Claims for Patent: 7,282,522

Summary for Patent: 7,282,522

Title:	Hydroxamic acid derivatives and the method for preparing thereof
Abstract:	The present invention provides hydroxamic acid derivatives which have anti-aging efficacy and a method for preparation thereof. It is further provided skin-care external compositions for preventing skin aging, containing the hydroxamic acid derivatives represented by the formula (I) as an active ingredient.
Inventor(s):	Rho; Ho-Sik (Suwon-si, KR), Baek; Heung-Soo (Seoul, KR), Kim; Su-Jong (Yongin-si, KR), Kim; Su-Nam (Suwon-si, KR), Chae; Byung-Geun (Seoul, KR), Lee; Byoung-Seok (Suwon-si, KR), Kim; Bae-Hwan (Suwon-si, KR), Choi; Gyu-Ho (Yongin-si, KR), Son; Eui-Dong (Suwon-si, KR), Lee; Hae-Kwang (Yongin-si, KR), Lee; Hye-Won (Yongin-si, KR), Cho; Jun-Cheol (Suwon-si, KR), Kim; Duck-Hee (Seoul, KR), Chang; Ih-Seop (Yongin-si, KR), Lee; Ok-Sub (Yongin-si, KR)
Assignee:	Amorepacific Corporation (Seoul, KR)
Application Number:	10/595,124
Patent Claims:	1. A hydroxamic acid derivative represented by the following formula(I): ##STR00007## wherein, R.sub.1is ##STR00008## wherein, R.sub.5 and R.sub.6 each independently represents a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms or a cyclic alkyl group having from 3 to 6 carbon atoms; R.sub.2 is CONH, NHCO, CONR.sub.7 or NR.sub.7CO, herein, R.sub.7 represents an alkyl group having from 1 to 10 carbon atoms; R.sub.3 is --(CH.sub.2).sub.n--, herein, n=0 or 1; and R.sub.4 is a hydrogen atom or an alkyl group having from 1 to 10 carbon atoms; on the proviso that compounds in which R.sub.1 is ##STR00009## wherein R.sub.5 and R.sub.6 each are H, R.sub.2 is CONH, and n=0, and compounds in which R.sub.1 is ##STR00010## wherein R.sub.5 is H and R.sub.6 is CH.sub.3, R.sub.2 is CONH and n=0 or 1 are excluded. 2. The hydroxamic acid derivative according to claim 1, which is selected from the group consisting of N-[4-(N-hydroxycarbamoyl)phenyl]benzamide, N-[4-(N-hydroxycarbamoyl)phenyl][3 -methyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl][4-ethyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl][4-propyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl][4-isopropylphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl][4-butyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl][4-tert-butyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl][3,4-dimethylphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]adamantyl carboxyamide, adamantyl- N-[4-(N-hydroxy-N-methylcarbamoyl)phenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-benzamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[4-methyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[3 -methyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[4-ethyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[4-propyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[4-isopropylphenyl]carboxyamide- , N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[4-butylphenyl]carboxyamide, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[4-tert-butylphenyl]carboxyamid- e, N-[4-(N-hydroxycarbamoyl)phenyl]-N-methyl-[3,4-dimethylphenyl]carboxyam- ide, N-[4-(N-hydroxycarbamoyl)phenyl]adamantyl-N-methylcarboxyamide, adamantyl-N-[4-(N-hydroxy-N-methylcarbamoyl)phenyl]-N-methylcarboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl]beuzamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][3 -methyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][4-ethyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][4-propyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][4-isopropyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][4-butyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][4-tert-butyiphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl][3,4-dimethylphenyl]carboxyamide, N-[4-(N-hydroxycarbamoylmethyl)phenyl]adamantyl carboxyamide, 2-[4-(adamantylcarbonylamino)phenyl]-N-hydroxy-N-methylacetamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[4-methyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[3-methyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[4-ethyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[4-propylphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[4-isopropylphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[4-butyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[4-tert-butyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-[3,4-dimethylphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-adamantyl carboxyamide, N-adamantyl [4-(N-hydroxy-N-methylcarbamoyl)phenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-benzamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[4-methyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[3-methyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[4-ethyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[4-propyiphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[4-isopropyiphenyl]carboxyamide- , [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[4-butylphenyl]carboxyamide, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[4-tert-butylphenyl]carboxyamid- e, [4-(N-hydroxycarbamoyl)phenyl]-N-methyl-N-[3,4-dimethylphenyl]carboxyam- ide, [4-(N-hydroxycarbamoyl)phenyl]-N-adamantyl-N-methylcarboxyamide, and N-adamantyl [4-(N-hydroxy-N-methylcarbamoyl)phenyl]-N-methylcarboxyamide. 3. A method for preparing a hydroxamic acid represented by the following formula (I): ##STR00011## wherein R.sub.1 is ##STR00012## wherein, R.sub.5 and R.sub.6 each independently represents a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms or a cyclic alkyl group having from 3 to 6 carbon atoms: R.sub.2 is CONH, NHCO. CONR.sub.7 or NR.sub.7CO, herein, R.sub.7 represents an alkyl group having from 1 to 10 carbon atoms: R.sub.3is --(CH.sub.2).sub.n--, herein, n=0 or1: and R.sub.4 is a hydrogen atom or an alkyl group having from 1 to 10 carbon atoms: on the proviso that compounds in which R.sub.1 is ##STR00013## wherein R.sub.5 and R.sub.6 each are H, R.sub.2 is CONH, and n=0, and compounds in which R.sub.1 is ##STR00014## wherein R.sub.5 is H and R.sub.6 is CH.sub.3, R.sub.2 is CONH and n=0 or 1 are excluded, which comprises the steps of: (a) reacting benzoic acid or adamantanecarboxylic acid with methyl 4-aminobenzoate or 4-aminophenylacetic acid methylester, to produce a benzamide compound; (b) optionally, substituting an amide bond of the benzamide formed in step (a) with an alkyl group, to produce an akyl-substituted benzamide compound; (c) hydrolyzing a methylester of the benzamide formed in step (a) or the alkyl-substituted benzamide compounds formed in step (b), to produce an acid; and (d) reacting said acid with hydroxylamine hydrochloride or N-methyl hydroxylamine hydrochloride, to produce a hydroxamic acid derivative. 4. A method for preparing a hydroxamic acid derivative represented by the following formula (I): ##STR00015## wherein, R.sub.1 is ##STR00016## wherein, R.sub.5 and R.sub.6 each independently represents a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms or a cyclic alkyl group having from 3 to 6 carbon atoms; R.sub.2 is CONH, NHCO, CONR.sub.7 or NR.sub.7CO, herein, R.sub.7 represents an alkyl group having from 1 to 10 carbon atoms; R.sub.3 is --(CH.sub.2).sub.n--, herein, n=0 or 1: and R.sub.4 is a hydrogen atom or an alkyl group having from 1 to 10 carbon atoms: on the proviso that compounds in which R.sub.1 is ##STR00017## wherein R.sub.5 and R.sub.6 each are H, R.sub.2 is CONH, and n=0, and compounds in which R.sub.1 is ##STR00018## wherein R.sub.5 is H and R.sub.6 is CH.sub.3, R.sub.2 is CONH and n=0 or 1 are excluded which comprises the steps of: (a) reacting aniline or adamantamine with monomethylterephthalate, to produce a benzamide compound; (b) optionally, substituting an amide bond of the benzamide formed in step (a) with an alkyl group, to produce an akyl-substituted benzamide compound (c) hydrolyzing a methylester of the benzamide formed in step (a) or the alkyl-substituted benzamide compounds formed in step (b), to produce an acid; and (d) reacting said acid with hydroxylamine hydrochloride or N-methyl hydroxylamine hydrochloride, to produce a hydroxamic acid derivative. 5. A skin-care external composition for preventing skin aging, containing the hydroxamic acid derivative according to claim 1 as an active ingredient. 6. A collagenase expression-inhibiting agent containing the hydroxamic acid derivative according to claim 1 as an active ingredient. 7. An elastase expression-inhibiting agent containing the hydroxamic acid derivative according to claim 1 as an active ingredient.

Details for Patent 7,282,522

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2023-08-26