US 5,962,499 AGranted

Nodulisporic acid derivatives

AssigneeMerck & Co., Inc.

InventorsPeter T. Meinke, Thomas Shih, Michael H. Fisher

Life of this patent

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Abstract

The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.

Claims31

Dependent claims

A compound having the formula I:

##STR114## wherein R.sub.1 is (1) hydrogen,
(2) optionally substituted C.sub.1 -C.sub.10 alkyl,
(3) optionally substituted C.sub.2 -C.sub.10 alkenyl,
(4) optionally substituted C.sub.2 -C.sub.10 alkynyl,
(5) optionally substituted C.sub.3 -C.sub.8 cycloalkyl,
(6) optionally substituted C.sub.5 -C.sub.8 cycloalkenyl
where the substitutents on the alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl are 1 to 3 groups independently selected from
(i) C.sub.1 -C.sub.5 alkyl,
(ii) X--C.sub.1 -C.sub.10 alkyl, where X is O or S(O).sub.m.
(iii) C.sub.3 -C.sub.8 cycloalkyl,
(iv) hydroxy,
(v) halogen,
(vi) cyano,
(vii) carboxy,
(viii) NY.sup.1 Y.sup.2, where Y.sup.1 and Y.sup.2 are independently hydrogen or C.sub.1 -C.sub.10 alkyl,
(ix) C.sub.1 -C.sub.10 alkanoylamino, and
(x) aroyl amino wherein said aroyl is optionally substituted with 1 to 3 groups independently selected from R.sup.f
(7) aryl C.sub.0 -C.sub.5 alkyl wherein said aryl is optionally substituted with 1 to 3 groups independently selected from R.sup.f,
(8) C.sub.1 -C.sub.5 perfluoroalkyl
(9) a 5-membered heterocycle containing 1 heteroatom selected from oxygen, sulfur and nitrogen atoms optionally substituted by 1 to 3 groups independently selected from hydroxy, oxo, C.sub.1 -C.sub.10 alkyl and halogen, and which may be saturated or partly unsaturated, R.sub.2, R.sub.3, and R.sub.4 are independently OR.sup.a, OCO.sub.2 R.sup.b, OC(O)NR.sup.c R.sup.d ;
or
R.sub.1 +R.sub.2 represent .dbd.O, .dbd.NOR.sup.a or .dbd.N--NR.sup.c R.sup.d ;
R.sub.5 and R6 are hydrogen;
or
R5 and R6 together represent --O--;
R.sub.7 is (1) CHO, or
(2) the fragment ##STR115## R.sub.8 is (1) hydrogen, (2) OR.sup.a, or
(3) NR.sup.c R.sup.d
R.sub.9 is (1) hydrogen, or
(2) OR.sup.a ;
R.sub.10 is (1) CN,
(2) C(O)OR.sup.b,
(3) C(O)N(OR.sup.b)R.sup.c,
(4) C(O)NR.sup.c R.sup.d,
(5) NHC(O)OR.sup.b,
(6) NHC(O)NR.sup.c R.sup.d,
(7) CH.sub.2 OR.sup.a,
(8) CH.sub.2 OCO.sub.2 R.sup.b,
(9) CH.sub.2 OC(O)NR.sup.c R.sup.d,
(10) C(O)NR.sup.c NR.sup.c R.sup.d, or
(11) C(O)NR.sup.c SO.sub.2 R.sup.b ;
---- represents a single or a double bond;
R.sup.a is (1) hydrogen,
(2) optionally substituted C.sub.1 -C.sub.10 alkyl,
(3) optionally substituted C.sub.3 -C.sub.10 alkenyl,
(4) optionally substituted C.sub.3 -C.sub.10 alkynyl,
(5) optionally substituted C.sub.1 -.sub.10 alkanoyl,
(6) optionally substituted C.sub.3 -C.sub.10 alkenoyl,
(7) optionally substituted C.sub.3 -C.sub.10 alkynoyl,
(8) optionally substituted aroyl,
(9) optionally substituted aryl,
(10) optionally substituted C.sub.3 -C.sub.7 cycloalkanoyl,
(11) optionally substituted C.sub.5 -C.sub.7 cycloalkenoyl,
(12) optionally substituted C.sub.1 -C.sub.10 alkylsulfonyl
(13) optionally substituted C.sub.3 -C.sub.8 cycloalkyl
(14) optionally substituted C.sub.5 -C.sub.8 cycloalkenyl where the substituents on the alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, alkynoyl, aroyl, aryl, cycloalkanoyl, cycloalkenoyl, alkylsulfonyl, cycloalkyl and cycloalkenyl are from 1 to 10 groups independently selected from hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, aryl C.sub.1 -C.sub.3 alkoxy, NR.sup.g R.sup.h, CO.sub.2 R.sup.b, CONR.sup.c R.sup.d and halogen,
(15) C.sub.1 -C.sub.5 perfluoroalkyl,
(16) arylsulfonyl optionally substituted with 1 to 3 groups independently selected from C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 perfluoroalkyl, nitro, halogen and cyano,
(17) a 5-membered heterocycle containing 1 heteroatom selected from oxygen, sulfur and nitrogen optionally substituted by 1 to 4 groups independently selected from C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkenyl, C.sub.1 -C.sub.5 perfluoroalkyl, amino, C(O)NR.sup.c R.sup.d, cyano, CO.sub.2 R.sup.b and halogen, and which may be saturated or partly unsaturated;
R.sup.b is (1) hydrogen,
(2) optionally substituted aryl,
(3) optionally substituted C.sub.1 -C.sub.10 alkyl,
(4) optionally substituted C.sub.3 -C.sub.10 alkenyl,
(5) optionally substituted C.sub.3 -C.sub.10 alkynyl,
(6) optionally substituted C.sub.3 -C.sub.15 cycloalkyl,
(7) optionally substituted C.sub.5 -C.sub.10 cycloalkenyl, or
(8) optionally substituted 5-membered heterocycle containing 1 heteroatom selected from oxygen, sulfur and nitrogen;
where the substituents on the aryl, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, or alkynyl are from 1 to 10 groups independently selected from
(i) hydroxy,
(ii) C.sub.1 -C.sub.6 alkyl,
(iii) oxo,
(iv) SO.sub.2 NR.sup.g R.sup.h,
(v) aryl C.sub.1 -C.sub.6 alkoxy,
(vi) hydroxy C.sub.1 -C.sub.6 alkyl,
(vii) C.sub.1 -C.sub.12 alkoxy,
(viii) hydroxy C.sub.1 -C.sub.6 alkoxy,
(ix) amino C.sub.1 -C.sub.6 alkoxy,
(x) cyano,
(xi) mercapto,
(xii) C.sub.1 -C.sub.6 alkyl-S(O)m,
(xiii) C.sub.3 -C.sub.7 cycloalkyl optionally substituted with 1 to 4 groups independently selected from R.sup.e,
(xiv) C.sub.5 -C.sub.7 cycloalkenyl,
(xv) halogen,
(xvi) C.sub.1 -C.sub.5 alkanoyloxy,
(xvii) C(O)NR.sup.g R.sup.h,
(xviii) CO.sub.2 R.sup.i,
(xix) formyl,
(xx) --NR.sup.g R.sup.h,
(xxi) 5-membered heterocycle, which may be saturated or partially unsaturated, containing 1 heteroatom selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 to 5 groups independently selected from R.sup.e,
(xxii) optionally substituted aryl, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from R.sup.e,
(xxiii) optionally substituted aryl C.sub.1 -C.sub.3 alkoxy, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from R.sup.e, and
(xxiv) C.sub.1 -C.sub.5 perfluoroalkyl;
R.sup.c and R.sup.d are independently selected from R.sup.b ;
or
R.sup.c and R.sup.d together with the N to which they are attached form a 5-membered ring containing 0 additional heteroatom, optionally substituted with 1 to 3 groups independently selected from R.sup.g, hydroxy, thioxo and oxo;
R.sup.e is (1) halogen,
(2) C.sub.1 -C.sub.7 alkyl,
(3) C.sub.1 -C.sub.3 perfluoroalkyl,
(4) --S(O).sub.m R.sup.i,
(5) cyano,
(6) nitro,
(7) R.sup.i O(CH.sub.2).sub.v --,
(8) R.sup.i CO.sub.2 (CH.sub.2).sub.v --,
(9) R.sup.i OCO(CH.sub.2).sub.v,
(10) optionally substituted aryl where the substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy,
(11) SO.sub.2 NR.sup.g R.sup.h, or
(12) amino;
R.sup.f is (1) C.sub.1 -C.sub.4 alkyl,
(2) X--C.sub.1 -C.sub.4 alkyl, where X is O or S(O).sub.m,
(3) C.sub.2 -C.sub.4 alkenyl,
(4) C.sub.2 -C.sub.4 alkynyl,
(5) C.sub.1 -C.sub.3 -perfluoroalkyl,
(6) NY.sup.1 Y.sup.2, where Y.sup.1 and Y.sup.2 are independently H or C.sub.1 -C.sub.5 alkyl,
(7) hydroxy,
(8) halogen, and
(9) C.sub.1 -C.sub.5 alkanoyl amino,
R.sup.g and R.sup.h are independently
(1) hydrogen,
(2) C.sub.1 -C.sub.6 alkyl optionally substituted with hydroxy, amino, or CO.sub.2 R.sup.i
(3) aryl optionally substituted with halogen, 1,2-methylenedioxy, C.sub.1 -C.sub.7 alkoxy, C.sub.1 -C.sub.7 alkyl or C.sub.1 -C.sub.3 perfluoroalkyl,
(4) aryl C.sub.1 -C.sub.6 alkyl, wherein the aryl is optionally substituted with C.sub.1 -C.sub.3 perfluorolkyl or 1,2-methylenedioxy;
(5) C.sub.1 -C.sub.5 alkoxycarbonyl,
(6) C.sub.1 -C.sub.5 alkanoyl,
(7) C.sub.1 -C.sub.5 alkanoyl C.sub.1 -C.sub.6 alkyl,
(9) aryl C.sub.1 -C.sub.5 alkoxycarbonyl,
(10) aminocarbonyl,
(11) C.sub.1 -C.sub.5 monoalkylaminocarbonyl
(12) C.sub.1 -C.sub.5 dialkylaminocarbonyl;
or
R.sup.g and R.sup.h together with the N to which they are attached form a 5-membered ring containing 0 additional heteroatom, optionally substituted with 1 to 3 groups independently selected from R.sup.e and oxo;
R.sup.i is (1) hydrogen,
(2) C.sub.1 -C.sub.3 perfluoroalkyl,
(3) C.sub.1 -C.sub.6 alkyl,
(4) optionally substituted aryl C.sub.0 -C.sub.6 alkyl, where the aryl substituents are from 1 to 3 groups independently selected from halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, and hydroxy;
m is 0 to 2;
and
v is 0 to 3;
and
a pharmaceutically acceptable salt thereof;
and
excluding nodulisporic acid, 29,30-dihydro-20,30-oxa-nodulisporic acid, and 3s1-hydroxy-20,30-oxa-29,30,31,32-tetrahydro-nodulisporic acid.

138 more elements

A compound of the formula wherein R.sup.x is selected from the group consisting of:

H, CH.sub.3, CH.sub.2 CH.sub.3, C(CH.sub.3).sub.3, CH.sub.2 CH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 OH, CH(CO.sub. CH.sub.3)CH.sub.2 OH, CH.sub.2 CO.sub.2 CH.sub.3, CH.sub.2 CH(OCH.sub.2 CH.sub.3).sub.2, CH.sub.2 CH.sub.20 CH.sub.2 CH.sub.2 OH, CH(CH.sub.3)(CH.sub.2).sub.3 C(CH.sub.3).sub.2 OH, (CH.sub.2).sub.3 OH, (CH.sub.2).sub.4 OH, (CH.sub.2).sub.5 OH, CH(CH.sub.2 OH)CH.sub.2 CH.sub.3, NHC(CH.sub.3).sub.3, CH.sub.2 CN, (CH.sub.2).sub.6 OH, CH.sub.2 CH(OH)CH.sub.3, CH(CH.sub.2 OH)CH.sub.2 CH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 SCH.sub.3, CH.sub.2 CH.sub.2 SCH.sub.2 CH.sub.3, CH.sub.2 CONH.sub.2, CH(CH.sub.3)(CH.sub.2 OH).sub.2, CH.sub.2 CH.sub.2 NHCH.sub.2 CH.sub.2 OH, CH(CH.sub.2 OH)(CH.sub.2).sub.3 CH.sub.3, CH(CH.sub.2 OCH.sub.3)CH.sub.3, (CH.sub.2).sub.2 SH, (CH.sub.2).sub.4 NH.sub.2, CH.sub.2 CH.sub.2 SO.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 S(O)CH.sub.3, CH(CH(CH.sub.3).sub.2)CH.sub.2 OH, (CH.sub.2).sub.3 NH.sub.2, (CH.sub.2).sub.3 N(CH.sub.2 CH.sub.3).sub.2, (CH.sub.2).sub.3 N(CH.sub.3).sub.2, OCH.sub.2 CH.sub.3, CH.sub.2 CH(OH)CH.sub.2 OH, OCH.sub.3, CH.sub.2 CH.sub.20 CH.sub.3, CH.sub.2 CH.sub.2 NHC(O)CH.sub.3, C(CH.sub.3).sub.2 CH.sub.2 OH, c-C.sub.3 H.sub.5, c-C.sub.6 H.sub.11, (CH.sub.2)3OCH.sub.2 CH.sub.3, CH.sub.2 CH.dbd.CH.sub.2, C(CH.sub.2 CH.sub.3)(CH.sub.2 OH).sub.2, CH.sub.2 C.ident.CH, CH.sub.2 CO.sub.2 CH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 F, (CH.sub.2).sub.3 O(CH.sub.2).sub.11 CH.sub.3, CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2, CH.sub.2 CH.sub.20 CH.sub.2 CH.sub.2 NH.sub.2, CH.sub.2 CF.sub.3, NHCH.sub.2 CO.sub.2 CH.sub.2 CH.sub.3, CH(CH.sub.3)CO.sub.2 CH.sub.3, C(CH.sub.3).sub.2 CH.sub.2 C(O)CH.sub.3, CH(CO.sub.2 CH.sub.2 CH.sub.3).sub.2, CH.sub.2 CH.sub.3, CH(CH.sub.2 CH.sub.2 CH.sub.3)CO.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 CH.sub.20 CH.sub.3, C(CH.sub.3).sub.2 C.dbd.CH, (CH.sub.2).sub.4 CH.sub.3, CH(CH.sub.2 CH.sub.2 CH.sub.3).sub.2, (CH.sub.2).sub.5 CH.sub.3, CH.sub.2 CH.sub.2 CO.sub.2 H, CH(CH(CH.sub.3).sub.2)CO.sub.2 CH.sub.3, OCH.sub.2 CO.sub.2 H, CH(CH(CH.sub.3).sub.2)CH.sub.2 OH, CH(CH(CH.sub.3).sub.2)CH.sub.2 OH, CH(CH.sub.3)CH.sub.2 OH, CH(CH.sub.3)CH.sub.2 OH, CH(CH.sub.3).sub.2, C(CH.sub.3).sub.3, (CH.sub.2)CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2 CH.sub.3, CH.sub.2 CH(CH.sub.3)OH, (CH.sub.2).sub.3 CH.sub.3, (CH.sub.2).sub.2 OCH.sub.2 CH.sub.3, 1-adamantyl, (CH.sub.2).sub.8 CH.sub.3, CH(CH.sub.3)CH(CH.sub.3).sub.2, (CH.sub.2).sub.3 NHCH.sub.3, (CH.sub.2).sub.2 N(CH.sub.2 CH.sub.3).sub.2, ##STR121## C(CH.sub.3).sub.2 CO.sub.2 CH.sub.3, C(CH.sub.3).sub.2 CO.sub.2 CH.sub.2 CH.sub.3, C(CH.sub.3).sub.2 CON(CH.sub.3).sub.2, C(CH.sub.3).sub.2 CONHCH.sub.2 CF.sub.3, C(CH.sub.3).sub.2 CON(CH.sub.3)CH.sub.2 CH.sub.3, CH(CH.sub.2 F).sub.2, C(CH.sub.2 F).sub.2 CO.sub.2 CH.sub.3, C(CH.sub.3).sub.2 CH.sub.2 F.

A compound of the formula ##STR122## wherein NR.sup.x R.sup.y is selected from the group consisting of:

N(CH.sub.3)CH.sub.2 C.ident.N, N(CH.sub.3)CH.sub.2 CH.sub.3, N(CH.sub.3)CH(CH.sub.3).sub.2, N(CH.sub.3)CH.sub.2 CH.sub.2 CH.sub.3, N(CH.sub.3)CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3, N(CH.sub.2 CH.sub.3)CH.sub.2 CH.sub.20 CH.sub.3, N(CH.sub.3)CH.sub.2 CH.sub.20 CH.sub.3, N(CH.sub.2 CH.sub.3)CH.sub.2 CH.sub.2 CH.sub.3, N(CH.sub.2 CH.dbd.CH.sub.2).sub.2, N(CH.sub.3)CH.sub.2 CH.sub.2 OH, N(CH.sub.2 CH(CH.sub.3)OH).sub.2, N(CH.sub.2 CH.sub.3).sub.2, N(CH.sub.2 CH.sub.2 OH).sub.2, N(CH.sub.2 CH.sub.3)CH(CH.sub.3).sub.2, N(CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3).sub.2, N(CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3).sub.2, N(CH.sub.3).sub.2,N(CH.sub.2 CH.sub.2 CH.sub.3).sub.2,N((CH.sub.2).sub.2 CH.sub.3)CH.sub.2 CH.sub.2 OH, N(CH.sub.3)CH.sub.2 C.ident.CH, N((CH.sub.2).sub.8 CH.sub.3).sub.2,N((CH.sub.2).sub.7 CH.sub.3).sub.2,N(CH.sub.3)(CH.sub.2).sub.2 NHCH.sub.3, N(CH.sub.3)(CH.sub.2).sub.3 NH.sub.2, NHCH(CH.sub.2 OH)CH.sub.2 Ph, NHPh(2-OH,4-CH.sub.3), NHCH.sub.2 Ph(4-NH.sub.2), NHPh(4-Cl), NHPh(4-CH.sub.2 CH.sub.2 OH), NHPh(2-CH.sub.2 CH.sub.2 OH), NHCH.sub.2 CH.sub.2 Ph, NHPh(2-CH.sub.2 OH), NHPh(3-N(CH.sub.3).sub.2, NHPh(4-SO.sub.2 NH.sub.2), NHNHPh, NHPh(2-CONH.sub.2), NHCH.sub.2 CH.sub.2 Ph(4-OH), NHCH.sub.2 CH.sub.2 Ph(4-SO.sub.2 NH.sub.2), NHPh(2-NH.sub.2), NHCH(CH.sub.2 CH(CH.sub.3).sub.2)CO.sub.2 CH.sub.2 Ph, NHSO.sub.2 CH.sub.2 Ph(4-C(CH.sub.3).sub.3), NHSO.sub.2 CH.sub.2 Ph, NHNHPh(2-F), NHCH.sub.2 Ph(4-CF.sub.3), NHPh(4-OCH.sub.2 Ph), NHPh(4-SCH.sub.3), NHCH(CH.sub.2 Ph)CO.sub.2 CH.sub.2 CH.sub.3, NHCH(CH.sub.2 Ph)CO.sub.2 CH.sub.3, NHCH.sub.2 Ph(4-OCH.sub.3), NHCH.sub.2 -1-naphthyl, NHPh(4-F), NHCH.sub.2 Ph(2-F), NHCH.sub.2 CH(Ph)OH, NHCH.sub.2 CH.sub.2 Ph(4-F), NHC(CH.sub.3).sub.2 CH.sub.2 Ph(3-F), NHPh(3,4-diF), NHCH.sub.2 Ph(3-CH.sub.3), NHNH(3-CH.sub.3)Ph, NHCH.sub.2 Ph(2-Cl), NHCH.sub.2 Ph(2,4-diCl), NHNHPh(4-CH.sub.3), NHCH.sub.2 Ph(4-Cl), NH(CH.sub.2).sub.3 Ph, NHCH.sub.2 CH.sub.2 Ph(4-Cl), NHCH.sub.2 CH.sub.2 N(CH.sub.3)Ph, NHCH.sub.2 Ph(3-CF.sub.3), NHCH.sub.2 Ph(2-CF.sub.3), NH(CH.sub.2).sub.4 Ph, N(CH.sub.3)CH(CH.sub.3)CH(CH.sub.3)Ph, N(CH.sub.3)CH(CH.sub.3)CH(CH.sub.3)Ph, N(CH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3, NHOCH.sub.2 Ph, NCH.sub.2 Ph(2,6-diF), N(CH.sub.3)CH(CH.sub.3)Ph, NHCH(CH.sub.3)Ph, N(CH.sub.3)CH.sub.2 Ph, NHCH.sub.2 Ph(3,4-diCl), N(CH.sub.3)CH(CH.sub.3)Ph, N(CH.sub.2 Ph)CH.sub.2 CH.sub.2 Ph, NHNHCH.sub.2 Ph, NHCH.sub.2 Ph(2,4-diF), NHNHPh(2,5-diCl), NHCH.sub.2 Ph(3-F), NHCH(Ph)CH.sub.2 Ph, NHCH.sub.2 Ph(3,4-diOH), NHCH.sub.2 Ph(3,4-diOCH.sub.3), N(CH.sub.3)CH.sub.2 Ph, N(CH.sub.2 CH.sub.3)CH.sub.2 Ph, N(CH.sub.3)CH(CH.sub.3)Ph, NHCH.sub.2 CH.sub.2 (3-F)Ph, NHCH(CH.sub.2 Ph)CH.sub.2 OH, ##STR123##

Dependencies are inferred from the claim text.

Facts

Application: 09/046,052Filed 23 Mar 1998 · continuation
Priority: 20 Mar 1995
Granted: 5 Oct 1999
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 491/14
In which the condensed system contains three hetero rings: ortho-condensed systems
A01N 43/90
Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds: having two or more relevant hetero rings,…
A01N 47/12
Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof: containing a —O—CO—N< group, or a thio analogue thereof,…
A01N 47/16
Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof: the nitrogen atom being part of a heterocyclic ring

Family

Serial406,619Parent of this continuation-in-part · filed 20 Mar 1995
Serial606,312Parent of this continuation-in-part · filed 11 Mar 1996
Serial716,012Parent of this continuation · filed 19 Sep 1996
US 5,962,499 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.

A compound having the formula I:

##STR114## wherein R.sub.1 is (1) hydrogen,
(2) optionally substituted C.sub.1 -C.sub.10 alkyl,
(3) optionally substituted C.sub.2 -C.sub.10 alkenyl,
(4) optionally substituted C.sub.2 -C.sub.10 alkynyl,
(5) optionally substituted C.sub.3 -C.sub.8 cycloalkyl,
(6) optionally substituted C.sub.5 -C.sub.8 cycloalkenyl
where the substitutents on the alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl are 1 to 3 groups independently selected from
(i) C.sub.1 -C.sub.5 alkyl,
(ii) X--C.sub.1 -C.sub.10 alkyl, where X is O or S(O).sub.m.
(iii) C.sub.3 -C.sub.8 cycloalkyl,
(iv) hydroxy,
(v) halogen,
(vi) cyano,
(vii) carboxy,
(viii) NY.sup.1 Y.sup.2, where Y.sup.1 and Y.sup.2 are independently hydrogen or C.sub.1 -C.sub.10 alkyl,
(ix) C.sub.1 -C.sub.10 alkanoylamino, and
(x) aroyl amino wherein said aroyl is optionally substituted with 1 to 3 groups independently selected from R.sup.f
(7) aryl C.sub.0 -C.sub.5 alkyl wherein said aryl is optionally substituted with 1 to 3 groups independently selected from R.sup.f,
(8) C.sub.1 -C.sub.5 perfluoroalkyl
(9) a 5-membered heterocycle containing 1 heteroatom selected from oxygen, sulfur and nitrogen atoms optionally substituted by 1 to 3 groups independently selected from hydroxy, oxo, C.sub.1 -C.sub.10 alkyl and halogen, and which may be saturated or partly unsaturated, R.sub.2, R.sub.3, and R.sub.4 are independently OR.sup.a, OCO.sub.2 R.sup.b, OC(O)NR.sup.c R.sup.d ;
or
R.sub.1 +R.sub.2 represent .dbd.O, .dbd.NOR.sup.a or .dbd.N--NR.sup.c R.sup.d ;
R.sub.5 and R6 are hydrogen;
or
R5 and R6 together represent --O--;
R.sub.7 is (1) CHO, or
(2) the fragment ##STR115## R.sub.8 is (1) hydrogen, (2) OR.sup.a, or
(3) NR.sup.c R.sup.d
R.sub.9 is (1) hydrogen, or
(2) OR.sup.a ;
R.sub.10 is (1) CN,
(2) C(O)OR.sup.b,
(3) C(O)N(OR.sup.b)R.sup.c,
(4) C(O)NR.sup.c R.sup.d,
(5) NHC(O)OR.sup.b,
(6) NHC(O)NR.sup.c R.sup.d,
(7) CH.sub.2 OR.sup.a,
(8) CH.sub.2 OCO.sub.2 R.sup.b,
(9) CH.sub.2 OC(O)NR.sup.c R.sup.d,
(10) C(O)NR.sup.c NR.sup.c R.sup.d, or
(11) C(O)NR.sup.c SO.sub.2 R.sup.b ;
---- represents a single or a double bond;
R.sup.a is (1) hydrogen,
(2) optionally substituted C.sub.1 -C.sub.10 alkyl,
(3) optionally substituted C.sub.3 -C.sub.10 alkenyl,
(4) optionally substituted C.sub.3 -C.sub.10 alkynyl,
(5) optionally substituted C.sub.1 -.sub.10 alkanoyl,
(6) optionally substituted C.sub.3 -C.sub.10 alkenoyl,
(7) optionally substituted C.sub.3 -C.sub.10 alkynoyl,
(8) optionally substituted aroyl,
(9) optionally substituted aryl,
(10) optionally substituted C.sub.3 -C.sub.7 cycloalkanoyl,
(11) optionally substituted C.sub.5 -C.sub.7 cycloalkenoyl,
(12) optionally substituted C.sub.1 -C.sub.10 alkylsulfonyl
(13) optionally substituted C.sub.3 -C.sub.8 cycloalkyl
(14) optionally substituted C.sub.5 -C.sub.8 cycloalkenyl where the substituents on the alkyl, alkenyl, alkynyl, alkanoyl, alkenoyl, alkynoyl, aroyl, aryl, cycloalkanoyl, cycloalkenoyl, alkylsulfonyl, cycloalkyl and cycloalkenyl are from 1 to 10 groups independently selected from hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.7 cycloalkyl, aryl C.sub.1 -C.sub.3 alkoxy, NR.sup.g R.sup.h, CO.sub.2 R.sup.b, CONR.sup.c R.sup.d and halogen,
(15) C.sub.1 -C.sub.5 perfluoroalkyl,
(16) arylsulfonyl optionally substituted with 1 to 3 groups independently selected from C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 perfluoroalkyl, nitro, halogen and cyano,
(17) a 5-membered heterocycle containing 1 heteroatom selected from oxygen, sulfur and nitrogen optionally substituted by 1 to 4 groups independently selected from C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkenyl, C.sub.1 -C.sub.5 perfluoroalkyl, amino, C(O)NR.sup.c R.sup.d, cyano, CO.sub.2 R.sup.b and halogen, and which may be saturated or partly unsaturated;
R.sup.b is (1) hydrogen,
(2) optionally substituted aryl,
(3) optionally substituted C.sub.1 -C.sub.10 alkyl,
(4) optionally substituted C.sub.3 -C.sub.10 alkenyl,
(5) optionally substituted C.sub.3 -C.sub.10 alkynyl,
(6) optionally substituted C.sub.3 -C.sub.15 cycloalkyl,
(7) optionally substituted C.sub.5 -C.sub.10 cycloalkenyl, or
(8) optionally substituted 5-membered heterocycle containing 1 heteroatom selected from oxygen, sulfur and nitrogen;
where the substituents on the aryl, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, or alkynyl are from 1 to 10 groups independently selected from
(i) hydroxy,
(ii) C.sub.1 -C.sub.6 alkyl,
(iii) oxo,
(iv) SO.sub.2 NR.sup.g R.sup.h,
(v) aryl C.sub.1 -C.sub.6 alkoxy,
(vi) hydroxy C.sub.1 -C.sub.6 alkyl,
(vii) C.sub.1 -C.sub.12 alkoxy,
(viii) hydroxy C.sub.1 -C.sub.6 alkoxy,
(ix) amino C.sub.1 -C.sub.6 alkoxy,
(x) cyano,
(xi) mercapto,
(xii) C.sub.1 -C.sub.6 alkyl-S(O)m,
(xiii) C.sub.3 -C.sub.7 cycloalkyl optionally substituted with 1 to 4 groups independently selected from R.sup.e,
(xiv) C.sub.5 -C.sub.7 cycloalkenyl,
(xv) halogen,
(xvi) C.sub.1 -C.sub.5 alkanoyloxy,
(xvii) C(O)NR.sup.g R.sup.h,
(xviii) CO.sub.2 R.sup.i,
(xix) formyl,
(xx) --NR.sup.g R.sup.h,
(xxi) 5-membered heterocycle, which may be saturated or partially unsaturated, containing 1 heteroatom selected from oxygen, sulfur and nitrogen, and optionally substituted with 1 to 5 groups independently selected from R.sup.e,
(xxii) optionally substituted aryl, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from R.sup.e,
(xxiii) optionally substituted aryl C.sub.1 -C.sub.3 alkoxy, wherein the aryl substituents are 1,2-methylenedioxy or 1 to 5 groups independently selected from R.sup.e, and
(xxiv) C.sub.1 -C.sub.5 perfluoroalkyl;
R.sup.c and R.sup.d are independently selected from R.sup.b ;
or
R.sup.c and R.sup.d together with the N to which they are attached form a 5-membered ring containing 0 additional heteroatom, optionally substituted with 1 to 3 groups independently selected from R.sup.g, hydroxy, thioxo and oxo;
R.sup.e is (1) halogen,
(2) C.sub.1 -C.sub.7 alkyl,
(3) C.sub.1 -C.sub.3 perfluoroalkyl,
(4) --S(O).sub.m R.sup.i,
(5) cyano,
(6) nitro,
(7) R.sup.i O(CH.sub.2).sub.v --,
(8) R.sup.i CO.sub.2 (CH.sub.2).sub.v --,
(9) R.sup.i OCO(CH.sub.2).sub.v,
(10) optionally substituted aryl where the substituents are from 1 to 3 of halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or hydroxy,
(11) SO.sub.2 NR.sup.g R.sup.h, or
(12) amino;
R.sup.f is (1) C.sub.1 -C.sub.4 alkyl,
(2) X--C.sub.1 -C.sub.4 alkyl, where X is O or S(O).sub.m,
(3) C.sub.2 -C.sub.4 alkenyl,
(4) C.sub.2 -C.sub.4 alkynyl,
(5) C.sub.1 -C.sub.3 -perfluoroalkyl,
(6) NY.sup.1 Y.sup.2, where Y.sup.1 and Y.sup.2 are independently H or C.sub.1 -C.sub.5 alkyl,
(7) hydroxy,
(8) halogen, and
(9) C.sub.1 -C.sub.5 alkanoyl amino,
R.sup.g and R.sup.h are independently
(1) hydrogen,
(2) C.sub.1 -C.sub.6 alkyl optionally substituted with hydroxy, amino, or CO.sub.2 R.sup.i
(3) aryl optionally substituted with halogen, 1,2-methylenedioxy, C.sub.1 -C.sub.7 alkoxy, C.sub.1 -C.sub.7 alkyl or C.sub.1 -C.sub.3 perfluoroalkyl,
(4) aryl C.sub.1 -C.sub.6 alkyl, wherein the aryl is optionally substituted with C.sub.1 -C.sub.3 perfluorolkyl or 1,2-methylenedioxy;
(5) C.sub.1 -C.sub.5 alkoxycarbonyl,
(6) C.sub.1 -C.sub.5 alkanoyl,
(7) C.sub.1 -C.sub.5 alkanoyl C.sub.1 -C.sub.6 alkyl,
(9) aryl C.sub.1 -C.sub.5 alkoxycarbonyl,
(10) aminocarbonyl,
(11) C.sub.1 -C.sub.5 monoalkylaminocarbonyl
(12) C.sub.1 -C.sub.5 dialkylaminocarbonyl;
or
R.sup.g and R.sup.h together with the N to which they are attached form a 5-membered ring containing 0 additional heteroatom, optionally substituted with 1 to 3 groups independently selected from R.sup.e and oxo;
R.sup.i is (1) hydrogen,
(2) C.sub.1 -C.sub.3 perfluoroalkyl,
(3) C.sub.1 -C.sub.6 alkyl,
(4) optionally substituted aryl C.sub.0 -C.sub.6 alkyl, where the aryl substituents are from 1 to 3 groups independently selected from halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, and hydroxy;
m is 0 to 2;
and
v is 0 to 3;
and
a pharmaceutically acceptable salt thereof;
and
excluding nodulisporic acid, 29,30-dihydro-20,30-oxa-nodulisporic acid, and 3s1-hydroxy-20,30-oxa-29,30,31,32-tetrahydro-nodulisporic acid.

138 more elements

Facts

Application

09/046,052Filed 23 Mar 1998 · continuation

Priority

20 Mar 1995

Granted

5 Oct 1999

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 491/14
In which the condensed system contains three hetero rings: ortho-condensed systems
A01N 43/90
Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds: having two or more relevant hetero rings,…
A01N 47/12
Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof: containing a —O—CO—N< group, or a thio analogue thereof,…
A01N 47/16
Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof: the nitrogen atom being part of a heterocyclic ring