Claims for Patent: 7,745,460

Summary for Patent: 7,745,460

Title:	Modulators of cellular adhesion
Abstract:	The present invention provides compounds having formula (I): ##STR00001## and pharmaceutically acceptable derivatives thereof, wherein R.sub.1-R.sub.4, n, p, A, B, D, E, L and AR.sup.1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).
Inventor(s):	Shen; Wang (San Mateo, CA), Barr; Kenneth (San Francisco, CA), Oslob; Johan D. (Sunnyvale, CA), Zhong; Min (Foster City, CA)
Assignee:	SARcode Corporation (San Francisco, CA)
Application Number:	11/978,388
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,745,460
Patent Claims:	1. A compound of the structure (I): ##STR00218## or pharmaceutically acceptable salts thereof; R.sup.1 and R.sup.2 are each independently hydrogen, --(CH.sub.2).sub.mOH, --(CH2).sub.maryl, --(CH2).sub.mheteroaryl, wherein m is 0-6, --CH(R.sup.1A)(OR.sup.1B), --CH(R.sup.1A)(NHR.sup.1B), U-T-Q, or an aliphatic, alicyclic, heteroaliphatic or heteroalicyclic moiety optionally substituted with U-T-Q, wherein U is absent, --O--, --S(O).sub.0-2--, --SO.sub.2N(R.sup.1A), --N(R.sup.1A)--, --N(R.sup.1A)C(.dbd.O)--, --N(R.sup.1A)C(.dbd.O)--O--, --N(R.sup.1A)C(.dbd.O)--N(R.sup.1B)--, --N(R.sup.1A)--SO.sub.2--, --C(.dbd.O)--, --C(.dbd.O)--O--, --O--C(.dbd.O)--, aryl, heteroaryl, alkylaryl, alkylheteroaryl, --C(.dbd.O)--N(R.sup.1A)--, --OC(.dbd.O)N(R.sup.1A)--, --C(.dbd.N--R.sup.1E)--, --C(.dbd.N--R.sup.1E)--O--, --C(.dbd.N--R.sup.1E)--N(R.sup.1A)--, --O--C(.dbd.N--R.sup.1E)--N(R.sup.1A)--, --N(R.sup.1A)C(.dbd.N--R.sup.1E)--, --N(R.sup.1A)C(.dbd.N--R.sup.1E)--O--, --N(R.sup.1A)C(.dbd.N--R.sup.1E)--N(R.sup.1B)--, --P(.dbd.O)(OR.sup.1A)--O--, or --P(.dbd.O)(R.sup.1A)--O--; T is absent, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; and Q is hydrogen, halogen, cyano, isocyanate, --OR.sup.1B; --SR.sup.1B; --N(R.sup.1B).sub.2, --NHC(.dbd.O)OR.sup.1B, --NHC(.dbd.O)N(R.sup.1B).sub.2, --NHC(.dbd.O)R.sup.1B, --NHSO.sub.2R.sup.1B, NHSO.sub.2N(R.sup.1B).sub.2, --NHSO.sub.2NHC(.dbd.O)OR.sup.1B, --NHC(.dbd.O)NHSO.sub.2R.sup.1B, --C(.dbd.O)NHC(.dbd.O)OR.sup.1B, C(.dbd.O)NHC(.dbd.O)R.sup.1B, --C(.dbd.O)NHC(.dbd.O)N(R.sup.1B).sub.2, --C(.dbd.O)NHSO.sub.2R.sup.1B, --C(.dbd.O)NHSO.sub.2N(R.sup.1B).sub.2, C(.dbd.S)N(R.sup.1B).sub.2, --SO.sub.2R.sup.1B, --SO.sub.2OR.sup.1B, --SO.sub.2N(R.sup.1B).sub.2, --SO.sub.2--NHC(.dbd.O)OR.sup.1B, --OC(.dbd.O)--N(R.sup.1B).sub.2, --OC(.dbd.O)R.sup.1B, --OC(.dbd.O)NHC(.dbd.O)R.sup.1B, --OC(.dbd.O)NHSO.sub.2R.sup.1B, --OSO.sub.2R.sup.1B, or an aliphatic heteroaliphatic, aryl or heteroaryl moiety, or wherein R.sup.1 and R.sup.2 taken together are an alicyclic or heterocyclic moiety; wherein each occurrence of R.sup.1A and R.sup.1B is independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, --C(.dbd.O)R.sup.1C, or --C(.dbd.O)NR.sup.1CR.sup.1D; wherein each occurrence of R.sup.1C and R.sup.1D is independently hydrogen, hydroxyl, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; and R.sup.1E is hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, --CN, --OR.sup.1C, --NR.sup.1CR.sup.1D or --SO2R.sup.1C; R.sup.3 is --C(.dbd.O)OR.sup.3A, --C(.dbd.O)H, --CH.sub.2OR.sup.3A, --CH.sub.2OC(.dbd.O)-alkyl, --C(.dbd.O)NH(R.sup.3A), or --CH.sub.2X.sup.0; wherein each occurrence of R.sup.3A is independently hydrogen, a protecting group, an aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl or heteroalkylheteroaryl moiety, or pharmaceutically acceptable salt or ester, or R.sup.3A, taken together with R.sup.1 and R.sup.2, forms a heterocyclic moiety; wherein X.sup.0 is a halogen selected from F, Br or I; R.sup.4 for each occurrence, is independently hydrogen, halogen, --CN, --NO.sub.2, an aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or is GR.sup.G1 wherein G is --O--, --S--, NR.sup.G2--, --CO--, --SO--, --SO.sub.2--, C(.dbd.O)O--, --C(.dbd.O)NR.sup.G2--, C(.dbd.O)--, --NR.sup.G2C(.dbd.O)-- or --SO.sub.2NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; n is an integer from 0-4; AR.sup.1 is a monocyclic or polycyclic aryl, heteroaryl, alkylaryl, alkylheteroaryl, alicyclic or heterocyclic moiety; A, B, D and E are connected by single bonds; wherein D is N; each occurrence of A, B, and E is CHR.sup.i wherein each occurrence of R.sup.i is independently hydrogen, halogen, --CN, --NO2, an aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or is -GR.sup.G1 wherein G is --O--, --S--, --NR.sup.G2, --CO--, --SO--, --C(.dbd.O)O--, --C(.dbd.O)NR.sup.G2--, --OC(.dbd.O)--, --NR.sup.G2C(.dbd.O)-- or --SO.sub.2NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heteroalicyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or any two adjacent occurrences of taken together, represent an alicyclic, heteroalicyclic, aryl, or heteroaryl moiety; p is an integer from 0-4; and, L is a substituted or unsubstituted C.sub.1-6 alkylidene or C.sub.2-6 alkenylidine chain wherein up to two non-adjacent methylene units are independently optionally replaced by --C(.dbd.O). 2. The compound of claim 1, wherein R.sup.3 is carboxyl or protected carboxyl, wherein R.sup.3 is C(.dbd.O)R.sup.3A, wherein R.sup.3A is hydroxy, alkoxy, cycloalkoxy, aralkoxy, arcycloalkoxy, aryloxy, alkylcarbonyloxyalkyloxy, alkoxycarbonyloxyalkyloxy, alkoxycarbonylalkyloxy, cycloalkylcarbonyloxyalkyloxy, cycloalkoxycarbonyloxyalkyloxy, cycloalkoxycarbonylalkyloxy, arylcarbonyloxyalkyloxy, aryloxycarbonyloxyalkyloxy, alkoxyalkylcarbonyloxyalkyloxy, or one of the structures: ##STR00219## 3. The compound of claim 1 wherein the compound has the structure: ##STR00220## wherein R.sup.4A and R.sup.4B are independently a halogen selected from F, Cl, Br or I; and R.sup.B1, R.sup.B2 and R.sup.E are independently hydrogen or substituted or unsubstituted lower alkyl. 4. The compound of claim 1, wherein --C(.dbd.O)NHC(R.sup.1)(R.sup.2)R.sup.3 is a moiety having the following structure: ##STR00221## wherein Ar.sub.2 is a cycloalkyl, heterocyclic, aryl or heteroaryl moiety; and R.sup.S is hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, or is -G.sup.0R.sup.G1 wherein G.sup.0 is --O--, --S-- or --NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic or heteroaromatic moiety. 5. The compound of claim 1, wherein --C(.dbd.O)NHC(R.sup.1)(R.sup.2)R.sup.3 is a moiety having the following structure: ##STR00222## wherein R.sup.1A is Ar.sub.2, SR.sup.1B or NR.sup.1BR.sup.1C; or an alkyl or heteroalkyl moiety; and Ar.sub.2 is a cycloalkyl, heterocyclic, aryl or heteroaryl moiety; wherein R.sup.1B and R.sup.1C are independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, or R.sup.1B and R.sup.1C, taken together with the nitrogen atom to which they are attached, form a heterocylic or heteroaryl moiety. 6. The compound of claim 1, wherein --C(.dbd.O)NHC(R.sup.1)(R.sup.2)R.sup.3 is a moiety having the following structure: ##STR00223## wherein Ar.sub.2 is a cycloalkyl, heterocyclic, aryl or heteroaryl moiety; and R.sup.2A is hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, --C(.dbd.O)R.sup.2B or --SO.sub.2R.sup.2B, wherein R.sup.2B is alkyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl or heteroaryl; or R.sup.2A, taken together with a substituent on Ar.sub.2, forms a substituted or unsubstituted heterocyclic or heteroaryl moiety. 7. The compound of claim 4, 5, or 6, wherein R.sup.3A is independently hydrogen, lower alkyl, phenyl or benzyl. 8. The compound of claim 4 or 6 wherein Ar.sub.2 is one of the following structures: ##STR00224## wherein s is an integer from 0-2; and each occurrence of R.sup.P1 is independently hydrogen, halogen, CN, isocyanate, NO.sub.2, --OR.sup.G1, --SR.sup.G1, --NR.sup.G1R.sup.G2--, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; each occurrence of Y is independently a bond or O; each occurrence of R.sup.P5 is independently lower alkyl, or when Y is OR.sup.P5 may also be hydrogen; each occurrence of R.sup.P2 is independently hydrogen, alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl, or heteroalkylheteroaryl moiety or a nitrogen protecting group; R.sup.P3 is lower alkyl or --N(R.sup.P2).sub.2; and R.sup.G1 and R.sup.G2 are independently hydrogen, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety. 9. The compound of claim 8 wherein Ar.sub.2 is one of the following structures: ##STR00225## 10. The compound of claim 4 or 6 wherein Ar.sub.2 is one of the following structures: ##STR00226## wherein R.sup.P3 is lower alkyl and R.sup.G1 is hydrogen or lower alkyl. 11. The compound of claim 5 wherein R.sup.1A is --NH.sub.2 or a moiety having the structure: ##STR00227## wherein R.sup.P1 is independently hydrogen, hydroxyl, lower alkyl or lower heteroalkyl; and each occurrence of R.sup.P2 is independently hydrogen or lower alkyl. 12. The compound of claim 11 wherein R.sup.1A is --NH.sub.2 or a moiety having the structure: ##STR00228## wherein R.sup.P1 is hydrogen or lower alkyl. 13. The compound of claim 5 wherein R.sup.1A is a moiety having one of the structures: ##STR00229## wherein s is an integer between 0 and 2; and each occurrence of R.sup.P1 is independently lower alkyl or is -GR.sup.G1 wherein G is --O-- or --NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; and each occurrence of R.sup.P2 is independently hydrogen, lower alkyl, aryl or heteroaryl. 14. The compound of claim 13 wherein R.sup.1A is a moiety having one of the structures: ##STR00230## wherein G is --O-- or --NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen or lower alkyl. 15. The compound of claim 6, wherein --NH(R.sup.2A)Ar.sub.2 is one of the following structures: ##STR00231## wherein X.sub.1 is N or CR.sup.P1; s is an integer from 0-5; and each occurrence of R.sup.P1 is independently hydrogen, halogen, CN, NO.sub.2, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or is --R.sup.G1 wherein G is --O--, --S--, --NR.sup.G2--, --CO--, --SO--, --SO.sub.2--, --C(.dbd.O)O--, --C(.dbd.O)NR.sup.G2--, --OC(.dbd.O)--, --NR.sup.G2C(.dbd.O)-- or --SO.sub.2NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; and R.sup.P3 is alkyl, heteroalkyl, aryl or heteroaryl. 16. The compound of claim 15, wherein --NH(R.sup.2A)Ar.sub.2 has the following structure: ##STR00232## wherein R.sup.P1 is hydrogen, halogen or lower alkyl. 17. The compound of any one of claims 4, 5, and 6, wherein Ar.sub.2 is one of the following structures: ##STR00233## wherein each occurrence of s is an integer from 0-6; X.sub.1, is CHR.sup.P1; X.sub.2 and X.sub.3 are independently CHR.sup.P1, NR.sup.P2, CHSO.sub.2R.sup.P3, or NSO.sub.2R.sup.P3; X.sub.5 is O, S or NR.sup.P2; each occurrence of R.sup.P1 is independently hydrogen, halogen, CN, isocyanate, NO.sub.2, --P(.dbd.O)(YR.sup.P5).sub.2, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or is -GR.sup.G1 wherein G is --O--, --S--, --NR.sup.G2--, --CO--, --SO--, --SO.sub.2--, --C(.dbd.O)O--, --C(.dbd.O)NR.sup.G2--, --OC(.dbd.O)--, --NR.sup.G2C(.dbd.O)-- or --SO.sub.2NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; each occurrence of Y is independently a bond or O; each occurrence of R.sup.P5 is independently alkyl, heteroalkyl, aryl or heteroaryl, or when Y is OR.sup.P5 may also be hydrogen; each occurrence of R.sup.P2 is independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl, or heteroalkylheteroaryl moiety or a nitrogen protecting group; wherein any two adjacent occurrences of R.sup.P1 and R.sup.P2, taken together, may form a cycloalkyl, heterocyclic, aryl or heteroaryl moiety; and each occurrence of R.sup.P3 is independently alkyl, aryl, heteroaryl or --N(R.sup.P2).sub.2. 18. The compound of claim 17 wherein Ar.sub.2 is one of the following structures: ##STR00234## wherein X.sub.1 is N or CR.sup.P1; s is an integer from 0-6; each occurrence of R.sup.P1 is independently hydrogen, halogen, CN, NO.sub.2, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or is --R.sup.G1 wherein G is --O--, --S--, --NR.sup.G2--, --CO--, --SO--, --SO.sub.2--, --C(.dbd.O)O--, --C(.dbd.O)NR.sup.G2--, --OC(.dbd.O)--, --NR.sup.G2C(.dbd.O)-- or --SO.sub.2NR.sup.G2--, and R.sup.G1 and R.sup.G2 are independently hydrogen, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety; and R.sup.P3 is independently lower alkyl or aryl. 19. The compound of claim 1, wherein L is a moiety having the structure: ##STR00235## 20. The compound of claim 1, wherein AR.sup.1 is one of the following structures: ##STR00236## wherein each occurrence of r is an integer from 0-6; X.sub.1, X.sub.2, X.sub.3 and X.sub.4 are independently N or CR.sup.Q1; X.sub.5 is O, S or NR.sup.Q2; AR.sup.3 is a heterocyclic, aryl or heteroaryl moiety; each occurrence of R.sup.Q1 is independently hydrogen, OR.sup.Q3, OCF.sub.3, SR.sup.Q3, halogen, CN, isocyanate, NO.sub.2, CF.sub.3, NR.sup.Q3QR.sup.Q4, --SO.sub.2R.sup.Q3, alkyl-NR.sup.Q3R.sup.Q4--, alkyl-C(.dbd.O)--NR.sup.Q3R.sup.Q4, alkyl-C(.dbd.O)R.sup.Q3, or an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl, or heteroalkylheteroaryl moiety, wherein each occurrence of R.sup.Q3 and R.sup.Q4 is independently hydrogen, a protecting group, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety; and R.sup.Q2 is hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl, or heteroalkylheteroaryl moiety or a nitrogen protecting group. 21. The compound of claim 20, wherein AR.sup.1 is one of the following structures: ##STR00237## wherein X.sup.0 is F or Cl; X.sub.2 is N or CR.sup.Q1; X.sub.5 is CH, O, S or NH; and R.sup.Q1 is hydrogen, methyl, --CF.sub.3, --OH, --OCH.sub.3, --OCF.sub.3 or halogen. 22. The compound of claim 21, wherein AR.sup.1 is one of the following structures: ##STR00238## 23. The compound of claim 22, wherein AR.sup.1 is one of the following structures: ##STR00239## 24. The compound of claim 1, wherein AR.sup.1-L- is one of the following structures: ##STR00240## 25. The compound of claim 8 wherein Ar.sub.2 is: ##STR00241## 26. The compound of claim 1 having the structure: ##STR00242## 27. The compound of claim 1 having the structure: ##STR00243## 28. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent, and optionally further comprising an additional therapeutic agent. 29. The pharmaceutical composition of claim 28, wherein the compound is present in an amount effective to modulate adhesion between intracellular adhesion molecules and the leukocyte integrin family of receptors. 30. The pharmaceutical composition of claim 28, wherein the intracellular adhesion molecules are selected from ICAM-1, ICAM-2 and ICAM-3. 31. The pharmaceutical composition of claim 28, wherein the compound is present in an amount effective to antagonize CD11/CD18 receptors associated with leukocytes. 32. The pharmaceutical composition of claim 28, wherein the compound is present in an amount effective to antagonize Mac-1 and/or LFA-1. 33. A method of treating an immune or inflammatory disorder in a subject mediated through the CD11/CD18 family of cellular adhesion molecules, the method comprising administering to a subject a therapeutically effective amount of a compound of claim 1, wherein the disorder is selected from psoriasis, inflammatory bowel disease, adult respiratory distress syndrome, dermatitis, meningitis, uveitis, eczema, asthma, poison ivy, poison oak, Sjorgen's syndrome, pulmonary fibrosis and rheumatoid arthritis. 34. The method of claim 33, wherein the CD11/CD18 family of cellular adhesion molecules is LFA-1. 35. A method of treating an immune or inflammatory disorder in a subject comprising administering to a subject in need thereof a compound of claim 1, wherein the disorder is selected from psoriasis, inflammatory bowel disease, adult respiratory distress syndrome, dermatitis, meningitis, uveitis, eczema, asthma, poison ivy, poison oak, Sjorgen's syndrome, pulmonary fibrosis and rheumatoid arthritis. 36. The compound of claim 1, wherein AR.sup.1 is: ##STR00244## wherein r is an integer from 0-6; each occurrence of R.sup.Q1 is independently hydrogen, OR.sup.Q3, OCF.sub.3, SR.sup.Q3, halogen, CN, isocyanate, NO.sub.2, CF.sub.3, NR.sup.Q3QR.sup.Q4, --SO.sub.2R.sup.Q3, alkyl-NR.sup.Q3R.sup.Q4--, alkyl-C(.dbd.O)--NR.sup.Q3R.sup.Q4, alkyl-C(.dbd.O)R.sup.Q3, or an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl, or heteroalkylheteroaryl moiety, wherein each occurrence of R.sup.Q3 and R.sup.Q4 is independently hydrogen, a protecting group, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety; L is a moiety having the structure: ##STR00245## --C(.dbd.O)NHC(R.sup.1)(R.sup.2)R.sup.3 is a moiety having the following structure: ##STR00246## wherein R.sup.S is hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, or is -G.sup.0R.sup.G1 wherein G.sup.0 is --O--, --S-- or --NR.sup.G2--; R.sup.G1 and R.sup.G2 are independently hydrogen, an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic or heteroaromatic moiety; R.sup.3A is hydrogen, a protecting group, a pharmaceutically acceptable salt or ester; Ar.sub.2 has the following structure: ##STR00247## wherein s is an integer from 0-6; each occurrence of R.sup.P1 is independently hydrogen, halogen, CN, isocyanate, NO.sub.2, --P(.dbd.O)(YR.sup.P5).sub.2, an alkyl, cycloalkyl, heteroalkyl, heterocyclic, aryl, heteroaryl, alkylaryl or alkylheteroaryl moiety, or is -GR.sup.G1 wherein G is --O--, --S--, --NR.sup.G2--, --CO--, --SO--, --SO.sub.2--, --C(.dbd.O)O--, --C(.dbd.O)NR.sup.G2--, --OC(.dbd.O)--, --NR.sup.G2C(.dbd.O)-- or --SO.sub.2NR.sup.G2--. 37. The compound of claim 36, wherein R.sup.S is hydrogen.