiz), 8.62 (1H, d, J=7.8Hz), 8.83 (1H, s) FP.B-MAS S: m/ z= 1251 (M++Na ) Elemental Analysis Calcd. for C52=~73~'T1002i SNa=5H2O
C 47.34, H 6.34, N 10.61 Found C 47.30, H 6.45, N 10.45 Example 30 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.8Hz), 0.96 (3H, t, J=6.7Hz), 1.05 (3H, t, J=5.8Hz), 1.2-1.5 (10H, m), 1.6-2.0 (5H, m.), 2.2-2.4 (3H, m), 2.5-2.6 (iH, m), 3.1-3.2 (1H, *_n), 3.7-4.5 (15H, m), 4. 7-5 . 0 ( 8H, m), 5.10 (1H, d, J=5 . 6Hz ), 5.17 (iH, d, J=3.lHz), 5.26 (iH, d, J=4.5Hz), 5.52 (1H, d, J=5 . 8Hz ) 6.73 (~H, d, J=8 . 2Hz ), 6. 8-7 . 0 (3H, m), 7.04 (1H, s), 7.2-7.4 (3H, m), 8.0-8.3 (3H, m), 8.68 (1H, d, J=2.3Hz), 8.7-8.8 (1H, m), 8.85 (1H, m) FAB-MASS : :n/z = 1214 (M++Na) Elemental Analysis Calcd. for C49H70N9022SNa=4H2O
C 1,116.55f H 6.22, N 9.97 Found : C 46.29, H 6.18, N 9.71 Example 31 IR (Nujol) : 3342, 2210, 1668, 1623 cm-1 NMR (DMSO-d6, b) : 0.88 (3H, t, J=6.7Hz), 0.97 (3H, d, J=6.7Hz), 1.08 (3H, d, J=6.7Hz), 1.20-1.60 (8H, m), 1.60-2.00 (5H, m), 2.05-2.50 (4H,-m), 3.05-3.30 (1H, m), 3.60-4.60 (15H, m),_4.65-5.18 (10H, m) , 5.24 (iH, d, 1=4.5Hz) , 5.58 (lri, d, J=6.OHz), 6.68-7.10 (4H, m) 7.15-7.6~ (5H, m), 7. 80-8 . 30 (6H, m) , 8. 84 ( li:, s), 9. 18 (1H, d, J=7.7Hz) FAB-MIASS : m/z = 1273.5 (M++Na;
Fxamnle 32 To a solution of 6-hentyloxy-2-naphthoic acid (0.358 g) and triethylamine (0.174 ml) in N,N-dimethylrormamide (10 ml) was added ciiphenylphosphoryl az i cie (0.4 ml), an ;
stirred for an nour at ambient temperature. Then, the reacTion mixture was stirred -for ar- hour at 100 C. After cooling, to the reaction mixture was added The Starting Compound (1 g) and L--(N,N-dimethylamino)pyridine (0.14:) g) , and stirred for 10 hours at a:p-bi enz temperature. The reaction mixture was pulverized with ethyl acetate.
The precipitate was collected by filtration, and dried under reduced pressure. The powder was dissolved in water, and subjected to column chromatography on ion exchange resin (DOWEX-50WX4) eluting with water. The fractions containing the object comnound were combined, and subjected to column chromatography on ODS (YMC-gel=ODS-PM=S-50) eluting with 50'~ acetonitrile aaueous solution. The fractions containing the object compound were combined, and evaporated under reduced pressure to re-ve acetonitrile. The residue was lvophwlized to give The Object Compound (29) (0.832 g).
IR (KBr) : 3350, 1664, 1629, 1546, 1240 cm-1 NMR ( DMSO-d6, b) . 0.88 (3H, t, J=6 . 6Hz ), 0.97 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.9Hz), 1.2-1.55 (8H, m), 1.55-2.0 (5H, m), 2.1-2.5 (4H, m), 3.18 (1H, m), 3.6-3.8 (31E, m), 3.9-4.5 (13H, m), 4.7-4.95 (3H, m), 5.0-5.3 (7H, m), 5.59 (1H, d, J=5 . 8Hz ), 6.52 (1H, d, J=8 .1Hz ), 6.73 (1H, d, J=8.2Hz), 6.83 (1H, d, J=8.2Hz), 6.90 (1H, s), 7.0-7.15 (3H, m), 7.2G (I H, s), 7.27-7.4 (3H, m) , 7. 6-7. 7 (2H, m) , 7. 87 (1H, s), 7. 95-8 .2 ( 2'r:, m), 8.69 (1H, s), 8.85 (;H, s) FAB-MS m/ z= 1264 (M++Na ) Elemental A..naivsis Calcd. fcr C53i:7;N9022SNa=5H2O
C 47.78, H 6.20, N 9.46 Found . C 47, .65, H 6.42, N 9.34 The Objecz Co:npound (33) was obtained according to a similar manner to that of Example 32.

Example 33 7k (KBr) 3350, 1666, 1629, 153 7, 1240 c:n-1 NMR (DMSO-d6, (5) 0.87 (3H, t, J=6.7Hz), 0.97 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.8Hz), 1.2-1.55 (8H, m), 1.55-2.0 (5H, m), 2.07-2.6 (4H, m), 3.18 (1H, m), 3.6-3.85 (3H, m), 3.9-4.5 (13H, m), 4.7-4.98 (3H, m), 5.0-5.3 (7H, m), 5.57 (1H, d, J=5.9Hz), 6.50 (1r, d, J=B. iHz) , 6.73 (1H, d, J=8.2Hz), 6.82 (iH, dd, J=8.2 and 1.7Hz) , 6.87 (1H, s), 6.97 (2H, d, J=8.8Hz), 7.05 (1H, d, J=1.7Hz), 7.10 (1H, s), 7.23-7.43 (2H, m), 7.38 (2H, d, J=8 . 8Hz ), 7.50 (2H, d, J=8 . 8Hz ), 7.52 (2H, d, J=8.8Hz), 8.0-8.15 (2H, m), 8.65 (1H, s), 8.84 (1H, s) FAB-MASS : m/z = 1290 (M++Na) Elemental Analysis Calcd. for C55'r_74Ng02LSNa=7H2O
C 47.38, H 6.36, N 9.04 Found : C 47.67, H 6.53, N 9.03 Example 34 A solution of The Starting Comnound (2.45 g), 3-[4-(4-pentylphenyl)phenyl]propiolic acid (0.90 g), 1-ethyl-3-(3'-dimethvlaminopropyl)carbodiimide hvdrochloricie (WSCD-riCl) (0.59 g) and triethylamine (0.43 ml) in N,N-ciimethylformamide (50 ml) was stirred for 15 hours at ambient temperature. The reaction mixture was diluted with ethyl acetate, and the resultant precipitate was collected by filtration, and washed in turn with ethyl acetate and diisopropyl ether, and dried under reduced pressure. The powder was dissolved in water, and was subjected to column chromatography on ion exchange resin (DOWEX-50WX4 (Na form, 50 ml)) eluting with water. The fractions containing the object compound were combined, and subjected to reversed phase chromatography on ODS
(YMC-gel=ODS-AM=S-50, 50 ml) eluting with (water acetonitrile = 10:0 - 7:3, V/V). The fractions containing the object compound were combined, and evaporated under reduced pressure to remove acetonitrile. The residue was lyophilized to give The Object Compound (31) (1.53 g).
IR (Nujol) : 3351, 2212, 1668, 1627 cm-1 NMR (DMSO-d6, b) : 0.87 ( 3H, t, J=6 . 5Hz ), 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.8Hz), 1.20-i.50 ( 4H, r.m) , 1. 50-2 . 00 ( 5H, m), 2. 03-2 . 55 (4H, rc 2.62 (2H, t, J=7.5Hz), 3.17 (1H, t, J=8.4Hz), 3.55-4.57 (15H, m), 4.65-5.13 (9H, m), 5.16 (1H, d, J=3.2Hz), 5.24 (?H, d, J=4.5Hz), 5.58 (1H, d, J=5. 8Hz) , 6.67-6.90 (3H, m), 6. 93-7 .10 (2H, :n) , 7.15-7.50 (4H, m), 7.50-7.90 (6H, m), 8.06 (iH, d, J=8.4Hz), 8.15 (iH, d, J=7.7Hz), 8.84 (1H, s), 9.19 (1H, d, J=7.lHz) FAB-MASS : m/z = 1255 (MT+Na) Elemental Analysis Calcd. for CSSii69N8021SNa=4H20 C 50.61, H 5.95, N 8.58 Found : C 50.47, H 6.00, N 8.54 Example 35 To a suspension of 1-hydroxybenzotriazole (501 mg) and 4-(4-heptylphenyl)benzoic acid (1 g) in dichloromethane (30 ml) was added 1-ethyl-3-(3'-WO 96/11210 PCTlJP95/01983 dimethylaminopropyl) carbodi imide hydrochloride (WSCD=uC' ) , (839 mg), and stirred for 3 hours at ambient temperature.
The reacticn mixture was added cc water. The organic layer was separated, and dried over magnesium sulfate.
The magnesium sulfate was filtered cff, and the filtrate was evaporated under reduced pressure to give 1-[4-(4-heptylphenyl)benzoyl]benzotriazole 3-oxide. To a solution of The Starting Compound (2.49 g) and 1-[4-(4-heptylphenyl)benzoyi]benzotriazole 3-oxide in N,N-dimethylformamide (25 ml) was added 4-(N,hT-ciimethylamino)pyridine (381 mg), and stirred for 12 hours at ambient temperature. The reaction mixture was pulverized with ethyl acetate. The precipitate was collected by filtration, and dried under reduced pressure.
The residue was dissolved in water, and subjected to column chromatography on ion exchange resin (DOWEX-50WX4) eluting with water. The fraction containing the object compound were combined, and subjected to column chromatography on ODS (YMC-gel=ODS-.ANI=S-50) eluting with 301 acetonitrile aqueous solution. The fractions containing the object compound were combined, and evaporated under reduced pressure to remove acetonitrile.
The residue was lyophilized to give The Object Compound (32) (1.99 g).
IR (Nujol) 3350, 2852, 1749, 1621, 1457, 1376, 1045 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.9Hz), 1.5-1.7 (2H, m), 1.7-2.2 (3H, m), 2.2-2.5 (3H, m), 2.6-2.8 (3H, m), 3.1-3.2 (1H, m), 3.7-4.6 (13H, m), 4. 7-5 . 2 (8H, m), 5.12 (1H, d, J=5 . 5Hz ), 5.18 (1H, d, J=2 . 9Hz ), 5.27 (1H, d, 3=4 . 4Hz ), 5.54 (1H, d, J=5.8Hz), 6.7-6.9 (3H, n-;), 7.05 (11-:, s), 7.2-7.4 (5H, m), 7.65 (2H, d, J=B.OHz), 7.74 (2H, d, J=8 . 3Hz ), 7.98 (2H, d, J=8 . 3Hz ), 8.11 - 20? -(1H, d, J=8.7Hz) ?8 (iH, d, J=8.4Hz) , 8.7b (1a, d, J=7 . 3Hz ), 8. 8~_ ( IH, s) FP3-MASS . ir.' z = 1259 (M+~Na) Elemental lznaivsis Calcd. for C55H73N80?1SNa=5H2O
C 49.77, H 6.3C, N 8.44 Found : C 49.98, H 6.44, N 8.41 The Object Compounds (36) to (107) were obtained according to a similar manner to that of Ex_am-cle 1.
1 o Fxample 36 IR (KBr) 3350, 1675.8, 1629.6, 1515.8 NMR (DMSO-d6, b) : 0.86 (6H, d, J=6.6Hz), 0.96 (3H, d, J=6. 6Hz) ,.'1. 06 (3H, d, J=5. 7Hz) , i. 1-1 . 3 (2H, m), 1.4-2.0 (6H, m), 2.0-2.7 (4H, m), 3.1-3.5 (9H, m), 3.66 (2H, t, J=7 . 3Hz ), 3. 6-4 . 5 (13H, ::) , 4. 7-5 . 6 (12H, m), 6.73 (1H, d, J=8.3Hz), 6.82 (lH, d, J=8.3Hz), 6.8-6.9 (1H, m), 7.02 (2H, d, J=9.0Hz), 7.04 (1H, s), 7.11 (2H, d, J=9.OHz), 7.2-7. 6(3H, m) , 7.50 (2H, d, J=9. OHz) , 7.82 (2H, d, J=9. 0Hz) , 8.1- (1H, d, J=8.5Hz), 8.28 (1H, d, J=8.5'r:z), 8.33 (1H, s), 8.45 (1H, d, J=7.OHz), 8.84 (1H, s) FAB-MASS : m/z = 1412 (M+Na) Elemental Analysis Calcd. for C60H80N13022SNa=9H2O
C 46.42, H 6.36, N 11.73 Found : C 46.64, H 6.43, N .62 ExamPle 37 IR (KBr) : 3350, 1668.1, 1629.6, 1268.9 cm-1 ?QMR (DMSO-d6, S) : 0.85 (3H, t, J=06.6Hz), 0.9E ;3H, d, J=6. 7Hz) , 1.07 (3H, d, J=5. 9Hz) , 1.2-1 . 4 ;--OH, m), 1.4-2.0 (5H, m), 2.0-2.5 (4H, m), 2.61 (2H, t, J=7.2Hz), 3.1-3.3 (1H, m), 3.6-4.5 (13H, m), 4.40 (2H, s), 4.6-5.3 (11H, m), 5.60 (lh, d, J=5.8Hz), 6.73 ( iH, d, J=8 . 2?iz ), 6.82 (1H, d, J=8 . 2Hz ), 6.6-6.9 (1H, mi, 7.04 (1H, s), 7.0-7.1 7.32 (2H, d, J=8.5Hz) , 7.2-7. 2m) , 7.58 (2H, d, J=8 . 5Hz ), 7. 93 (1H, d, J=7Hz ), B. 04 (1H, a, J=9.4Hz) , 8.41 (1H, s) , 8.44 (1H, d, J=9.4Hz) , 8.84 (1H, s) FAB-MASS : m/z = 1294 (M+Na) Flemen-a_ Aralysls Calcd. ~o- ~-53"7aNi , 022SNa=7H2O
C 4_=.S2, H 6.34, N 11.02 Found . C 45.47, H 6.27, N 10.93 Example 38 Major product ?R (KBr) 3349.7, 1670.1, 1627.6, 1508.1 cm-1 NY,R (DMSO-d6, (5) : 0.96 (3H, d, J=6. 6"rIz) , 1.06 (3H, d, J=5.7Hz), 1.2-1.6 (8H, m), .1.6-2.1 (5H, m), 2.1-2.7 (4H, m), 3.0-3.2 (SH, m), 3.21 (3H, s), 3.30 (2H, t, J=6.5Hz), 3.3-3.5 (4H, m), 3.6-4.5 (15H, m), 4. 7-5 . 3 (11H, m), 5.49 (1H, d, J=5 . 9Hz ), 6.73 ( iH, d, J=8.3Hz), 6.8-6.9 (4H, m), 6.95 (2H, d, J=9.2Hz), 7.01 (2H, d, J=8.5Hz), 7.04 (1H, s), 7.20 (1H, s), 7.2-7.5 (2H, m), 7.81 (2H, d, J=9.SHz), 8.09 (1H, d, J=8.7Hz), 8.28 (1H, d, J=8.7Hz), 8.45 (iH, d, J=6 . 7Hz ), 8.84 ( iH, s) FAB-MASS : m/z = 1389 (M+Na) Elemental Analysis Calcd. 1 or C60h83~''10O23SNa8H2C
C 47.68, H 6.60, N 9.27 Found : C 47.83, H 6.72, N 9.27 Minor product iR (KBr) : 3338.2, 1646.9, 1511.9 cm-~
NTMIR (DMSO-d6, b) : 0.90 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.7Hz), 1.3-1.6 (4H, m), 1.6-2.7 (11H, m), 3.G-3.2 (5H, .m), 3.3-3.5 (4H, m), 3.6-4.5 (15H, m), 4.7-5.3 (13H, m), 5.48 (IH, d, J=5.9Hz), 5.7-6.0 (1H, m), 6.73 (1H, d, J=8.2Hz), 6.8-6. 9(4?I, m), 6. 94 (2H, d, J=9. 3Hz ), 7. 01 (2H, d, J=8. 6Hz ), 7. 04 'r?, s; ,-.2-7.5 (3H, m) , 7.81 (2H, d, J=8. 6Hz) , 8 . C 6 ( ,~~'ri, .~'., J=8. 7Hz ) , 8 . 25 (1H, d, J=8 . 7Hz ) , 8. 42 (1H, d, J=6 . 7Hz ), 8.84 (1H, s) FAB-hL.SS . m./z = 1357 (M+Na) Elemental Pnaysis Calcd. fcr C59H79N10O22SNa 9H2O
C 47.32, H 6.53, N 9.35 Found C 47.08, H 6.66, N 9.25 Exampie 39 I~ (KBr) 3350, 1670.1, 1631.5, 1510.0, 1234.2 cr.',-1 NIMIB (DMSO-d6, 5) . 0.87 (3H, t, J=6 . 7Hz ), 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.6Hz), 1.2-1.5 (8H, m), 1.6-2.? (5H, m), 2.1-2.7 (4H, m), 3.0-3.3 (5H, m), 3.3-3.5 (4H, _n), 3.6-3.8 (2H, m), 3.88 (2H, d, J=6.4Hz), 3.8-4.5 (11H, m),4.7-5.1 (8H, m), 5.10 (1u, d, J=5. 6Hz) , 5.16 (1H, d, J=3.lHz), 5.25 (1H, d, J=4.5Hz), 5.48 (1H, d, J=5.9Hz), 6.73 (1H, d, J=8 . 2Hz ), 6. 8-6 . 9 (4H, r.l) , 6.94 (2H, d, J=9. 3Hz ), 7.01 (2H, d, J=8.7Hz), 7.04 (1H, s), 7.2-7.5 (3H, m), 7.81 (2H, d, J=8.7Hz), 8.06 (1i?, d, J=8Hz), 8.25 (1H, d, J=6.7Hz), 8.43 (1H, d, J=6.7Hz), 8.85 (1H, s) FJz.B-MASS m/z = 1359 (M+Na) Elemental Analysis Calcd. for C59h81~'T10022SNa=5H90 C 49.64, H 6.43, N 9.81 Found C 49.49, H 6.54, N 9.72 Example 40 IR (KBr) 3355.5, 1670.1, 1627.6, 1510.0 1236.1 cm--NMR (DMSO-d6, b) : 0.89 (6H, d, J=6.5Hz), 0.96 (3H, d, J=6.7Hz), 1.05 (3H, d, J=5.7Hz), 1.2-1.4 (2H, m), 1. 5-2 .1 (6H, m), 2. 1-2 . 7 (4H, nm) , 3. 0-3 . 6 (9H, r.:) , 3. 6-4 . 5 (15H, m), 4.5-5.4 (12H, r~~) ,'6.73 (iH, d, J=8.2Hz), 6.8-6.9 (4H, m), 6.96 (2::, d, J=9. 6Hz) , WO 96/11210 PCTlJP95/01983 7.02 (2H, d, J=8.7Hz), 7.05 (IH, s) , 7.2-7.5 (3H, m), 7.8% (2H, d, J=8.7Hz), 8.08 (1H, ;, J=8Hz), 8.27 (1H, d, J=6.7Hz) , 8.46 (1H, d, J=6.7Hz) , 8.8~
(1H, s) FAB-MASS : m/z = 1345 (M1Na) Elemental Analysis Calcd. .
':or C58r79N1C022SNa=8H?0 C 47.47, H 6.52, N 9.54 Found : C 47.47, H 6.54, N 9.51 Example 41 IR. (KBr) . 3347.6, 1668.1, 1629.6, 1510.0, 1234.2 cm-1 NMR (DMSO-d6, 5) : 0.89 (3H, t, J= 7.OHz) , 0.96 (3H, d, J=6.7Hz) , 1.05 (3H, d, J=5.8Hz),_. 2-1 .5 (4H, m), 1. 6-2. 1(5H, m), 2.1-2.7 (4H, m), 3. 0-3. 6(9H, m), 3.6-3.8 (2H, m), 3.8-4.5 (13H, m;, 4.7-5.6 (i2H, m) , 6.73 (1H, d, J=8.2Hz), 6.8-6. 9(4H, m) , 6.96 (2H, d, J=8.7Hz), 7.02 (2H, d, J=9. 0Hz) , 7.04 (1H, s), 7.2-7.5 (3H, m), 7.82 (2H, d, J=8.7Hz), 8.07 (1H, d, J=8Hz), 8.27 (1H, d, J=6.7Hz), 8.45 (1H, d, J=6.7Hz), 8.85 (1H, s) FAB-MASS m/z = 1331 (M+Na) Eiemental Analysis Calcd. for C57H77N10O22SNa6HqO C 48.30, H 6.33, N 9.88 Found C 48.20, H 6.58, N10.03 Example 42 Mixture zroduct IR (KBr) : 3344, 1670.1, 1631.5 cm-1 NA'IR (DMSO-d6, (5) : 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.9Hz), 1.2-1.5 (8H, r.m), 1.6-2.1 (7H, m), 2.1-2.7 (4H, m), 3.1-3.3 (1H, m), 3.6-4.5 (15H, m), 4.45 and 4.70 (2H, t, J=7. 1Hz) , 4.6-5.3 (11H, m), 5.52 (1H, d, J=5.9Hz), 6.73 (iH, d, J=8.2Hz), 6.83 (1H, d, J=8.2Hz), 6.85 (iH, s), 7.03 (2H, d, J=8.6Hz), 7.05 (1H, s), 7.2-7.5 (3H, m), 7.68 (2H, d, J=8 . 6Hz) , 7.71 (2H, d, J=8. 4Hz) , 7.96 (2H, d, J=8.4Hz), 8.12 (1H, d, J=c.SHz), 8.30 (1H, d, J=7.0Hz) rAB-MASS m/z = 1357. (M+Na) Elemental Anaiysis Calcd. ~oY C57H75Iv120225Na4ri20 C 48.64, H 5.94, N 11.94 Found C 48.91, H 5.88, N1i.86 Example 43 -R (KBr) : 3350, 1666.2, 1651.5 cm ~

NNR (DMSO-d6, (5) : 0.96 (3H, d, J=6 . 7Hz ), 1.05 ( 6H, d, J=6.3Hz), 1.06 (3H, d, J=5.7Hz;, 1.2-1.6 (10%, m;, 1.6-2.1 (7H, m), 2.1-2.7 (6H, 2.8-3.0 (2~, 3.0-3.2 (1141, m) , 3.4-3.7 (2H, m) , 3.6-3.8 (2H, m) , 3.8-4.5 (13H, m), 4.7-5.6 (12H, m), 6.73 (1H, d, J=8.2Hz), 6.8-7.0 (2H, m), 7.03 (2H, d, J=8.7Hz), 7.06 (1H, s), 7.2-7.5 (3H, m), 7.67 (2H, d, J=8.7Hz), 7.71 ('H, d, J=8.4Hz), 7.96 (2H, d, J=8.4Hz), 8.04 (-H, d, J=8.5Hz), 8.31 (1H, d, J=8.5Hz), 8.73 (1H, d, J=7.0Hz), 8.90 (1H, s) EAB-MASS m/z = 1402 (M+Na) Examlple 44 IR (KBr pelet) : 3350, 2929, 2856, 1670, 1631, 1510, 1243, 1045 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6.8Hz), 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.7Hz), 1.6-2.0 (5H, m), 2.2-2.5 (5H, m), 2.6-2.7 (1H, m), 3.0-3.3 (5H, m), 3.6-4.5 (19H, m), 4.77 (2H, d, J=5.9Hz), 4.8-5.1 (6H, m), 5.10 (1H, d, J=5 . 6Hz ), 5.1 7(1H, d, J=3.1Hz), 5.25 (1H, d, J=4.5Hz), 5.50 (1H, d, J=5.8Hz), 6.7-7.0 (8H, m), 7.04 (1H, s), 7.2-7.4 (3H, r.m), 8.0-8.2 (2H, m), 8.26 (1H, d, J=8.OHz), 8.55 (1H, d, J=7 . 3Hz ), 8.67 (1H, d, J=1. 2Hz ), 8.85 (1H, s) =PB-NLASS : m/z = 1374.3 (M+Na+) Elemental Analysis Calcd. for C59H82N1!V22NaS=5.5H?0 C 48.82, H 6.46, N 10.61 Found : C 48.89, H 6.74, N i0.S0 Exampie 45 IR (KBr) : 3350, 2935, 1668, 1623, 1538, 1257, 1174, 1047 cm-1 NMR (DN_SO-d6, 5) : 0. 8-1 .? (6H, m), 1.09 (3H, d, J=5.7Hz), 1.2-1.6 (6H, at), 1.7-2.1 (SH, m.), 2.2-2.4 (3H, m), 2.5-2.6 (1H, m), 3.6-3.8 ;2H, m), 3.8-4.6 (14H, m), 4.8-5.2 (7H, m), 5.18 (1H, d, J=3. lHz), S.26 (1H, d, J=4.5Hz), 5.54 (1H, d, J=5.8Hz), 6. 7-7. 5 (9H, Q, 7.82 (1H, d, J=8 . 5Hz ), 7.96 (1H, d, J=8.7Hz), 8. 1-8. 4(5H, m), 8. 8-9. 0(2::, m) FAB-MASS m/z = 1302.6 (M+Na+) Elemental Analysis Calcd. for C55H70N9O23SNa=6H2O C 47.58, H 5.95, N 9.08 Found : C 47.46, H 6.04, N 9.05 Example 46 IR (KBr) : 3355, 2958, 1670, 1627, 1521, 1247, 1047 cm 1 NMR (DMSO-d6, b) : 0. 9-1 . 0 (6H, .n) , 1.08 (3H, d, J=5.6Hz), 1.4-1.6 (2H, m), 1.7-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.7-3.8 (2H, m), 3.9-4.6 (13H, m), 4.8-5.1 (8H, m), 5.11 (1H, d, J=5 . 6Hz ), 5.17 (1H, d, J=3 . 1Hz ), 5.26 (1H, d, J=4 . 5Hz ), 5.54 (1H, d, J=5 . 9Hz ), 6. 7- 6. 9 (3H, m), 7.0-7.2 (3H, m), 7.3-7.5 (3H, m), 7.7-7.9 (8H, 1*t) , 8.02 (2H, d, J=8.4Hz), 8.08 (1H, d, J=8.4Hz), 8.32 (1H, d, J=7.7Hz), 8.81 (iH, d, J=7.OHz), 8.85 (1H, s) FAB-MASS m/z = 1309.3 (M+Na)+
F.lementai Analysis Calcd. for C581=71N8022NaS=6H20 C 49.92, H c.CC, N 8.03 Found . C 49.92, H 5.97, N 8.03 Example 47 IR (KBr) . 3350, 2933, 1668, 1629, 1517, 1249, 1045 cm-1 NMR (DMSO-d6, b) . 0.88 (3H, :., J=6.7Hz) , 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.89z), 1.7-2.7 (8H, m), .. . 1- .-, ~ (1H, m), 3.6-4.7. (1 -., m) , 4 . 7-5. 2 ( 8H, m) , 5.18 (1??, d, J=3 . 1Hz ), 5.27 (1H, d, J=4 . 5Hz ), 5.56 (1-rI, d, J=5 . 8Hz ), 6. 7- 7. 0 (3H, m) , 7. 0-7 . 2 (3H, 7.2-7.,, (3H, m), 8.0-8.4 (6H, T), 8.85 (IH, _), 8.96 (1H, d, J=7.OHz), 9.07 (1H, s) FAB-MASS : m/z = 1276.6 (M+NaT) IS Elemental Analvsis Calcd. for C54H72N9022NaS=SH20 C 48.25, H 6.15, N 9.38 Found . C 48.10, H 6.14, N 9.30 Example 48 IR (KBr) : 3350, 2931, 1668, 1629, 1537, 1049 cm-1 P1MR (DMSO-d6, (5) : 0.86 (3H, t, J=6.9Hz), 0.9-1.5 (16H, m), 1.6-2.4 (8H, m), 2.5-2.7 (1H, m), 3.1-3.3 (1H, m), 3.5-5.6 (25H, m), 6.6-7.4 (8H, m), 7.8-8.4 (6H, m), 8.7-9. 0(2H, m), 9.00 (1H, d, J=2.4Hz) FAB-MASS : m/z = 1331.4 (M+Na*) Elemental Analysis Calcd. for C56H73N10023NaS=8H2C
C 46.28, H 6.17, N 9.64 Found . C 46.50; H 6.27, N 9.65 Example 49 IR (KBr pelet) 3300, 2931, 1668, 1650, 1629, 1538, 1515, 1268, 1049 cm-1 NMR (DMSO-d6,. 6) : 0.87 (3H, t, J=6.6Hz), 0.97 (3H, d, J=6.7Hz), 1.10 (3H, d, J=5.6Hz), 1.2-1.4 (6H, m), 1.5-1.7 (2H, m), 1.7-2.1 (3H, m), 2.1-2.4 (3H, m), 2.6-2.7 (3H, m), 3.1-3.2 (1H, m), 3.7-3.9 (2H, m), 3.9-4.5 (12H, m), 4.8-5.1 (7:, m) , 5.ii (1H, d, J=5.5Hz), 5.18 (?H, d, J=3.1Hz), 5.27 (1H, d, J=4.5Hz), 5.55 (11-1, d, J=5.8Hz), 6.7-7.0 (3H, m), 7.06 (1H, s), 7.3- 7._ (5H, Tn) , 7.72 (2H, d, J=8.2Hz), 7.9-8.2 (5H, m), 8.3-8.4 (4H, m), 8.9-9.0 (2H, m) FA3-T?kSS : m/z = 1260.5 (M+Na+) Elemental Analysis Calcci. for C6,H74N9022SNa=6H2O
C 50.58, H 5.98, N 8.70 Found : C 50.34, H 6.16, N 8.55 Example 50 IR (KBr) : 3369, 2958, 2935, 1670, 1629, 1525, 1473, 1247, 1047 cm-1 NMR (DMSO-d6, b) : 0.95 (3H, t, J=7.3Hz), 0.97 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.7Hz), 1.3-1.6 (2H, m), 1.7-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.7-4.6 (15H, m), 4.7-5.1 (8H, m), 5.10 (1H, d, J=5 . 6Hz ), 5.18 (1H, d, J=3 . 1Hz ), 5.26 (1H, d, J=4 . 4Hz ), 5.56 (1H, d, J=5 . 7Hz ), 6. 7-7 . u (3H, m), 7.1-7.2 (3H, m), 7.2-7.4 (3H, m), 7.70 (2H, d, J=8.6Hz), 7.78 (2H, d, J=8.4Hz), 8.1-8.4 (6H, m), 8.85 (1H, s), 8.99 (1H, d, J=7.OHz), 9.13 (1H, d, J=1 . 6Hz ) FAB-MASS : m/z = 1310.1 (M+Na)+
Elemental Analvsis Calcd. for C57H70N9022NaS=7H2O
~ 47.20, H 6.12, N 8.69 Found : C 47.42, H 6.19, N 8.92 Example 51 IR (KBr) : 3351, 2937, 2875, 1670, 1627, 1533, 1245, 1047 cm-1 NMR (DMSO-d6, S) : 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.7Hz), 1.5-1.7 (2H, m), _.7-2.1 (7H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.2 (1H, m), 3.7-3.8 (2H, m), 3.9-4.6 (15H, m), 4.7-4.9 (3ri, m), 5. 0-5 .~ ( 5H, m), 5.10 (1'i, d, J=5 . 6Hz ), S. 17 (1H, d, J=3 . lHz ), 5.26 ( iH, d, J=4 . 5Hz ), 5.52 (1H, d, J=5 . 9Hz ), 6. 7-7 . 1 (9H, m), 7. 2-7 . 5 (5H, m), 7.68 (2H, d, J=8.2Hz), 7.72 (2H, d, J=6.7Hz), 7.96 (2H, d, J=8.2Hz), 8.06 (1'ri, d, J=8.4Hz), 8.28 (1H, d, J=7.7Hz), 8.76 (1H, d, J=7.OHz), 8.8-5 (iH, s) FAB-MASS m/z = 1339.3 (M+Na+) Elemental Analysis Calcd. for C59H73N8023NaS=7H?0 C 49.09, H 6.08, N 7.76 Found : C 49.04, H 6.08, N 7.82 Example 52 IR (KBr) : 3350; 2954, 2937, 1670, 1631, 1440, 1257, 1047 cm-1 NMR (DMSO-d6, b) : 0. 89 (3H, t, J='. 8Hz) , 0.97 (3H, d, J=6.7Hz), 1.09 (2H, d, J=5.8Hz), 1.2-1.5 (6H, m), 1.7-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.2 (1H, m), 3.7-4.6 (15u, m), 4.7-5.3 (11H, m), 5.5-5.6 (1H, m), 6.7-6.9 (iH, m), 7.0-7.5 (6H, m), 8.0-8.4 (8H, m), 8.85 (1H, s), 8.96 (1H, d, J=7 . 0Hz ) APCI-MASS : m/z = 1329.0 (M+Na)j Elemental Anaiysis Calcd. for C56H7iNi0093NaS=6H2O
C 47.52, H 5.91, N 9.90 Found : C 47.42, H 6.05, N 9.90 Example 53 IR (KBr) : 3350, 2952, 1666, 1629, 1537, 1519, 1255 cm-1 NMR (DMSO-d6, b) : 0.89 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.4Hz), 1.08 (3H, d, J=5.6Hz), 1.7-2.4 (8H, m), 2.5-2.6 (1H, m), 3.7-4.5 (15H, m), 4.7-5.1 (8H, rr:), 5.11 (1H, d, J=5 . 5Hz ), 5.17 (1H, d, J=3 .1Hz ), 5. 2 6 (1H, d, J=3 .1Hz ), 5. 56 (1'r?, d, J=5 . 7Hz ), 6.73 (1H, d, J=8.2Hz), 6.7-7.0 (2H, m), 7.05 (1H, s), 7.13 (2: , ci, J=8.7Hz) , 7.2-7.5 (3H, m) , 7.97 (2ii, d, J=8.? ?~; , c .1-8.4 (6r, m), 8.85 (1H, s), 8.92 (1H, d, u T-'.OHz) - 5 FAB-N'~P_SS 1345.3 (M+Na) ~
Eiemental A_nalvsis Calcd. for ' 56fi71N1OC22S2Na 8'ri20 C 45.84, H 5.98, N 9.55 Found : C 45.87, H 6.07, N 9.55 Example 54 1R (KBr pelet) . 3350, 2931, 1670, 1652, 1628, 1442, 1247, 1047 cm-1 I%TY-R (DMSO-d6, 5) 0.86 (3H, t, J=6.6Hz), 0.97 (3H, d, J=6.8Hz), 1.12 (3H, d, J=6.8Hz), _.2-1.5 (10H, m), 1. 7-2 . 0 ( 5H, Tn) , 2. 2-2 . 4 (3H, m), 2. 5-2 . 6 (1'n', m), 3.1-3.2 (1H, m), 3.72 (2H, br), 3.8-4.5 (17H, m), 4 . 7-5 . 2 (9H, m) ,5.26 (1H, d, J=4 . 6Hz ), 5. 57 (1H, d, J=5 . 7Hz ), 6. 7-7 .1 (7H, :tt) , 7. 3-7 . 5 (3H, m), 7.66 (2H, d, J=8.7Hz), 8.1 0(1H, d, J=7. 6Hz) , 8.17 (1H, d, J=7.6Hz), 8.76 (1H, d, j=7.OHz), 8.85 (1H, s) FAB-MASS : m/z = 1293 (M+NaT) Elemental -Analysis Calcd. for C54H75Ni0022NaS=7Hq0 C 46.41, H 6.42, N 10.C2 Found : C 46.51, H 6.43, N 9.95 Example 55 1R. (KBr) : 3345, 2937, 1650, 1511, 1249, 1047 cm-~
I~?MR (DMSO-d5, b) : 0.91 (3H, t, J=7 . OHz ), 0.96 (3H, t, J=7.8Hz), 1.09 (3H, d, J=o.8Hz), 1.3-1.5 (4H, m), 1.6-2.1 (5H, m), 2.1-2.5 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.7-3.9 (2H, m), 3.9-4.6 (13H, m), 4.79 (2H, d, J=5.9Hz), 4.8-4.9 (lri, m), 4.9-5.2 (5H, m), 5.10 (1H, d, J=5 . 9Hz ), 5.17 (1H, d, J=3 .1Hz ), 5.25 ( li-i, d, J=4 . 6Hz ), 5.53 (1H, d, -=5 . 9Hz ), 6. 7-7 . 0 ( 3'r'., m) , 7. 0-7 . 2 (3H, m), 7.19 (1H, s), 7. 3-7 . 5 (3H, r'! ), 7. 7-8 . 1 ( 6'r., m), 8.08 d, J=10.OHz), 8.26 (1H, d, J=8.8Hz), 8.77 (1H, rr.) , 8.85 (1H, s) , 13.32 (1H, s) FAB-NLkSS m/ z= 1314 . 0 (M+Na )+
Elemental Pnalysis Calcd. for C56H71N10022SNa=8H2O
C 46.86, H 6.11, N 9.76 Found C 46.93, H 5.87, N 9.74 Example 56 IR (KBr) 3350, 2958, 2935, 2873, 11 606, _6210, 124, 7, 1045 cm-1 NMR (DMSO-d6, b) . 0.9-1.1 (6H, m), 1.08 (3H, d, J=6. OHz) , 1. 4-1. 6(2H, m), 1. 6-2. 1( 5H, m), 2. 1-2 . 4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1ii, m), 3.6-4.5 (15H, m), 4.7-5.1 (8H, m), 5.10 (1H, d, J=5.5Hz), 5.17 (1H, d, J=2.9Hz,), 5.25 (1H, d, 3=4.5Hz), 5.55 (1H, d, J=5.7Hz), 6.7-6.9 (3H, m), 7. ri-7.5 (8' m), 7.68 (2H, d, J=8. 9Hz) , 7.73 (2H, d, J=8. 3liz) , 8.01 (2H, d, J=8.3Hz), 8.10 (1H, d, J=8.4Hz), 8.26 (1H, d, J=7.7Hz), 8.8-9.0 (2H, m) FP.B-MIASS m/z = 1299.:, (M+Na)1 ~iemental Analysis Calcd. for C56H69N8O23NaS 6H2O
C 48.55, H 5.89, N 8.09 Found C 48.52, H 5.94, N 8.07 Examn e 57 IR (KBr) : 3355.5, 1662.3, 1629.6, 1267.0 cm-1 IqNR (DMSO-d6, b) : 0.88 (3H, t, J=6.8Hz), 0.93 (3'ri, d, J=8.4Hz), 0.97 (3H, d, J=6.7Hz), 1.2-1.5 (4H, m), 1.5-1.95 (5H, m), 2.1-2.45 (4H, m), 2.5-2.7 (4H, m), 3.17 (1H, m), 3.55-4.45 (14H, m), 4.6-5.3 (13H, m), 5.56 (1H, d, J=5.6Hz), 6.72 (1H, d, J=8.1Hz), 6.75 (IH, s), 6.77 (1:-i, d, J=8.1Hz), 7.04 (1H, s), 7.10 (1H, s), 7.2-7.45 (10H, m), 7.53 (4H, d, J=6 . 6Hz ), 7. 85 (1?:, d, J=7Hz ), 7. 92 (1H, d, J=7Hz) , 8. 05 (1 H, d, J=7Hz ), 8. 22 (1H, d, J=7Hz ), 8. 84 (1H, s) FAB-MASS : m/z = 1408.(M+Na) Examplz 58 IR (KBr) : 3347.8, 1664.3, 1631.5, 1245.8 c~-1 NMR (DMSO-d6, (S) : 0.86 (3H, L, j=6.6?iz), 0.96 13H, d, J=6.6Hz), 1.04 (3H, d, J=5.7Hz), 1.15-2.6 (21H, m) , 3 . = 6 (1H, m), 3 . .,-4 . S- (16H, m) , 4 . 6-5 . 4 (13H, m), 5.47 (1H, d, J=5.7H7), 6.73 (1H, d, J=8.2H7) 6.78-6.85 (4H, m), ~.05 (1H, s), 7.10 (1H, s), 7.10 (2H, d, J=8.6Hz), 7.25-7.4-E" (6H, m), 7.72 (, H, d, J=7Hz), 7.91 (1H, d, J=7Hz ), 8.01) (1H, d, J=9 . 3Hz ), 8.20 (1H, d, J=7Hz ), 8.85 (1H, s) FAB-MASS m/z = 1390 (M+Na) Elemental Ar.alysis Calcd. ffcr C60H82N9OqaSNa=5H?O
C 49.41, H 6.36, N 8.64 Found C 49.77, H 6.71, N 8.71 Example 59 IR (KBr) : 3353.6, 1670.1, 1627.6, 1247.7 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6. 5Hz ), 0.97 (3H, d, J=6.8Hz), 1.01 (3H, d, J=5.4Hz), 1.1-1.55 (12H, m), 1.55-1.95 (SH, m), 2.05-4.7 (4H, :r.), 3.16 (1H, m), 3.5-4.5 (16H, m), 4.6-5.3 (13H, m), 5.55 (1H, d, J=5 . 6Hz ), 6. 7-6 . 9 (5H, m) , 7.05 (1"r., s), 7. 1 (1H, s), 7.15 (1H, d, J=8.5Hz), 7.25-7.5 (6H, m), 7.7/3 (1H, d, J=8 . 4Hz ), 7. 92 (1H, d, J=7Hz ), 8.08 (1H, d, J=8.4Hz), 8.18 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1390 (M+Na) Example 60 NMR (DMSO-d6, 5) . 0.85 (3H, t, J=6 . 6Hz ), 0.96 (3H, d, J=6.6Hz), 1.05 (3H, d, J=5.6Hz), 1.1-1.5 (22H, m), 1.5-2.5 (9H, m), 2.5-3.5 (4H, m), 3.5-4.45 (luH, m) , 4.4~-5.45 (12H, m) , 6.72 (11-i, d, J=8.2Hz) ,E .79 (1H, s) , 6. 81 (1H, d, J= 8. 2'riz ), 7. 04 (111, s) , 7. 05-7. 5 ( 8H, m), 7. 9-.8 . 3 (3H, m), 8.84 (1H, s) FP13-M-ASS : m/z = 1325 (M+Na) Elemental Analysis Calcd. Tor C58ri89N8022SNa=6ri20 ,. 49.35, H 7.14, N 7.94 Found C 49.33, H 7.04, N 7.87 Example 61 IR (KBr) 340C, 1668.1, 1629.6, 1270.9 cm-1 NMR (DMSO-d6, b) . 0.96 (3H, d, J=6.8Hz), 1.06 (3H, d, J=5.7Hz), 1.1-2.0 (33H, m), 2.1-2.5 (4H, m), 3.2C
(3H, s), 3:28 (2H, t, J=6. 5Hz) , 3.1-3.3 !iH, m), 3.6-4.45 (14H, m), 4.6-5.3 (13H, m), 5.49 (1H, d, J=6.lHz), 6.70 (1H, s), 6.72 (1H, d, J=8.2Hz), 6.80 (1H, d, J=8.2Hz), 7.03 (1H, s), 7.0-7.1 (1H, m), 7.15 (1H, s), 7.2-7.45 (6H, m), 8.0-8.3 (3H, m), 8.83 (1H, s) FP.B-MASS : m/z = 1426 (M+Na) Elemental Analysis Calcd. for C62H94N9OqaSNa=5H2O
C 49.82, H 7.01, N 8.43 Found : C 49.86, H 7.31, N 8.40 Example 62 IR (KBr) : 3355.5, 1668.1, 1629.6, 1274.7 cm-1 NMR (DMSO-d6, b) : 0.85 (3H, t, J=6.5Hz), 0.96 (314--, d, J=6 . 7Hz ), 1.04 (3H, d, J=5. 9Hz ), -. 1-2 . 6 (34H, m), 3.2 (1H, m), 3.6-4.55 (14H, m), 4.7-5.3 (11H, m), 5.47 (1H, d, J=5. 9Hz) , 6.72 (1H, d, J=8. iHz) , 6.79 (1H, s ) , 6.81 (1H, d, J=8 .1Hz ) , 7.05 (1H, s ) , 7.11 (1H, s), 7.2-7.5 (2H, m), 8.0-8.15 (2H, m), 8.20 (1H, d, J=8.oHz), 8.84 (1H, s) FAB-MASS m/z = 1235 (M+Na) Elemental Analvsis Calcd. for C5iH81N8022SNa=7H2C

C 4S.73, H 7.15, N c.37 Found . C 45.55, H 7.24, N 8.23 Example 63 IR (KBr) . 3353.6, 1664.3, 162 7. 6 c~.-NMR (DMSO-d6, b) . 0.86 i3H, J=6.6Hz), 0.95 (3H, d, J=6 . 7Hz i, 1.04 (3H, d, J=5 . 7Hz ), _. 2-2 . 7 (30H, ?:;) , 3. 16 ( i'ri, m) , 3. 6-4. 5 (13H, m) , 4. 7-5 . 3 ( ilH, m) , 5.51 ('H, d, J=6.OHz), 5.74 (iH, s), 6.72 (1H, d, J=8 . 2Hz ), 6.75 (1H, s), 6.77 ( lri, d, J=8 . 2Hz ), 7. 05 (i'ri, s), 7.2-7.5 (3H, *-r) , 8.0-8.3 (3H, r.',) , 8.85 (1H, s) FP3-MASS : m/z = 1204 (M+Na) Elementa- Analysis Calcd. for C50n77N8O21SNa5:-i9O 15 C 47.24, H 6.90, N 8.81 Found : C 46.98, H 7.12, N 8.72 Example 64 Major product iR (KBr) . 3400, 1675.8, 1631.5, 1511.9, 1234.2 cm ~
NMR (DMSO-d6, b) . 0.96 (3H, d, J=6 . 6Hz ), 11.05 (3H, d, J=5.8Hz), 1.2-1.6 (10H, m), 1.6-2.1 (5H, m), 2.1-2.7 (4H, m), 3.05-3.2 (4H, m), 3.20 (3H, s), 3.29 (2H, t, J=6.4Hz), 3.3-3.5 (5H, m), 3.6-4.5 (15H, m), 4.7-5.3 (11H, m), 5.50 (1H, d, J=5.8Hz), 6.73 (1H, d, J=8.2Hz), 6.8-7.1, (9H, m), 7.2-7.5 (3H, m), 7.81 (2H, d, J=8.6Hz), 8.08 (1H, d, J=8.2Hz), 8.24 (iH, d, J=7Hz), 8.44 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1403 (M+Na;
Elemental A.nalysis Calcd. ior C61H85~''i0023SNa=9H2O
C 47.47, H 6.73, N 9.07 Found : C 47.43, H 7.06, N 9.03 Minor product IR (KBr) : 3350, 1668.1, 1631.5, 1511.9, 1234.2 cm-1 NMR (DMSO-d6, 6) 0.96 (3H, d, J=6.6Hz), 1.07 (3H, d, J=5 . 8Hz ), 1. 2-1 . 5 ( 6r, m), 1. 55-2 .1 (7H, m), 2. 1-2. 65 (4H, m), 3. 0-3 . 6 (9H, m), 3. 7-4 . 5 (15H, m) , 4.7-5.6 (14H, m),.5.7-6.C (1H, m), 6.72 (1H, d, J=8.OHz), 6.75-7.= (9H, m), 7.25-7.5 (3:?, m), 7.81 (2H, d, J=8.3Hz), 8.08 (1H, d, J=8.2Hz), 8.25 (1H, d, J=7Hz), 8.45 (1H, d, J=7Hz) , 8.85 (1H, s) FAB-?~'~ASS : m/z = 137' (M+Na) Fleme~tzl Analysis Calcd. ior C60H81N10022SNa=8H20 C 48.25, H 6.55, N 9.38 Found : C 48.10, H 6.81, N 9.40 Example 65 IR (KBr) : 3450, 1168.1, 1635.3 cm-NM-R (DMSO-d6, b) : 0.88 (3H, t, J=6.5Hz), 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=6Hz), 1.2-1.5 (6H, m), 1. 6-2 . 1 (5H, m), 2. 1-2 . 7 ( 4H, m) , 3. 1-3 . 4 (9H, m), 3.6-4.5 (15H, m), 4.7-5.3 (11H, m), 5.49 (1H, d, J=5.8Hz), 6.73 (1H, d, J=8.2Hz), 6.8-7.0 (2H, m), 6.83 (2H, d, J=9.OHz) , 6.94 (2H, d, J=9. OHz) , 7.04 (1H, s), 7.12 (1H, t, J=8.4Hz), 7.2-7.5 (3H, m), 7.65-7.8 (2H, m), 8.09 (1H, d, J=8.4Hz), 8.25 (1H, d, J=7Hz), 8.63 (1H, d, J=7Hz), 8.84 (1H, s) F_z3-MASS : m/z = 1363 (M+Na) Elemental Analysis Calcd. for C58'ri78FN10O22SNa=5H2O
C 48.67, H 6.20, N 9.79 Found : C 48.83, H 6.15, N 9.74 Ex_ample 66 1R (siBr) : 3400, 1668.1, 1635.3, 1510.0, 1240.0 cm-1 NMR (DMSO-d6, (5) . 0.88 (3H, -,, J=6.6Hz), 1.2-1.5 (6H, m), 1.5-2.05 (5H, m), 2.1-2.65 (4H, m), 3.1-3.3 (9H, m), 3.6-4.5 (15H, m), 4.7-5.3 (11H, m), 5.51 (1H, d, J=5.8Hz), 6.73 (1H, d, J=8.2Hz), 6.8-6.9 (4H, m), 6.94 (2H, d, J=9.2Hz), 7.04 (1H, s), 7.24 (1H, d, J=8.5Hz) , 7.15-7.5 (3H, m) , 7.86 (1H, dd, J=8.6 and 2.1Hz), 8.02 (1H, d, J=2.1Hz), 8.04 (1H, d, J=8.4Hz), 8.23 (1H, d, J=7Hz), 8.70 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1379 (M+Na) Elemental Analysis Calcd. for C581i78C1N10022SNa=6H2O
C 47.52, H 6.19, N 9.55 Found : C 47.78, H 6.23, N 9.55 Example 67 IR (KBr) 3400, 1670 cm-1 N?MR (DMSO-d6, 5) . 0.96 (3H, d, J=6.7Hz), 1.05 (3H, d, J=5.7Hz), 1.4-2.65 (17H, m), 2.65-3.6 (8H, rrL), 3.6-4. 5 (15H, m), 4. 6-5 . 3 (11H, m) , 5.44 ( lii, d, J=6 . OHz ), 6.73 (1H, d, J=8 . 2Hz ), 6.81 (1H, s), 6.83 (1H, d, J=8 . 2Hz ), 6.98 (2H, d, J=8 . 9Hz ), 7.05 (1H, s), 7.2-7.5 (3H, *-n) , 7.80 (2H, d, J=8. 9Hz) , 8.05 (1H, d, J=8 . 4Hz ), 8.26 (1H, d, J=7Hz), 8.39 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1229 (M+Na) Elemental Analysis Calcd. for C52H74N10021S=5H?0 C 48.14, H 6.53, N 10.80 Found : C 48.29, H 6.33, N 10.95 Example 68 IR (KBr) 3400, 1652.7, 1635.3, 1511.9, 1241.9 cm-1 NMR (DMSO-d6, b) : 0.88 (3H, t, J=6. 6Hz) , 0.97 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.7Hz), 1.2-1.5 (6H, m), 1.6-2.0 (5H, m), 2.1-2.6 (4H, m), 3.0-3.3 (5H, 3.6-4.6 (19H, m), 4.7-5.3 (11H, m), 5.53 (1H, d, J=5. 6Hz ), 6.73 (1H, d, J=8 . 2Hz ), 6. 75-7 . 0 (2H, m), 6.83 (2H, d, J=9.2Hz), 6.95 (2H, d, J=9.2Hz), 7.05 (1H, s),.7.12 (1H, s ) , 7 . 25-7 . 5 (2H, m), 7.42 (1H, d, J=9.5Hz), 7.84 (1H, d, J=9.5Hz), 7.9-8.1 (2H, m), 8.71 (iH, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/7 = 1347 (M+Na) Elemental ArG-vsis Caicci. for C56H77Ni 2022SNa=7H2O
C 46.34, H 6.32, N 11.58 F.ound C 46.38, H 6.18, N 11.36 Example 69 NNR (DMSO-dG, 6) : 0.88 (3H, t, J=6. 6Hz) , 0.97 (3H, d, J=6.7Hz;, 1.08 (3H, d, J=5.8Hz), 1.2-1.5 (6H, m), 1.6-2.05 (5H, m), 2.1-2.6 (4H, m), 3.0-3.3 (5H, m), 3.4-3.55 (4H, m), 3.7-4.6 (15H, m), 4.7-5.3 (11H, m), 5.52 (1H, d, J=5.8Hz), 6.73 (1H, d, J=8.lHz), ~.8-6.9 (2H, r.) , 6.83 (2H, d, J=9.3Hz', 06.95 (2''_ , d, J=9.3Hz) 7.05 (1H, s), 7.14 (1H, s), 7.3-7.6 (3H, m), 7.84 (1H, d, J=8. 6Hz) , 7.95-8.1 (2H, m), 8.40 (1H, s), 8.42 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1346 (M+Na) Elemental Analysis Calcd. for C57H78Ni1022SNa=5H20 C 48.40, H 6.27, N 10.89 Found : C 48.32, H 6.44, N 10.86 Exampie 70 IR (KBr) : 3400, 1668.1, 1629.6, 1511.9 c:n-1 IQMR (DMSO-d6, b) : 0.96 (3H, d, J=6.7Hz),?.06 (3H, d, J=5.7Hz), 1.15-1.5 (6H, m), 1.6-2.0 (7H, m), 2.1-2.65 (5H, m), 3.1-3.5 (9H, m), 3.6-4.5 (13H, m), 4. 7-5 . 3 (11H, m), 5.46 (1H, d, J=5 . 9Hz ), 6.73 (1H, d, J=8.2Hz), 6.81 (lii, s), 6.84 (1H, d, J=8.2Hz), 6.91 (2H, d, J=8.7Hz), 6.95-7.05 (3H, m), 7.09 (2H, d, J=8.7Hz), 7.25-7.5 (3H, m), 7.81 (2H, d, J=8.8Hz), 8.09 (1H, d, J=7Hz), 8.25 (1H, d, J=7Hz), 8.04 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1327 (M+Na) Elemental Analysis Calcd. for C58H77N10021SNa=5H2O
C 49.92, H 6.28, N 10.03 Found : C 49.75, H 6.41, N? 0.25 Example 71 IR (KBr) . 3350, 1668.1, 1629.6, 1511.9, 1232.3 cm-1 NMR (DMSO-d6, 5) . 0.85 (3H, t, J=6 . 5Hz ), 0.96 ( 3-r.', d, J=6.7Hz), 1.06 (3H, d, J=6.0Hz), 1.2-1.4 (6H, m), 1.4-1.6 (2H, m), 1.7-2.1 (3H, m), 2.1-2.7 (6H, m), 3.1-3.5 (9H, m), 3.72 (2H, m), 3.8-4.5 (11H, m), 4.7-5.3 (11H, m), 5.47(~H, d, J=5.9Hz), 6.73 (IH, d, J=8.2Hz), 6.8-6. 9(2H, :n) , 6.91 (2H, d, J=8.6Hz), 6.95-7.15 (5-Ti, m), 7.25-7.5 (3H, m), 7.81 (2H, d, J=8. 8Hz) , 8.09 (1H, d, J=8.4Hz), 8.26 (1H, d, J=7Hz), 8.40 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1329 (M+Na) Elemental Analysis Calcd. for C58H79Ni0Na02iS=6H2O
C 49.22, H 6.48, N 9.90 Found C 49.33, H 6.67, N 9.89 Example 72 IR (KBr) : 3450, 1668.1, 1631.5, 1240.0 cm-1 NMR (DMSO-d6, 5) : 0.96 (3H, d, J=6 . 6Hz ), 1. 05 (3H, d, J=5.6Hz), 1.3-1.7 (4H, m), 1.7-2.1 (7H, m), 2.1-2.73 (6H, m), 2.75-3.05 (4H, m), 3.05-4.5 (18H, m), 4. 7-5. 5(12i?, m) , 6.72 (iH, d, J=8 . 3Hz ), 6. 77-6 . 9 (2H, m), 6.96 (2H, d, J=8.6Hz), 7.05 (iH, s), 7.1-7.5 (8H, m), 7.80 (2H, d, J=8.6Hz), 8.06 (?H, d, J=8.4Hz), 8.28 (iH, d, J=7Hz), 8.41 (iH, d, J=7Hz), 8.84 (iH, s) FA3-MP,SS : m/z = 1305 (M+Na) Elemental Analvsis Calcd. for C58H78~'T10021S-8H20 C 48.80, H 6.64, N 9.81 Found : C 48.88, H 6.50, N 9.81 Example 73 IR (KBr) : 1673.9, 1646.9, 1510.0 1238.1 cm-1 NM-R (DMSO-d6, b) : 0.87 (3H, t, J=o'.4Hz), 0.96 (3H, d, J=6.6Hz), 1.05 (3H, d, J=5.6Hz), 1.2-1.5 (6H, m), 1.5-2.0 (9H, m), 2.1-2.8 (ll:i, m), 3.1-3.4 (5ri, m), 3.4-4.5 (17H, m), 4.6-5.5 (12ri, m), 6.6-7.0 (9H, m), 7.04 (iH, s), 7.2-7.5 (3H, m), 7.78 (2H, d, J=8 . 7Hz ), 8.05 ( lH, d, J=8 . 4Hz ), 8.24 ( i'rI, d, J=7Hz), 8.39 (1H, d, J=7Hz), 8.84 (1H, s) FA3-M.kSS : m/ z= 1326 (?4Y-SO,+Na ) Elementai Analysis Calcd. fcr C63==89N110225 9H20 C 48.92, H 6.97, N 9.96 Found : C 48.77, H 6.73, N 9.94 Example 74 IR (KBr) : 3450, 1670.1, 1631.5, 1280.5 cm-~
NMR (DMSO-d6, b) . 0.87 (3H, t, ,7=7.OHz), 0.96 (3H, t, J=6.8Hz), 1.05 (3H, d, J=5.6Hz), 1.1-1.65 (13h, m), 1. 65-2 . 1 (7H, m), 2. 1-2 . 65 ( SH, m), 3. 17 (1H, :r.) , 3.6-4.5 (13H, m), 4.7-5.3 (ilii, m), 5.49 (1H, d, J=5 . 9Hz ), 6.72 ( iH, d, J=8 . 2Hz ), 6.82 (1H, d, J=8.2Hz), 6.84 (1H, s), 7.04 (1'ri, s), 7.29 (2H, d,.
J=8.3Hz), 7.2-7.5 (3H, m), 7.80 (2H, d, J=8.3Hz), 8.10 (1H, d, J=8.4Hz), 8.26 (1H, d, J=7Hz), 8.65 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1237 (M+Na) Elemental Analysis Calcd. for C53H75N8021SNa=6H20 C 48.10, H 6.63, N 8.47 Found : C 48.26, H 6.62, N 8.46 Example 75 IR (KBr) . 3400, 1670.1, 10'27.6, 127.2.8 cm-1 rTMR (DMSO-d6, o) : 0.96 (3H, d, J=3. "':Hz) , 1.08 (3H, d, J=5.7Hz), 1.2-1.6 (iOH, m), 1.6-2.1 (5-H, m), 2.1-2.7 (4H, m), 3.0-3.3 (iH, m), 3.20 (3H, s), 3.29 (2H, t, J=6.4Hz), 3.73 (2H, m), 3.9-4.6 (13H, m), 4.7-5.3 (11H, m), 5.53 (1H, d, J=5.8Hz), 6.73 (1H, d, J=8.3Hz), 6.83 (1H, d, J=8.3Hz), 6.91 (1H, s), 7.05 (1H, s), 7.23 (1H, dd, J=9.0 and 2.3Hz), 7.3--_ 226 7.5 (4H, m), 7.8-8.0 (3H, m), 8.09 (1::, d, J=8.4Hz), 8.33 (1H, d, J=7Hz), 8.44 (1H, s), 8.80 (1H, d, J=7Hz), 8.85 (1H, s) FAB-MASS m/z = 1293 (M+Na) Elemental Analysis Calcd. fcr C55H75N8023SNa=6H2O
C 47.89, H 6.36, N 8.12 Found . C 47.81, H 6.26, N 8.05 Example 76 7n. (hBr) 3361.3, 1668.1, 1635.3, 1627.6 cm-1 NY_.R (DMSO-d6, 5) . 0.86 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.8Hz), 1.19-1.25 (8H, m) , 1.25-2.00 (5H, m), 2.02-2.53 (4H, m), 2.44 (3H, s), 2.61 (2H, t, J=7.6Hz), 3.05-3.27 (1H, m), 3.55-4.50 (13H, m), 4.65-5.65 (12H, in), 6.42 (1H, s), 6.65-6.95 (3H, m), 7.05 (iH, d, J=0.4Hz), 7.13-7.50 (5H, m), 7.50-7.88 (6H, n:), 8.10 (1H, d, J=9.0Hz), 8.25 (1?-i, d, J=8.4Hz), 8.40 (1H, d, J=7.OHz), 8.85 (1H, s) FAB-MASS : m/z = 1299.3 (M+Na-1) Elemental Analysis Calcd. for C58H77NRNaO2155H2C
C 50.94, H 6.41, N 8.19 Found : C 50.99, H 6.40, N 8.15 Exa le 77 IR (Nujol) 3351.7, 1670.1, 1652.7, 1623.8 cm-1 NJMIR (DMSO-d6, 5) : 0.86 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.8Hz), 1.13-1.45 (8H, m), 1.47-1.96 (5H, m), 2.06-2.66 (8H, m), 2.81 (2H, t, J=7.6Hz), 3.04-3.30 (1H, m), 3.53-4.50 (13H, m), 4.53-5.70 (12H, m), 6.64-6.88 (3H, m), 7.04 (1H, d, J=0.4Hz), 7.13-7.60 (11H, m), 8.10 (1H, d, J=9.0Hz), 8.18 (1H, d, J=8.4Hz), 8.30 (1H, d, J=7.0Hz), 8.85 (1H, s) FAB-MASS : m/z = 1287.4 (M+Na-i) ' 2G7 -Eiemental Analysi s Calca. fcr C57H77NQNaG21S=5'r.?0 C 50.51, H 6.46, N 8.27 Found C 50.84, H 6.60, N 8.33 Example 78 IR (KBr) . 3361.3, 1683.6, 1670.1, 1662.3, 1652.7, 1646.9, 1635.3, 1627.6, 1623.8 cm-1 NMR (DMSO-d6, o) : C.97 (3H, d, J=6.7Hz), 1.07 (3H, d, J=S. 6Hz) , 1.28-2. 00 (13H, *n) , 2. 08-2. 60 (4H, m) , iC 3.07-3.30 (1H, r. , 3.60-4.66 (17H, m), 4.66-5.12 (9H, m) , 5.11 (1H, d, J=3 . 1'riz ), 5.25 (1H, d, J=4 . 6Hz ) , _". 52 (1 H, d, J=6 . 0Hz ) , 6 . 62-6 . 95 (4H, m) , 6.95-7.15 (3H, m), 7.20-7.50 (3H, m), 7.50-7.85 (7H, m), 8.12 (1H, d, J=8 . 4Hz ), 8.35 (1H, d, J=7.7Hz), 8.53 (1H, d, J=7.0Hz), 8.85 (1H, s) FAB-MASS : mJ z= 1319 . 7 (M+Na-1) Elemental Analvsis Calcd. for C77H74N8Na022SF=8'ri20 C 47.49, H 6.29, N 7.77 Found C 47.79, H 6.16, N 7.93 Example 79 (KEr) : 3354.9, 1668.1, 1662.3, 1654.6, 1646.9, 1627.6 cm-1 NNR (DMSO-d6, (5) : 0.85 (3H, t, J=6.7Hz), 0.90-1.10 (6H, m), 1. 10-1 . 40 (8H, m), 1. 48-1. 95 (5H, m), 2.05-2.46 (4H, m), 2.60 (2H, t, J=7.6Hz), 3.07-3.23 (1H, m), 3.55-4.45 (14H, m), 4.67-5.32 (11H, n:.), 5.48-5.63 (1H, m), 6.22 (1H, , J=5.3Hz), 6.65-6.89 (3H, m), 6.97-7.15 (2H, m), 7.20-7.68 (lOH, m), 7.85-8.20 (3H, m), 8.84 (iH, s) FAB-MASS m/z = 1289.4 (M+Na-1) Elemental Analysis Calcd. for C56H75N8NaO22S=3H2O
C 50.90, H 6.18, N 8.48 Found : C 50.80, E 6.44, N 8.29 Example 80 7R (KBr) : 3361.3, 1664.3, 1631.5, 1600.6 cm-i NMR (DMSO-d6, (5) : 0.86 (3H, t, J=6.7Hz), 0.98 (3H, d, J=6.7Hz), 1.16 (3H, t, J=~.9Hz), 1.20-1.45 (8H, m), 1.50-1.70 (2H, m), 1.70-2.05 (3H, m), 2.10-2.57 (4H, r.) , 2.63 (2H, t, J=7 . 6Hz; , 3. 10-3 . 30 (1: , m) , 3.68-4.50 (13H, m), 4.78-5.32 (11H, m), 5.66 ;1H, d, J=5.7Hz), 6.68-7.02 (3H, m), 7.04 (1H, d, J=0.4Hz), 7.25-7.48 (4H, m;, 7.60-8.08 (7H, m), 8.10 (1H, d, J=8.4Hz), 8.28 (1H, c;, J=7.7Hz), 8.85 (1H, s), 9.30 (1H, d, J=7.1Hz) FAB-MASS : m/z = 1287. 5(M+Na-1 ) Elemental Anaivsis Calcd. -ffcr C55,H73N8Na022S=3Hq0 C 50.53, H 6.09, N 8.-=:7 Found : C 50.66, H 6.01, N 8.22 Example 81 IR (KBr) . 3349.7, 1668.1, 1627.6 cm-1 NMR (DMSO-d6, b) : 0.815 (3H, t, J=6 . 7Hz ), 0.96 (3H, d, J=6. 7Hz) , 1.09 (3H, d, J=5. 8'r?z) , 1.18-1.48 (8H, m), 1.50-2.10 (5H, m), 2.10-2.45 (3H, m), 2.50-2.65 (1H, m), 2.77 (2H, t, J=7. 6Hz) , 3.05-3.25 (iH, r,:) , 3.60-4.65 (13H, m), 4.67-5.60 (12H, m), 6.65-6.97 (3H, m), 7.05 (1H, d, J=0.4Hz), 7.21-7.43 (4H, m), 7.76 (11i, s), 7.83-8.05 (3H, m), 8.10 (1H, d, J=9.OHz), 8.29 (1H, d, j=8.4Hz), 8.48 (1H, s), 8.64-9.03 (2H, m) FAB-MASS : m/z = 1233.0 (M+Na-'_) Elemental Analvsis Calcd. for C53H7, N8Na020S=3?i20 C 50.96, H 6.22, N 8.96 Found : C 50.62, H 6.40, N 8.92 Example 82 IR (KBr) . 3361.3, 1670.1, 1627.6 cm-i NMR (DMSO-d6, b) : 0.88 (3H, ;., J=6.7Hz), 0.96 (3?-:, d, J=6.7Hz), 1.09 (3H, d, J=5.9Hz), ;.18-1.43 (6H, m), 1.50-2.10 (5H, m), 2.10-2.69 (4H, m), 2.77 (2H, t, J=7.6Hz), 3.07-3.29 (1H, m), 3.60-4.62 (13H, m), 4.69-5.23 (10H, rn), 5.27 (1H, d, J=4.5Hz), 5.55 (1H, d, J=5.9Hz), 6.68-7.00 (3H, m), 7.05 (lH, d, J=0.4Hz), 7.25-7.53 (4H, m), 7.76 (1H, s',, 7.84-8.05 (3H, m) , 8.13 (1H, d, J=8.4Hz) , 8.33 (1H, d, J=7.7Hz), 8.48 (1H, s), 8.73-9.00 (2H, m) FAB-MASS m/z = 1219.4 (M+Na-1) i0 Elemental Analysis Calcd. for C52H69N8NaO21S=5H?O
C 48.51, H 6.19, N 8.71 Found : C 48.67, -'-' 6.34, N 8.74 Example 83 IR (KBr) : 3357.5, 1668.1, 1627.6 cm-1 NMR (DMSO-d6, b) : 0.97 (3H, d, J=6.7Hz), 1.07 (3H, d, J=6.OHz), 1.20-1.62 (10H, m), 1.62-2.00 (5H, m), 2.10-2.65 (4H, m), 3.20 (3H, s), 3.08-3.45 (1H, m), 3.28 (2H, t, J=6.5Hz), 3.53-4.50 (15H, m), 4.68-5.13 (9H, m), 5.17 (1H, d, J=3. 1Hz) , 5.25 (1H, d, J=4.4Hz), 5.53 (1H, d, J=6.OHz), 6.68-6.95 (4H, m), 6.95-7.11 (3H, m), 7.20-7.52 (3H, m), 7.55-7.95 (7H, m), 8.13 (iH, d, J=8.4Hz), 8.30 (1H, d, J=7.7Hz), 8.52 (iH, d, J=7.OHz), 8.85 (iH, s) FAB-MASS : m/z = 1345.2 (M+Na-1) Elemental Analysis Calcd. for C59H79N8NaO23S=8H2O
C 48.29, H 6.53, N 7.64 Found : C 48.44, H 6.58, N. 7.75 Example 84 IR (KBr) : 3353.6, 1662.3, 1627.6 cm-1 NMR (DMSO-36, (5) : 0.96 (3H, d, J=6 . 7Hz ), 1.07 (3H, d, J=5.5Hz),.1.40-1.65 (2H, m), 1.65-2.00 (5H, m), 2.00-2.67 (6H, m), 3.08-3.30 (1H, m), 3.50-4.50 (15H, m), 4.68-5.13 (11H, m), 5.18 (1H, d, J=3 . 1Hz ), 5. 2 6 ( iH, d, J= ~_ . 5Hz ), S. 53 (1F, d, J=6. OHz' , 3.70-6. 00 (lri, r,t) , 6. 63-6. 95 (4H, m) , 6.9-7, -%.i3 (3H, m), 7.20-7.- 2 (31-1, n), 7.52-7.95 (7H, m) , 8. 12 (1H, d, J=8. 4Hz ),. 8. 31 (iH, d, J=7.7Hz;, 8.53 (1H, d, J=7.OHz), 8.85 (i'ri, s) F zli3-MASS m/z = 1285. 4(M+Na-1 ) -lemental Analysis Calcd. ;or C56rI71N8022SNa=8Hq0 C 47.79, H 6.23, N 7.96 Found C 47.59, H 6.32, N 8.06 Examble 85 =R (KBr) . 3363.2, 1670.1, 1627.6 cTn NMR (DMSO-d6, (5) : 0.89 (6H, d, J=6.5Hz), 0.96 (3H, d, J=6.7Hz), 1.07 (3H, d, J=5.7Hz;, 1.22-1.41 (2H, m), 1.50-1.97 (6H, r.m), 2.11-2.65 (4H, m), 3.10-3.30 (?H, m) , 3.60-4.50 (15H, m), 4.70-5.08 (8H, m), 5.10 ( iH, d, J=5 . 6Hz ), 5.1. 6(1H, d, J=3 .1Hz ), 5.25 (1H, d, J=4.5Hz), 5.50 (1H, d, J=5.9Hz), 6. 65-6.92 (4H, m), 6.92-7.12 (3F., m), 7.21-7.50 (3H, m), 7.52-7.90 (7H, m), 8.12 (1H, d, J=8.4Hz), 8.30 (1H, d, J=7.7Hz), 8.56 (i:-i, d, J=7.OHz), 8.85 (1H, s) FAB-M.~SS : m/z = 1287.6 (M+Na-i) Elemental Analysis Calcd. for C56H73N8Na022S=6.5H20 C 48.66, H 6.27, N 8.11 Found C 48.67, H 6.32, N 8.20 Example 86 TR (KBr) : 3361.3, 1683.6, 1670.1, 1654.6, 1635.3, 1623.8 cm-1 NMR (DMSO-d6, 6) : 0.97 (3H, d, J=6.7Hz), 1.07 (3H, d, J=5.6Hz), 1.30-2.00 (11H, m), 2.10-2.70 (4H, m), 3.05-3.15 (1H, m), 3.55-4.70 (17H, m), 4.70-5.11 (9H, m), 5.16 (1H, d, J=3 .1Hz ), 5.25 (1H, d, J=4.5Hz), 5.52 (2H, d, J=6.0Hz), 6.65-6.95 (4H, m), 6.95-7.10 (3H, m), 7.10-7.50 (3H, m), 7.50-7.85 (7H, *n) , 8.12 (1H, d, J=8.4Hz), 8.30 (IH, d, J=8 . 3Hz ), 8.52 (1H, d, J=7 . O.T-iz ), 8.85 ( i::, s) FAB-MASS : m/z = 1305.2 (M+Nz-i) Elemental Analysis Calcd. for C56H72N8Na022SF=6H~0 C 48.34, H 6.09, N 8.0-5 Founci : C 48.47, H 6.29, N 7.95 Examiple 87 IR (KBr) : 3359.4, 1668.1, 1654.6, 1625.7, --m-1 NMR (DMSO-d6, 5) : 0.97 (3H, d, J=6 . 7Hz ), 1.07 (3H, d, J=6. OHz ), 1. 22-1 . 62 (6H, m), 1. 62-2 . 00 ( 5H, m), 2.10-2.65 (4H, m), 3.20 (3H, s), 3.05-3.40 (1''., m), 3.31 (2H, t, J=6 . 5?iz ), 3. 60-4 . 55 (15H, m), 4. 65-5. 13 (9H, rn), 5.16 (1H, d, J=3 . 1Hz ), 5. 2 0' (1H, d, J=4 . 4Hz ), 5.53 (1H, d, J=6. OHz ), 6. 68- 6. 95 (4H, rr.), 6.95-7.20 (3H, m), 7.20-7.58 (3H, m), 7.58-7.90 (7H, m), 8.13 (1H, d, J=8 . 4Hz ), 8.32 (1H, d, J=7.7Hz), 8.53 (1H, d, J=7. OHz) , 8.85 (1H, s) FAB-MASS : m/z = 1317 . ~" (M+Na-1) Elemental Analysis Calc for C57H75N8Na023S=7Hq0 C 48.16, H 6.31, N 7.88 Fot; -:: : C 48.21, H 6.60, N 7.78 xample 8 IR r) 3350, 2954, 1"68, 1629, 1538, 1511, 1454, 1249 cm-i NMR (I)MSO-d6, 5) : 0.88 (3h, t, J=7. iHz) , 0.96 (3u, d, J=7.5Hz), 1.08 (2H, d, J=5.7Hz), 1.2-1.5 (6H, m), 1.6-2.4 (8H, m), 2.6-2.7 (1H, m), 3.1-3.3 (1H, m), 3. 6-4 . 5 (19H, m), 4. 7-5 . 3 (8H, :n) , 6.73 (1H, d, J=8.2Hz), 6.8-7.1 (5H, m), 7.19 (1H, s), 7.3-7.5 (3H, m), 7.75 (2H, d, J=8.7Hz), 7.8-8.0 (4H, m), 8.08 (1H, d, J=8 . 9Hz ), 8.30 (1H, d, J=7 . 7Hz ), 8.7-9.0 (3H, m) FAB-MASS : m/z = 1327 (M+Na+) Eiemental P.nalysis Calcd. for C57H73Ni0022NaS9H2O
C 46.65, H 6.2,5, N 9.54 Founa C 46.95, H 6.22, N 9.55 Example 89 7R. (KBr) : 3376, 2931, 2858, 1662, 1631, 1521, 1444, 1245, 1047 cm-1 N-v-R (DMSO-d6, 5) : 0. 97 (3H, d, J=6 . 7Hz ), 1.09 (3H, d, j=5 . 9Hz ), 1. 3-1 . 6 (6H, m) , 1. 7-2 . 1 ( 5H, m), 2. 2-2 . 4 (3H, *~.) , 2. 5-2 . 6 (? H, m), 3.21 ( 3'rI, s), 3. 2-3 . 4 (3H, m), 3. 6-4. 5(16Fi, m), 4.79 (2H, ci, J=6. OHz) , 4.9-5.2 (5H, m), 5.10 (1H, d, J=3.6Hz), 5.18 (1H, d, J=3 . lHz ), 5.26 (1H, d, J=4 . 5Hz ), 5.53 (1H, d, J=6.OHz),.6.73 (1H, d, J=8.2Hz), 6. 8-7. 0(2H, m), 7.0-7.2 (3H, m), 7.3-7.5 (3H, m), 7.6-7.9 (8H, m), 8.01 (2H, d, J=8.4Hz), 8.12 (1H, d, J=8.4Hz), 8.31 (1H, d, J=7.7Hz), 8.79 (iH, d, J=7.OHz), 8.85 (1H, s) FAB-MASS : m/z = 1367 (M+Na+) Elemental Analysis Calcd. for C61H77N8023NaS=6.5Hq0 C 50.10, H 6.20, N 7.66 Found : C 50.09, H 6.17, N 7.62 Example 90 IR (KBr) 3363, 2937, 2869, 1646, 1444, 1255 cm-1 NMR ( DMSO-d6, b) : 0.97 (3H, d, J=6 . 7Hz ), 1.08 (3H, d, J=5.7Hz), 1.2-1.6 (10H, m), 1.7-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.7 (iH, m), 3.20 (3H, s), 3.2-3.4 (1H, r.i), 3.6-4.6 (16H, m), 4.7-5.2 (8H, m), 5.16 (1H, d, J=3 .1Hz ), 5.24 (1H, d, J=4 . 5Hz ), 5.54 (1Fi, d, J=5 . 8Hz ), 6.73 (1H, d, J=8 . 2Hz ), 6. 8-7 . 0 (2H, m), 7.1-7.4 (6H, m), 7.97 (2H, d, J=8.8Hz), 8.0-8.4 (6H, m), 8.84 (iH, s), 8.92 (iH, d, J=7.OHz) FAB-MASS : m/z = 1403.6 (M+NaT) Elemental Analysis Calcd. fcr C59H77N10023NaSq=6H2O

C 47.58, H 6.C2, N 9.40 Found . C 47.72, H 6.12, N 9.42 Example 91 7r~. (KBr) . 3350, 1668, 1654, 1625, 1537, 152~., 1245, 1047 cm-1 NMR ( DNSO-d6, b) : 0. 9-1. 1 (6H, rn) , 1. 07 (3H, d, J=5.7Hz), 1.4-2.0 (71H, m), 2.2-2.5 (3H, in), 2.5-2.0 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (16H, m), 4.7-5.11 (7H, ra), 5.09 (1H, d, J=5.6Hz), 5.16 (1H, d, J=3 . 1Hz ), 5.25 (1H, d, J=4 . 4Hz ), 5.53 (1H, d, J=6 . 0Hz ), 6. 73 (iH, d, J=8 . 4Hz ), 6. 8-7 . 2 (6H, ir:) 7. 2-7 . 5 (4H, m), 7. 5-7 . 8 (6H, :a) , 8.11 (IH, d, J=8 . 4Hz ), 8. 32 (1H, d, J=7 . 7Hz ), 8.54 (1H, d, J=7.0Hz), 8.84 (1H, s) FAB-MASS : m/z = 1259 (M+Na Elemer.tal Analysis Calcd. for C54h69N8022NaS=8H2O
C 46.95, H 6.20, N 8.11 Found : C 47.20. H 6.23, N 8.28 Example 92 TR (KBr) : 3359, 2929, 2852, 1668, 1650, 1631, 1533, 1515 cm-1 NMR (DMSO-d6, b) : 0.96 (3H, d, J=6.7Hz), 1.09 (3H, d, J=6.1Hz), 1.2-1.6) (5H, m), 1.6-2.5 (10H, rr.), 2.5-2.6 (1H, n:) , 3.18 (iH, m), 3.7-4.5 (15H, m), 4. 8-5. 2 (8H, m), 5.17 (1H, d, J=3 .1Hz ), 5.26 (1u, d, J=4.5Hz), 5.55 (1H, d, J=5.9Hz'), 6.73 (1H, d, J=8.1Hz), 6.81 (1H, s), 6.85 (1ri, s) , 7.05 (1H, s), 7.2-7.4 (3H, m), 7.45 (2H, d, J=8.2: z) , 7.96 (2H, d, J=8.2Hz), 8.0-8.2 (4H, s), 8.2-8.3 (1H, m), 8.85 (1H, s), 8.9-9.0 (?H, d, J=7.0Hz) FAB-MASS : m/z = 1327.5 (M+Na)T
vlemental Analysis Calcd. for C56H69N10021S2Na=6H2O
C 47.59, H 5.78, N 9.91 Faunci C 47.89, H 5.76, N 9.93 Examn-le 93 IR (KBr) . 3350, 1654, 1629, 1517, 1249, 1047 cm-1 NMR. (DMSO-d6, 5) 0 . 9-; . - ( 6H, m) , _ . 11 ( 3H, d, J=5.9Hz;, 1.6-2.0 (5H, s), 2.1-2.4 1,3H, s), 2.6-2.7 ( ~'ri, m), 3._11 -3.3 ('-.:, m , 3 .6-4._ ;16ri, m), 4. /-5._ ( 7H, m), 5.10 (1H, d, J=5 . 6Hz ), 5. 1 i (1H, d, j=3.lHz), 5.25 (1H, d, -=4.5Hz), 5.55 (1H, d, J=5.7Hz), 6.7-6.9 (3H, m), 7.0-7.5 (6H, m), 7.74 (2H, d, J=8. 8?Iz) , 7.91 (2H, d, J=B. 5Hz) , 8. 1-8 .4 (8H, 8.84 (1H, s), 8.97 (1H, d, J=7.0Hz) FP.B-M.kSS : m/z = 1363.5 (M+Na)' Elemental nnalysis Calcd. for CS9H6qNj0023SNa=5H2O
C 49.51, H 5.56, N 9.79 Found C 49.39, H 5.63, N 9.77 Example 94 ?B (KBr) . 3355, 2929, 2856, 1664, 1631, 1519, 1440, 1282 cm-~
NMR (DMSO-d6, 5) : 0.84 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.7Hz), 1.07 (3H, t, J=5.8Hz), 1.2-1.5 (12H, m), 1.7-2.0 (5H, m), 2.2-2.4 (3H, m), 2.5-2.7 (?R:, m), 2.94 (2H, t, J=7. 4Hz) , 3. 1-3. 3(1H:, r.m) , 3. 6-4. 6 (14H, m), 4. 8-5 . 2 ( 7f:, m), 5.10 (1H, d, J=3 . 6Hz ), 5.17 (1H, d, J=3 .1Hz ), 5.26 ( IR:, d, J=4 . 5Hz ), 5.55 (1H, d, J=5.9Hz), E.73 (1H, d, J=8.2Hz), 6. 8-7. 0 (2H, m), 7. 0-7. 5(4H, r.), 8.0-8.2 (5H, m), 8.27 (1H, d, J=7.7Hz), 8.85 (1~, s), 8.93 (1H, d, J=7.OHz) FAB-MASS : m/z = 1279 (M+NaT) Elemental Analysis Calcd. for C53H73N10022SNa=5.5H20 C 46.93, H 6.24, N 10.33 Found : C 46.93, H 6.46, N 10.31_ Example 95 IR (KBr) : 3363, 1673, 1648, 1538, 1253 cm-1 NMR (DMSO-d6, 5) 0.92 (3H, :., J=6 . 8Hz ), 0.97 (3H, d, J=6.8Hz), 1.10 (3H, d, J=5.8Hz), 1.2-1.5 (6H, m), ~.7-2.1 (51-1, m), 2.1-2.4 (3H, m), 2.5-2.6 (iH, 3 . 1-3 . 3 (1H, m) , 3 . 6-4 . 5 ( 1 6 H, m) , 4. 7-5. 1 (9::, 5. 16 d, J=3. lHz ), 5.24 (1H, d, J=4. 5Hz ), 5. 54 (1H, d, J=5 . 8Hz ), 6.73 (1H, d, ~=3 . 2Hz ), 6. 8-7 . 4 (8H, m), 8.04 (2H, d, J=8. 8Hz) , 8.13 (2H, d, J=B. 6Hz) , 8.2-8.4 (4H, m), 8.84 (1H, s), 8.98 (1H, d, J=7.OHz) FAB-MASS m/z = 1329.6 (M+Na)T

Elemental Analysis Calcd. for C56H71N10023SNa=7H20 C 46.92, H 5.97, N 9.77 Found C 46.86, H 5.99, N 9.77 Example 96 IR (KBr) 3355, 2929, 1666, 1648, 1631, 1515, 1442, 1047 cm-1 NMR (DMSO-d6, 5) : 0.87 (3H, t, J=6 . 7Hz ), 0.97 (3H, d, J=6.7Hz), 1.10 (3H, d, J=5.8Hz), 1.2-1.5 (10H, m), 1. 7-2 . 1 (5H, m), 2. 1-2 . 4 (3H, r~,) , 2. 5-2 . 6 (1H, m), 3.1-3.3 (1H, m), 3.6-4.6 (16H, m), 4.79 (2H, d, J=5 . 9Hz ), 4. 8-5. 2( 5'r., m), 5.09 (1H, d, J=5 . 5Hz ), 5.16 (1H, d, J=3 . 1Hz ), 5.23 (1H, d, J=4 . 5Hz ), 5.53 ( iH, d, J=5 . 9Hz ), 6.73 (1H, d, J=8 . OHz ), 6. 8-6 . 9 (2H, m), 7.0-7.5 (6H, m), 7.97 (2H, d, J=8.8Hz), 8.0-8.3 (6H, m), 8.83 (iH, s), 8.88 (1H, d, J=7.OHz) FAB-MASS : m/z = 1373.5 (M+Na)t Elemental Analysis Calcd. Tcr C58H75N10022S2Na=6H20 C 47.73, H 6.01, N 9.60 Found : C 47.57, H 5.92, N 9.53 Example 97 IR (KBr) 3361, 2925, 2852, 1668, 1650, 1631, 1538, 1452, 1049 cm-, NMR (DMSO-d6, b) 0.87 (3H, ::, J=6.9Hz), 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.7Hz), 1.2-1.4 (11H, m), 1.4-1.6 (2H, m), 1.7-2.1 (5H, m), 2.1-2.5 (5H, m), 2. 5-2. 6(1H, m) , 3. 1-3.3 (2 H, TM,) , 3.7-4.: (14H, m) , 4.7-õ.0 (7H, m), 5.09 (1H, d, J=5.6Hz), 5.16 (iH, d, J=3.1Hz), 5.25 (1H, d, J=4.5Hz), 5.54 (1H, d, J=5 . 8Hz ), 6.73 (1H, d, J=8 . 2Hz ), 6. 8-7 . 0 (2H, d), 7.04 (1H, s), 7.2-7.5 (3H, m), 8.03 (4H, s), 8.0-8.3 (2H, m), 8.84 (1H, s), 8.95 (lii, d, J=7.OHz;
FAB-MASS . m/z = 1321.9 ("f+NG)_ Elemental Analysis Calcd. -or C55H-75N;0O21S2Na=5H2O
C 47.54, H 6.17, N 10.08 Found : C.47.38, H 6.12, N 9.99 Example 98 IR (KBr) 3374, 2937, 2875, 1658, 1629, 1531, 1436, 1255, 1047 cm-i NMR (DMSO-d6, b) : 0. 9-1.11 (6H, m), 1.09 (3H, d, J=5.7Hz), 1.2-1.5 (4H, ra), 1.7-2.1 (5H, m), 2.2-2.5 (3H, m), 2.6-2.7 (1H, m), 3.2-3.3 (iH, m), 3.6-4-(16H, m), 4.80 (2H, d, J=5.8Hz), 4.8-5.2 (5H, m), 5.10 (1H, d, J=5 . 5Hz ), 5.17 (1H, d, J=3 . OHz ), 5.24 (1H, d, J=4.5Hz), 5.53 (1H, d, J=5.8Hz), 6.73 (1H, d, J=8.2Hz), 6.8-7.0 (2H, m), 7.06 (1H, s), 7.10 ( 2F:, d, J=8 . 9Hz ), 7. 2-7 . 5 ( 3i?, m), 7.68 (1H, s), 7.86 (2'r?, d, J=8.8Hz), 8.0-8.4 (6H, m) , 8.84 (IH, s), 8.90 (1H, d, J=7.OHz) FAB-MASS : m/z = 1314 (M+NaT) Elemental Analysis Calcd. for C56H70N9023NaS=6H2O
C 48.03, H 5.90, N 9.00 Found : C 47.92, H 5.83, N 8.88 ExamQle 99 IR (KBr) . 3345, 1646, 1633, 1531, 1257 cm-1 NMR (DMSO-dc, b) . 0.97 (3H, d, J=6.7Hz), 1.11 (3H, d, J=~.7Hz;,, 1.2-1.6 (lOH, m), 1.7-2.5 (8H, m), 2.6-2.7 (iH, m), 3.21 (3H, s), 3.3-3.4 (iH, m), 3.-1-4.6 (16H, m), 4. 8-5 . 2 (8H, m) , 5. 16 (1H, d, J=3 . 1- , 5.24 (1H, d, J=4.5Hz), 5.55 (1H, d, J=5.7Hz), .7-6.9 (3H, m), 7.0-7.5 (6H, m), 8.0-8.3 (8H, m), 8.84 (1H, s), 8.96 (iH, d, J=7.OHz) F_AB-MASS : m/z = 1387.7 (M+Na Elementa' A-nalysis Calcd. fcr C59H771\T10024NaS=6H2O
C 48.09, H 6.09, N 9.51 Found : C 47.81, H 5.83, N 9.38 Examiple 100 IR (KBr) : 33= _', 1668, 1631, 1429, 1284, 1047 cm-1 NMR (DMSO-d6, b) : 0.97 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.8Hz), 1.8-2.4 (6H, m), 2.5-2.6 (1H, m), 3.1-3.2 (1H, m), 3.7-4.6 (14H, m), 4.7-5.2 (7H, m), 5.10 (1H, d, J=5 . 5Hz ) , 5.17 (1H, d, J=3 .1Hz ) , 5.24 (1H, d, J=5 . 5Hz ), 5.53 (1H, d, J=5 . 8Hz ), 6.75 ( iH, d, J=8.2Hz), 6.8-6.9 (2H, m), 7.05 (iH, s), 7.3-7.6 (9H, m), 7. 8-7 . 9 (4H, m), 8. 0-8 . 2 ( 5H, m), 8. 2-8 . 3 (1H, m), 8.34 (1H, d, J=9 . 3Hz ), 8. 7-8 . 8 ( iH, m), 8.85 (1H, s) FAB-MASS : m/z = 1332.7 (M+Na+) Elemental Analysis Calcd. for C58H65N10022SNa=8H2O
C 47.93, H 5.62, N 9.64 Found : C 47.83, H 5.53, N 9.56 Example 101 IR (KBr) : 3353, 2929, 2856, 16vt_, 1631, 1612, 1496, 1440, 1259 cm-1 NMR (DMSO-d6, b) : 0.87 (3H, t, J=6.6Hz), 0.97 (3H, d, J=6 . 5Hz ), 1.09 (3H, d, J=5 . 9Hz ), 1. 2-1. 5(10;r,, m), 1.7-2.1 (5H, m), 2.2-2.5 (3H, m), 2.6-2.7 (iH, m), 3.1-3.2 (1H, m) , 3.6-4.5 (16H, m), 4.7-5.0 (3H, m) 5. 0-5 .- ( 5H, m) , S. 10 (1H, d, J=3 . 1Hz ), S. 2 6 ! 1H, d, J=a . 2Hz ), 5. 56 ( iH, G, J=5 . 5Hz ), 6. 7 (1H, d, J=8.1Hz), 6.8-7.0 (2H, m), 7.05 (1H, s), 7.1-7.5 (5H, :r.) , 8.0-84 (8H, 8. 85 (?H, s) , ~o.95 (1'r:, d, J=7.OHz) FAB-MASS : r.:/z = 1357.3 (M+Na Elemental Analysis Calcd. for C58H75N10023NaS=7H20 C 47.67, H 6.14, N 9.58 Found C 47.63, H 6.42, N 9.52 Example 102 iR (KBr) . 3361, 1670, i 648, 1633, 1540, 1519, 1249 cm-1 NNR (DMSO-d6, 5) : 0.89 (3H, z, J=7.OHz), 0.97 (3H, d, J=6.8Hz), 1.10 (3H, d, J=5.7Hz), 1.2-1.5 (6H, m), 1.6-2.4 (8H, m), 2.5-2.7 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (16H, m), 4.80 (2H, d, J=5.8Hz), 4.8-5.2 (5H, m), 5.10 (1H, d, J=5.4uz), 5.18 (1H, d, J=3.1Hz), 5.25 (1H, d, J=4.3Hz), 5.55 (iH, d, J=5.7Hz), 6.73 (1H, d, J=8.2Hz', 6.8-7.0 (271-1, m), 7. 0-7 . 5 (6H, m), 8.02 (1H, d, J=5 . 3Hz ), 8. 0- 8. 4 (4H, m), 8.42 (2H, d, J=8.4Hz), 8.48 (2H, d, J=8. 9Hz) , 8. 8-9. 0(3H, m) FAB-MASS : m/z = 1339.3 (:f4+NaT) Elemental Analysis Calcd. for C58H73N10022SNa=6H20 C 48.87, H 6.01, N 9.83 Found : C 49.16, T-i 5.92, N 9.86 Examgle 103 IR (KBr) : 3350, 2971, 2859, 1672, 1629, 1537, 1442, 1247, 1047 cm-1 NMR (DMSO-d6, b) : 0.96 (3H, d, J=6.8Hz), 1.0-1.2 (6H, m), 1.2-1.6 (12H, m), 1.7-2.-m (8H, m), 2.5-2.6 (1H, m), 3.2-3.6 (7H, m), 3.7-4.5 (16H, m), 4.76 (2H, d, J=5. 6Hz ), 4. 8-5 . 1 (5H, m) , 5.09 (1H, d, J=5 . 5Hz i, 1.16 (1H, d, J=3 . 1Hz ), 5.23 ( lri, d, J=5 . 5Hz ), 3.51 (1'ri, d, J=5 . 9Hz ), 6.73 (1H, d, J=8 . 2Hz ), 6. 8-6 . 9 (2H, m), 7.0-7.1 (3H, m), 7.3-7.5 (3H, m), 7.67 (2H, d, J=6. 9Hz) , 7.71 (2H, d, J=6. 9Hz) , 7.95 (2H, d, J=8.4Hz), 8.05 (1H, d, J=7.OHz), 8.23 (1H, d, J=7.7Hz), 8.70 (iH, d, J=7.OHz', 8.84 (1H, s) FAB-MASS m/z = 1377.1 (M+Na+) Elemental Analysis Calcd. ro= C60H83N8024NaS=5H2O
C 49.86, H 6.49, N 7.75 Found : C 49.74, H 6.73, N 7.68 Examgle 104 IR (KBr) : 3349, 2937, 2858, 1672, 1629, 1537, 1444, 1249, 1047 cm-1 NMR (DMSO-ci6, b) 0.96 (3H, d, J=6.7Hz), 1.08 (3H, d, J=5.6Hz), 1.2-1.7 (14H, m), 1.7-2.1 (5H, m), 2.1-2.4 (5H, m), 2. 5-2 . 6 (1'r'., m), 3. 1-3 . 2 (1H, m.) , 3. 4-3. 6 (4H, m), 3. 7-4 . 5 (16H, m), 4.77 (2H, d, J=5.7Hz), 4.8-5.2 (5H, m), 5.09 (1H, d, J=5.6Hz), 5.16 ( iH, d, J=3 . iHz ), 5.24 (1H, d, J=4 . 5Hz ), 5.51 (1H, d, J=5.8Hz), 6.73 (iH, d, J=8.2Hz), 6.8-6.9 (2H, m), 7.0-7.1 (3H, m), 7.3-7.5 (3H, m), 7.6-7.8 (4H, m), 7.96 (2H, d, J=8. 4Hz), 8. i0 (1H, d, J=8.4Hz), 8.24 (1H, d, J=7.7Hz), 8.71 (1H, d, J=7.OHz), 8.89 (1H, s) FAB-M_ASS : m/z = 1386.5 (M+Na+) Elemental Analysis Calcd. for C6iH82N9023NaS=6H20 C 49.76, H 6.43, N 8.56 Found C 49.99, H 6.39, N 8.52 Example 105 IR (KBr) : 3350, 2933, 2856, 1664, 1631, 1604, 1511, 1450, 1243, 1045 cm-1 NNR (DMSO-d6, 6) : 0.86 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.5Hz), 1.05 (3H, d, J=5.7Hz), 1.2-1.5 (8H, m), 1. 6-2. 0 ( 5H, m) , 2. 1-2. 4 (3H, m) , 2. 5-2. 6 (1"r., m) , 3.0-3.3 (5H, m), 3.o-4.4 (20H, m), 4.7-5.1 (7H, m), 5.i0 (1H, d, J=5.5Hz), 5.16 (1H, d, J=3.1Hz), 5.27 (1H, d, J=4.5Hz), 5.51 (1H, d, J=6.OHz), 6.7-7.i (9H, m), 7.2-7.5 (3H, m) , 8.0-8.2 (2H, m), 8.2-8.4 (1H, :n), 8.4-8.0 (1H, m), 8.66 (iH, d, J=2.2Hz), 8.85 (1H, s) FAH-MASS : m/z = 1360 (M+Na Elemental Analysis Calcd. for C58H80N11022SNa=6H20 C 48.16, H 6.41, N 10.65 Found : C 47.91, H 6.31, N 10.56 ExampIe 106 iR (KEr) : 3369, 3345, 2935, 1672, 1629, 1511, 1245, 1047 cm-1 NMR (DMSO-d6, b) : 0.96 (3H, d, J=6.7Hz), 1.06 (3H, d, J=5.8Hz), 1.3-1.6 (10H, m), 1.6-2.C (5H, m), 2.1-2. 4(3H, m), 2.5-2. o(iH, _n) , 3.20 (3H, s), 3.28 (2H, t, J=6.4Hz), 3.1-3. ~(5H, m), 3.7-4. 5(20H, m) , 4. 7-5 . 1 (7H, m), 5.08 (1H, d, J=5 . 5Hz ), 5. i5, (1H, d, J=3 .1Hz ), 5.23 (1H, d, J=4 . 5Hz ), 5.48 (1 H, d, J=5 . 8Hz ), 6.73 (1H, d, J=8 . 2Hz ), 6.82 (2H, d, J=9. 1Hz) , 6.94 (2ii, d, J=9. 1Hz) , 6. 9-7. 0(1H, m), 7.04 (iH, s), 7.3-7.5 (3H, m), 8.0-8.1 (2H, m), 8.27 (1H, d, J=7.7Hz), 8.49 (1H, cd, J=7.OHz), 8.66 (1'rI, d, J=2 . 2Hz ), 8.84 (1H, s) FAB-MASS : m/z = 1404 (M+Na Example 107 IR (KBr) : 3357, 1647, 1631, 1537, 1444, 1249, 1049 cm 1 NMR (DMSO-d6, 5) : 0.9-1.1 ( 6H, m), 1.09 ( 3H, d, J=5.9Hz), 1.6-2.4 (8H, m), 2.4-2.5 (1H, m), 3.1-3.3 (1H, m), 3.6-4.5 (16H, m), 4.8-5.2 (7H, m), 5.10 _ 241 -(1H, d, J=5 . 6Hz ), 5.17 (11-i, d, J=3 . lHz ), 5.25 (1H, d, J=4 . 5Hz ), 5.55 (1H, d, J=5 . 9Hz ), 6.73 (1H, d, J=8.2Hz), 6.8-7.0 (2H, m), 7.0-7.6 (6H, m), 7.73 (2H, d, J=8.7Hz), 7.86 (21H, d,.J=8.5Hz), 8.0-8.3 (8H, m), 8.84 (1H, s), 8.9-9.0 (1H, m) FAB-NLASS m/z = 1379.4 (M+Na)T
Elemental Analysis Calcd. fcr C5oH69~T10G22S2Na=6H2O
C 48.36, H 5.57, N 9.5c' Found : C 48.18, H 5.60, N 9.36 The Object Compounds (108) to (117) were obtained according to a similar manner to that of Example 27.
Example 108 !R (KBr) . 3350, 2933, 1670, 1627, 1521, 1436, 1272, 1047 cm-1 NMR (DMSO-d6, b) : 0.85 (3H, t, J=6.7Hz), 0.92 (3H, d, J=6 . 7Hz ), 1. 1-1. 4(11H, m), 1. 7-2 . 4 (9H, m), 3.1-3.2 (1H, m), 3.5-5.4 (27H, m), 6.6-7.2 (8H, m), 7.5-7.8 (3H, m), 7.8-8.C (3H, m), 8.1-8.8 (3H, m) FAB-MASS : m/z = 1249.4 (M+Na+) Elemental Analysis Calcd. for C52H7,N10021NaS=7H2O
C 46.15, H 6.33, N 10.35 Found : C 46.12, H 6.35, N 10.24 Example 109 IR (Kbr pelet) . 3361, 2933, 2856, 1670, 1652, 1616, 1540, 1508, 1448, 1261, 1047 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6. 6Hz) , 0.97 (3H, d, J=6 . 8Hz ), 1.12 ( 3H, d, J=6 . 8Hz ), 1. 2-1 . 5 (10H, r.m) , 1.7-2.0 (5H, m), 2.2-2.6 (4H, m), 3.1-3.2 (1H, m), 3.7-4.4 (16H, m), 4.8-5.3 (10H, m), 5.59 (1H, d, J=6.OHz), 6.7-6.9 (3H, m), 7.0-7.4 (7H, m), 7.8-8.2 (4H, m), 8.8-9.0 (2H, m) FA3-MP.SS : m/z = 1280.3 (M+Na+;

Elemental Analysis Calcd. for C54H72N9023NaS=7H20 C 46.45, H 6.21, N 9.03 Found : C 46.68, H 6.44, N 9.03 Example 110 IR (KBr) : 3350, 2931, 1670, 1627, 1540, 1436, 1276, 1047 cm-1 NMR (DMSO-d6, o) : 0.87 (3H, t, J=6.8Hz), 0.93 (2H, d, J=8.8Hz), 1.08 (2H, d, J=5.9Hz), 1.2-1.4 (4H, m), 1.5-1.7 (2H, m), 1.7-2.1 (3H, m), 2.1-2.4 (3H, m), 2.6-2.7 (3H, m), 3.1-3.3 (1H, m), 3.6-4.5 (17H, m), 4.7-5.4 (8H, m), 6.73 (1H, d, J=8.2Hz), 6.83 (2H, d, J=8.2Hz), 7.0-7.1 (1H, m), 7.2-7.5 (5H, m), 7.65 (2H, d, J=8.2Hz), 7.74 (2H, d, J=8.4Hz), 7.98 (2H, d, J=8 . 4Hz ), 8.08 (1H, d, J=8 . 5Hz ), 8.25 (1H, d, J=8.5Hz), 8.74 (1H, d, J=7.6Hz), 8.7-9.0 (1H, br) FPR-MASS : m/z = 1231.2 (M+Na+) Elemental Analysis Calcd. for C53H69N8021NaS=3H20 C 50.39, H 5.98, N 8.87 Found : C 50.34, H 6.25, N 8.90 ExamFl e 111 IR (KBr) : 3353.6, 1670.1, 1652.7, 1623.8 cm-1 NMR (DMSO-d6, S) 0.96 (3H, d, J=6.7Hz), 1.07 (3H, d, J=5.6Hz), 1.20-1.62 (8H, m), 1.62-2.00 (5H, n,), 2. 10-2. 65 (4H, m), 3.20 (3H, s), 3.08-3.40 (iH, m), 3.30 (2H, t, J=6.5Hz), 3.53-4.50 (15H, m), 4.68-5.13 (9H, m), 5.16 (1H, d, J=2 . 9Hz ), 5.26 ( iH, d, J=4.5Hz), 5.53 (1H, d, J=5.9Hz), 6.68-6.95 (4H, m), 6.95-7.11 (3H, m), 7.20-7.52 (3H, m), 7.55-7.95 ( 7H, m), 8.13 (1H, d, J=8 . 4Hz ), 8.31 (1H, d, J=7.7Hz), 8.53 (1H, d, J=7.OHz), 8.85 (1H, s) FAB-MASS : m/z = 1331.5 (M+Na-1) Elemental Analysis Calcd. for C58H77N8NaO23S=6H20 C 49.15, H 6.33, N 7.91 Found : C 49.07, H 6.53, N 7.84 Example 112 IR (KBr) : 3350, 2937, 1673, 1646, 1631, 1538, 1519, 1456, 1247, 1049 cm-1 NMR (DMSO-d6, b) : 0.97 (3H, d, J=6.6Hz), 1.07 (3H, d, J=5.7Hz), 1.3-2.4 (25H, m), 2.5-2.6 (1H, m), 3.2-3.4 (1H, m), 3.5-4. 6(20H, m), 4. 8-5. 7(11iI, m), 6.73 (1H, d, J=8.OHz), 6.9-7.0 (2H, m), 7.0-7.2 (3H, m), 7.3-7.6 (3H, m), 7.74 (2H, d, J=8.5Hz), 7.77 (2H, d, J=8.3Hz), 8.02 (2H, d, J=8.3Hz), 8.13 (1H, d, J=8 . 4Hz ), 8.30 (1H, d, J=7 . 7Hz ), 8.77 (1?:, d, J=7 . OHz ), 8.85 ( iH, s) FAB-MASS m/z = 1389 (M+Na Elemental Analysis Calcd. for C61H83N8024NaS=7H2O
C 49.06, H 6.55, N 7.50 Found : C 49.03, H 6.54, N 7.56 Example 113 NMR (DMSO-d6, b) : 0.84 (3H, t, J=6.7Hz), 0.96 (3H, d, J=6.7Hz), 1.07 (3H, d, J=5.9Hz), 1.1-1.3 (14H, m), 1.7-2.1 (5H, m), 2.2-2.5 (3H, m), 2.6-2.7 (1H, m), 3.1-3.3 (1H, m), 3.7-4.5 (16H, m), 4.7-5.1 (7H, *-n), 5.10 (1H, d, J=5.5Hz), 5.16 (1H, d, J=3.lHz), 5.25 (1H, d, J=4.5Hz), 5.49 (1H, d, J=5.7Hz), 6.53 (iH, d, J=3. iHz) , 6.73 (1H, d, J=8.2Hz), 6. 8-6. 9(2H, m), 7.05 (1H, m), 7.31 (iH, d, J=8.iHz), 7.4-7.6 (4H, m), 7.70 (iH, d, J=6.7Hz), 8.08 (iH, d, J=8.4Hz), 8.18 (1H, s), 8.31 (1H, d, J=7.7Hz), 8.57 (iH, d, J=7.OHz), 8.85 (1'r:, s) FAB-MASS : m/z = 1264 (M+Na+) Elemental Analysis Calcd. for C54H76N9021NaS=6H2O
C 48.03, H 6.57, N 9.34 Found : C 48.02, H 6.61, N 9.28 Example 114 IR (KBr) : 3350, 2937, 1668, 1631, 1537, 1247, 1047 cm-1 NMR (DMSO-zi,, ~; . 0.85 (3H, t, J=7.4Hz), 0.96 (3H, d, J=6.5Hz), 1.07 (3H, d, J=5.7Hz), 1.3-1.7 (7H, m), 1. 7-2 .1 ( 5H, m), 2. 2-2 . 4 (3H, m), 2. 6-2 . 7 (1H, m), 3.0-3.8 (16H, m), 3.8-4.6 (11H, m), 4.7-5.3 (6H, 6.73 ! 1H, d, J=8 . 2Hz ), 6. 8-7 . 0 (2H, m) , 7. 0-7 . 2 (3H, m), 7.3-7.5 (3H, m), 7.6-7.8 (4H, m), 7.96 (2H, d, J=8 . 3Hz ), 8.11 (1H, d, J=8 . 2Hz ), 8.26 (1H, d, J=7.6Hz), 8.6-9.0 (2H, m) FAB-MASS : m/z = 1319.4 (M+Nat) Eiemental Analysis Calcd. for C57H77N8023NaS=8H?0 C 47.50, H 6.50, N 7.77 Found : C 47.72, H 6.85, N 7.85 Example 115 IR (KBr) 3350, 1666, 1631, 1546, 1276, 1247 cm-1 NMR (DMSO-d6, (5) : 0.97 (3H, d, J=7.5Hz), 1.08 (3H, d, J=5.7Hz), 1.4-1.6 (4H, m), 1.6-2.1 (5H, m), 2.1-2.4 (3H, m), 2.5-2.6 (1H, m), 3.1-3.3 (1H, m), 3.23 (3H, s), 3.3-3.5 (2H, m), 3.7-4.5 (16H, m), 4.79 (2H, d, J=6 . 2Hz ), 4. 8-5 . 1 (5H, m), 5.11 (1H, d, J=5 . 6Hz ), 5.18 (1H, d, J=3 .1Hz ), 5.26 (1H, d, J=4.4Hz), 5.54 (1H, d, J=5.7Hz), 6.73 (1H, d, J=8.1Hz), 6.8-7.0 (2H, m), 7.0-7.1 (3H, m), 7.3-7.5 (3H, m), 7.6-7.9 (8H, m), 8.01 (2H, d, J=8.4Hz), 8.08 (1H, d, J=8.4Hz), 8.32 (1H, d, J=7.7Hz), 8.80 (1H, d, J=7.OHz), 8.85 (1H, s) FAB-MASS : m/z = 1353.9 (M+Na+) Elemental Analysis Calcd. for C60H75N8023NaS=9.5H20 C 47.96, H 6.31, N 7.46 Found : C 47.97, H 6.25, N 7.41 Example 116 IR (KBr) : 3450, 2935, 1675, 1650, 1540, 1513, 1454, _ 245 -1047 cm-i NMR (DMSO-ci6, (5) : 0.97 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.9Hz), 1.60 (6H, s), 1.7-2.4 (6H, m), 2.5-2.6 (1H, m), 3.1-3.6 (5H, m), 3.7-4.5 (14H, m), 4.7-5.0 (3H, m), 5. 0-5 . 2 (4H, m), 5.11 (1H, d, J=5 . 5Hz ), 5.18 (1H, d, J=3.1Hz), 5.26 (1H, d, J=4.5Hz), 5.56 (1H, d, J=6.OHz), 6.8-7.5 (9H, m), 7.84 (2H, d, J=8. 8Hz) , 8.0-8.4 (6H, *_r,) , 8.85 (1H, s), 8.91 (1H, d, J=7 . OHz ) FAB-MASS : m/z = 1328 (M+Na) +

Elemental Analysis Calcd. for C55H68N11021S2Na=8H2O
C 45.55, H 5.84, N 10.62 Found : C 45.62, H 5.70, N 10.54 Example 117 IR (KBr) . 3350, 2939, 1664, 1627, 1531, 1446, 1249, 1049 cm-1 NMR (DMSO-d6, b) : 0.8-1.0 (6H, m), 1.4-1.9 (9H, m), 2.0-2.5 (4H, m), 3.1-3.2 (1H, m), 3.22 (3H, s), 3.3-3.4 (2H, m), 3.51 (2H, s), 3.6-4.4 (16H, m), 4. 7-5 . 2 (7H, m), 5.07 (1H, d, J=5 . 6Hz ), 5.17 (1H, d, J=3 . 1Hz ), 5.23 (1H, d, J=4 . 5Hz ), 5.54 (1H, d, J=5.9Hz), 6.7-6.8 (3H, rn), 7.0-7.4 (8H, m), 7.5-7.7 (4H, m), 7.70 (4H, s), 8.1-8.2 (2H, m), 8.51 (1H, d, J=7. OHz) , 8.83 (1H, s) FAB-MASS m/z = 1367.6 (M+Na+) Elemental Analysis Calcd. for C61H77N8O93SNa=6.5H2O
C 50.01, H 6.20, N 7.66 Found : C 50.30, H 6.50, N 7.75 Example 118 To a solution of The Object Compound (61) (0.25 g) in methanol (50 ml) was added dry 10'c palladium on carbon (0.2 g) and stirred for 6 hours under hydrogen atmosphere. The palladium on carbon was filtered off, and the filtrate was evaporated under reduced pressure to give Object Compound 118 (1179 mg).
IR (KBr) : 3400, 1668.1, 1627.6 cm-1 NMR (DMSO-d6, b) : 0.92 (3H, d, J=6.7Hz), 1.1-2.45 (40H, m), 3.20 (3H, s), 3.28 (2H, t, J=6.5Hz), 3.0-3.4 (1H, m), 3.5-4.7 (14H, m), 4.95-5.5 (12H, m), 6.55 (1H, d, J=8.4Hz), 6.84 (1H, s), 6.86 (iH, d, J=8.4Hz), 7.0-7.3 (4H, m'õ 7.9-8.3 (4H, m) FAB-MASS : m/z = 1292 (M+Na) Elemental Analysis Calcd. for C54H88N9022SNa=5H2O
C 47.67, H 7.26, N 9.26 Found C 47.72, H 7.35, N 8.95 The Object Compgounds (119) to (121) were obtained according to a similar manner to that of Example 118.
Example 119 NMR (DMSO-d6, b) 0.87 (3H, t, J=6.6Hz), 1.00 (3H, d, J=7.3Hz), 1.03 (3H, d, J=6.OHz), 1.2-1.5 (4H, m), 1.5-2.0 (5H, m), 2.1-2.7 (8H, m), 3.17 (IH, m), 3.6-4.5 (14H, m), 4.65-5.7 (12H, m), 6.72 (1H, d, J=8.lHz), 6.75 (1H, s), 6.80 (1H, d, J=8.1Hz), 7.05 (1H, s), 7.1-7.7 (15H, m), 8.0-8.6 (4H, m), 8.85 (1H, s) FAB-MASS : m/z = 1274 (M4Na) Elemental Analysis Calcd. for C55H74N9021SNa=7H?0 C 47.93, N 6.43, N 9.15 Found : C 48.12, N 6.56, N 9.03 Example 120 IR (KBr) : 3355.5, 1672.0 1629.6 cm-1 NMR (DMSO-d6, b) : 0.86 (3H, t, J=6. 6Hz) , 0.98 (3H, d, J=6.5Hz), 1.03 (3H, d, J=6.OHz), 1.2-2.6 (21H, m), 3.18 (1H, m), 3.6-4.5 (16H, m), 4.65-5.55 (12H, m), 6.6-7.5 (10H, m), 8.0-8.6 (4H, m), 8.89 (1H, s) -FAB-I~'IASS : m/z = 1256 (M+Na) Example 121 IR (KEr) : 3357.5, 1?.4, 1629.6,. 1249.6 cm-1 NMR (DMSO-d6, 5) : 0. 6 (3H, t, J=6.6Hz), 0.96 (3H, d, J=6.8Hz), 1.03 (3H, d, J=6.OHz), 1.1-1.5 (12H, m), 1.6-2.0 (5H, m), 2.0-2.5 (4H, m), 3.07 (1H, m), 3.5-4.5 (16H, m), 4.6-5.6 (12H, m), 6.72 (1H, d, J=8.1Hz), 6.7-6.9 (4H, m), 7.04 (1H, s), 7.16 (1H, s), 7.1-7.5 (2H, m), 7.25 (2H, d, J=8.6Hz), 8.0-8.2 (3H, m), 8.46 (1H, d, J=7Hz), 8.84 (1H, s) FAB-MASS : m/z = 1256 (M+Na) Elemental Analysis Calcd. for C52H76N9O22SNa=7H2O
C 45.91, H 6.67, N 9.27 Found : C 45.98, H 6.67, N 9.10 Example 122 A solution of Object Compound (11) (795 mg) in water (16 ml) was left for 240 hours. The solution was subjected to column chromatography on ODS (YMC-gel ODS-A.MS50) and eluted with 25 ; CH3CN/HqO. The fractions containing Object Compound were combined and the acetonitrile was removed under reduced pressure. The residue was lyophilized to give Object Compound (123) (38 mg).
IR (KBr) : 33(1, 2~56, 2875, 1668, 1627, 1521, 1249, 10 i7 c: '-NMR (DMSO-d6, b) : 0.8-1.5 (19H, m), 1.6-2.4 (13H, m), 3.1-3.2 (1H, m), 3.5-4.1 (12H, m), 4.1-4.7 (10H, m), 4. 9-5. 6(5H, m), 5.98 (1H, d, J=10. 6Hz) , 6. =,6 (1H, d, J=10.6Hz), 6.7-7.3 (12H, m), 7.4-8.0 (7H, m) FAB-MASS : m/z = 1273.1 (N!+Na+) Elemental Analysis Calcd. for C55H71N8O22NaS=11H2O
C 45.58, H 6.47, N 7.73 Found : C 45.83, H 6.26, N 7.75 The following compound (123) was obtained according to a similar manner to that of Example 1.

IR (KBr): 3324, 2937, 2873, 1664, 1629, 1442, 1257 cm-1 NMR (DMSO-d6, b) : 0.91 (3H, t, J=7.lHz), 0.96 (3H, d, J=6.7Hz), 1.09 (3H, d, J=5.7Hz), 1.3-1.5 (4H, m), 1.7-2.6 (9H, m), 3.1-3.3 (1H, m), 3.7-4.6 (16H, m), 4.7-5.1 (7H, m), 5.11 (1H, d, J=5.6Hz), 5.17 (1H, d, J=3.lHz), 5.26 (1H, d, J=4.5Hz), 5.55 (1H, d, J=5.8Hz), 6.7-6.9 (3H, m), 7.0-7.6 (6H, m), 7.97 (2H, d, J=8.8Hz), 8.0-8.4 (6H, m), 8.85 (1H, s), 8.92 (1H, d, J=7.OHz) FAB-MASS: m/z=1331 (M+Na+) Elemental Analysis Calcd. for C55H69N10O22NaS2:

C 45.45, H 5.89, N 9.64 Found: C 45.71, H 5.68, N 9.60

Claims

1. A polypeptide compound or a pharmaceutically acceptable salt thereof of the following general formula:

wherein R1 is naphthyl (C1-C6) alkoxy (C1-C6) alkanoyl which may have 1 to 3 substituent(s) selected from the group consisting of (C1-C6) alkoxy, (C7-C20) alkoxy, (C1-C6) alkyl, (C7-C20) alkyl, (C7-C20) alkoxy (C1-C6) alkyl, phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, naphthyl having (C1-C6) alkoxy, naphthyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkyl, phenyl having (C7-C20) alkyl, naphthoyl having (C7-C20) alkoxy, phenyl substituted with phenyl having (C1-C6) alkyl, and oxo;

(C1-C6) alkanoyl substituted with pyrazolyl which has (C1-C6) alkyl and phenyl having (C7-C20) alkoxy;

(C1-C6) alkoxy (C7-C20) alkanoyl, in which (C7-C20) alkanoyl may have amino or protected amino;

benzoyl substituted with cyclo (C3-C6) alkyl having (C1-C6) alkyl;

indolylcarbonyl having (C7-C20) alkyl;
naphthoyl having (C1-C6) alkyl;
naphthoyl having (C7-C20) alkyl;

benzoyl substituted with phenyl having (C1-C6) alkoxy (C1-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (C1-C6) alkoxy (C1-C6) alkoxy;

benzoyl substituted with phenyl which has phenyl having (C1-C6) alkoxy (C1-C6) alkoxy;

benzoyl substituted with phenyl having tetrahydropyranyloxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having phenoxy (C1-C6) alkoxy;

(C1-C6) alkanoyl substituted with oxazolyl which has phenyl having (C7-C20) alkoxy;

(C7-C20) alkanoyl having hydroxy;

(C7-C20) alkanoyl having benzyl and hydroxy;
3-methyl-tridecenoyl;

(C1-C6) alkanoyl substituted with pyridyl or pyridazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkoxy, (C7-C20) alkoxy (C1-C6) alkyl, phenyl having (C7-C20) alkoxy, phenyl substituted with phenyl having (C1-C6) alkoxy, piperazinyl substituted with phenyl having (C7-C20) alkoxy, piperazinyl substituted with phenyl having (C1-C6) alkoxy (C7-C20) alkoxy, and piperazinyl substituted with phenyl having (C1-C6) alkoxy;

(C1-C6) alkanoyl substituted with benzothiophenyl which may have 1 to 3 (C7-C20) alkoxy;

(C1-C6) alkanoyl substituted with benzo[b]furanyl which may have 1 to 3 substitutent(s) selected from the group consisting of (C7-C20) alkoxy and (C1-C6) alkyl;

(C1-C6) alkanoyl substituted with benzooxazolyl which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl substituted with phenyl having (C1-C6) alkyl, and pyridyl having (C7-C20) alkoxy;

(C1-C6) alkanoyl substituted with piperidyl or piperazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C7-C20) alkoxy, and naphthoyl having (C7-C20) alkoxy;

phenyl (C3-C6) alkenoyl substituted with phenyl which may have 1 to 3 substituent(s) selected from the group consisting of (C1-C6) alkoxy, (C1-C6) alkyl, (C7-C20) alkyl, (C1-C6) alkoxy (C1-C6) alkyl, halo (C1-C6) alkoxy, (C2-C6) alkenyloxy, halo (C7-C20) alkoxy, and (C1-C6) alkoxy (C7-C20) alkoxy;

naphthyl (C3-C6) alkenoyl which may have 1 to (C7-C20) alkoxy;

2-propynoyl, (2- or 3-) butynoyl, (2- or 3- or 4-) pentynoyl, or (2- or 3- or 4- or 5-) hexynoyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of naphthyl having (C7-C20) alkoxy, and phenyl substituted with phenyl having (C1-C6) alkyl;

phenyl (C2-C6) alkanoyl substituted with phenyl which has 1 to 3 substituent(s) selected from the group consisting of (C1-C6) alkoxy, (C7-C20) alkoxy, (C1-C6) alkyl, (C7-C20) alkyl, and phenyl having (C1-C6) alkoxy (C1-C6) alkyl, in which phenyl (C2-C6) alkanoyl may have hydroxy, oxo, protected amino or amino; or (C2-C6) alkanoyl substituted with naphthyl having (C7-C20) alkoxy;

benzoyl substituted with pyrrolidinyl, imidazolidinyl, piperidyl, or piperazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkyl, phenyl having (C1-C6) alkoxy (C7-C20) alkoxy, phenyl having (C7-C20) alkenyloxy, piperidyl substituted with phenyl having (C1-C6) alkoxy, piperidyl, cyclo (C3-C6) alkyl having phenyl, phenyl having cyclo (C3-C6) alkyl, and phenyl substituted with triazolyl having oxo and (C1-C6) alkyl, in which benzoyl may have halogen;

benzoyl substituted with oxazolyl, isoxazolyl, or oxadiazolyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkoxy (C7-C20) alkoxy, and phenyl substituted with phenyl having (C1-C6) alkoxy;

benzoyl substituted with pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl, or tetrazolyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl and phenyl having (C1-C6) alkoxy;

benzoyl substituted with thiazolyl, isothiazolyl, thiadiazolyl, or dihydrothiazinyl, each of which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, cyclo (C3-C6) alkyl having (C1-C6) alkyl, phenyl substituted with phenyl having (C1-C6) alkoxy, phenyl having cyclo (C3-C6) alkyl, phenyl having piperidine, and phenyl having (C1-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (C1-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (C1-C6) alkyl; or benzoyl substituted with phenyl having (C7-C20) alkyl.

2. A compound or pharmaceutically acceptable salt of claim 1, wherein:
R1 is benzoyl substituted with piperazinyl which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkyl, phenyl having (C1-C6) alkoxy (C7-C20) alkoxy, phenyl having (C7-C20) alkenyloxy, piperidyl substituted with phenyl having (C1-C6) alkoxy, cyclo (C3-C6) alkyl having phenyl, phenyl having cyclo (C3-C6) alkyl, and phenyl substituted with triazolyl having oxo and (C1-C6) alkyl, in which benzoyl may have halogen;

benzoyl substituted with isoxazolyl which may have 1 to 3 substituent(s) selected from the group consisting of (C7-C20) alkyl, phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkoxy (C7-020) alkoxy, and phenyl substituted with phenyl having (C1-C6) alkoxy;

benzoyl substituted with phenyl having (C1-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with phenyl having (C1-C6) alkyl;
benzoyl substituted with phenyl having (C7-C20) alkyl;
phenyl (C3-C6) alkenoyl substituted with phenyl which may have 1 to 3 substituent(s) selected from the group consisting of (C1-C6) alkoxy, (C1-C6) alkyl, (C7-C20) alkyl, (C1-C6) alkoxy (C1-C6) alkyl, halo (C1-C6) alkoxy, (C1-C6) alkenyloxy, halo (C7-C20) alkoxy and (C1-C6) alkoxy (C7-C20) alkoxy;

benzoyl substituted with thiadiazolyl which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, cyclo (C3-C6) alkyl having (C1-C6) alkyl, phenyl substituted with phenyl having (C1-C6) alkoxy, phenyl having cyclo (C3-C6) alkyl, phenyl having piperidyl, and phenyl having (C1-C6) alkoxy (C7-C20) alkoxy; or benzoyl substituted with oxadiazolyl which may have 1 to 3 substituent(s) selected from the group consisting of phenyl having (C1-C6) alkoxy, phenyl having (C7-C20) alkoxy, phenyl having (C1-C6) alkoxy (C7-C20) alkoxy, (C7-C20) alkyl and phenyl substituted with phenyl having (C1-C6) alkoxy.

3. The compound or pharmaceutically acceptable salt of claim 2, wherein:
R1 is benzoyl substituted with phenyl having (C1-C6) alkoxy (C7-C20) alkoxy; or benzoyl substituted with phenyl having (C1-C6) alkyl.

4. The compound or pharmaceutically acceptable salt of claim 2, wherein:
R1 is benzoyl substituted with piperazinyl which may have phenyl having (C1-C6) alkoxy;

benzoyl substituted with isoxazolyl which may have phenyl having (C1-C6) alkoxy;

benzoyl substituted with thiadiazolyl which may have phenyl having (C1-C6) alkoxy (C7-C20) alkoxy; or benzoyl substituted with oxadiazolyl which may have phenyl having (C1-C6) alkoxy.

5. The compound or pharmaceutically acceptable salt of claim 2, wherein:
R1 is phenyl (C3-C6) alkenoyl substituted with phenyl which may have (C1-C6) alkoxy.

6. A process for the preparation of a polypeptide compound of the formula (I):

wherein:

R1 is as defined in claim 1 which comprises, reacting a compound of the formula:
or of its reactive derivative at the amino group or a salt thereof, with a compound of the formula:

R1-OH (III) wherein R1 is as defined in claim 1, or its reactive derivative at the carboxy group or a salt thereof, to give a compound (I) of the formula:

wherein R1 is as defined in claim 1, or a salt thereof.

7. A pharmaceutical composition which comprises, as the active ingredient, a compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with pharmaceutically acceptable carriers of excipients.

8. The use of a compound of claim 1 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing fungal infections.

9. A compound of claim 1 or a pharmaceutically acceptable salt thereof for use as a medicament for treating or preventing fungal infections.

10. The use of the compound of claim 1 or a pharmaceutically acceptable salt thereof for the prophylactic and/or the therapeutic treatment of fungal infections caused by pathogenic microorganisms in a human being or an animal.

11. A compound of claim 1, in which R1 is or a pharmaceutically acceptable salt thereof.

12. A sodium salt of the compound of any one of claims 1 to 5 and 11.