Claims for Patent: 6,441,021

Summary for Patent: 6,441,021

Title:	Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same
Abstract:	Compounds having a metalloproteinase inhibitory activity, represented by the formula (I), its optically active isomers, their pharmaceutically acceptable salts, or hydrates thereof ##STR1##
Inventor(s):	Wantanabe; Fumihiko (Nara, JP), Tsuzuki; Hiroshige (Kyoto, JP), Ohtani; Mitsuaki (Nara, JP)
Assignee:	Shionogi & Co., Ltd. (Osaka, JP)
Application Number:	09/710,904
Patent Claims:	1. A composition for inhibiting metalloproteinase which comprises a compound of formula I: ##STR647## wherein R.sup.1 is optionally substituted heteroarylalkyl; R.sup.2 is hydrogen atom or optionally substituted lower alkyl; R.sup.3 is optionally substituted arylene; R.sup.4 is a bond, --(CH.sub.2)m--, --CH.dbd.CH-- or --C.ident.C--; R.sup.5 is optionally substituted aryl; Y is --NHOH or --OH; and m is 1 or 2; provided R.sup.2 is hydrogen atom when Y is --NHOH, with the proviso that R.sup.5 and R.sup.3 together do not form a biphenyl group, and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 2. A composition for inhibiting metalloproteinase which comprises a compound of formula I: ##STR648## wherein R.sup.1 is optionally substituted heteroarylalkyl; R.sup.2 is hydrogen atom or optionally substituted lower alkyl; R.sup.3 is optionally substituted arylene; R.sup.4 is a bond, --(CH.sub.2)m--, --CH.dbd.CH-- or --C.ident.C--; R.sup.5 is optionally substituted aryl; Y is --NHOH or --OH; and m is 1 or 2; provided R.sup.2 is hydrogen atom when Y is --NHOH, R.sup.5 is aryl substituted by lower alkyl or optionally substituted aryl when R.sup.4 is a bond, with the proviso that R.sup.5 and R.sup.3 together do not form a biphenyl group, and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 3. A compound of the formula I: ##STR649## wherein R.sup.1 is optionally substituted heteroarylalkyl; R.sup.2 is hydrogen atom or optionally substituted lower alkyl; R.sup.3 is optionally substituted arylene; R.sup.4 is a bond, --(CH.sub.2)m--, --CH.dbd.CH-- or --C.ident.C--; R.sup.5 is optionally substituted aryl; Y is --NHOH or --OH; and m is 1 or 2; provided R.sup.2 is hydrogen atom when Y is --NHOH, R.sup.5 is aryl substituted with lower alkyl or optionally substituted aryl when R.sup.4 is a bond, and R.sup.3 is not 1,2-phenylene, and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 4. A compound of formula II: ##STR650## wherein R.sup.6 is --CH.dbd.CH-- or --C.ident.C--; R.sup.7 is optionally substituted aryl; R.sup.8 and R.sup.9 are each independently hydrogen atom, lower alkoxy, or nitro; R.sup.1 is optionally substituted heteroarylalkyl;[,] R.sup.2 is hydrogen atom or optionally substituted lower alkyl; Y is--NHOH or --OH; and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 5. A compound of formula III: ##STR651## wherein R.sup.10 is --(CH.sub.2)m--; m is 1 or 2; R.sup.1 is optionally substituted heteroarylalkyl; R.sup.2 is hydrogen atom or optionally substituted lower alkyl; R.sup.7 is optionally substituted aryl; R.sup.8 and R.sup.9 are each independently hydrogen atom, lower alkoxy, or nitro; Y is--NHOH or --OH; and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 6. A compound of formula V: ##STR652## wherein R.sup.12 is --CH.dbd.CH-- or --C.ident.C--; R.sup.1 is optionally substituted heteroarylalkyl; R.sup.1 is hydrogen atom or optionally substituted lower alkyl; R.sup.7 is optionally substituted aryl; R.sup.8 and R.sup.9 are each independently hydrogen atom, lower alkoxy or nitro; and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 7. A compound of formula X: ##STR653## wherein R.sup.12 is --CH.dbd.CH-- or --C.ident.C--; R.sup.1 is optionally substituted heteroarylalkyl; R.sup.7 is optionally substituted aryl; R.sup.8 and R.sup.9 are each independently hydrogen atom, lower alkoxy or nitro; and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 8. The compound of claim 3, wherein R.sup.1 is (indole-3-yl)methyl. 9. The compound of claim 3, wherein R.sup.5 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkoxy, alkylthio, and alkyl. 10. The compound of claim 3, wherein a configuration of asymmetric carbon atoms bonding with R.sup.1 is R configuration. 11. A pharmaceutical composition comprising a compound of claim 3. 12. A pharmaceutical composition comprising a compound of claim 8. 13. A pharmaceutical composition comprising a compound of claim 9. 14. A pharmaceutical composition comprising a compound of claim 10. 15. A method of inhibiting the activity of a metalloproteinase, comprising administering to a subject in need thereof an effective amount of a compound of formula I: ##STR654## wherein R.sup.1 is optionally substituted heteroarylalkyl; R.sup.1 is hydrogen atom or optionally substituted lower alkyl; R.sup.3 is optionally substituted arylene; R.sup.4 is a bond, --(CH.sub.2)m--, --CH.dbd.CH-- or --C.ident.C--; R.sup.5 is optionally substituted aryl; Y is --NHOH or --OH; and m is 1 or 2; provided R.sup.2 is hydrogen atom when Y is --NHOH, with the proviso that R.sup.5 and R.sup.3 together do not form a biphenyl group, and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 16. A method of inhibiting the activity of a type-IV collagenase, comprising administering to a subject in need thereof an effective amount of a compound of formula I: ##STR655## wherein R.sup.1 is or optionally substituted heteroarylalkyl; R.sup.2 is hydrogen atom or optionally substituted lower alkyl; R.sup.3 is optionally substituted arylene; R.sup.4 is a bond, --(CH.sub.2)m--, --CH.dbd.CH-- or --C.ident.C--; R.sup.5 is optionally substituted aryl; Y is --NHOH or --OH; and m is 1 or 2; provided R.sup.2 is hydrogen atom when Y is --NHOH, with the proviso that R.sup.5 and R.sup.3 together do not form a biphenyl group, and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof. 17. The compound of claim 4, wherein R.sup.7 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkoxy, alkylthio, and alkyl. 18. The compound according to claim 3, wherein R.sup.1 is optionally substituted heteroarylalkyl; R.sup.2 is hydrogen or optionally substituted lower alkyl; R.sup.3 is optionally substituted arylene; R.sup.4 is --CH.sub.2)m--, --CH.dbd.CH-- or --C.ident.C--; R.sup.5 is optionally substituted aryl; and m is 1 or 2, its optically active substance, a pharmaceutically acceptable salt thereof, or a hydrate thereof.

Details for Patent 6,441,021

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2016-01-23