Patent ID: 6322770
Filing Date: 2001-11-27
Classification: A61K,A61P,C07D

Abstract:
A compound of formula:(Q).sub.d --L.sub.n --C.sub.h or (Q).sub.d --L.sub.n d--(C.sub.h).sub.d,wherein:Q is a compound of Formula Ia: ##STR84##or pharmaceutically acceptable salt forms thereof, wherein: X.sup.1d, X.sup.2d, X.sup.3d, and X.sup.4d are independently selected from nitrogen or carbon provided that at least two of X.sup.1d, X.sup.2d, X.sup.3d and X.sup.4d are carbon; R.sup.1d is selected from: ##STR85##A.sup.d and B.sup.d are independently --CH.sub.2 --, --O--, --N(R.sup.2d)--, or --C(.dbd.O)--;A.sup.1d and B.sup.1d are independently --CH.sub.2 -- or --N(R.sup.3d)--;D.sup.d nis --N(R.sup.2d)--, --O--, --S--, --C(.dbd.O)-- or --SO.sub.2 --;E.sup.d--F.sup.d is --C(R.sup.4d).dbd.C(R.sup.5d)--, --N.dbd.C(R.sup.4d)--, --C(R.sup.4d).dbd.N--, or --C(R.sup.4d).sub.2 C(R.sup.5d).sub.2 --;J.sup.d, K.sup.d, L.sup.d and M.sup.d are independently selected from --C(R.sup.4d)--, --C(R.sup.5d)-- or --N--, provided that at least one of J.sup.d, K.sup.d, L.sup.d and M.sup.d is not --N--;R.sup.2d is selected from: H, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.6 alkyl)carbonyl, (C.sub.1 -C.sub.6 alkoxy)carbonyl; (C.sub.1 -C.sub.6 alkyl)aminocarbonyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, heteroaryl(C.sub.1 -C.sub.6 alkyl)carbonyl, heteroarylcarbonyl, aryl(C.sub.1 -C.sub.6 alkyl)-, (C.sub.1 -C.sub.6 alkyl)carbonyl--, arylcarbonyl, C.sub.1 -C.sub.6 alkylsulfonyl, arylsulfonyl, aryl(C.sub.1 -C.sub.6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C.sub.1 -C.sub.6 alkyl)sulfonyl, aryloxycarbonyl, or aryl(C.sub.1 -C.sub.6 alkoxy)carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, and nitro;R.sup.3d is selected from: H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, or heteroaryl(C.sub.1 -C.sub.6 alkyl)-;R.sup.4d and R.sup.5d are independently selected from: H, C.sub.1 -C.sub.4 alkoxy, NR.sup.2d R.sup.3d, halogen, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, (C.sub.1 -C.sub.6 alkyl)carbonyl, (C.sub.1 -C.sub.6 alkoxy)carbonyl, arylcarbonyl, or alternatively, when substituents on adjacent atoms, R.sup.4d and R.sup.5d can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or non-aromatic ring system, said carbocyclic or heterocyclic ring being optionally substituted with 0-2 groups selected from: C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, cyano, amino, CF.sub.3, or NO.sub.2 ;U.sup.d is selected from:--(CH.sub.2).sub.n.sup.d --,--(CH.sub.2).sub.n.sup.d (CR.sup.7d.dbd.CR.sup.8d)(CH.sub.2).sub.m.sup.d --,--(CH.sub.2).sub.n.sup.d (C.dbd.C)(CH.sub.2).sub.m.sup.d --,--(CH.sub.2).sub.t.sup.d Q(CH.sub.2).sub.m.sup.d --,--(CH.sub.2).sub.n.sup.d O(CH.sub.2).sub.m.sup.d --,--(CH.sub.2).sub.n.sup.d N(R.sup.6d)(CH.sub.2).sub.m.sup.d ----(CH.sub.2).sub.n.sup.d C(.dbd.O)(CH.sub.2).sub.m.sup.d --,--(CH.sub.2).sub.n.sup.d (C.dbd.O)N(R.sup.6d)(CH.sub.2).sub.m.sup.d ----(CH.sub.2).sub.n.sup.d N(R.sup.6d)(C.dbd.O)(CH.sub.2).sub.m.sup.d --, or--(CH.sub.2).sub.n.sup.d S(O).sub.p.sup.d (CH.sub.2).sub.m.sup.d --;wherein one or more of the methylene groups in U.sup.d is optionally substituted with R.sup.7d ;Q.sup.d is selected from 1,2-cycloalkylene, 1,2-phenylene, 1,3-phenylene, 1,4-phenylene, 2,3-pyridinylene, 3,4-pyridinylene, 2,4-pyridinylene, or 3,4-pyridazinylene;R.sup.6d is selected from: H, C.sub.1 -C.sub.4 alkyl, or benzyl;R.sup.7d and R.sup.8d are independently selected from: H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, or heteroaryl(C.sub.0 -C.sub.6 alkyl)-;R.sup.10d is selected from: H, C.sub.1 -C.sub.4 alkoxy substituted with 0-1 R.sup.21d, N(R.sup.6d).sub.2, halogen, NO.sub.2, CN, CF.sub.3, CO.sub.2 R.sup.17d, C(.dbd.O)R.sup.17d, CONR.sup.17d R.sup.20d, --SO.sub.2 R.sup.17d, --SO.sub.2 NR.sup.17d R.sup.20d, C.sub.1 -C.sub.6 alkyl substituted with 0-1 R.sup.15d or 0-1 R.sup.21d, C.sub.3 -C.sub.6 alkenyl substituted with 0-1 R.sup.15d or 0-1 R.sup.21d, C.sub.3 -C.sub.7 cycloalkyl substituted with 0-1 R.sup.15d or 0-1 R.sup.21d, C.sub.4 -C.sub.11 cycloalkylalkyl substituted with 0-1 R.sup.15d or 0-1 R.sup.21d, aryl substituted with 0-1 R.sup.15d or 0-2 R.sup.11d or 0-1 R.sup.21d, or aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-1 R.sup.15d or 0-2 R.sup.11d or 0-1 R.sup.21d ;R.sup.11d is selected from H, halogen, CF.sub.3, CN, NO.sub.2, hydroxy, NR.sup.2d R.sup.3d, C.sub.1 -C.sub.4 alkyl substituted with 0-1 R.sup.21d, C.sub.1 -C.sub.4 alkoxy substituted with 0-1 R.sup.21d, aryl substituted with 0-1 R.sup.21d, aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-1 R.sup.21d, (C.sub.1 -C.sub.4 alkoxy)carbonyl substituted with 0-1 R.sup.21d, (C.sub.1 -C.sub.4 alkyl)carbonyl substituted with 0-1 R.sup.21d, C.sub.1 -C.sub.4 alkylsulfonyl substituted with 0-1 R.sup.21d, or C.sub.1 -C.sub.4 alkylaminosulfonyl substituted with 0-1 R.sup.21d ;W.sup.d is selected from:--C(R.sup.12d).sub.2).sub.q.sup.d C(.dbd.O)N(R.sup.13d)--, or--C(.dbd.O)--N(R.sup.13d)--(C(R.sup.12d).sub.2).sub.q.sup.d --;X.sup.d is --C(R.sup.12d)(R.sup.14d)--C(R.sup.12d)(R.sup.15d)--; or alternatively, W.sup.d and X.sup.d can be taken together to be ##STR86##R.sup.12d is selected from H, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, (C.sub.1 -C.sub.4 alkyl)carbonyl, aryl, or aryl(C.sub.1 -C.sub.6 alkyl)-;R.sup.13d is selected from H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkylmethyl, or aryl(C.sub.1 -C.sub.6 alkyl)-;R.sup.14d is selected from:H, C.sub.1 -C.sub.6 alkylthio(C.sub.1 -C.sub.6 alkyl)-, aryl(C.sub.1 -C.sub.10 alkylthioalkyl)-, aryl(C.sub.1 -C.sub.10 alkoxyalkyl)-, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkoxyalkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 --C.sub.10 alkynyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkylalkyl, aryl(C.sub.1 -C.sub.6 alkyl)-, heteroaryl(C.sub.1 -C.sub.6 alkyl)-, aryl, heteroaryl, CO.sub.2 R.sup.17d, C(.dbd.O)R.sup.17d, or CONR.sup.17d R.sup.20d, provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 0-1 R.sup.16d or 0-2 R.sup.11d ;R.sup.15d is selected from: H, R.sup.16d, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkoxyalkyl, C.sub.1 -C.sub.10 alkylaminoalkyl, C.sub.1 -C.sub.10 dialkylaminoalkyl, (C.sub.1 -C.sub.10 alkyl)carbonyl, aryl(C.sub.0 -C.sub.6 alkyl)carbonyl, C.sub.1 -C.sub.10 alkenyl, C.sub.1 -C.sub.10 alkynyl ,C.sub.3 --C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkylalkyl, aryl(C.sub.1 -C.sub.6 alkyl)-, heteroaryl(C.sub.1 -C.sub.6 alkyl)-, aryl, heteroaryl, CO.sub.2 R.sup.17d, C(.dbd.O)R.sup.17d, CONR.sup.17d R.sup.20d, SO.sub.2 R.sup.17d, or SO.sub.2 NR.sup.17d R.sup.20d, provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 0-2 R.sup.11d ;Y.sup.d is selected from: --COR.sup.19d, --SO.sub.3 H, --PO.sub.3 H, tetrazolyl, --CONHNHSO.sub.2 CF.sub.3, --CONHSO.sub.2 R.sup.17d, --CONHSO.sub.2 NHR.sup.17d, --NHCOCF.sub.3, --NHCONHSO.sub.2 R.sup.17d, --NHSO.sub.2 R.sup.17d, --OPO.sub.3 H.sub.2, --OSO.sub.3 H, --PO.sub.3 H.sub.2, --SO.sub.3 H, --SO.sub.2 NHCOR.sup.17d, --SO.sub.2 NHCO.sub.2 R.sup.17d, ##STR87##R.sup.16d is selected from:--N(R.sup.20d)--C(.dbd.O)--O--R.sup.17d,--N(R.sup.20d)--C(.dbd.O)--R.sup.17d,--N(R.sup.20d)--C(.dbd.O)--NH--R.sup.17d,--N(R.sup.20d)SO.sub.2 --R.sup.17d, or--N(R.sup.20d)SO.sub.2 --NR.sup.20d R.sup.17d ;R.sup.17d is selected from: C.sub.1 -C.sub.10 alkyl optionally substituted with a bond to L.sub.n, C.sub.3 -C.sub.11 cycloalkyl optionally substituted with a bond to L.sub.n, aryl(C.sub.1 -C.sub.6 alkyl)-optionally substituted with a bond to L.sub.n, (C.sub.1 -C.sub.6 alkyl)aryl optionally substituted with a bond to L.sub.n, heteroaryl(C.sub.1 -C.sub.6 alkyl)-optionally substituted with a bond to L.sub.n, (C.sub.1 -C.sub.6 alkyl)heteroaryl optionally substituted with a bond to L.sub.n, biaryl(C.sub.1 -C.sub.6 alkyl)-optionally substituted with a bond to L.sub.n, heteroaryl optionally substituted with a bond to L.sub.n, aryl optionally substituted with a bond to L.sub.n, or a bond to L.sub.n, wherein said aryl or heteroaryl groups are also optionally substituted with 0-3 substituents selected from the group consisting of: C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, aryl, heteroaryl, halo, cyano, amino, CF.sub.3, and NO.sub.2 ;R.sup.18d is selected from:H,--C(.dbd.O)--O--R.sup.17d,--C(.dbd.O)--R.sup.17d,--C(.dbd.O)--NH--R.sup.17d,--SO.sub.2 --R.sup.17d, or--SO.sub.2 --NR.sup.20d R.sup.17d ;R.sup.19d is selected from: hydroxy, C.sub.1 -C.sub.10 alkyloxy, C.sub.3 -C.sub.11 cycloalkyloxy, aryloxy, aryl(C.sub.1 -C.sub.6 alkoxy), C.sub.3 -C.sub.10 alkylcarbonyloxyalkyloxy, C.sub.3 -C.sub.10 alkoxycarbonyloxyalkyloxy, C.sub.2 -C.sub.10 alkoxycarbonylalkyloxy, C.sub.5 -C.sub.10 cycloalkylcarbonyloxyalkyloxy, C.sub.5 -C.sub.10 cycloalkoxycarbonyloxyalkyloxy, C.sub.5 -C.sub.10 cycloalkoxycarbonylalkyloxy, C.sub.7 -C.sub.11 aryloxycarbonylalkyloxy, C.sub.8 -C.sub.12 aryloxycarbonyloxyalkyloxy, C.sub.8 -C.sub.12 arylcarbonyloxyalkyloxy, C.sub.5 -C.sub.10 alkoxyalkylcarbonyloxyalkyloxy, C.sub.5 -C.sub.10 (5-alkyl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, C.sub.10 --C.sub.14 (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, or (R.sup.11d)(R.sup.12d)N--(C.sub.1 -C.sub.10 alkoxy);R.sup.20d is selected from: H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, or heteroaryl(C.sub.1 -C.sub.6 alkyl)-;R.sup.21d is selected from: COOH or N(R.sup.6d).sub.2 ;m.sup.d is 0-4;n.sup.d is 0-4;t.sup.d is 0-4;p.sup.d is 0-2;q.sup.d is 0-2; andr.sup.d is 0-2;with the following provisos:(1).sub.t.sup.d, n.sup.d, m.sup.d and q.sup.d are chosen such that the number of atoms connecting R.sup.1d and y.sup.d is in the range of 10-14; and(2).sub.n.sup.d and m.sup.d are chosen such that the value of n.sub.d plus m.sup.d is greater than one unless U.sup.d is --(CH.sub.2).sub.t.sup.d Q.sup.d (CH.sub.2).sub.m.sup.d --;d is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;L.sub.n is a linking group having the formula:(CR.sup.6 R.sup.7).sub.g --(W).sub.h --(CR.sup.6a R.sup.7a).sub.g' --(Z).sub.k --(W).sub.h' --(CR.sup.8 R.sup.9).sub.g"" --(W).sub.h"" --(CR.sup.8a R.sup.9a).sub.g""'--(W).sub.h""' --(CR.sup.8b R.sup.9b).sub.g""""--;W is independently selected at each occurrence from the group: O, S, NH, NHC(.dbd.O), C(.dbd.O)NH, C(.dbd.O), C(.dbd.O)O, OC(.dbd.O), NHC(.dbd.S)NH, NHC(.dbd.O)NH, SO.sub.2, SO.sub.2 NH, (OCH.sub.2 CH.sub.2).sub.s, (CH.sub.2 CH.sub.2 O).sub.s', (OCH.sub.2 CH.sub.2 CH.sub.2).sub.s"", (CH.sub.2 CH.sub.2 CH.sub.2 O).sub.t, and (aa).sub.t' ;aa is independently at each occurrence an amino acid;Z is selected from the group: aryl substituted with 0-3 R.sup.10, C.sub.3-10 cycloalkyl substituted with 0-3 R.sup.10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.10 ;R.sup.6, R.sup.6a, R.sup.7, R.sup.7a, R.sup.8, R.sup.8a, R.sup.8b, R.sup.9, R.sup.9a and R.sup.9b are independently selected at each occurrence from the group: H, .dbd.O, COOH, SO.sub.3 H, PO.sub.3 H, C.sub.1 -C.sub.5 alkyl substituted with 0-3 R.sup.10, aryl substituted with 0-3 R.sup.10, benzyl substituted with 0-3 R.sup.10, and C.sub.1 -C.sub.5 alkoxy substituted with 0-3 R.sup.10, NHC(.dbd.O)R.sup.11, C(.dbd.O)NHR.sup.11, NHC(.dbd.O)NHR.sup.11, NHR.sup.11, R.sup.11 and a bond to C.sub.h ;R.sup.10 is independently selected at each occurrence from the group: a bond to C.sub.h, COOR.sup.11, C(.dbd.O)NHR.sup.11, NHC(.dbd.O)R.sup.11, OH, NHR.sup.11, SO.sub.3 H, PO.sub.3 H, --OPO.sub.3 H.sub.2, --OSO.sub.3 H, aryl substituted with 0-3 R.sup.11, C.sub.1-5 alkyl substituted with 0-1 R.sup.12, C.sub.1-5 alkoxy substituted with 0-1 R.sup.12, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.11 ;R.sup.11 is independently selected at each occurrence from the group: H, alkyl substituted with 0-1 R.sup.12, aryl substituted with 0-1 R.sup.12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R.sup.12, C.sub.3-10 cycloalkyl substituted with 0-1 R.sup.12, polyalkylene glycol substituted with 0-1 R.sup.12, carbohydrate substituted with 0-1 R.sup.12, cyclodextrin substituted with 0-1 R.sup.12, amino acid substituted with 0-1 R.sup.12, polycarboxyalkyl substituted with 0-1 R.sup.12, polyazaalkyl substituted with 0-1 R.sup.12, peptide substituted with 0-1 R.sup.12, wherein the peptide is comprised of 2-10 amino acids, 3,6-O-disulfo-B-D-galactopyranosyl, bis(phosphonomethyl)glycine, and a bond to C.sub.h ;R.sup.12 is a bond to C.sub.h ;k is selected from 0, 1, and 2;h is selected from 0, 1, and 2;h' is selected from 0, 1, 2, 3, 4, and 5;h"" is selected from 0, 1, 2, 3, 4, and 5;h""' is selected from 0, 1, 2, 3, 4, and 5;g is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;g' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;g"" is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;g""' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;g"""" is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;s is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;s' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;s"" is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;t is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;t' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;C.sub.h is a metal bonding unit having a formula selected from the group: ##STR88##A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, A.sup.7, and A.sup.8 are independently selected at each occurrence from the group: NR.sup.13, NR.sup.13 R.sup.14, S, SH, S(Pg), O, OH, PR.sup.13, PR.sup.13 R.sup.14, P(O)R.sup.15 R.sup.16, and a bond to L.sub.n ;E is a bond, CH, or a spacer group independently selected at each occurrence from the group: C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, C.sub.3-10 cycloalkyl substituted with 0-3 R.sup.17, heterocyclo-C.sub.1-10 alkyl substituted with 0-3 R.sup.17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O, C.sub.6-10 aryl--C.sub.1-10 alkyl substituted with 0-3 R.sup.17, C.sub.1-10 alkyl-C.sub.6-10 aryl-substituted with 0-3 R.sup.17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17 ;R.sup.13 and R.sup.14 are each independently selected from the group: a bond to L.sub.n, hydrogen, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, C.sub.1-10 cycloalkyl substituted with 0-3 R.sup.17, heterocyclo-C.sub.1-10 alkyl substituted with 0-3 R.sup.17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O, C.sub.6-10 aryl-C.sub.1-10 alkyl substituted with 0-3 R.sup.17, C.sub.1-10 alkyl-C.sub.6-10 aryl-substituted with 0-3 R.sup.17, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17, and an electron, provided that when one of R.sup.13 or R.sup.14 is an electron, then the other is also an electron; alternatively, R.sup.13 and R.sup.14 combine to form .dbd.C(R.sup.20)(R.sup.21);R.sup.15 and R.sup.16 are each independently selected from the group: a bond to L.sub.n, --OH, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.17, aryl substituted with 0-3 R.sup.17, C.sub.3-10 cycloalkyl substituted with 0-3 R.sup.17, heterocyclo-C.sub.1-10 alkyl substituted with 0-3 R.sup.17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O, C.sub.6-10 aryl-C.sub.1-10 alkyl substituted with 0-3 R.sup.17, C.sub.1-10 alkyl-C.sub.6-10 aryl-substituted with 0-3 R.sup.17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.17 ;R.sup.17 is independently selected at each occurrence from the group: a bond to L.sub.n, .dbd.O, F, Cl, Br, I, --CF.sub.3, --CN, --CO.sub.2 R.sup.18, --C(.dbd.O)R.sup.18, --C(.dbd.O)N(R.sup.18).sub.2, --CHO, --CH.sub.2 OR.sup.18, --OC(.dbd.O)R.sup.18, --OC(.dbd.O)OR.sup.18a, --OR.sup.18, --OC(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 C(.dbd.O)R.sup.18, --NR.sup.19 C(.dbd.O)OR.sup.18a, --NR.sup.19 C(.dbd.O)N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 N(R.sup.18).sub.2, --NR.sup.19 SO.sub.2 R.sup.18a, --SO.sub.3 H, --SO.sub.2 R.sup.18a, --SR.sup.18, --S(.dbd.O)R.sup.18a, --SO.sub.2 N(R.sup.18).sub.2, --N(R.sup.18).sub.2, --NHC(.dbd.S)NHR.sup.18, .dbd.NOR.sup.18, NO.sub.2, --C(.dbd.O)NHOR.sup.18, --C(.dbd.O)NHNR.sup.18 R.sup.18a, --OCH.sub.2 CO.sub.2 H, 2-(1-morpholino)ethoxy, C.sub.1 -C.sub.5 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 cycloalkylmethyl, C.sub.2 -C.sub.6 alkoxyalkyl, aryl substituted with 0-2 R.sup.18, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O;R.sup.18, R.sup.18a, and R.sup.19 are independently selected at each occurrence from the group: a bond to L.sub.n, H, C.sub.1 -C.sub.6 alkyl, phenyl, benzyl, C.sub.1 -C.sub.6 alkoxy, halide, nitro, cyano, and trifluoromethyl;Pg is a thiol protecting group;R.sup.20 and R.sup.21 are independently selected from the group: H, C.sub.1 -C.sub.10 alkyl, --CN, --CO.sub.2 R.sup.25, --C(.dbd.O)R.sup.25, --C(.dbd.O)N(R.sup.25).sub.2, C.sub.2 -C.sub.10 1-alkene substituted with 0-3 R.sup.23, C.sub.2 -C.sub.10 1-alkyne substituted with 0-3 R.sup.23, aryl substituted with 0-3 R.sup.23, unsaturated 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.23, and unsaturated C.sub.3-10 carbocycle substituted with 0-3 R.sup.23 ; alternatively, R.sup.20 and R.sup.21, taken together with the divalent carbon radical to which they are attached form: ##STR89##R.sup.22 and R.sup.23 are independently selected from the group: H, R.sup.24, C.sub.1 -C.sub.10 alkyl substituted with 0-3 R.sup.24, C.sub.2 -C.sub.10 alkenyl substituted with 0-3 R.sup.24, C.sub.2 -C.sub.10 alkynyl substituted with 0-3 R.sup.24, aryl substituted with 0-3 R.sup.24, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R.sup.24, and C.sub.3-10 carbocycle substituted with 0-3 R.sup.24 ; alternatively, R.sup.22, R.sup.23 taken together form a fused aromatic or a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O;a and b indicate the positions of optional double bonds and n is 0 or 1;R.sup.24 is independently selected at each occurrence from the group: .dbd.O, F, Cl, Br, I, --CF.sub.3, --CN, --CO.sub.2 R.sup.25, --C(.dbd.O)R.sup.25, --C(.dbd.O)N(R.sup.25).sub.2, --N(R.sup.25)3+, --CH.sub.2 OR.sup.25, --OC(.dbd.O)R.sup.25, --OC(.dbd.O)OR.sup.25a, --OR.sup.25, --OC(.dbd.O)N(R.sup.25).sub.2, --NR.sup.26 C(.dbd.O)R.sup.25, NR.sup.26 C(.dbd.O)OR.sup.25a, --NR.sup.26 C(.dbd.O)N(R.sup.25).sub.2, --NR.sup.26 SO.sub.2 N(R.sup.25).sub.2, --NR.sup.26 SO.sub.2 R.sup.25a, --SO.sub.3 H, --SO.sub.2 R.sup.25a, --SR.sup.25, S(.dbd.O)R.sup.25a, --SO.sub.2 N(R.sup.25).sub.2, --N(R.sup.25).sub.2, .dbd.NOR.sup.25, --C(.dbd.O)NHOR.sup.25, --OCH.sub.2 CO.sub.2 H, and 2-(1-morpholino)ethoxy; and,R.sup.25, R.sup.25a, and R.sup.26 are each independently selected at each occurrence from the group: hydrogen and C.sub.1 -C.sub.6.