US 5,683,999 AGranted

Cyclic urea HIV protease inhibitors

AssigneeThe DuPont Merck Pharmaceutical Company

InventorsPrabhakar Kondaji Jadhav, Soo Sung Ko

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Abstract

This invention relates to substituted cyclic ureas and derivatives thereof, including compounds of formula (II): ##STR1## said compounds being useful as inhibitors of HIV protease. The present invention also relates to pharmaceutical compositions comprising such compounds and to method of using these compounds for the treatment HIV infection. The present invention also relates to the use of such compounds in processes for the identification of HIV protease inhibitors and for the inhibition or detection of HIV in a bodily fluid sample.

Claims18

Dependent claims

A compound of the formula (I):

##STR174## or a pharmaceutically acceptable salt form thereof wherein:
R.sup.1 is --CH.sub.2 --X--Y--Z;
X is selected from:
C.sub.1 -C.sub.4 alkyl, aryl substituted with 0-2 R.sup.7, wherein said aryl group is phenyl or naphthyl,
C.sub.3 -C.sub.6 cycloalkyl, or a heterocycle selected from the group consisting of pyridine, thiophene, furan, thiazole, indazole, thieno2,3-c!pyrazole and thieno3,2-c!pyrazole, said heterocycle being substituted with 0-2 R.sup.7 ;
Y is selected from:
--(CH.sub.2).sub.n O--,
--(CH.sub.2).sub.n S--,
--(CH.sub.2).sub.n NH--,
--(CH.sub.2).sub.n C(.dbd.O)NH--,
--(CH.sub.2).sub.n SO.sub.2 NH--
--(CH.sub.2).sub.m NHC(.dbd.O)--,
--(CH.sub.2).sub.n NHCO.sub.2 --,
--(CH.sub.2).sub.m OC(.dbd.O) NH--,
--(CH.sub.2).sub.n NHC(.dbd.O) NH--,
--(CH.sub.2).sub.n C(.dbd.NH) NH--;
n is 0-2;
m is 1-2;
Z is selected from:
2-, 3-, or 4-pyridinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrimidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrazinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
4-pyrimidon-2-yl or 2-pyrimidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
6H-1,3,4-thiadiazin-2-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5-uracilyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-, 3-, or 4-quinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
1-, 3-, or 4-isoquinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5- or 6-coumarinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
3-tetrahydrofuranyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2- or 3-pyrrolidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-imidazolidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
or ##STR175## Q is O, S or NH;
Q.sup.1 is CR.sup.5 or N;
R.sup.2 is selected from:
R.sup.1 ;
--CH.sub.2 --X--Y.sup.1 --Z.sup.1 ;
hydrogen;
(C.sub.3 -C.sub.6 cycloalkyl)methyl substituted with 0-2 R.sup.7 ;
C.sub.1 -C.sub.6 alkyl substituted with 0-2 R.sup.7 ;
C.sub.3 -C.sub.6 alkenyl substituted with 0-2 R.sup.7 ;
C.sub.3 -C.sub.6 alkynyl substituted with 0-2 R.sup.7 ;
benzyl substituted with 0-5 R.sup.9 ;
2-naphthylmethyl substituted with 0-2 R.sup.9 ;
2- or 3-thienylmethyl, 2- or 3-furanylmethyl, or 2-, 3- or 4-pyridinylmethyl, said thienyl, furanyl or pyridinyl being substituted with 0-2 R.sup.9 ;
or
5- or 6-indazolylmethyl, 5-benzotriazolylmethyl, 5-benzoxazolonylmethyl, 6-benzoxazolonylmethyl, 5-benzimidazolylmethyl, 5-benzoxazolylmethyl, or 5-benzisoxazolylmethyl, said indazolyl, benzimidazolyl, benzoxazolyl and benzisoxazolyl being substituted with 0-1 R.sup.10 ;
Y.sup.1 is selected from:
--(CH.sub.2).sub.n O(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n S(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n NH(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n C(.dbd.O) NH(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n SO.sub.2 NH(CH.sub.2).sub.m --
--(CH.sub.2).sub.m NHC(.dbd.O)(CH.sub.2).sub.m --,
(CH.sub.2).sub.n NHCO.sub.2 (CH.sub.2).sub.m --,
--(CH.sub.2).sub.m OC(.dbd.O)NH(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n NHC(.dbd.O)NH(CH.sub.2).sub.m --, or
--(CH.sub.2).sub.n C(.dbd.NH)NH(CH.sub.2).sub.m --;
Z.sup.1 is selected from:
hydrogen;
C.sub.1 -C.sub.5 alkyl substituted with 0-2 R.sup.7 ;
C.sub.2 -C.sub.5 alkenyl substituted with 0-2 R.sup.7 ;
C.sub.2 -C.sub.5 alkynyl substituted with 0-2 R.sup.7 ;
C.sub.3 -C.sub.6 cycloalkyl substituted with 0-2 R.sup.7 ;
aryl substituted with 0-2 R.sup.9, wherein said aryl group is phenyl or naphthyl;
2-, 3-, or 4-pyridinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrimidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrazinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
4-pyrimidon-2-yl- or 2-pyrimidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
6H-1,3,4-thiadiazin-2-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5-uracilyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-, 3-, or 4-quinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
1-, 3-, or 4-isoquinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5- or 6-coumarinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
3-tetrahydrofuranyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2- or 3-pyrrolidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-imidazolidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
or ##STR176## R.sup.3 and R.sup.4 are independently selected from:
benzyl, 4-fluorobenzyl, 2-pyrrolylmethyl, 3-methoxybenzyl, 4-methoxybenzyl, ethyl, isobutyl, cyclohexylmethyl, n-hexyl, 4-nitrobenzyl, 4-aminobenzyl, 3-hydroxybenzyl, 4-hydroxybenzyl, 4-benzyloxybenzyl, 4-thiomethylbenzyl, 2-thienylmethyl, 3-thienylmethyl, 2-thiazolylmethyl, 4-pyridylmethyl 3,4-methylenedioxybenzyl, 3,4-ethylenedioxybenzyl, 1,4-benzoxazin-6-yl-methyl, 4-N,N-dimethylaminobenzyl or 2-naphthylmethyl;
R.sup.5 and R.sup.6 are independently selected from:
hydrogen, halogen, --CN, --NO.sub.2, --OH, --CO.sub.2 R.sup.8, --CONHR.sup.8, --NR.sup.11 R.sup.12, --SR.sup.8, --SO.sub.m R.sup.13, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 haloalkoxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, phenoxy, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, C.sub.7 -C.sub.10 arylalkyl wherein said aryl group is phenyl or naphthyl, C.sub.2 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.4 alkylcarbonyloxy, C.sub.1 -C.sub.4 alkylcarbonyl, benzyloxy, C.sub.3 -C.sub.6 cycloalkoxy, or phenyl, said phenyl being optionally substituted with Cl, F, Br, --CN, --NO.sub.2, --NR.sup.11 R.sup.12, --CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or --OH, or
alternatively, R.sup.5 and R.sup.6, when substituents on adjacent carbons, can be taken together with the carbon atoms to which they are attached to form a 5-6 membered fused carbocyclic or heterocyclic ring system wherein said fused heterocyclic ring is selected from pyridine, thiophene, pyrimidine, pyrazine, or pyridazine, said carbocyclic or heterocyclic ring system being optionally substituted with 1-3 groups independently selected from:
Cl, F, Br, --CN, --NO.sub.2, --CF.sub.3, --CO.sub.2 R.sup.8, --COR.sup.8, --OCOR.sup.8, --NR.sup.11 R.sup.12, --CONHR.sup.8, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or --OH;
R.sup.7 is selected from:
hydrogen, halogen, --CN, --NO.sub.2, --OR.sup.8, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 haloalkoxy, --CO.sub.2 R.sup.8, --COR.sup.8, --CONHR.sup.8, --NR.sup.11 R.sup.12, --OCOR.sup.8, C.sub.1 -C.sub.6 alkyl, phenyl substituted with 0-2 R.sup.10, or
a 5- or 6-membered heterocycle selected from pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, oxazolidinyl, thiazolyl, 1,3,4-thiadiazolyl, oxazolyl, or 1,3,4-oxadiazolyl heteroatoms independently selected from oxygen, nitrogen;
R.sup.8 is hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl substituted with 0-2 R.sup.10, or a 5- or 6-membered heterocycle selected from pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl indolyl, oxazolidinyl, thiazolyl, 1,3,4-thiadiazolyl, oxazolyl, or 1,3,4-oxadiazoyl heteroatoms independently selected from oxygen, nitrogen;
R.sup.9 is selected from:
C.sub.1 -C.sub.3 alkyl, OR.sup.8, NR.sup.11 R.sup.12, hydroxymethyl, CN, F, Cl, Br, CF.sub.3, --CO.sub.2 R.sup.8, --COR.sup.8, --CONHR.sup.11, --CH(NOH), --C(.dbd.NOH)CH.sub.3, --C(.dbd.NOH)NH.sub.2, --NHC(.dbd.O)NHR.sup.11, --NHC(O)OR.sup.11, --COH(R.sup.8).sub.2, methylenedioxy, ethylenedioxy, phenyl substituted with 0-2 R.sup.10, or
a 5- or 6-membered heterocycle selected from pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, oxazolidinyl, thiazolyl, 1,3,4-thiadiazolyl, oxazolyl, or 1,3,4-oxadiazolyl heteroatoms independently selected from oxygen, nitrogen;
R.sup.10 is selected from:
C.sub.1 -C.sub.3 alkyl, OR.sup.8, NR.sup.11 R.sup.12, F, Cl, Br, --COR.sup.8, --CO.sub.2 R.sup.8, --CH.sub.2 OR.sup.8, or --CH.sub.2 C(.dbd.O)R.sup.8 ;
R.sup.11 is selected from:
hydrogen or C.sub.1 -C.sub.4 alkyl;
R.sup.12 is selected from:
hydrogen, C.sub.1 -C.sub.4 alkyl, glycinyl, alanyl, alanyl-alanyl, phenylglycinyl, phenylalanyl or N-methylglycinyl, N,N-dimethylglycinyl;
R.sup.13 is selected from:
hydrogen, phenyl, benzyl, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 alkoxyalkyl.

94 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/613,554Filed 11 Mar 1996 · continuation in part
Priority: 17 Mar 1995
Granted: 4 Nov 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 243/04
Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms: having the nitrogen atoms in…
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Serial406,240Parent of this continuation-in-part · filed 17 Mar 1995
US 5,683,999 AThis patent

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

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Abstract

A compound of the formula (I):

##STR174## or a pharmaceutically acceptable salt form thereof wherein:
R.sup.1 is --CH.sub.2 --X--Y--Z;
X is selected from:
C.sub.1 -C.sub.4 alkyl, aryl substituted with 0-2 R.sup.7, wherein said aryl group is phenyl or naphthyl,
C.sub.3 -C.sub.6 cycloalkyl, or a heterocycle selected from the group consisting of pyridine, thiophene, furan, thiazole, indazole, thieno2,3-c!pyrazole and thieno3,2-c!pyrazole, said heterocycle being substituted with 0-2 R.sup.7 ;
Y is selected from:
--(CH.sub.2).sub.n O--,
--(CH.sub.2).sub.n S--,
--(CH.sub.2).sub.n NH--,
--(CH.sub.2).sub.n C(.dbd.O)NH--,
--(CH.sub.2).sub.n SO.sub.2 NH--
--(CH.sub.2).sub.m NHC(.dbd.O)--,
--(CH.sub.2).sub.n NHCO.sub.2 --,
--(CH.sub.2).sub.m OC(.dbd.O) NH--,
--(CH.sub.2).sub.n NHC(.dbd.O) NH--,
--(CH.sub.2).sub.n C(.dbd.NH) NH--;
n is 0-2;
m is 1-2;
Z is selected from:
2-, 3-, or 4-pyridinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrimidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrazinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
4-pyrimidon-2-yl or 2-pyrimidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
6H-1,3,4-thiadiazin-2-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5-uracilyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-, 3-, or 4-quinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
1-, 3-, or 4-isoquinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5- or 6-coumarinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
3-tetrahydrofuranyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2- or 3-pyrrolidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-imidazolidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
or ##STR175## Q is O, S or NH;
Q.sup.1 is CR.sup.5 or N;
R.sup.2 is selected from:
R.sup.1 ;
--CH.sub.2 --X--Y.sup.1 --Z.sup.1 ;
hydrogen;
(C.sub.3 -C.sub.6 cycloalkyl)methyl substituted with 0-2 R.sup.7 ;
C.sub.1 -C.sub.6 alkyl substituted with 0-2 R.sup.7 ;
C.sub.3 -C.sub.6 alkenyl substituted with 0-2 R.sup.7 ;
C.sub.3 -C.sub.6 alkynyl substituted with 0-2 R.sup.7 ;
benzyl substituted with 0-5 R.sup.9 ;
2-naphthylmethyl substituted with 0-2 R.sup.9 ;
2- or 3-thienylmethyl, 2- or 3-furanylmethyl, or 2-, 3- or 4-pyridinylmethyl, said thienyl, furanyl or pyridinyl being substituted with 0-2 R.sup.9 ;
or
5- or 6-indazolylmethyl, 5-benzotriazolylmethyl, 5-benzoxazolonylmethyl, 6-benzoxazolonylmethyl, 5-benzimidazolylmethyl, 5-benzoxazolylmethyl, or 5-benzisoxazolylmethyl, said indazolyl, benzimidazolyl, benzoxazolyl and benzisoxazolyl being substituted with 0-1 R.sup.10 ;
Y.sup.1 is selected from:
--(CH.sub.2).sub.n O(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n S(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n NH(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n C(.dbd.O) NH(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n SO.sub.2 NH(CH.sub.2).sub.m --
--(CH.sub.2).sub.m NHC(.dbd.O)(CH.sub.2).sub.m --,
(CH.sub.2).sub.n NHCO.sub.2 (CH.sub.2).sub.m --,
--(CH.sub.2).sub.m OC(.dbd.O)NH(CH.sub.2).sub.m --,
--(CH.sub.2).sub.n NHC(.dbd.O)NH(CH.sub.2).sub.m --, or
--(CH.sub.2).sub.n C(.dbd.NH)NH(CH.sub.2).sub.m --;
Z.sup.1 is selected from:
hydrogen;
C.sub.1 -C.sub.5 alkyl substituted with 0-2 R.sup.7 ;
C.sub.2 -C.sub.5 alkenyl substituted with 0-2 R.sup.7 ;
C.sub.2 -C.sub.5 alkynyl substituted with 0-2 R.sup.7 ;
C.sub.3 -C.sub.6 cycloalkyl substituted with 0-2 R.sup.7 ;
aryl substituted with 0-2 R.sup.9, wherein said aryl group is phenyl or naphthyl;
2-, 3-, or 4-pyridinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrimidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-pyrazinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
4-pyrimidon-2-yl- or 2-pyrimidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
6H-1,3,4-thiadiazin-2-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5-uracilyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-, 3-, or 4-quinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
1-, 3-, or 4-isoquinolinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
5- or 6-coumarinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
3-tetrahydrofuranyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2- or 3-pyrrolidinyl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
2-imidazolidon-4-yl, substituted with 0-1 R.sup.5 and 0-1 R.sup.6 ;
or ##STR176## R.sup.3 and R.sup.4 are independently selected from:
benzyl, 4-fluorobenzyl, 2-pyrrolylmethyl, 3-methoxybenzyl, 4-methoxybenzyl, ethyl, isobutyl, cyclohexylmethyl, n-hexyl, 4-nitrobenzyl, 4-aminobenzyl, 3-hydroxybenzyl, 4-hydroxybenzyl, 4-benzyloxybenzyl, 4-thiomethylbenzyl, 2-thienylmethyl, 3-thienylmethyl, 2-thiazolylmethyl, 4-pyridylmethyl 3,4-methylenedioxybenzyl, 3,4-ethylenedioxybenzyl, 1,4-benzoxazin-6-yl-methyl, 4-N,N-dimethylaminobenzyl or 2-naphthylmethyl;
R.sup.5 and R.sup.6 are independently selected from:
hydrogen, halogen, --CN, --NO.sub.2, --OH, --CO.sub.2 R.sup.8, --CONHR.sup.8, --NR.sup.11 R.sup.12, --SR.sup.8, --SO.sub.m R.sup.13, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 haloalkoxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, phenoxy, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, C.sub.7 -C.sub.10 arylalkyl wherein said aryl group is phenyl or naphthyl, C.sub.2 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.4 alkylcarbonyloxy, C.sub.1 -C.sub.4 alkylcarbonyl, benzyloxy, C.sub.3 -C.sub.6 cycloalkoxy, or phenyl, said phenyl being optionally substituted with Cl, F, Br, --CN, --NO.sub.2, --NR.sup.11 R.sup.12, --CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or --OH, or
alternatively, R.sup.5 and R.sup.6, when substituents on adjacent carbons, can be taken together with the carbon atoms to which they are attached to form a 5-6 membered fused carbocyclic or heterocyclic ring system wherein said fused heterocyclic ring is selected from pyridine, thiophene, pyrimidine, pyrazine, or pyridazine, said carbocyclic or heterocyclic ring system being optionally substituted with 1-3 groups independently selected from:
Cl, F, Br, --CN, --NO.sub.2, --CF.sub.3, --CO.sub.2 R.sup.8, --COR.sup.8, --OCOR.sup.8, --NR.sup.11 R.sup.12, --CONHR.sup.8, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or --OH;
R.sup.7 is selected from:
hydrogen, halogen, --CN, --NO.sub.2, --OR.sup.8, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 haloalkoxy, --CO.sub.2 R.sup.8, --COR.sup.8, --CONHR.sup.8, --NR.sup.11 R.sup.12, --OCOR.sup.8, C.sub.1 -C.sub.6 alkyl, phenyl substituted with 0-2 R.sup.10, or
a 5- or 6-membered heterocycle selected from pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, oxazolidinyl, thiazolyl, 1,3,4-thiadiazolyl, oxazolyl, or 1,3,4-oxadiazolyl heteroatoms independently selected from oxygen, nitrogen;
R.sup.8 is hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl substituted with 0-2 R.sup.10, or a 5- or 6-membered heterocycle selected from pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl indolyl, oxazolidinyl, thiazolyl, 1,3,4-thiadiazolyl, oxazolyl, or 1,3,4-oxadiazoyl heteroatoms independently selected from oxygen, nitrogen;
R.sup.9 is selected from:
C.sub.1 -C.sub.3 alkyl, OR.sup.8, NR.sup.11 R.sup.12, hydroxymethyl, CN, F, Cl, Br, CF.sub.3, --CO.sub.2 R.sup.8, --COR.sup.8, --CONHR.sup.11, --CH(NOH), --C(.dbd.NOH)CH.sub.3, --C(.dbd.NOH)NH.sub.2, --NHC(.dbd.O)NHR.sup.11, --NHC(O)OR.sup.11, --COH(R.sup.8).sub.2, methylenedioxy, ethylenedioxy, phenyl substituted with 0-2 R.sup.10, or
a 5- or 6-membered heterocycle selected from pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, oxazolidinyl, thiazolyl, 1,3,4-thiadiazolyl, oxazolyl, or 1,3,4-oxadiazolyl heteroatoms independently selected from oxygen, nitrogen;
R.sup.10 is selected from:
C.sub.1 -C.sub.3 alkyl, OR.sup.8, NR.sup.11 R.sup.12, F, Cl, Br, --COR.sup.8, --CO.sub.2 R.sup.8, --CH.sub.2 OR.sup.8, or --CH.sub.2 C(.dbd.O)R.sup.8 ;
R.sup.11 is selected from:
hydrogen or C.sub.1 -C.sub.4 alkyl;
R.sup.12 is selected from:
hydrogen, C.sub.1 -C.sub.4 alkyl, glycinyl, alanyl, alanyl-alanyl, phenylglycinyl, phenylalanyl or N-methylglycinyl, N,N-dimethylglycinyl;
R.sup.13 is selected from:
hydrogen, phenyl, benzyl, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 alkoxyalkyl.

94 more elements

Facts

Application

08/613,554Filed 11 Mar 1996 · continuation in part

Priority

17 Mar 1995

Granted

4 Nov 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 243/04
Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms: having the nitrogen atoms in…
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links