Novel biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists are claimed along with methods of using such compounds in the treatment of conditions such as hypertension and other diseases, as well as pharmaceutical compositions containing such compounds.

Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists

Compounds are disclosed having formula (I) wherein D, E, G, L, M, A, R'1, L', and M' are defined herein. The compounds of the invention are angiotensin II receptor antagonists.

Angiotensin ii receptor antagonists

A range of 3-oxybenzamide compounds (I) and related quinazolinone compounds (II) are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. The compounds disclosed include 3-benzyloxybenzamides, 3-oxybenzamides in which a chain of 5 or more methylene groups terminate in a halogen atom or in a purin-9-yl moiety, certain benzoxazole-4-carboxamide compounds and certain quinazolinone compounds. In formula (I) X and Y together may form a bridge -X-Y- that represents the grouping (a), (b) or (c) wherein R5 is H, alkyl, aryl or aralkyl.

Benzamide analogs, useful as parp (adp-ribosyltransferase, adprt) dna repair enzyme inhibitors

The invention relates to N-substituted hetero-cyclic derivatives. These derivatives have the formula (see fig.I) in which: R1 and R2 are similar or different and are each independently hydrogen or a group selected from a C1-C6 alkyl, a C1-C4 alkoxy, an amino, an aminomethyl, a carboxyl, an alkoxycarbonyl in which the alkoxy is C1-C4, a cyano, a tetrazolyl, a methyltetrazolyl, a methylsulfonylamino, a trifluoromethylsulfonylamino, a trifluoromethylsulfonylaminomethyl, an N-cyano-acetamide, an N-hydroxyacetamide, an N-4-carboxy-1,3-thiazol-2-yl)acetamide, a ureido, a 2-cyano-guanidinocarbonyl, a 2-cyanoguanidinomethyl, an imidazol-1-ylcarbonyl and a 3-cyano-2-methylisothio-ureidomethyl, with the proviso that at least one of the substituents R1 or R2 is other than hydrogen; R3 is a hydrogen, a C1-C6 alkyl which is unsubstituted or substituted by one or more halogen atoms, a C2-C6 alkenyl, a C3-C7 cycloalkyl, a phenyl, a phenylalkyl in which the alkyl is C1-C3, or a phenyl-alkenyl in which the alkenyl is C2-C3, said phenyl groups being unsubstituted or monosubstituted or polysubstituted by a halogen atom, a C1-C4 alkyl, a C1-C4 halogenoalkyl, a C1-C4 polyhalogenoalkyl, a hydroxyl or a C1-C4 alkoxy; R4 and R5 are each independently a C1-C6 alkyl, a phenyl or a phenylalkyl in which the alkyl is C1-C3, said alkyl, phenyl and phenylalkyl groups being unsubstituted or substituted by one or more halogen atoms or by a group selected from a C1-C4 perfluoro-alkyl, a hydroxyl and a C1-C4 alkoxy; or R4 and R5 together form a group of the formula =CR7R8, in which R7 is hydrogen, a C1-C4 alkyl or a phenyl and R8 is a C1-C4 alkyl or a phenyl; or else R4 and R5 together are either a group of the formula (CH2)n or a group of the formula (CH2)pY-(CH2)q, in which Y is either an oxygen-atom, or a sulfur atom, or a carbon atom substituted by a C1-C4 alkyl group, a phenyl or a phenylalkyl in which the alkyl is C1-C3, or a group N-R6, in which R6 is a hydrogen, a C1-C4 alkyl, a phenylalkyl in which the alkyl is C1-C3, a C1-C4 alkylcarbonyl, a C1-C4 halo-genoalkylcarbonyl, a C1-C4 polyhalogenoalkylcarbonyl, a benzoyl, an alpha-aminoacyl or an N-protecting group, or R4 and R5, together with the carbon atom to which they are bonded, form an indane or an adamantane; - p + q = m; - n is an integer between 2 and 11; - m is an integer between 2 and 5; - X is an oxygen atom or sulfur atom; and - z and t are zero or one is zero and the other is one; and its salts (sic).

N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present

A compound of general formula (I) and a pharmacologically acceptable salt thereof wherein A represents (a), (b) or (c), B represents a carboxylic acid residue or a tetrazole residue, and X represents O, NH or S(O)t. The compound (I) has an angiotensin (II) antagonism and is used as hypotensive, cardiac failure remedy, anxiolytic drug and agent for mnemonics.

Pyridine derivative with angiotensin ii antagonism

Novel substituted quinazolinones of the formula (I), which are useful as angiotensin II antagonists, are disclosed. ##STR1##

Substituted quinazolinones as angiotensin II antagonists.

PURPOSE: To obtain a new substd. quinazolinone having angiotensin II antagonistic action which is useful for treatment of hypertension and congestive failure. CONSTITUTION: This compd. is a compd. of formula I [wherein L is bonded to J and K to form an arom. ring; J is -(=M) (in which M is O, etc.), and others; K is -(=M), etc.; R 1 is -SO 2 N-(R 25 )-OR 25 (in which R 25 is H or an aryl, etc.); R 2a and R 2b are H, a halogen or NO 2 , etc.; R 3a is H, a halogen or 1-6C alkyl, etc.; R 3b is H or a halogen, etc.; R 6 is an aryl or halogen, etc.; X is a C-C single bond or -CO-, etc.; (r) is 1 or 2; E is a single bond or -S(O) x (CH 2 ) s (in which (x) is 0-2 and (s) is 0-5) and others) such as 2-propyl-6-[(N-ethyl-carbamoyl) amino]-3-[2'-(3,3-dimethyl-butyl)-oxycarbonylsulfonamide)-biphenyd-4-yl)-methyl]- quinazolin-4(3H)-one. The compd. of the formula I is obtained, for example, by allowing a compd. of formula II to react with a compd. of formula III. COPYRIGHT: (C)1993,JPO

Substituted quinazolinone having acidic functional group as angiotensin ii antagonist

L'invention porte sur des pyrroles aryliques, des compositions renfermant de tels composes et des methodes de traitement. Les maladies mediation par la cytokine englobent les maladies ou etats pathologiques caracterises par une production excessive ou dereglee d'une ou plusieurs cytokines. L'interleukine-1 (IL-1), l'interleukine-6 (IL-6), l'interleukine-8 (IL-8) et le facteur de necrose tumorale sont des cytokines qui entrent en jeu dans l'immunoregulation et d'autres aspects physiologiques, comme l'inflammation.

Pyrroles aryliques de substitution, compositions renfermant de telles composes et methodes d'utilisation de ces substances

L'invention se rapporte a des pyrroles d'aryle substitues en position 2 et 5 correspondant a la formule (I) ou a un de leurs sels pharmaceutiquement acceptables, ainsi qu'a des compositions contenant de tels composes et a leurs modes d'utilisation. Les composes sont utiles dans le traitement des maladies induites par les cytokines, qui sont des maladies ou des pathologies dans lesquelles la production ou l'activite d'une ou de plusieurs cytokines est excessive ou non regulee. L'interleukine-1 (IL-1), l'interleukine-6 (IL-6), l'interleukine-8 (IL-8) et le facteur de necrose tumorale (TNF) figurent parmi les cytokines qui interviennent dans l'immunomodulation et dans d'autres processus physiologiques, tels que l'inflammation. Lesdits composes ont egalement une activite antagoniste vis-a-vis du glucagon.

Pyrroles d'aryle substitues en position 2 et 5, compositions contenant de tels composes et leurs modes d'utilisation

Substituierte 1-(2H)-Isoquinolinone

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