(12) United States Patent
`Tabuchi et al.
`
`111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US006586617Bl
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 6,586,617 Bl
`Jul. 1, 2003
`
`(54) SULFONAMIDE DERIVATIVES
`
`(75)
`
`Inventors: Takanori Tabuchi, Tsukuba (1P);
`Tetsuhiro Yamamoto, Toride (1P);
`Masaharu Nakayama, Tsukuba (1P)
`
`(73) Assignee: Sumitomo Chemical Takeda Agro
`Company, Limited, Tokyo (1P)
`
`JP
`JP
`wo
`wo
`wo
`wo
`wo
`wo
`
`63-307851
`1-156952
`96/36596
`97/24135
`97/31910
`98/45255
`99/06037
`00/50391
`
`12/1988
`6/1989
`11/1996
`7/1997
`9/1997
`10/1998
`2/1999
`8/2000
`
`OTHER PUBLICATIONS
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21) Appl. No.:
`
`09/958,953
`
`(22) PCT Filed:
`
`(86) PCT No.:
`
`Apr. 17,2000
`PCT I JP00/027 64
`
`§ 371 (c)(l),
`(2), ( 4) Date: Dec. 18, 2001
`
`(87) PCT Pub. No.: W000/65913
`
`PCT Pub. Date: Nov. 9, 2000
`
`(30)
`
`Foreign Application Priority Data
`
`Apr. 28, 1999
`
`(JP) ........................................... 11-123162
`
`Int. Cl? .............................................. C07C 255/50
`(51)
`(52) U.S. Cl. ........................ 558/394; 558/413; 568/931
`(58) Field of Search ................................. 558/394, 413;
`568/931
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`3,772,320 A
`4,492,683 A
`4,853,328 A
`4,906,650 A
`5,026,625 A
`5,612,353 A
`6,130,320 A
`
`. ... ... 548/332.5
`11/1973 Zeller hoff et a!.
`1!1985 Nagpal ....................... 514/542
`8/1989 Okazaki et a!. ............... 435/28
`................. 514/369
`3/1990 Becket a!.
`6/1991 Riediker et a!.
`............ 430/281
`3/1997 Ewing eta!. ............... 514/309
`* 10/2000 Lamm et a!.
`............... 534/642
`
`FOREIGN PATENT DOCUMENTS
`
`DE
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`FR
`HU
`HU
`JP
`JP
`JP
`JP
`
`19725447 A1
`0 206 581
`0206581 A2
`432892
`0 570 594
`0 621 273
`0 778 267
`1 044 962
`2 000 450
`191 074
`198 371
`61-286366
`62-190104
`63-227552
`63-238006
`
`12/1997
`12/1986
`12/1986
`6/1991
`11/1993
`10/1994
`6/1997
`10/2000
`9/1969
`1!1987
`10/1989
`12/1986
`8/1987
`9/1988
`10/1988
`
`Derek R. Buckle et al., "Inhibition of Cyclic Nucleotide
`Phosphodiesterase by Derivatives of 1,3-Bis(cyclopropyl(cid:173)
`methyl)xanthine", 1. Med. Chern., vol. 37, No. 4, pp.
`476-485, 1994.
`Francisca Lopes et al., "Acyloxymethyl as a Drug Protecting
`Group. Part 6: N-Acyloxymethyl- and N-[Arninocarbony(cid:173)
`loxy)methyl]sulfonamides as Prodrugs of Agents Contain(cid:173)
`ing a Secondary Sulfonamide Group", Bioorganic &
`Medicinal Chemistry, vol. 8, No. 4, pp. 707-716, 2000.
`1.S. Sukla et al., "Studies on Some Newer Possible Biologi(cid:173)
`of
`cally Active Agents:
`Part
`II.
`Synthesis
`N-(Y-aminopropyl)-2-heterocyclic-p-arylidene aminoben(cid:173)
`zenesulphonamides and N'(Y-aminopropyl)-2-heterocyclic
`sulphanalamides and their Antibacterial Activity", 1. Indian
`Chern. Soc., vol. LVI, pp. 401-403, Apr. 1979.
`D. Buckle et al., "Inhibition of Cyclic Nucleotide Phos(cid:173)
`phodiesterase by Derivatives of 1,3-Bis( cyclopropylmeth(cid:173)
`yl)xanthine", 1. Med. Chern., vol. 37, No. 4, pp. 476-485,
`1994.
`F. Lopes et al., "Acyloxymethyl as a Drug Protecting Group.
`Part 6: N-Acyloxymethyl- and N-[(Arninocarbonyloxy)m(cid:173)
`ethyl]sulfonamides as Prodrugs of Agents Containing a
`Secondary Sulfonamide Group", Bioorganic & Medicinal
`Chemistry., vol. 8, No. 4, pp. 707-716, 2000.
`1. Sukla et al., "Studies on Some Newer Possible Biologi(cid:173)
`cally Active Agents:
`Part
`II.
`Synthesis
`of
`N-(y-aminopropyl)-2-heterocyclic-p-arylidene aminoben(cid:173)
`zenesulphonamides
`and N'(y-amino-propyl)-2-hetero(cid:173)
`cyclic Sulphanalamides and their Antibacterial Activity", 1.
`Indian Chern. Soc., vol. LVI, pp. 401-403, Apr. 1979.
`Warner M. Linfield et al., Antibacterially Substituted Anil(cid:173)
`ides of Carboxylic and Sulfonic Acids, 1. Med. Chern., 26,
`pp. 1741-1746, 1983.
`
`* cited by examiner
`
`Primary Examiner---Ceila Chang
`Assistant Examiner---Golam M. M. Shameem
`(74) Attorney, Agent, or Firm-Wenderoth, Lind & Ponack,
`L.L.P.
`
`(57)
`
`ABSTRACT
`
`The present invention relates to microbicides for agricultural
`or horticultural use containing a sulfonamide derivative.
`
`6 Claims, No Drawings
`
`Par Pharm., Inc.
`Exhibit 1037
`Page 001
`
`

`

`US 6,586,617 Bl
`
`1
`SULFONAMIDE DERIVATIVES
`
`This application is a 371 of PCT/JP00/02764 Apr. 17,
`2000.
`
`TECHNICAL FIELD
`
`This invention relates to sulfonamide derivatives useful as
`microbicides for agricultural or horticultural use.
`
`BACKGROUND ART
`
`5
`
`2
`be substituted, formyl group or an alkylsulfonyl group
`which may be substituted), or (8) a -S(O)nR4 (wherein n
`represents an integer from 0 to 2, and R4 is a hydrogen atom
`or a hydrocarbon group which may be substituted)],
`(hereafter, they may also be mentioned as compounds (1°)),
`or more specifically compounds (I) to (V)(as will be stated
`below) or salts thereof have unexpectedly a very strong
`microbicidal activity, while, on the contrary, they revealed
`only a low toxicity to human being and farm animals, fishes
`10 and natural enemies. The present inventors carried out an
`intensive research based on these findings and have com(cid:173)
`pleted the present invention. Thus, the present invention
`relates to:
`[1] A microbicidal composition for agricultural or horti-
`15 cultural use comprising a compound of Formula (I):
`
`or a salt thereof
`[ whereinA1 is (1) an aryl group which may be substituted
`or (2) a heterocyclic group which may be substituted,
`X1 is (1) a chemical bond, (2) a methylene group which
`may be substituted, or (3) a vinylene group which may
`be substituted, B1 is a five-membered heterocyclic
`group (except for an isoxazolyl group) or a condensed
`heterocyclic group which may be substituted, Z1 is (1)
`a hydrocarbon group which may be substituted, (2) an
`acyl group which may be substituted, (3) formyl group,
`(4) an amino group which may be substituted, (5) a
`group which is represented by -N=CR1 R2(wherein
`each R1 and R2 is respectively a hydrogen atom or a
`hydrocarbon group which may be substituted), (6) a
`cyclic amino group, (7) a group which is represented by
`-OR3 (wherein R3 is a hydrogen atom, a hydrocarbon
`group which may be substituted, an acyl group which
`may be substituted, formyl group or an alkylsulfonyl
`group which may be substituted) or (8) a group repre(cid:173)
`sented by -S(O)nR4 (wherein, n stands for an integer
`from 0 to 2, R4 stands for a hydrogen atom or a
`hydrocarbon group which may be substituted).]
`[2] A microbicidal composition for agricultural or horti(cid:173)
`cultural use described in [1] above, wherein B1 is a five-
`45 membered heterocyclic group which contains hetero-atoms
`selected from nitrogen atoms and sulfur atoms as the ring(cid:173)
`constructing hetero atom in addition to the carbon atoms
`which may be substituted, or B1 is a condensed heterocyclic
`group which may be substituted.
`[3] A microbicidal composition described in [1] above,
`wherein A 1 is (1) an aryl group which may be substituted
`with 1 to 5 substituents selected from a group of substituents
`(T) which consists of (i) a C1 _4 alkyl group which may be
`substituted with 1 to 5 substituents selected from halogens,
`55 hydroxy, imino, hydroxyimino, cl-4 alkoxyimino,
`hydrazono, mono- or di-C1 _4 alkylhydrazono and C1 _4
`alkylthio, (ii) a C3 _6 cycloalkyl group which may be substi(cid:173)
`tuted with 1 to 5 halogens, (iii) a c2-4 alkenyl group which
`may be substituted with 1 to 5 substituents selected from
`60 halogen, cyano, and nitro, (iv) a C3 _0 cycloalkenyl group
`which may be substituted with 1 to 5 halogens, (v) a C2 _4
`alkynyl group which may be substituted with 1 to 5
`halogens, (vi) hydroxyl group, (vii) a cl-4 alkoxy group
`which may be substituted with 1 to 5 substituents selected
`65 from halogen and cl-4 alkoxy group, (viii) formyloxy group,
`(ix) a C1 _4 alkyl-carbonyloxy group which may be substi(cid:173)
`tuted with 1 to 5 halogens, (x) a cl-4 alkoxy-carbonyloxy
`
`20
`
`A lot of microbicides have ever been synthesized and used
`as microbicides for agriculture or horticulture. They have
`contributed greatly to supply agricultural products con(cid:173)
`stantly. However, it is well-known that frequent use of
`restricted number of compounds has led to outbreak of
`microbes which are resistant to those drugs. In addition,
`recent rise in demand for the safety and environmental
`influence of chemical substances has made it desirable to
`develop safer microbicides for agricultural or horticultural
`use. This has given an intention to the researches to explore
`and research novel compounds with microbicidal activity.
`As for sulfonamide derivatives, a lot of compounds have
`also been synthesized so far from the interests in their
`biological or chemical characteristics. A majority of them 25
`are, however, synthetic intermediates, medicines, com(cid:173)
`pounds prepared for the aim of elucidating chemical reaction
`mechanism or reagents. As for sulfonamide derivatives
`related to microbicides, there may be cited those described
`in Japanese Patent Publication for Laid-Open 286366/1986, 30
`Japanese Patent Publication for Laid-Open 239264/1988,
`Japanese Patent Publication for Laid-Open 238006/1988,
`Japanese Patent Publication for Laid-Open 307851!1988,
`Japanese Patent Publication for Laid-Open 156952/1989,
`and in J. Med. Chern. 1983,26, 1741, and in DE19725447, 35
`and so on.
`Nevertheless, no sulfonamide derivative has been devel(cid:173)
`oped yet, which is safe and has little influence on human
`beings and firm animals, natural enemies, and the
`environment, and exert excellent protective effects even on 40
`drug -resistant microbes.
`
`50
`
`Disclosure of Invention
`The present inventors have made intensive efforts for
`many years in order to find out compounds which have
`excellent microbicidal action and solve the problems men(cid:173)
`tioned above. As the results, they have found that the
`compounds represented by the formula I0 or salts thereof.
`Formula I0
`:
`
`[wherein, A 0 is (1) an aryl group which may be substituted,
`or (2) a heterocyclic group which may be substituted, X0 is
`(1) a chemical bond, (2) a methylene group which may be
`substituted or (3) a vinylene group which may be
`substituted, B0 is a heterocyclic group which may be sub(cid:173)
`stituted or an aryl group which may be substituted, Z0 is (1)
`a hydrocarbon group which may be substituted, (2) an acyl
`group which may be substituted, (3) formyl group, ( 4) an
`amino group which maybe substituted, (5) -N=CR1 R2
`(wherein R1 and R2 is a hydrogen atom or a hydrocarbon
`group which may be substituted), (6) a cyclic amino group,
`(7) -OR3 (wherein R3 is a hydrogen atom, a hydrocarbon
`group which may be substituted, an acyl group which may
`
`Par Pharm., Inc.
`Exhibit 1037
`Page 002
`
`

`

`US 6,586,617 Bl
`
`3
`group which may be substituted with 1 to 5 halogens, (xi)
`mercapto group, (xii) a C1 _4 alkylthio group which may be
`substituted with 1 to 5 halogens, (xiii) a cl-4 alkyl(cid:173)
`carbonylthio group which may be substituted with 1 to 5
`halogens, (xiv) a cl-4 alkoxy-carbonylthio group which may 5
`be substituted with 1 to 5 halogens, (xv) a cl-4 alkylsulfinyl
`group which may be substituted with 1 to 5 halogens, (xvi)
`a C1 _4 alkylsulfonyl group which may be substituted with 1
`to 5 halogens, (xvii) a sulfamoyl group, (xviii) a mono- or
`di-C1 _4 alkylsulfamoyl group, (xix)a group represented by 10
`
`15
`
`4
`structed either with a five- to six-membered heterocy(cid:173)
`clic ring and benzene rings or with a five- to six(cid:173)
`membered heterocyclic ring and another (the same or
`different) five- to six-membered heterocyclic rings and
`may be substituted with substituents selected from the
`group of substituents (T) mentioned above, Z1 is (1) a
`hydrocarbon group which is selected from (i) a cl-6
`alkyl group which may be substituted with 1 to 5
`substituents selected from (a) halogen, (b) amino, (c)
`mono- or di-C1 _4 alkylamino, (d) hydroxy, (e) C1 _4
`alkoxy which may be substituted with 1 to 5 halogens,
`(f) mercapto, (g) cl-4 alkylthio, (h) cl-4 alkylsulfinyl,
`(i) cl-4 alkylsulfonyl, G) cyano, (k) cl-4 alkoxy(cid:173)
`carbonyl, (1) carbamoyl and (m) a mono- or di-C1 _4
`alkyl-carbamoyl group, (ii) a C2 - 6 alkenyl group which
`may be substituted with 1 to 5 substituents selected
`from (a) halogen, (b) amino, (c) mono- or di-C1 _4
`alkylamino, (d) hydroxy, (e) cl-4 alkoxy which may be
`substituted with 1 to 5 halogens, (f) mercapto, (g) C1 _4
`alkylthio, (h) cl-4 alkylsulfinyl, (i) cl-4 alkylsulfonyl,
`G) cyano, (k) C1 _4 alkoxy-carbonyl, (1) carbamoyl, and
`(m) mono- or di-C 1 _4 alkyl-carbamoyl, (iii) a C2 _6
`alkynyl group which may be substituted with 1 to 5
`substituents selected from (a) halogen, (b) amino, (c)
`mono- or di-C1 _4 alkylamino, (d) hydroxy, (e) C1 _4
`alkoxy which may be substituted with 1 to 5 halogens,
`(f) mercapto, (g) cl-4 alkylthio, (h) cl-4 alkylsulfinyl,
`(i) cl-4 alkylsulfonyl, G) cyano, (k) cl-4 alkoxy(cid:173)
`carbonyl, (1) carbamoyl, and (m) mono- or di-C1 _4
`alkyl-carbamoyl, (iv) a c3-6 cycloalkyl group which
`may be substituted with 1 to 5 substituents selected
`from (a) C1 _4 alkyl which may be substituted with 1 to
`5 halogens, (b) halogen, (c) amino, (d) mono- or di-C1 _4
`alkylamino, (e) hydroxy, (f) cl-4 alkoxy which may be
`substituted with 1 to 5 halogens, (g) mercapto, (h) C1 _4
`alkylthio, (i) cl-4 alkylsulfinyl, G) cl-4 alkylsulfonyl,
`(k) cyano, (1) cl-4 alkoxy-carbonyl, (m) carbamoyl,
`and (n) mono- or di-C1 _4 alkyl-carbamoyl, (v) a C3 _6
`alkadienyl group which may be substituted with 1 to 5
`substituents selected from (a) halogen, (b) amino, (c)
`mono- and di-C1 _4 alkylamino, (d) hydroxy, (e) C1 _4
`alkoxy which may be substituted with 1 to 5 halogens,
`(f) mercapto, (g) cl-4 alkylthio, (h) cl-4 alkylsulfinyl,
`(i) cl-4 alkylsulfonyl, G) cyano, (k) cl-4 alkoxy(cid:173)
`carbonyl, (1) carbamoyl and (m) mono- or di- C1 _4
`alkyl-carbamoyl or (vi) C6 _14 aryl group which may be
`substituted with 1 to 5 substituents selected from (a)
`C1 _4 alkyl which may be substituted with 1 to 5
`halogens, (b) halogen, (c) amino, (d) mono- or di-C1 _4
`alkylamino, (e) hydroxy, (f) cl-4 alkoxy which may be
`substituted with 1 to 5 halogens, (g) mercapto, (h) C1 _4
`alkylthio, (i) cl-4 alkylsulfinyl, G) cl-4 alkylsulfonyl,
`(k) cyano, (1) C1 _4 alkoxy-carbonyl, (m) carbamoyl and
`(n) mono- or di-C1 _4 alkyl-carbamoyl, (2) an acyl group
`selected from (i) cl-4 alkyl-carbonyl, (ii) cl-4 alkoxy(cid:173)
`carbonyl, (iii) cl-4 alkylthio-carbonyl, (iv) cl-4 alkoxy(cid:173)
`thiocarbonyl, (v) cl-4 alkylthio-thiocarbonyl, (vi)
`mono- or di-C1 _4 alkyl-carbamoyl and (vii) mono- or
`di-C1 _4 alkyl-thiocarbamoyl, each of which may be
`substituted with 1 to 5 halogens, (3) formyl group, (4)
`an amino group which may be substituted with one or
`two substituents selected from (a) cl-4 alkyl, (b) cl-4
`alkyl-carbonyl which may be substituted with 1 to 5
`halogens, (c) C1 _4 alkoxy-carbonyl, (d) mono- or
`di-C1 _4 alkyl-carbamoyl and (e) mono- or di-C1 _4 alkyl(cid:173)
`thiocarbamoyl, (5) a group represented by
`-N=CR1R2 (wherein R1 and R2 are the same or
`
`(wherein, ring C is a 3- to 6-membered heterocyclic group
`containing nitrogen), (xx) an amino group which may be
`substituted with one or two substituents selected from a C1 _4
`alkyl, c2-4 alkenyl, c2-4 alkynyl, hydroxy, cl-4 alkoxy, 20
`formyloxy, cl-4 alkyl-carbonyloxy, formyl and cl-4 alkyl(cid:173)
`carbonyl, (xxi) a 3- to 6-membered cyclic amino group,
`(xxii) formyl group. (xxiii) a cl-4 alkyl-carbonyl group
`which may be substituted with 1 to 5 halogens, (xxiv) a C1 _4
`alkoxy-carbonyl group which may be substituted with 1 to
`5 halogens, (xxv) a cl-4 alkylthio-carbonyl group, (xxvi) a
`cl-4 alkoxy-thiocarbonyl group, (xxvii) cl-4 alkylthio(cid:173)
`thiocarbonyl group, (xxviii) carbamoyl group, (xxix) a
`mono- or di-C1 _4 alkylcarbamoyl group, (xxx) a group
`represented by
`
`25
`
`30
`
`0-co-
`
`(wherein, ring C is a 3- to 6-membered heterocyclic group
`containing nitrogen), (xxxi) thiocarbamoyl group, (xxxii) a
`mono- or di-C1 _4 alkyl-thiocarbamoyl group, (xxxiii) a
`group represented by
`
`0-cs-
`
`35
`
`40
`
`45
`
`(wherein, ring C is a 3- to 6-membered heterocyclic group
`containing nitrogen), (xxxiv) halogen atom, (xxxv) carboxyl
`group, (xxxvi) thiocyanato group, (xxxvii) isothiocyanato
`group, (xxxviii) cyano group, (xxxix) isocyano group, (xl)
`azido group, (xli) nitroso group, (xlii) nitro group, (xliii) 50
`azocyano group, (xliv) azoxycyano group and (xlv) sulfa
`group, or (2) a heterocyclic group which may be substituted
`with 1 to 5 substituents selected from the group of substitu(cid:173)
`ents (T) mentioned above,
`X1 is (1) a chemical bond, (2) a methylene group which 55
`may be substituted with one or two substituents
`selected from cl-4 alkyl, cl-4 alkoxy, cl-4 alkylthio,
`halogen atom and cyano or (3) a vinylene group which
`may be substituted with one or two substituents
`selected from c1-4 alkyl, c1-4 alkoxy, c1-4 alkylthio, 60
`halogen atom, and cyano, B1 is (1) a five-membered
`heterocyclic group which is composed of the ring(cid:173)
`constructing heteroatoms besides carbon atoms
`selected from nitrogen and sulfur atoms, and which
`may be substituted with 1 to 5 substituents selected 65
`from the group of substituents (T) mentioned above, or
`(2) a condensed heterocyclic group which is con-
`
`Par Pharm., Inc.
`Exhibit 1037
`Page 003
`
`

`

`US 6,586,617 Bl
`
`5
`different, and are a hydrogen atom and a C1 _4 alkyl
`group), (6) a three- to six-membered cyclic amino
`group, (7) a group represented by -OR3 (wherein R3
`is a hydrogen atom, a C1 _4 alkyl group which may be
`substituted with 1 to 5 halogens, a cl-4 alkyl-carbonyl 5
`group which may be substituted with 1 to 5 halogens,
`a C1_4 alkoxy-carbonyl group which may be substituted
`with 1 to 5 halogens, formyl group or a cl-4 alkylsul(cid:173)
`fonyl group which may be substituted with 1 to 5
`halogens), or (8) a group represented by -S(O)nR4 10
`(wherein n is an integer from 0 to 2, and R4 is (a) a
`hydrogen atom, (b) a C1 _4 alkyl group which may be
`substituted with 1 to 5 halogens or (c) a C6 _14 aryl
`group which may be substituted with 1 to 5 C1 _4 alkyl 15
`groups.
`[ 4] A microbicidal composition for agricultural or horti(cid:173)
`cultural use described in [1] above, where A 1 is a C6 _14 aryl
`group which may be substituted with 1 to 3 alkyl group, X1
`is a chemical bond, B 1 is a thienyl group, a pyrazolyl group, 20
`an isothiazolyl group, an imidazolyl group, a thiazolyl
`group, a thiadiazolyl group, a dioxaindanyl group or an
`imidazopyridyl group, each of which may be substituted
`with 1 to 5 substituents selected from C1 _4 alkyl which may
`be substituted with 1 to 5 halogens, cl-4 alkoxy, cl-4 25
`alkylthio, cyano, halogens and nitro, Z 1 is a cl-6 alkyl group
`or a cl-4 alkoxy group.
`[5] A microbicidal composition for agricultural or horti(cid:173)
`cultural use comprising a compound of Formula (II):
`
`30
`
`35
`
`45
`
`or a salt thereof,
`[wherein, A2 is (1)an aryl group which may be substituted
`with 1 to 5 substituents selected from a group of
`substituents (T') which consists of (i) a C1 _4 alkyl group
`which may be substituted with 1 to 5 substituents 40
`selected from halogen, hydroxy, imino, hydroxyimino,
`C1 _4 alkoxyimino, hydrazono, mono- or di-C1 _4 alkyl(cid:173)
`hydrazono and cl-4 alkylthio, (ii) a c3-6 cycloalkyl
`group which may be substituted with 1 to 5 halogens,
`(iii) a C2 _4 alkenyl group which may be substituted with
`substituents selected from halogens, cyano and nitro,
`(iv) a C3 _6 cycloalkenyl group which may be substi(cid:173)
`tuted with 1 to 5 halogens, (v) a c2-4 alkynyl group
`which may be substituted with 1 to 5 halogens, (vi) 50
`hydroxy group, (vii) a cl-4 alkoxy group which may be
`substituted with 1 to 5 substituents selected from halo(cid:173)
`gens and cl-4 alkoxy, (viii) formyloxy group, (ix) a
`C1 _4 alkyl-carbonyloxy group which may be substi(cid:173)
`tuted with 1 to 5 halogens, (x) a cl-4 alkoxy- 55
`carbonyloxy group which may be substituted with 1 to
`5 halogens, (xi) mercapto group, (xii) a C1 _4 alkylthio
`group which may be substituted with 1 to 5 halogens,
`(xiii) a cl-4 alkyl-carbonylthio group which may be
`substituted with 1 to 5 halogens, (xiv) a cl-4 alkoxy- 60
`carbonylthio group which may be substituted with 1 to
`5 halogens, (xv) a cl-4 alkylsulfinyl group which may
`be substituted with 1 to 5 halogens, (xvi) a cl-4
`alkylsulfonyl group which may be substituted with 1 to
`5 halogens, (xvii) sulfamoyl group, (xviii) a mono- or 65
`di-C1 _4 alkylsulfamoyl group, (xix) a group represented
`by
`
`6
`
`(wherein, ring C is a three- to six-membered heterocy(cid:173)
`clic group containing nitrogen), (xx) an amino group
`which may be mono- or disubstituted with one or two
`substituents selected from cl-4 alkyl, c2-4 alkenyl, c2-4
`alkynyl, hydroxy, cl-4 alkoxy, formyloxy, cl-4 alkyl(cid:173)
`carbonyloxy, formyl and C1 _4 alkyl-carbonyl, (xxi) a
`three- to six-membered cyclic amino group, (xxii)
`formyl group, (xxiii) a cl-4 alkyl-carbonyl group which
`may be substituted with 1 to 5 halogens, (xxiv) a C1 _4
`alkoxy-carbonyl group which may be substituted with
`1 to 5 halogens, (xxv) a cl-4 alkylthio-carbonyl group,
`(xxvi) a cl-4 alkoxy-thiocarbonyl group, (xxvii) a cl-4
`alkylthio-thiocarbonyl group, (xxviii) carbamoyl
`group, (xxix) a mono- or di-C1 _4 alkylcarbamoyl group,
`(xxx) a group represented by
`
`8-co-
`
`(wherein, ring C is a three- to six-membered heterocy(cid:173)
`clic group containing nitrogen), (xxxi) thiocarbamoyl
`group, (xxxii) a mono- or di-C1 _4 alkyl-thiocarbamoyl
`group, (xxxiii) a group represented by
`
`8-cs-
`
`(wherein, ring C is a three- to six-membered heterocy(cid:173)
`clic group containing nitrogen), (xxxiv) halogen atom,
`(xxxv) carboxyl group, (xxxvi) thiocyanato group,
`(xxxvii) isothiocyanato group, (xxxviii) cyano group,
`(xxxix) isocyano group, (xl) azido group, (xli) nitroso
`group, (xlii) nitro group, (xliii) azocyano group and
`(xliv) sulfa group or (2) a heterocyclic group, which
`may be substituted.
`X2 is (1) a chemical bond, (2) a methylene group which
`may be substituted or (3) a vinylene group which may
`be substituted, B 2 is an aryl group which may be
`substituted, Z 2 is (1) an alkyl group which may be
`substituted with substituents selected from mono- or
`di-C 1 _6 alkylamino, hydroxy, halogens, C1 _6 alkoxy,
`cl-6 alkoxy-carbonyl, cl-6 alkylthio and cyano, (2)
`vinyl group, (3) an allyl group, ( 4) a propadienyl group,
`(5) an alkynyl group which may be substituted, (6) a
`cycloalkyl group which may be substituted, (7) an aryl
`group which may be substituted, (8) an acyl group
`which may be substituted, (9) formyl group, (10) an
`amino group which may be substituted, (11) a group
`represented by -N=CR1R2 (wherein R1 and R2 are
`the same or different, and are a hydrogen atom and a
`hydrocarbon group which may be substituted
`respectively), (12) a cyclic amino group, (13) a group
`represented by -OR3 (wherein R3 is a hydrogen atom,
`a hydrocarbon group which may be substituted, an acyl
`group which may be substituted, formyl group, or an
`alkylsulfonyl group which may be substituted), or (14)
`a group represented by -S(O)nR4 (wherein, n is an
`integer from 0 to 2, and R4 is a hydrogen atom or a
`hydrocarbon group which may be substituted).
`
`Par Pharm., Inc.
`Exhibit 1037
`Page 004
`
`

`

`US 6,586,617 Bl
`
`7
`[6] A microbicidal composition for agricultural or horti(cid:173)
`cultural use described in [5] above, [wherein, A2 is (1)a
`C6 _14 aryl group which may be substituted with 1 to 5
`substituents selected from a group of substituents (T') which
`consists of (i) a C1 _4 alkyl group which may be substituted
`with 1 to 5 substituents selected from halogen, hydroxy,
`imino, hydroxyimino, cl-4 alkoxyimino, hydrazono, mono(cid:173)
`or di-C 1 _4 alkylhydrazono and C1 _4 alkylthio, (ii) a C3 _6
`cycloalkyl group which may be substituted with 1 to 5
`halogens, (iii) C2 _4 alkenyl group which may be substituted
`with 1 to 5 substituents selected from halogens, cyano and
`nitro, (iv) a C3 _6 cycloalkenyl group which may be substi(cid:173)
`tuted with 1 to 5 halogens, (v) a c2-4 alkynyl group which
`may be substituted with 1 to 5 halogens, (vi) hydroxy group,
`(vii) a C1_4 alkoxy group which may be substituted with 1 to
`5 substituents selected from halogens and C1 _4 alkoxy, (viii)
`formyloxy group, (ix) a cl-4 alkyl-carbonyloxy group which
`may be substituted with 1 to 5 halogens, (x) a C1 _4 alkoxy(cid:173)
`carbonyloxy group which may be substituted with 1 to 5
`halogens, (xi) mercapto group, (xii) a C1 _4 alkylthio group
`which may be substituted with 1 to 5 halogens, (xiii) a C1 _4
`alkyl-carbonylthio group which may be substituted with 1 to
`5 halogens, (xiv) a cl-4 alkoxy-carbonylthio group which
`may be substituted with 1 to 5 halogens, (xi) a C1 _4 alkyl(cid:173)
`sulfinyl group which may be substituted with 1 to 5
`halogens, (xvi) a cl-4 alkylsulfonyl group which may be
`substituted with 1 to 5 halogens, (xvii) sulfamoyl group,
`(xviii) a mono- or di-C 1 _4 alkylsulfamoyl group, (xix) a
`group represented by
`
`8
`cyanato group, (xxxviii) cyano group, (xxxix) isocyano
`group, (xl) azido group, (xli) nitroso group, (xlii) nitro
`group, (xliii) azocyano group and (xliv) sulfa group, or (2)
`heterocyclic group which may be substituted with 1 to 5
`5 substituents selected from a group of substituents (T) which
`consists of (i) C1 _4 alkyl group which may be substituted
`with 1 to 5 substituents selected from halogens, hydroxy,
`imino, hydroxyimino, cl-4 alkoxyimino, hydrazono, mono(cid:173)
`or di-C1 _4 alkylhydrazono and C1 _4 alkylthio, (ii) a C3 _6
`10 cycloalkyl group which may be substituted with 1 to 5
`halogens, (iii) C2 _4 alkenyl group which may be substituted
`with 1 to 5 substituents selected from halogens, cyano and
`nitro, (iv) C3 _6 cycloalkenyl group which may be substituted
`with 1 to 5 halogens, (v) a C2 _4 alkynyl group which may be
`15 substituted with 1 to 5 halogens, (vi) hydroxy group, (vii)
`C1 _4 alkoxy group which may be substituted with 1 to 5
`substituents selected from halogens and C1 _4 alkoxy, (viii)
`formyloxy group, (ix) cl-4 alkyl-carbonyloxy group which
`may be substituted with 1 to 5 halogens, (x) C1 _4 alkoxy-
`20 carbonyloxy group which may be substituted with 1 to 5
`halogens, (xi) mercapto group, (Xii) C1 _4 alkylthio group
`which may be substituted with 1 to 5 halogens, (xiii) a C1 _4
`alkyl-carbonylthio group which may be substituted with 1 to
`5 halogens, (xiv) a cl-4 alkoxy-carbonylthio group which
`25 may be substituted with 1 to 5 halogens, (xv) a C1 _4
`alkylsulfinyl group which may be substituted with 1 to 5
`halogens, (xvi) a cl-4 alkylsulfonyl group which may be
`substituted with 1 to 5 halogens, (xvii) sulfamoyl group,
`(xviii) a mono- or di-C 1 _4 alkylsulfamoyl group, (xix) a
`30 group represented by
`
`35
`
`(wherein, ring C is a three- to six-membered heterocyclic
`group containing nitrogen), (xx) an amino group which may
`be substituted with one or two substituents selected from
`cl-4 alkyl, c2-4 alkenyl, c2-4 alkynyl, hydroxy, cl-4 alkoxy,
`formyloxy, cl-4 alkyl-carbonyloxy, formyl and cl-4 alkyl- 40
`carbonyl, (xxi) a three to six-membered cyclic amino group,
`(xxii) formyl group, (xxiii) a cl-4 alkyl-carbonyl group
`which may be substituted with 1 to 5 halogens, (xxiv) a C1 _4
`alkoxy-carbonyl group which may be substituted with 1 to
`5 halogens, (xxv) a cl-4 alkylthio-carbonyl group, (xxvi) a 45
`cl-4 alkoxy-thiocarbonyl group, (xxvii) a cl-4 alkylthio(cid:173)
`thiocarbonyl group, (xxviii) carbamoyl group, (xxix) a
`mono- or di-C 1 _4 alkylcarbamoyl group, (xxx) a group
`represented by
`
`(wherein, ring C is a three- to six-membered heterocyclic
`group containing nitrogen), (xx) an amino group which may
`be substituted with one or two substituents selected from
`cl-4 alkyl, c2-4 alkenyl, c2-4 alkynyl, hydroxy, cl-4 alkoxy,
`formyloxy, cl-4 alkyl-carbonyloxy, formyl and cl-4 alkyl(cid:173)
`carbonyl, (xxi) three- to six-membered cyclic amino group,
`(xxii) formyl group, (xxiii) cl-4 alkyl-carbonyl group which
`may be substituted with 1 to 5 halogens, (xxiv) C1 _4 alkoxy-
`carbonyl group which may be substituted with 1 to 5
`halogens, (xxv) cl-4 alkylthio-carbonyl group, (xxvi) a cl-4
`alkoxy-thiocarbonyl group, (xxvii) cl-4 alkylthio(cid:173)
`thiocarbonyl group, (xxviii) a carbamoyl group, (xxix)
`mono- or di-C 1 _4 alkylcarbamoyl group, (xxx) a group
`50 represented by
`
`8-co-
`
`8-co-
`
`(wherein, ring C is a three- to six-membered heterocyclic 55
`group containing nitrogen), (xxxi) thiocarbamoyl group
`(xxxii) a mono- or di-C1 _4 alkyl-thiocarbamoyl group,
`(xxxiii) a group represented by
`
`60
`
`8-cs-
`
`(wherein, ring C is a three- to six-membered heterocyclic
`group containing nitrogen), (xxxi) thiocarbamoyl group,
`(xxxii) mono- or di-C1 _4 alkyl-thiocarbamoyl group, (xxxiii)
`a group represented by
`
`8-cs-
`
`(wherein, ring C is a three- to six-membered heterocyclic 65
`group containing nitrogen), (xxxiv) halogen atom, (xxxv)
`carboxyl group, (xxxvi) thiocyanato group, (xxxvii) isothio-
`
`(wherein, ring C is a three- to six-membered heterocyclic
`group containing nitrogen), (xxxiv) halogen atom, (xxxv)
`
`Par Pharm., Inc.
`Exhibit 1037
`Page 005
`
`

`

`US 6,586,617 Bl
`
`9
`carboxyl group, (xxxvi) thiocyanato group, (xxxvii) isothio(cid:173)
`cyanato group, (xxxviii) cyano group, (xxxix) isocyano
`group, (xl) azido group, (xli) nitroso group, (xlii) nitro
`group, (xliii) azocyano group and (xliv) azoxycyano group,
`and (xlv) sulfa group, X2 is (1) a chemical bond, (2) a 5
`methylene group which may be substituted with one or two
`substituents selected from c1-4 alkyl, c1-4 alkoxy, c1-4
`alkylthio, halogen atoms, and cyano, or (3) a vinylene group
`which may be substituted with one or two substituents
`selected from c1-4 alkyl, c1-4 alkoxy, c1-4 alkylthio, halogen 10
`atoms and cyano, B2
`is an aryl group which may be
`substituted with 1 to 5 substituents selected from the group
`of substituents (T) described above, Z2 is (1) C1 _6 alkyl
`group which may be substituted with 1 to 5 substituents
`selected from mono- or di-C 1 _4 alkylamino, hydroxy, 15
`halogen, c1-4 alkoxy, c1-4 alkoxy-carbonyl, c1-4 alkylthio
`and cyano, (2) vinyl group, (3) allyl group, (4) propadienyl
`group, (5) C2 _6 alkynyl group which may be substituted with
`1 to 5 substituents selected from (a) halogen, (b) amino, (c)
`mono- or di-C 1 _4 alkylamino, (d) hydroxy, (e) a C1 _4 alkoxy 20
`substituted with 1 to 5 halogens, (t) mercapto, (g) C1 _4
`alkylthio, (h) c1-4 alkylsulfinyl, (i) c1-4 alkylsulfonyl, G)
`cyano, (k) C1 _4 alkoxy- carbonyl, (1) carbamoyl and (m)
`mono- or di-C1 _4 alkyl-carbamoyl, (6) C3 _6 cycloalkyl group
`which may be substituted with 1 to 5 substituents selected 25
`from (a) C1 _4 alkyl which may be substituted with 1 to 5
`halogens, (b) halogen, (c) amino, (d) mono- or di-C1 _4
`alkylamino, (e) hydroxy, (t) c1-4 alkoxy which may be
`substituted with 1 to 5 halogens, (g) mercapto, (h) C1 _4
`alkylthio, (i) c1-4 alkylsulfinyl, G) c1-4 alkylsulfonyl, (k) 30
`cyano, (1) C1 _4 alkoxy-carbonyl, (m) carbamoyl and (n)
`mono- or di-C 1 _4 alkyl-carbamoyl, (7) C6_14 aryl group
`which may be substituted with 1 to 5 substituents selected
`from (a) C1 _4 alkyl which may be substituted with 1 to 5
`halogens, (b) halogen, (c) amino, (d) mono- or di-C1 _4 35
`alkylamino, (e) hydroxy, (t) c1-4 alkoxy which may be
`substituted with 1 to 5 halogens, (g) mercapto, (h) C1 _4
`alkylthio, (i) c1-4 alkylsulfinyl, G) c1-4 alkylsulfonyl, (k)
`cyano, (1) C1 _4 alkoxy-carbonyl, (m) carbamoyl and (n)
`mono- or di-C1 _4 alkyl-carbamoyl, (8) acyl group selected 40
`from (i) c1-4 alkyl-carbonyl, (ii) c1-4 alkoxy-carbonyl, (iii)
`c1-4 alkylthio-carbonyl, (iv) c1-4 alkoxy-thiocarbonyl, (v)
`C1 _4 alkylthio-thiocarbonyl, (vi) mono- or di-C1 _4 alkyl(cid:173)
`carbamoyl and (vii) mono- or di-C1 _4 alkyl-thiocarbamoyl,
`each of which may be substituted with 1 to 5 halogens, (9) 45
`formyl group, (10) amino group which may be substituted
`with one or two substituents selected from (a) C1 _4 alkyl, (b)
`C1 _4 alkyl-carbonyl which may be substituted with 1 to 5
`halogens, (c) C1 _4 alkoxy-carbonyl, (d) mono- or di-C1 _4
`alkyl-carbamoyl and (e) mono- or di-C 1 _4 alkyl- 50
`thiocarbamoyl, (11) a group represented by -N=CR1 R2
`(wherein R1 and R2 are the same or different, and are a
`hydrogen atom and a c1-4 alkyl group), (12) three- to
`six-membered cyclic amino g