US 5,691,329 AGranted

Compounds containing basic and acidic termini useful as fibrinogen receptor antagonists

AssigneeThe DuPont Merck Pharmaceutical Company

InventorsWilliam Frank DeGrado, Chu-Biao Xue

Life of this patent

Estimating the term…

Abstract

This invention relates to novel compounds containing basic and acidic termini, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.

Claims10

Dependent claims

A compound of Formula I:

##STR469## or a pharmaceutically acceptable salt form thereof wherein:
R.sup.1 is selected from:
##STR470## q is 1, 2, or 3;
r is 2, 3, or 4;
R.sup.6 and R.sup.6a are independently selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, (C.sub.1 -C.sub.7 alkyl)carbonyl, arylcarbonyl, (C.sub.1 -C.sub.10 alkoxy)carbonyl, C.sub.4 -C.sub.11 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C.sub.1 -C.sub.10 alkyl)carbonyl, or aryl(C.sub.1 -C.sub.10 alkoxy) carbonyl;
R.sup.7 and R.sup.7a are selected independently from:
H or C.sub.1 -C.sub.4 alkyl;
R.sup.6b is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
R.sup.6e is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
alternatively, R.sup.6e and R.sup.7 can be taken together with the nitrogen and carbon atom to which they are attached to form a 5-7-membered nitrogen heterocycle, said heterocycle optionally including one additional N, O or S atom;
U is selected from:
--CH.sub.2 --CH.sub.2 --CH.sub.2 -substituted with 0-4 R.sup.3,
--X--CH.sub.2 --CH.sub.2 -substituted with 0-4 R.sup.3,
--CH.sub.2 --X--CH.sub.2 -substituted with 0-4 R.sup.3,
--CH.sub.2 --CH.sub.2 --X-substituted with 0-4 R.sup.3,
--CH.sub.2 --CH.dbd.CH-substituted with 0-4 R.sup.3,
--CH.dbd.CH--CH.sub.2 -substituted with 0-4 R.sup.3,
--CH.sub.2 --C.tbd.C-substituted with 0-2 R.sup.3,
--C.dbd.C--CH.sub.2 -substituted with 0-2 R.sup.3,
--CH.dbd.CH-substituted with 0--2 R.sup.3,
--C.dbd.C--,
--CH.sub.2 --CH.sub.2 -substituted with 0-4 R.sup.3,
--X--CH.sub.2 -substituted with 0--2 R.sup.3,
--CH.sub.2 --X-substituted with 0--2 R.sup.3,
--X--, or
--CH.sub.2 -substituted with 0-2 R.sup.3 ;
X is selected from:
O, S, S(.dbd.O), SO.sub.2, SO.sub.2 N(R.sup.6c), N(R.sup.6c)SO.sub.2, N(R.sup.6c), N(R.sup.12), N(R.sup.6c)C(.dbd.O);
with the proviso that when R.sup.1 is ##STR471## then X is not S, S(.dbd.O), or SO.sub.2 N(R.sup.6c);
R.sup.12 and R.sup.13 are independently selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkoxycarbonyl, C.sub.1 -C.sub.10 alkylcarbonyl, C.sub.1 -C.sub.10 alkylsulfonyl, aryl(C.sub.1 -C.sub.10 alkyl)sulfonyl, arylsulfonyl, aryl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl(C.sub.1 -C.sub.10 alkyl), arylcarbonyl, C.sub.4 -C.sub.11 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, aryloxycarbonyl, or aryl(C.sub.1 -C.sub.10 alkoxy) carbonyl;
R.sup.6c is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
R.sup.3 is independently selected from:
H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-;
vis-Q-Y-;
Q is a heterocyclic ring selected from oxazole, isoxazole, oxazoline, or isoxazoline, said heterocyclic ring being substituted with 0-2 R.sup.5, wherein, the bonds between Q and Y and between Q and U are at 1 and 3 positions of Q;
Y is selected from:
C(.dbd.O) or S(O).sub.2 ;
R.sup.5 is selected independently from:
H, F, Cl, Br, I, CF.sub.3, CN, CHO, CO.sub.2 R.sup.5a, C(.dbd.O)R.sup.5a, CONHR.sup.5a, CON(R.sup.5a).sub.2, OC(.dbd.O)R.sup.5a, OCO.sub.2 R.sup.5a, OR.sup.5a, OC(.dbd.O) N(.sup.5a).sub.2, OCH.sub.2 CO.sub.2 R.sup.5a, CO.sub.2 CH.sub.2 CO.sub.2 R.sup.5a, N(R.sup.12)R.sup.5a, NO.sub.2, NR.sup.5a C(.dbd.O)R.sup.5a, NR.sup.5a C(.dbd.O) OR.sup.5a, NR.sup.5a SO.sub.2 N(R.sup.12)R.sup.5a, NR.sup.5a SO.sub.2 R.sup.5b, SR.sup.5a, S(.dbd.O)R.sup.5b, SO.sub.2 R.sup.5b, SO.sub.2 N(R.sup.5a).sub.2, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.2 to C.sub.6 alkynyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl),
C.sub.1 to C.sub.6 alkyl substituted with 0-4 R.sup.5c,
C.sub.2 to C.sub.6 alkenyl substituted with 0-4 R.sup.5c,
C.sub.2 to C.sub.6 alkynyl substituted with 0-4 R.sup.5c,
C.sub.3 to C.sub.11 cycloalkyl substituted with 0-3 R.sup.5c,
C.sub.4 to C.sub.15 cycloalkylalkyl substituted with 0-3 R.sup.5c,
aryl substituted with 0-3 R.sup.5c,
aryl(C.sub.1 -C.sub.10 alkyl) substituted with 0-3 R.sup.5c ;
R.sup.5a is selected from:
H, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.15 cycloalkylalkyl, aryl, or aryl(C.sub.1 -C.sub.10 alkyl);
R.sup.5b is selected from:
C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.3 to C.sub.15 cycloalkyl, C.sub.4 to C.sub.11 cycloalkylalkyl, aryl, or aryl(C.sub.1 -C.sub.10 alkyl);
R.sup.5c is selected from:
H, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 haloalkyl, CN, C.sub.1 -C.sub.4 alkoxy, NO.sub.2 ;
R.sup.8 is selected from:
H;
C.sub.1 -C.sub.6 alkyl substituted with 0-4 R.sup.3a ;
C.sub.2 -C.sub.6 alkenyl substituted with 0-4 R.sup.3a ;
C.sub.2 -C.sub.6 alkynyl substituted with 0-4 R.sup.3a ;
C.sub.3 -C.sub.8 cycloalkyl substituted with 0-4 R.sup.3a ;
aryl substituted with 0-4 R.sup.3a ;
aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.3a ;
a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-3 R.sup.3a ;
C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.3a ;
(R.sup.12) (R.sup.5a) NC(.dbd.O)-;
piperidyl-C(.dbd.O)-;
##STR472## substituted with 0-4 R.sup.3a ;
or ##STR473## substituted with 0-4 R.sup.3a ;
R.sup.3a is selected from H, halogen, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-;
R.sup.9 is selected from:
H,
--R.sup.15,
--N(R.sup.6d)C(.dbd.O)-O-R.sup.15a,
--N(R.sup.6d)C(.dbd.O)-R.sup.15,
--N(R.sup.6d)C(.dbd.O)-NH-R.sup.15,
--N(R.sup.6d)NH-C(.dbd.O)-O-R.sup.15a,
--N(R.sup.6d)NH-C(.dbd.O)-R.sup.15,
--N(R.sup.6d)NH-C(.dbd.O)-NH-R.sup.15,
--N(R.sup.6d)S(.dbd.O).sub.2 -O-R.sup.15b,
--N(R.sup.6d)S(.dbd.O).sub.2 -R.sup.15,
--N(R.sup.6d)C(.dbd.S)NHR.sup.15,
--N(R.sup.6d)P(.dbd.S)OR.sup.15a,
--N(R.sup.6d)P(.dbd.O)OR.sup.15a,
--N(R.sup.6d)P(.dbd.S)(R.sup.15a).sub.2,
--N(R.sup.6d)P(.dbd.O)(R.sup.15a).sub.2,
--N(R.sup.12)(R.sup.5a),
--CH.dbd.CH-R.sup.15, or
--C.tbd.C--R.sup.15 ;
R.sup.6d is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
R.sup.15 is selected from:
H,
C.sub.1 -C.sub.8 alkyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkenyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkynyl substituted with 0-4 R.sup.3a,
C.sub.3 -C.sub.8 cycloalkyl substituted with 0-4 R.sup.3a,
aryl substituted with 0-4 R.sup.3a,
aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.3a,
a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-3 R.sup.3a,
C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.3a ;
R.sup.15a is selected from:
C.sub.1 -C.sub.8 alkyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkenyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkynyl substituted with 0-4 R.sup.3a,
C.sub.3 -C.sub.8 cycloalkyl substituted with 0-4 R.sup.3a,
aryl substituted with 0-4 R.sup.3a,
aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.3a,
a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-3 R.sup.3a,
C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.3a ;
R.sup.10 is selected from CO.sub.2 R.sup.16, CO.sub.2 R.sup.13b, SO.sub.3 H, tetrazolyl, or PO.sub.3 H;
R.sup.16 is selected from:
H, C.sub.1 to C.sub.10 alkyl, C.sub.3 to C.sub.11 cycloalkyl, aryl, aryl(C.sub.1 to C.sub.6 alkyl)-, C.sub.3 to C.sub.10 alkylcarbonyloxyalkyl, C.sub.3 to C.sub.10 alkoxycarbonyloxyalkyl, C.sub.2 to C.sub.10 alkoxycarbonyl, C.sub.5 to C.sub.10 cycloalkylcarbonyloxyalkyl, C.sub.5 to C.sub.10 cycloalkoxycarbonyloxyalkyl, C.sub.5 to C.sub.10 cycloalkoxycarbonyl, aryloxycarbonyl, aryloxycarbonyloxy(C.sub.1 to C.sub.6 alkyl)-, arylcarbonyloxy(C.sub.1 to C.sub.6 alkyl)-, C.sub.5 to C.sub.12 alkoxyalkylcarbonyloxyalkyl, (5-(C.sub.1 -C.sub.5 alkyl)-1,3-dioxacyclopenten-2-one-yl)methyl, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyl, or (R.sup.12)(R.sup.5 a)N-(C.sub.1 -C.sub.10 alkyl)-;
R.sup.13b is selected independently from:
--CH(R.sup.36)OC(.dbd.O)R.sup.37 ;
--CH(R.sup.36)OC(.dbd.O)OR.sup.38 ;
##STR474## R.sup.36 is C.sub.1 -C.sub.4 linear alkyl or H;
R.sup.37 is selected from:
(a) H;
(b) C.sub.1 -C.sub.8 alkyl or C.sub.3 -C.sub.8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from:
(i) C.sub.1 -C.sub.4 alkyl;
(ii) C.sub.3 -C.sub.8 cycloalkyl;
(iii) C.sub.1 -C.sub.5 alkoxy;
(iv) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O) (C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N(R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
(c) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O)(C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N (R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
R.sup.38 is selected from:
(a) C.sub.1 -C.sub.8 alkyl or C.sub.3 -C.sub.8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from:
(i) C.sub.1 -C.sub.4 alkyl;
(ii) C.sub.3 -C.sub.8 cycloalkyl;
(iii) C.sub.1 -C.sub.5 alkoxy;
(iv) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O) (C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N(R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
(b) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O)(C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N(R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
R.sup.39 is C.sub.1 -C.sub.4 alkyl, benzyl, or phenyl.

136 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/694,043Filed 8 Aug 1996 · division
Priority: 28 Dec 1993
Granted: 25 Nov 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 213/81
Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals: amides; Imides
C07C 257/18
With replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines: having carbon atoms of amidino groups bound to…
C07C 271/22
With the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms: to carbon atoms of hydrocarbon radicals…
C07C 311/06
Having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms: to acyclic carbon atoms of hydrocarbon…

Family

Serial174,552Parent of this continuation-in-part · filed 28 Dec 1993
Serial343,159Parent of this division · filed 22 Nov 1994
US 5,563,158 AParent of this division
US 5,691,329 AThis patent

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

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Abstract

A compound of Formula I:

##STR469## or a pharmaceutically acceptable salt form thereof wherein:
R.sup.1 is selected from:
##STR470## q is 1, 2, or 3;
r is 2, 3, or 4;
R.sup.6 and R.sup.6a are independently selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, (C.sub.1 -C.sub.7 alkyl)carbonyl, arylcarbonyl, (C.sub.1 -C.sub.10 alkoxy)carbonyl, C.sub.4 -C.sub.11 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C.sub.1 -C.sub.10 alkyl)carbonyl, or aryl(C.sub.1 -C.sub.10 alkoxy) carbonyl;
R.sup.7 and R.sup.7a are selected independently from:
H or C.sub.1 -C.sub.4 alkyl;
R.sup.6b is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
R.sup.6e is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
alternatively, R.sup.6e and R.sup.7 can be taken together with the nitrogen and carbon atom to which they are attached to form a 5-7-membered nitrogen heterocycle, said heterocycle optionally including one additional N, O or S atom;
U is selected from:
--CH.sub.2 --CH.sub.2 --CH.sub.2 -substituted with 0-4 R.sup.3,
--X--CH.sub.2 --CH.sub.2 -substituted with 0-4 R.sup.3,
--CH.sub.2 --X--CH.sub.2 -substituted with 0-4 R.sup.3,
--CH.sub.2 --CH.sub.2 --X-substituted with 0-4 R.sup.3,
--CH.sub.2 --CH.dbd.CH-substituted with 0-4 R.sup.3,
--CH.dbd.CH--CH.sub.2 -substituted with 0-4 R.sup.3,
--CH.sub.2 --C.tbd.C-substituted with 0-2 R.sup.3,
--C.dbd.C--CH.sub.2 -substituted with 0-2 R.sup.3,
--CH.dbd.CH-substituted with 0--2 R.sup.3,
--C.dbd.C--,
--CH.sub.2 --CH.sub.2 -substituted with 0-4 R.sup.3,
--X--CH.sub.2 -substituted with 0--2 R.sup.3,
--CH.sub.2 --X-substituted with 0--2 R.sup.3,
--X--, or
--CH.sub.2 -substituted with 0-2 R.sup.3 ;
X is selected from:
O, S, S(.dbd.O), SO.sub.2, SO.sub.2 N(R.sup.6c), N(R.sup.6c)SO.sub.2, N(R.sup.6c), N(R.sup.12), N(R.sup.6c)C(.dbd.O);
with the proviso that when R.sup.1 is ##STR471## then X is not S, S(.dbd.O), or SO.sub.2 N(R.sup.6c);
R.sup.12 and R.sup.13 are independently selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkoxycarbonyl, C.sub.1 -C.sub.10 alkylcarbonyl, C.sub.1 -C.sub.10 alkylsulfonyl, aryl(C.sub.1 -C.sub.10 alkyl)sulfonyl, arylsulfonyl, aryl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl(C.sub.1 -C.sub.10 alkyl), arylcarbonyl, C.sub.4 -C.sub.11 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, aryloxycarbonyl, or aryl(C.sub.1 -C.sub.10 alkoxy) carbonyl;
R.sup.6c is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
R.sup.3 is independently selected from:
H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-;
vis-Q-Y-;
Q is a heterocyclic ring selected from oxazole, isoxazole, oxazoline, or isoxazoline, said heterocyclic ring being substituted with 0-2 R.sup.5, wherein, the bonds between Q and Y and between Q and U are at 1 and 3 positions of Q;
Y is selected from:
C(.dbd.O) or S(O).sub.2 ;
R.sup.5 is selected independently from:
H, F, Cl, Br, I, CF.sub.3, CN, CHO, CO.sub.2 R.sup.5a, C(.dbd.O)R.sup.5a, CONHR.sup.5a, CON(R.sup.5a).sub.2, OC(.dbd.O)R.sup.5a, OCO.sub.2 R.sup.5a, OR.sup.5a, OC(.dbd.O) N(.sup.5a).sub.2, OCH.sub.2 CO.sub.2 R.sup.5a, CO.sub.2 CH.sub.2 CO.sub.2 R.sup.5a, N(R.sup.12)R.sup.5a, NO.sub.2, NR.sup.5a C(.dbd.O)R.sup.5a, NR.sup.5a C(.dbd.O) OR.sup.5a, NR.sup.5a SO.sub.2 N(R.sup.12)R.sup.5a, NR.sup.5a SO.sub.2 R.sup.5b, SR.sup.5a, S(.dbd.O)R.sup.5b, SO.sub.2 R.sup.5b, SO.sub.2 N(R.sup.5a).sub.2, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.2 to C.sub.6 alkynyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl),
C.sub.1 to C.sub.6 alkyl substituted with 0-4 R.sup.5c,
C.sub.2 to C.sub.6 alkenyl substituted with 0-4 R.sup.5c,
C.sub.2 to C.sub.6 alkynyl substituted with 0-4 R.sup.5c,
C.sub.3 to C.sub.11 cycloalkyl substituted with 0-3 R.sup.5c,
C.sub.4 to C.sub.15 cycloalkylalkyl substituted with 0-3 R.sup.5c,
aryl substituted with 0-3 R.sup.5c,
aryl(C.sub.1 -C.sub.10 alkyl) substituted with 0-3 R.sup.5c ;
R.sup.5a is selected from:
H, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.3 to C.sub.11 cycloalkyl, C.sub.4 to C.sub.15 cycloalkylalkyl, aryl, or aryl(C.sub.1 -C.sub.10 alkyl);
R.sup.5b is selected from:
C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.6 alkenyl, C.sub.3 to C.sub.15 cycloalkyl, C.sub.4 to C.sub.11 cycloalkylalkyl, aryl, or aryl(C.sub.1 -C.sub.10 alkyl);
R.sup.5c is selected from:
H, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 haloalkyl, CN, C.sub.1 -C.sub.4 alkoxy, NO.sub.2 ;
R.sup.8 is selected from:
H;
C.sub.1 -C.sub.6 alkyl substituted with 0-4 R.sup.3a ;
C.sub.2 -C.sub.6 alkenyl substituted with 0-4 R.sup.3a ;
C.sub.2 -C.sub.6 alkynyl substituted with 0-4 R.sup.3a ;
C.sub.3 -C.sub.8 cycloalkyl substituted with 0-4 R.sup.3a ;
aryl substituted with 0-4 R.sup.3a ;
aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.3a ;
a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-3 R.sup.3a ;
C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.3a ;
(R.sup.12) (R.sup.5a) NC(.dbd.O)-;
piperidyl-C(.dbd.O)-;
##STR472## substituted with 0-4 R.sup.3a ;
or ##STR473## substituted with 0-4 R.sup.3a ;
R.sup.3a is selected from H, halogen, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-;
R.sup.9 is selected from:
H,
--R.sup.15,
--N(R.sup.6d)C(.dbd.O)-O-R.sup.15a,
--N(R.sup.6d)C(.dbd.O)-R.sup.15,
--N(R.sup.6d)C(.dbd.O)-NH-R.sup.15,
--N(R.sup.6d)NH-C(.dbd.O)-O-R.sup.15a,
--N(R.sup.6d)NH-C(.dbd.O)-R.sup.15,
--N(R.sup.6d)NH-C(.dbd.O)-NH-R.sup.15,
--N(R.sup.6d)S(.dbd.O).sub.2 -O-R.sup.15b,
--N(R.sup.6d)S(.dbd.O).sub.2 -R.sup.15,
--N(R.sup.6d)C(.dbd.S)NHR.sup.15,
--N(R.sup.6d)P(.dbd.S)OR.sup.15a,
--N(R.sup.6d)P(.dbd.O)OR.sup.15a,
--N(R.sup.6d)P(.dbd.S)(R.sup.15a).sub.2,
--N(R.sup.6d)P(.dbd.O)(R.sup.15a).sub.2,
--N(R.sup.12)(R.sup.5a),
--CH.dbd.CH-R.sup.15, or
--C.tbd.C--R.sup.15 ;
R.sup.6d is selected from:
H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.15 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)-;
R.sup.15 is selected from:
H,
C.sub.1 -C.sub.8 alkyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkenyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkynyl substituted with 0-4 R.sup.3a,
C.sub.3 -C.sub.8 cycloalkyl substituted with 0-4 R.sup.3a,
aryl substituted with 0-4 R.sup.3a,
aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.3a,
a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-3 R.sup.3a,
C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.3a ;
R.sup.15a is selected from:
C.sub.1 -C.sub.8 alkyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkenyl substituted with 0-4 R.sup.3a,
C.sub.2 -C.sub.8 alkynyl substituted with 0-4 R.sup.3a,
C.sub.3 -C.sub.8 cycloalkyl substituted with 0-4 R.sup.3a,
aryl substituted with 0-4 R.sup.3a,
aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.3a,
a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-3 R.sup.3a,
C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-4 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.3a ;
R.sup.10 is selected from CO.sub.2 R.sup.16, CO.sub.2 R.sup.13b, SO.sub.3 H, tetrazolyl, or PO.sub.3 H;
R.sup.16 is selected from:
H, C.sub.1 to C.sub.10 alkyl, C.sub.3 to C.sub.11 cycloalkyl, aryl, aryl(C.sub.1 to C.sub.6 alkyl)-, C.sub.3 to C.sub.10 alkylcarbonyloxyalkyl, C.sub.3 to C.sub.10 alkoxycarbonyloxyalkyl, C.sub.2 to C.sub.10 alkoxycarbonyl, C.sub.5 to C.sub.10 cycloalkylcarbonyloxyalkyl, C.sub.5 to C.sub.10 cycloalkoxycarbonyloxyalkyl, C.sub.5 to C.sub.10 cycloalkoxycarbonyl, aryloxycarbonyl, aryloxycarbonyloxy(C.sub.1 to C.sub.6 alkyl)-, arylcarbonyloxy(C.sub.1 to C.sub.6 alkyl)-, C.sub.5 to C.sub.12 alkoxyalkylcarbonyloxyalkyl, (5-(C.sub.1 -C.sub.5 alkyl)-1,3-dioxacyclopenten-2-one-yl)methyl, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyl, or (R.sup.12)(R.sup.5 a)N-(C.sub.1 -C.sub.10 alkyl)-;
R.sup.13b is selected independently from:
--CH(R.sup.36)OC(.dbd.O)R.sup.37 ;
--CH(R.sup.36)OC(.dbd.O)OR.sup.38 ;
##STR474## R.sup.36 is C.sub.1 -C.sub.4 linear alkyl or H;
R.sup.37 is selected from:
(a) H;
(b) C.sub.1 -C.sub.8 alkyl or C.sub.3 -C.sub.8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from:
(i) C.sub.1 -C.sub.4 alkyl;
(ii) C.sub.3 -C.sub.8 cycloalkyl;
(iii) C.sub.1 -C.sub.5 alkoxy;
(iv) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O) (C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N(R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
(c) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O)(C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N (R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
R.sup.38 is selected from:
(a) C.sub.1 -C.sub.8 alkyl or C.sub.3 -C.sub.8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from:
(i) C.sub.1 -C.sub.4 alkyl;
(ii) C.sub.3 -C.sub.8 cycloalkyl;
(iii) C.sub.1 -C.sub.5 alkoxy;
(iv) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O) (C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N(R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
(b) aryl substituted with 0-2 groups independently selected from:
halogen, phenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, NO.sub.2, --S(C.sub.1 -C.sub.5 alkyl), --S(.dbd.O)(C.sub.1 -C.sub.5 alkyl), --SO.sub.2 (C.sub.1 -C.sub.5 alkyl), --OH, --N(R.sup.12)(R.sup.5a), --CO.sub.2 R.sup.5a, --C(.dbd.O)N(R.sup.12)(R.sup.5a), or --C.sub.v F.sub.w where v=1 to 3 and w=1 to (2v+1);
R.sup.39 is C.sub.1 -C.sub.4 alkyl, benzyl, or phenyl.

136 more elements

Facts

Application

08/694,043Filed 8 Aug 1996 · division

Priority

28 Dec 1993

Granted

25 Nov 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 213/81
Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals: amides; Imides
C07C 257/18
With replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines: having carbon atoms of amidino groups bound to…
C07C 271/22
With the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms: to carbon atoms of hydrocarbon radicals…
C07C 311/06
Having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms: to acyclic carbon atoms of hydrocarbon…