184698-54-2Relevant academic research and scientific papers
N-AROYLAMINO ACID AMIDES AS ENDOTHELIN INHIBITORS
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, (2008/06/13)
The present invention relates to the compounds of formula (I) STR1 wherein R is carboxy, esterified carboxy, carbamoyl, N-(alkyl or aryl)-carbamoyl, cyano, 5-tetrazolyl or CONH--SO 2--R 4 ; R. sub.1 is hydrogen, lower alkyl, aryl-lower alkyl or cycloalkyl-lower alkyl; R 2 is hydrogen or lower alkyl, or R 1 and R 2 represent lower alkylene to form together with the carbon and nitrogen atoms to which they are attached an azacycloalkane ring; R 3 is heterocyclic or carbocyclic (aryl or biaryl)-lower alkyl; Y is lower alkylidenyl, 3-to 10-membered cycloalkylidenyl which may be substituted by oxo, alkylenedioxy, hydroxy, acyloxy, lower alkoxy; or Y is 5-to 10-membered cycloalkylidenyl fused to a saturated or unsaturated carbocyclic 5-or 6-membered ring; or Y is 5-to 8-membered oxacycloalkylidenyl, 5-to 8-membered (thia-, oxothia-or dioxothia-) cycloalkylidenyl, or 5-to 8-membered azacycloalkylidenyl optionally N-substituted by lower alkyl or aryl-lower alkyl; R 4 represents hydrogen, lower alkyl, carbocyclic aryl, heterocyclic aryl, cycloalkyl, (carbocyclic aryl, heterocyclic aryl, cycloalkyl, hydroxy, acyloxy, or lower alkoxy)-lower alkyl, lower alkyl substituted by carboxyl, by esterified carboxyl or by amidated carboxyl; Ar represents carbocyclic or heterocyclic aryl; and pharmaceutically acceptable salts thereof; which are useful as endothelin inhibitors in mammals.
Discovery of IRL 3461: A novel and potent endothelin antagonist with balanced ET(A)/ET(B) affinity
Sakaki, Junichi,Murata, Toshiki,Yuumoto, Yoko,Nakamura, Ikushi,Frueh, Thomas,Pitterna, Thomas,Iwasaki, Genji,Oda, Kyoko,Yamamura, Takaki,Hayakawa, Kenji
, p. 2241 - 2246 (2007/10/03)
IRL 3461, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5- isoxazolyl)-phenyl]-alanyl]-(L)-valineamide, a potent and bifunctional (ET(A) + ET(B)) [Ki(ET(A))=1.8 nM, Ki(ET(B))=1.2 nM] antagonist was discovered by structural modification of IRL 2500, an ET(B) selective antagonist. IRL 3461 was found to be stable on incubation with human, rat, mouse, and guinea pig plasmas.
Endothelin receptor antagonists
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, (2008/06/13)
The present invention provides novel compounds represented by the general formula I: STR1 wherein R 1 is a straight or branched lower alkyl, a cycloalkyl-lower alkyl, an aryl-lower alkyl, a cycloalkyl, an aryl an aryl-cycloalkyl, lower alkoxy, an aryloxy, or a heteroaryl;R 2 is hydrogen, a straight or branched lower alkyl, a cycloalkyl, or a cycloalkyl-lower alkyl;R 3 and R 3 '' are each the same or different and each is hydrogen atom, a straight or branched lower alkyl, a cycloalkyl, an aryl-lower alkyl, an aryl, or a heteroaryl; orR 3 and R 3 '' together form a ring structure;R 3 "" is hydrogen, lower alkyl or an aryl; orR 2 and R 3 "" together form a lower alkylene group --(CH 2) n -- wherein n is an integer of 1, 2 or 3; orR 2 and R 3 "" together form a group represented by the formula: --(CH 2) p --Ar-- or --Ar--(CH 2) p --, respectively, wherein p is zero or an integer of 1 or 2, and Ar is an arylene or heteroarylene;C( X) is C( O), C( S), C( NH), C( N-lower alkyl); C NH--OH, or CH 2 ;Y is a direct bond, --NH--, a lower alkyl-N, an oxygen atom, or methylene; orC( X) is CHOH and Y is a direct bond or methylene;R 4 is --(CH 2) s --Ar'' wherein s is zero or an integer of 1, 2 or 3; and Ar'' is an aryl, or a heteroaryl; andR 5 is carboxy, substituted or unsubstituted carboxamide, PO(OH) 2, tetrazole, CH 2 OH, CN, or hydrogen;and salts thereof.
Antagonists of endothelin receptors
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, (2008/06/13)
The present invention provides novel compounds having pharmacological properties represented by the general formula I STR1 processes for the manufacture, pharmaceutical compositions and the use of the compounds of formula I and salts thereof.
