摘要:
A compound of the formula: ##STR1## in which R.sup.4 is acyl,R.sup.5 is lower alkyl,R.sup.6 is optionally substituted ar(lower)alkyl or optionally substituted heterocyclic-(lower)alkyl,R.sup.7 is lower alkyl or lower alkylthio(lower)alkyl,R.sup.8 is carboxy or protected carboxy,A is lower alkylene,Z is a group of the formula: ##STR2## wherein R.sup.1 is hydrogen, lower alkyl, common amino-protective group or optionally substituted ar(lower)alkyl,R.sup.2 is hydrogen, lower alkyl, optionally substituted ar(lower)alkyl, optionally substituted heterocyclic-(lower)alkyl, optionally substituted cyclo(lower)alkyl(lower)alkyl, common amino-protective group, amino(or protected amino)(lower)alkyl, optionally substituted heterocyclic-carbonyl or cyclo(lower)alkyl, andR.sup.3 is optionally substituted heterocyclic(lower)alkyl, andm is an integer of 0 to 2,or pharmaceutically acceptable salts thereof, useful as endothelin antagonist.
摘要:
Peptide compounds of the formula (I') ##STR1## in which R.sup.1 is acyl,R.sup.2 is lower alkyl, cyclo(lower)alkyl(lower)alkyl or optionally substituted heterocyclic(lower)alkyl,R.sup.3 is optionally substituted heterocyclic(lower)alkyl or optionally substituted ar(lower)alkyl,R.sup.4 is lower alkyl, amino(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl or optionally substituted heterocyclic(lower)alkyl,R.sup.5 is carboxy, protected carboxy, carboxy(lower)alkyl or protected carboxy(lower)alkyl,R.sup.6 is hydrogen, lower alkyl, C.sub.6-10 ar(lower)alkyl amino(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl, or heterocyclic(lower)alkyl,R.sup.7 is hydrogen or lower alkyl, andA is --O--, --NH--, lower alkylimino or lower alkylene, or a pharmaceutically acceptable salt thereof are disclosed. The compounds can be used to treat and prevent endothelin mediated diseases such as hypertension. The preparation of such peptides is also disclosed.
摘要:
A compound of the formula: ##STR1## in which R.sup.3 is hydrogen or lower alkyl, R.sup.4 is pyridyl (lower) alkyl; andR.sup.1, R.sup.2, R.sup.5 and A are defined in the description;or a pharmaceutically acceptable salt thereof, which have endothelin antagonistic activity.
摘要:
Peptide compounds of the formula (I') ##STR1## in which R.sup.1 is acyl,R.sup.2 is lower alkyl, cyclo(lower)alkyl(lower)alkyl or optionally substituted heterocyclic(lower)alkyl,R.sup.3 is optionally substituted heterocyclic(lower)alkyl or optionally substituted ar(lower)alkyl,R.sup.4 is lower alkyl, amino(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl or optionally substituted heterocyclic(lower)alkyl,R.sup.5 is carboxy, protected carboxy, carboxy(lower)alkyl or protected carboxy(lower)alkyl,R.sup.6 is hydrogen, lower alkyl, C.sub.6-10 ar(lower)alkyl amino(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl, or heterocyclic(lower)alkyl,R.sup.7 is hydrogen or lower alkyl, andA is --O--, --NH--, lower alkylimino or lower alkylene, or a pharmaceutically acceptable salt thereof are disclosed. The compounds can be used to treat and prevent endothelin mediated diseases such as hypertension. The preparation of such peptides is also disclosed.
摘要:
A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl optionally substituted with a substituent selected from the group consisting of acyl, hydroxy, lower alkoxy, aryl, lower alkylthio and a group of the formula: ##STR2## in which R.sup.5 is hydrogen or acyl and R.sup.6 is hydrogen or lower alkyl; aryl; or amino optionally substituted with substituent(s) selected from the group consisting of lower alkyl and acyl; andR.sup.2 is hydrogen or lower alkyl; orR.sup.1 and R.sup.2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted with substituent(s) selected from the group consisting of lower alkyl, hydroxy(lower )alkyl, lower alkoxy(lower)alkyl, acyl(lower)alkyl, oxo and acyl;R.sup.3 is hydrogen or lower alkyl; andR.sup.4 is lower alkyl;and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same.
摘要:
A compound of formula (I) wherein A is a sulfonyl or a carbonyl; R1 is an optionally substituted aryl, an optionally substituted heterocyclic group, an optionally substituted lower alkyl or an optionally substituted lower alkenyl; R2 is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group; R3 is an optionally substituted lower alkyl, an optionally substituted lower alkoxy, an optionally substituted aryloxy, an optionally substitued lower alkenyl, an optionally substituted aryl, an optionally substituted heterocyclic group or an optionally substitued amino; R4 is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group; R5 is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group; and R10 is a hydroxy or a protected hydroxy, and a pharmaceutically acceptable salt thereof. The compound of the present invention is useful as a medicament for prophylactic and therapeutic treatment of MMP- or TNF&agr;-mediated diseases.
摘要翻译:式(I)的化合物,其中A是磺酰基或羰基; R1是任选取代的芳基,任选取代的杂环基,任选取代的低级烷基或任选取代的低级烯基; R2是氢,任选取代的低级烷基,任选取代的芳基或任选取代的杂环基; R 3是任选取代的低级烷基,任选取代的低级烷氧基,任选取代的芳氧基,任选取代的低级烯基,任选取代的芳基,任选取代的杂环基或任选取代的氨基; R4是氢,任选取代的低级烷基,任选取代的芳基或任选取代的杂环基; R5是氢,任选取代的低级烷基,任选取代的芳基或任选取代的杂环基; R 10为羟基或被保护的羟基及其药学上可接受的盐。 本发明的化合物可用作用于预防和治疗MMP或TNFα介导的疾病的药物。
摘要:
A compound of formula (I) wherein A is a sulfonyl or a carbonyl; R1 is an optionally substituted aryl, an optionally substituted heterocyclic group, an optionally substituted lower alkyl or an optionally substituted lower alkenyl; R2 is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group; R3 is an optionally substituted lower alkyl, an optionally substituted lower alkoxy, an optionally substituted aryloxy, an optionally substituted lower alkenyl, an optionally substituted aryl, an optionally substituted heterocyclic group or an optionally substituted amino; R4 is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group; R5 is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally substituted heterocyclic group; and R10 is a hydroxy or a protected hydroxy, and a pharmaceutically acceptable salt thereof. The compound of the present invention is useful as a medicament for prophylactic and therapeutic treatment of MMP-or TNF&agr;-medicated diseases.
摘要翻译:式(I)的化合物,其中A是磺酰基或羰基; R1是任选取代的芳基,任选取代的杂环基,任选取代的低级烷基或任选取代的低级烯基; R2是氢,任选取代的低级烷基,任选取代的芳基或任选取代的杂环基; R3是任选取代的低级烷基,任选取代的低级烷氧基,任选取代的芳氧基,任选取代的低级烯基,任选取代的芳基,任选取代的杂环基或任选取代的氨基; R4是氢,任选取代的低级烷基,任选取代的芳基或任选取代的杂环基; R5是氢,任选取代的低级烷基,任选取代的芳基或任选取代的杂环基; R 10为羟基或被保护的羟基及其药学上可接受的盐。 本发明的化合物可用作用于预防和治疗MMP或TNFα药物疾病的药物。
摘要:
A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl optionally substituted aryl; or amino optionally substituted; andR.sup.2 is hydrogen or lower alkyl; orR.sup.1 and R.sup.2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted;R.sup.3 is hydrogen or lower alkyl; andR.sup.4 is lower alkyl;and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same
摘要:
A compound of the formula: ##STR1## wherein R.sup.1 is aryl optionally substituted with a substituent selected from the group consisting of halogen and halo(lower)alkyl; lower alkyl or cyclo(lower)alkyl; andR.sup.2 is hydrogen or lower alkyl, orR.sup.1 and R.sup.2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted with a substituent selected from the group consisting of lower alkyl and esterified carboxy,R.sup.3 is hydrogen or lower alkyl, andR.sup.4 is lower alkyl,and its pharmaceutically acceptable salt, a process for the preparation thereof and pharmaceutical composition comprising the same.