| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | April 2, 2002 |
| PATENT TITLE |
Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists |
| PATENT ABSTRACT | The present invention describes novel imidazo-pyridines, -pyridazines, and -triazines of formula I: ##STR1## wherein A and B can be C or N and D is aryl or heteroaryl or pharmaceutically acceptable salt forms thereof, which are useful as CRF antagonists |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | June 25, 1999 |
| PATENT REFERENCES CITED |
Mataka et al, Reduction of 4,7-Diphenyl-1,2,5-thia (oxa) diazolo [3,4-c]pyridines Affording 2,5-Diphenyl-3,4-diaminopyridines and Ring Closure of the Diamines to Fluorescent Azaheterocycles, Jrnl of Heterocyclic Chem., 19/6,1481-1488, (1982). Kiyama et al., Synthesis and Evaluation of Novel Nonpeptide Angiotensin II Receptor Antagonists . . . , Chem. Pharm Bull., 43/3, 450-460, (1995). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed as new and desired to be secured by Letter Patent of United States is: 1. A compound of formula (Ia): ##STR24## or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein: D is an aryl or heteroaryl group attached through an unsaturated carbon atom; X is selected from the group CH--R.sup.9, N--R.sup.10, O, S(O).sub.n and a bond; n is 0, 1 or 2; R.sup.1 is selected from the group C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, --SO.sub.2 --C.sub.1-10 alkyl, --SO.sub.2 --R.sup.1a, and --SO.sub.2 --R.sup.1b ; R.sup.1 is substituted with 0-1 substituents selected from the group --CN, --S(O).sub.n R.sup.14b, --COR.sup.13a, --CO.sub.2 R.sup.13a, --NR.sup.15a COR.sup.13a, --N(COR.sup.13a).sub.2, --NR.sup.15a CONR.sup.13a R.sup.16a, --NR.sup.15a CO.sub.2 R.sup.14b, --CONR.sup.13a R.sup.16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C.sub.3-8 cycloalkyl, wherein 0-1 carbon atoms in the C.sub.4-8 cycloalkyl is replaced by a group selected from the group --O--, --S(O).sub.n --, --NR.sup.13a --, --NCO.sub.2 R.sup.14b --, --NCOR.sup.14b -- and --NSO.sub.2 R.sup.14b --, and wherein N.sub.4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R.sup.13a, CO.sub.2 R.sup.14b, COR.sup.14b and SO.sub.2 R.sup.14b ; R.sup.1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R.sup.1a, R.sup.1b, R.sup.1c, C.sub.1-6 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --OR.sup.13a, --NR.sup.13a R.sup.16a, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, and C.sub.3-8 cycloalkyl which is substituted with 0-1 R.sup.9 and in which 0-1 carbons of C.sub.4-8 cycloalkyl is replaced by --O--; provided that R.sup.1 is other than a cyclohexyl-(CH.sub.2).sub.2 -- group; R.sup.1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R.sup.1a being substituted with 0-1 --OR.sup.17 and 0-5 substituents independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, SH, --S(O).sub.n R.sup.18, --COR.sup.17, --OC(O)R.sup.18, NR.sup.15a COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15a CONR.sup.17a R.sup.19a, --NR.sup.15a CO.sub.2 R.sup.18, --NR.sup.17a R.sup.19a, and --CONR.sup.17a R.sup.19a ; R.sup.1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.17, SH, --S(O).sub.m R.sup.18, --COR.sup.17, --OC(O)R.sup.18, NR.sup.15a COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15a CONR.sup.17a R.sup.19a, --NR.sup.15a CO.sub.2 R.sup.18, --NR.sup.17a R.sup.19a, and --CONR.sup.17a R.sup.19a, and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R.sup.15a, CO.sub.2 R.sup.14b, COR.sup.14b and SO.sub.2 R.sup.14b ; R.sup.1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.13a, SH, --S(O).sub.n R.sup.14b, --COR.sup.13a, --OC(O)R.sup.14b, --NR.sup.15a COR.sup.13a, --N(COR.sup.13a).sub.2, --NR.sup.15a CONR.sup.13a R.sup.16a, --NR.sup.15a CO.sub.2 R.sup.14b, --NR.sup.13a R.sup.16a, and --CONR.sup.13a R.sup.16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R.sup.13a, CO.sub.2 R.sup.14b, COR.sup.14b and SO.sub.2 R.sup.14b and wherein any sulfur atom is optionally monooxidized or dioxidized; provided that R.sup.1 is other than a --(CH.sub.2).sub.1-4 -aryl, --(CH.sub.2).sub.1-4 -heteroaryl, or --(CH.sub.2).sub.1-4 -heterocycle, wherein the aryl, heteroaryl, or heterocycle group is substituted or unsubstituted; R.sup.2 is selected from the group C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.2-4 alkenyl, and C.sub.2-4 alkynyl and is substituted with 0-3 substituents selected from the group --CN, hydroxy, halo and C.sub.1-4 alkoxy; alternatively R.sup.2, in the case where X is a bond, is selected from the group --CN, CF.sub.3 and C.sub.2 F.sub.5 ; R.sup.8 is independently selected at each occurrence from the group H, Br, Cl, F, I, --CN, C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfinyl, C.sub.1-4 alkylsulfonyl, amino, C.sub.1-4 alkylamino, (C.sub.1-4 alkyl).sub.2 amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C.sub.1-7 alkyl, C.sub.3-8 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkyl sulfinyl, C.sub.1-4 alkylsulfonyl, C.sub.1-6 alkylamino and (C.sub.1-4 alkyl).sub.2 amino; p1 R.sup.9 and R.sup.10 are independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkyl and C.sub.3-8 cycloalkyl; R.sup.13 is selected from the group H, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, aryl, aryl(C.sub.1-4 alkyl)--, heteroaryl and heteroaryl(C.sub.1-4 alkyl)--; R.sup.13a and R.sup.16a are independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, and C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl; R.sup.14 is selected from the group C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, aryl, aryl(C.sub.1-4 alkyl)--, heteroaryl and heteroaryl(C.sub.1-4 alkyl)-- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C.sub.1-4 alkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy C.sub.1-4 haloalkoxy, and dimethylamino; R.sup.14a is selected from the group C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C.sub.1-4 alkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, and dimethylamino; R.sup.14b is selected from the group C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, and C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl; R.sup.15 is independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C.sub.1-4 alkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, and dimethylamino; R.sup.15a is independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, and C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl; R.sup.17 is selected at each occurrence from the group H, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, C.sub.1-2 alkoxy-C.sub.1-2 alkyl, C.sub.1-4 haloalkyl, R.sup.14 S(O).sub.n --C.sub.1-4 alkyl, and R.sup.17b R.sup.19b N--C.sub.2-4 alkyl; R.sup.18 and R.sup.19 are independently selected at each occurrence from the group H, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, C.sub.1-2 alkoxy-C.sub.1-2 alkyl, and C.sub.1-4 haloalkyl; alternatively, in an NR.sup.17 R.sup.19 moiety, R.sup.17 and R.sup.19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N.sub.4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R.sup.13, CO.sub.2 R.sup.14, COR.sup.14 and SO.sub.2 R.sup.14 ; alternatively, in an NR.sup.17b R.sup.19b moiety, R.sup.17b and R.sup.19b taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N.sub.4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R.sup.13, CO.sub.2 R.sup.14, COR.sup.14 and SO.sub.2 R.sup.14 ; R.sup.17a and R.sup.19a are independently selected at each occurrence from the group H, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl and C.sub.1-4 haloalkyl; aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, methylenedioxy, C.sub.1-4 alkoxy-C.sub.1-4 alkoxy, --OR.sup.17, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, --NO.sub.2, SH, --S(O).sub.n R.sup.18, --COR.sup.17, --CO.sub.2 R.sup.17, --OC(O)R.sup.18, --NR.sup.15 COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15 CONR.sup.17 R.sup.19, --NR.sup.15 CO.sub.2 R.sup.18, --NR.sup.17 R.sup.19, and --CONR.sup.17 R.sup.19 and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C.sub.1-3 alkyl, C.sub.1-3 alkoxy, Br, Cl, F, I, --CN, dimethylamino, CF.sub.3, C.sub.2 F.sub.5, OCF.sub.3, SO.sub.2 Me and acetyl; heteroaryl is independently selected at each occurence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.17, SH, --S(O).sub.m R.sup.18, --COR.sup.17, --CO.sub.2 R.sup.17, --OC(O)R.sup.18, --NR.sup.15 COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15 CONR.sup.17 R.sup.19, --NR.sup.15 CO.sub.2 R.sup.18, --NR.sup.17 R.sup.19, and --CONR.sup.17 R.sup.19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R.sup.15, CO.sub.2 R.sup.14a, COR.sup.14a and SO.sub.2 R.sup.14a ; and, provided that when D is imidazole or triazole, R.sup.1 is other than unsubstituted C.sub.1-6 linear or branched alkyl or C.sub.3-6 cycloalkyl. 2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1. 3. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated, by antagonizing CRF, in mammals, comprising: administering to the mammal in need of such treatment a therapeutically effective amount of a compound of claim 1. 4. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, in mammals, comprising: administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (I): ##STR25## or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein: A is N or C--R.sup.7 ; B is N or C--R.sup.8 ; provided that when A is N that B must be C--R.sup.8, and that when B is N that A must be C--R.sup.7 ; D is an aryl or heteroaryl group attached through an unsaturated carbon atom; X is selected from the group CH--R.sup.9, N--R.sup.10, O, S(O).sub.n and a bond; n is 0, 1 or 2; R.sup.1 is selected from the group C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, --SO.sub.2 --C.sub.1-10 alkyl, --SO.sub.2 --R.sup.1a, and --SO.sub.2 --R.sup.1b ; R.sup.1 is substituted with 0-1 substituents selected from the group --CN, --S(O).sub.n R.sup.14b, --COR.sup.13a, --CO.sub.2 R.sup.13a, --NR.sup.15a COR.sup.13a, --N(COR.sup.13a).sub.2, --NR.sup.15a CONR.sup.13a R.sup.16a, --NR.sup.15a CO.sub.2 R.sup.14b, --CONR.sup.13a R.sup.16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C.sub.3-8 cycloalkyl, wherein 0-1 carbon atoms in the C.sub.4-8 cycloalkyl is replaced by a group selected from the group --O--, --S(O).sub.n --, --NR.sup.13a --, --NCO.sub.2 R.sup.14b --, --NCOR.sup.14b -- and --NSO.sub.2 R.sup.14b --, and wherein N.sub.4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R.sup.13a, CO.sub.2 R.sup.14b, COR.sup.14b and SO.sub.2 R.sup.14b ; R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R.sup.1a, R.sup.1b, R.sup.1c, C.sub.1-6 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --OR.sup.13a, --NR.sup.13a R.sup.16a, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, and C.sub.3-8 cycloalkyl which is substituted with 0-1 R.sup.9 and in which 0-1 carbons of C.sub.4-8 cycloalkyl is replaced by --O--; R.sup.1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R.sup.1a being substituted with 0-5 substituents independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.17, SH, --S(O).sub.n R.sup.18, --COR.sup.17, --OC(O)R.sup.18, --NR.sup.15a COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15a CONR.sup.17a R.sup.19a, --NR.sup.15a CO.sub.2 R.sup.18, --NR.sup.17a R.sup.19a, and --CONR.sup.17a R.sup.19a ; R.sup.1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.17, SH, --S(O).sub.m R.sup.18, --COR.sup.17, --OC(O)R.sup.18, --NR.sup.15a COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15a CONR.sup.17a R.sup.19a, --NR.sup.15a CO.sub.2 R.sup.18, --NR.sup.17a R.sup.19a, and --CONR.sup.17a R.sup.19a and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R.sup.15a, CO.sub.2 R.sup.14b, COR.sup.14b and SO.sub.2 R.sup.14b ; R.sup.1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.13a, SH, --S(O).sub.n R.sup.14b, --COR.sup.13a, --OC(O)R.sup.14b, --NR.sup.15a COR.sup.13a, --N(COR.sup.13a).sub.2, --NR.sup.15a CONR.sup.13a R.sup.16a, --NR.sup.15a CO.sub.2 R.sup.14b, --NR.sup.13a R.sup.16a, and --CONR.sup.13a R.sup.16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R.sup.13a, CO.sub.2 R.sup.14b, COR.sup.14b and SO.sub.2 R.sup.14b and wherein any sulfur atom is optionally monooxidized or dioxidized; R.sup.2 is selected from the group C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.2-4 alkenyl, and C.sub.2-4 alkynyl and is substituted with 0-3 substituents selected from the group --CN, hydroxy, halo and C.sub.1-4 alkoxy; alternatively R.sup.2, in the case where X is a bond, is selected from the group --CN, CF.sub.3 and C.sub.2 F.sub.5 ; R.sup.7 and R.sup.8 are independently selected at each occurrence from the group H, Br, Cl, F, I, --CN, C.sub.1-4 alkyl, C.sub.3-8 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfinyl, C.sub.1-4 alkylsulfonyl, amino, C.sub.1-4 alkylamino, (C.sub.1-4 alkyl).sub.2 amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C.sub.1-7 alkyl, C.sub.3-8 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkyl sulfinyl, C.sub.1-4 alkylsulfonyl, C.sub.1-6 alkylamino and (C.sub.1-4 alkyl).sub.2 amino; R.sup.9 and R.sup.10 are independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkyl and C.sub.3-8 cycloalkyl; R.sup.13 is selected from the group H, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, aryl, aryl(C.sub.1-4 alkyl)-, heteroaryl and heteroaryl(C.sub.1-4 alkyl)-; R.sup.13a and R.sup.16a are independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, and C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl; R.sup.14 is selected from the group C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, aryl, aryl(C.sub.1-4 alkyl)--, heteroaryl and heteroaryl(C.sub.1-4 alkyl)-- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C.sub.1-4 alkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy C.sub.1-4 haloalkoxy, and dimethylamino; R.sup.14a is selected from the group C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C.sub.1-4 alkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, and dimethylamino; R.sup.14b is selected from the group C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, and C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl; R.sup.15 is independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C.sub.1-4 alkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, nitro, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, and dimethylamino; R.sup.15a is independently selected at each occurrence from the group H, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, and C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl; R.sup.17 is selected at each occurrence from the group H, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, C.sub.1-2 alkoxy-C.sub.1-2 alkyl, C.sub.1-4 haloalkyl, R.sup.14 S(O).sub.n --C.sub.1-4 alkyl, and R.sup.17b R.sup.19b N--C.sub.2-4 alkyl; R.sup.18 and R.sup.19 are independently selected at each occurrence from the group H, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl, C.sub.1-2 alkoxy-C.sub.1-2 alkyl, and C.sub.1-4 haloalkyl; alternatively, in an NR.sup.17 R.sup.19 moiety, R.sup.17 and R.sup.19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N.sub.4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R.sup.13, CO.sub.2 R.sup.14, COR.sup.14 and SO.sub.2 R.sup.14 ; alternatively, in an NR.sup.17b R.sup.19b moiety, R.sup.17b and R.sup.19b taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N.sub.4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R.sup.13, CO.sub.2 R.sup.14, COR.sup.14 and SO.sub.2 R.sup.14 ; R.sup.17a and R.sup.19a are independently selected at each occurrence from the group H, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-6 alkyl and C.sub.1-4 haloalkyl; aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, methylenedioxy, C.sub.1-4 alkoxy-C.sub.1-4 alkoxy, --OR.sup.17, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, --NO.sub.2, SH, --S(O).sub.n R.sup.18, --COR.sup.17, --CO.sub.2 R.sup.17, --OC(O)R.sup.18, --NR.sup.15 COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15 CONR.sup.17 R.sup.19, --NR.sup.15 CO.sub.2 R.sup.18, --NR.sup.17 R.sup.19, and --CONR.sup.17 R.sup.19 and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C.sub.1-3 alkyl, C.sub.1-3 alkoxy, Br, Cl, F, I, --CN, dimethylamino, CF.sub.3, C.sub.2 F.sub.5, OCF.sub.3, SO.sub.2 Me and acetyl; and, heteroaryl is independently selected at each occurence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, Br, Cl, F, I, C.sub.1-4 haloalkyl, --CN, nitro, --OR.sup.17, SH, --S(O).sub.m R.sup.18, --COR.sup.17, --CO.sub.2 R.sup.17, --OC(O)R.sup.18, --NR.sup.15 COR.sup.17, --N(COR.sup.17).sub.2, --NR.sup.15 CONR.sup.17 R.sup.19, --NR.sup.15 CO.sub.2 R.sup.18, --NR.sup.17 R.sup.19, and --CONR.sup.17 R.sup.19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R.sup.15, CO.sub.2 R.sup.14a, COR.sup.14a and SO.sub.2 R.sup.14a. |
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