cas 114772-38-2, Methyl 4'-bromomethyl biphenyl-2-carboxylate

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Synthesis method of 4-bromomethyl-2-methyl formate biphenyl
The invention discloses a synthesis method of 4-bromomethyl-2-methyl formate biphenyl. The method comprises the following steps: performing bromination reaction in a mode of synchronously dropwise adding bromine and hydrogen peroxide, re-oxidizing hydrobromic acid formed after the reaction into bromine, and performing bromination reaction again, so that the bromine can fully participate in the reaction so as to reduce the use amount of bromine raw materials and improve the yield of the 4-bromomethyl-2-methyl formate biphenyl, waste difficult to treat cannot be generated, hydrogen peroxide is cheap and easy to obtain, and the production cost is remarkably saved.
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Paragraph 0025; 0031-0032; 0038

(2021/07/14)

Synthetic method of 4'-bromomethylbiphenyl-2-carboxylate
The invention discloses a synthetic method of 4'-bromomethylbiphenyl-2-carboxylate. The synthetic method comprises the following steps: 1, hydrolyzing 4'-methyl-2-cyanobiphenyl to obtain 4'-methyl-2-biphenyl formic acid; 2, esterifying 4'-methyl-2-biphenyl formic acid to obtain 4'-methyl-2-biphenyl formate; and 3, reacting 4'-methyl-2-biphenyl formate under the illumination of 15000-20000lx at 20-30DEG C for 4-6h to obtain 4'-bromomethylbiphenyl-2-carboxylate. The synthetic method of 4'-bromomethylbiphenyl-2-carboxylate allows 4'-bromomethylbiphenyl-2-carboxylate to be obtained after hydrolysis, esterification and bromination of 4'-methyl-2-cyanobiphenyl used as an initial material. The route of the method is short, so the problem of raw material waste caused by bromine removal and bromo group introduction is avoided; and a bromination reaction is an illumination reaction, so 4'-bromomethylbiphenyl-2-carboxylate can be directly used in telmisartan synthesis without purifying, thereby the cost is reduced.
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Paragraph 0058; 0059

(2017/02/02)

New telmisartan-derived PPARγ agonists: Impact of the 3D-binding mode on the pharmacological profile
In previous studies, the 4′-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid was identified as pharmacophoric core for PPARγ activation. In this structure-activity relationship study the C2-alkyl chain was elongated and the 2-COOH group was changed to a carbamide/carbonitrile or shifted to the 3- or 4-position. Furthermore, the benzo[d]imidazole was exchanged by 2,3-dihydrobenzo[d]thiazole or 1H-indole. C2-propyl derivatives showed the profile of partial agonists, while elongation of the C2-chain to that of an n-heptyl group or a 4-COOH shift changed the pharmacological profile to that of a potent full agonist. This finding can be explained by binding to the LBD in different ligand conformations. Two anchoring points (Tyr473 and Arg288) exist in the LBD, which have to be contacted to achieve receptor activation. In a crystal violet chemosensitivity assay using COS-7?cells and LNCaP cells expressing PPARγ only the carbamide derivatives influenced the cell growth, independently on the presence of the PPARγ. Therefore, receptor mediated cytotoxicity can be excluded.
Obermoser, Victoria,Urban, Margarethe E.,Murgueitio, Manuela S.,Wolber, Gerhard,Kintscher, Ulrich,Gust, Ronald
supporting information
p. 138 - 152
(2016/08/30)

Synthesis method of 4'-halogenated methylbiphenyl-2-formic aid alkyl ester
The invention discloses a synthesis method of a 4'-halogenated methylbiphenyl-2-formic acid alkyl ester compound, and belongs to the technical field of organic synthesis. The method includes the following steps that 1, biphenyl-2-formic acid (I) and low alkyl alcohol are subjected to an esterification reaction under an acid catalyst to prepare biphenyl-2-formic acid alkyl ester (II); 2, the temperature in a four-mouth bottle containing biphenyl-2-formic acid alkyl ester (II), paraformaldehyde and a solvent is controlled to be within 20-50 DEG C, zinc halide is added, a dehydrating agent is added drop by drop, liquid chromatography monitoring is performed till the raw materials disappear about 2-5 h later, the reaction is finished, the temperature is lowered to the room temperature, an oil layer is washed, crystallization is performed to prepare 4'-halogenated methylbiphenyl-2-formic acid alkyl ester (III), and recrystallization purification is performed to prepare a pure product of 4'-halogenated methylbiphenyl-2-formic acid alkyl ester (III). According to the method, with biphenyl-2-formic acid as the starting raw material, the sartan drug intermediate 4'-halogenated methylbiphenyl-2-formic acid alkyl ester is prepared; the process is simple, conditions are easy to control, the raw materials are cheap and easy to get, production cost is low, environmental pollution is small, and the method is suitable for industrial production.
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(2016/12/01)

Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies
New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards β-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of β-tubulin.
Shashikumar, Nellisara D,Krishnamurthy, Ganganaika,BhojyaNaik, Halehatti S,Lokesh, Mayasandra R,Jithendrakumara, Kaginalli S
p. 205 - 212
(2016/03/01)

Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies
New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards ?-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of β-tubulin. Indian Academy of Sciences.
Shashikumar, Nellisara D.,Krishnamurthy, Ganganaika,Bhojyanaik, Halehatti S.,Lokesh, Mayasandra R.,Jithendrakumara, Kaginalli S.
p. 205 - 212
(2014/04/03)

Synthesis and evaluation of quinazoline derivatives as phosphodiesterase 7 inhibitors
The latest scientific findings concerning PDE7 and PDE4 inhibition suggest that selective small-molecule inhibitors of both enzymes could provide a novel approach to treat a variety of immunological diseases. In this context, we describe a new series of quinazoline derivatives from quinazolin-4-thiones which include a substituted biphenyl fragment. Some of these compounds show inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7.
Sánchez, Ana I.,Martínez-Barrasa, Valentín,Burgos, Carolina,Vaquero, Juan J.,Alvarez-Builla, Julio,Terricabras, Emma,Segarra, Víctor
p. 2370 - 2378
(2013/05/09)

1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl} -pyrrolidine-2-carboxamide: Investigation of structural variations
We recently reported a series of 1-acyl-N-(biphenyl-4-ylmethyl)pyrrolidine- 2-carboxamides as AT1 receptor ligands. The most potent compound of the series, 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}- pyrrolidine-2-carboxamide, showed an interesting affinity for the receptor. To investigate the influence of structure variations on affinity, the synthesis of additional compounds belonging to this series has been performed. Biological tests run on the newly synthesized compounds on CHO-hAT1 cells stably expressing the human AT1 receptor confirm our previous hypothesis, i.e. that, within this series, the length of the acyl chain, the substitution of the amidic group and the nature of the acidic one are crucial for the receptor interaction, being a valeric chain, a secondary amidic function and the tetrazole moiety, respectively, the optimal ones. New 1-acyl-N-(biphenyl-4- ylmethyl)pyrrolidine-2-carboxamides have been designed by enlarging our previously reported series in order to clarify the requirements for AT 1 receptor interaction. Copyright
Catalano, Alessia,Carocci, Alessia,Di Mola, Antonia,Bruno, Claudio,Vanderheyden, Patrick M. L.,Franchini, Carlo
scheme or table
p. 617 - 626
(2012/06/29)

NOVEL BLT2-MEDIATED DISEASE, AND BLT2 BINDING AGENT AND COMPOUND
[PROBLEM] The compound that selectively binds to BLT2 and the preventive and/or therapeutic drug for BLT2-mediated disease such as skin disease are needed. [MEANS FOR SOLVING THE PROBLEMS] The present invention provides the compound with BLT2 binding activity, salt thereof, solvate thereof or prodrug thereof. Since the compound with BLT2 binding activity, particularly the compound represented by the formula (I) , salt thereof, solvate thereof or prodrug thereof (symbols in formula have the same meanings as specification.) have BLT2 binding activity, it is useful for prevention and/or therapy of BLT2 mediated diseases, e.g., dermatosis, intestinal disease, HIV infection, acquired immunodeficiency syndrome, rejection to transplant, transplant rejection, graft-versus-host disease, autoimmune disease, allergic disease, inflammation, infection, ulcers, lymphoma, malignant tumor, leucaemia, arterial sclerosis, hepatitis, hepatic cirrhosis or cancer, etc.
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Page/Page column 35

(2010/11/25)

An efficient and impurity-free process for telmisartan: An antihypertensive drug
Telmisartan (1), a substituted dibenzimidazole derivative, is an antihypertensive drug, essentially used to control blood pressure. An improved, cost-effective, and impurity-free process for telmisartan (1) suitable for large-scale production is described here by addressing various process development issues. The overall yield obtained from this newly developed process is around 50% (over five steps) compared to the literature reported process (21%, over eight steps).
Reddy, Kikkuru Srirami,Srinivasan, Neti,Reddy, Chinta Raveendra,Kolla, Naveenkumar,Anjaneyulu, Yerremilli,Venkatraman, Sundaram,Bhattacharya, Apurba,Mathad, Vijayavitthal T.
p. 81 - 85
(2012/12/26)

PROCESS FOR PREPARING TELMISARTAN
A process for preparing telmisartan and intermediates formed in the process.
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Page/Page column 33

(2008/06/13)

2,3-Diaminopyridine as a platform for designing structurally unique nonpeptide bradykinin B1 receptor antagonists
A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described.
Feng, Dong-Mei,Wai, Jenny M.,Kuduk, Scott D.,Ng, Christina,Murphy, Kathy L.,Ransom, Richard W.,Reiss, Duane,Chang, Raymond S.L.,Harrell, Charles M.,MacNeil, Tanya,Tang, Cuyue,Prueksaritanont, Thomayant,Freidinger, Roger M.,Pettibone, Douglas J.,Bock, Mark G.
p. 2385 - 2388
(2007/10/03)

2-(biarylalkyl)amino-3-(alkanoylamino)pyridine derivatives
Compounds disclosed herein are bradykinin B1 antagonist compounds useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
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Page/Page column 14

(2010/02/05)

2-(Biarylalkyl)amino-3-(cyanoalkanoylamino)pyridine derivatives
Compounds disclosed herein are bradykinin B1 antagonist compounds useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
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Page/Page column 14

(2010/02/05)

Method for preparing bromomenthyl-biphenyl derivatives
The present invention relates to a process for the preparation of 4′-bromomethyl-biphenyl derivatives of the formula: by reacting a 4′-methyl-biphenyl derivative of the formula: with a brominating agent a in a hydrobromic acid/alkali metal bromate system in a two-phase medium, and under photo-iradiation, where R is as defined in the specification.
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(2008/06/13)

Correlation of anti-HIV activity with anion spacing in a series of cosalane analogues with extended polycarboxylate pharmacophores
Cosalane and its synthetic derivatives inhibit the binding of gp120 to CD4 as well as the fusion of the viral envelope with the cell membrane. The binding of the cosalanes to CD4 is proposed to involve ionic interactions of the negatively charged carboxylates of the ligands with positively charged arginine and lysine amino acid side chains of the protein. To investigate the effect of anion spacing on anti-HIV activity in the cosalane system, a series of cosalane tetracarboxylates was synthesized in which the two proximal and two distal carboxylates are separated by 6-12 atoms. Maximum activity was observed when the proximal and distal carboxylates are separated by 8 atoms. In a series of cosalane amino acid derivatives containing glutamic acid, glycine, aspartic acid, β-alanine, leucine, and phenylalanine residues, maximum activity was displayed by the di(glutamic acid) analogue. A hypothetical model has been devised for the binding of the cosalane di(glutamic acid) conjugate to CD4. In general, the compounds in this series are more potent against HIV-1RF in CEM-SS cells than they are vs HIV-1IIIB in MT-4 cells, and they are least potent vs HIV-2ROD in MT-4 cells.
Santhosh,Paul,De Clercq,Pannecouque,Witvrouw,Loftus,Turpin,Buckheit, Jr.,Cushman
p. 703 - 714
(2007/10/03)

Identification of optimal anion spacing for anti-HIV activity in a series of cosalane tetracarboxylates
The binding of the anti-HIV agent cosalane to CD4 is thought to involve ionic interactions of negatively charged carboxylates of the ligand with positively charged residues on the surface of the protein. An investigation of the optimal anion distances for anti-HIV activity in a series of cosalane tetracarboxylate analogues has been completed, and maximal activity results when the two proximal and the two distal carboxylates are separated by eight atoms. (C) 2000 Elsevier Science Ltd.
Paul, Gitendra C.,De Clercq, Erik,Pannecouque, Christophe,Witvrouw, Myriam,Loftus, Tracy L.,Turpin, Jim A.,Buckheit Jr., Robert W.,Cushman, Mark
p. 2149 - 2152
(2007/10/03)

Nonpeptide angiotensin II receptor antagonists: Synthesis and biological activity of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives
A series of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives have been obtained and tested as non peptide AII receptor antagonists. Modification of the classical biphenyl moiety to a 4-arylthienyl fragment afforded interesting activities.
Delgado,Pastor,Garcia-Navio,Vaquero,Alvarez-Builla,Sunkel,De Casa-Juana,Priego,Santos,Statkow,Straumann
p. 147 - 155
(2007/10/03)

Process for the preparation of imidazopyridine derivatives, and intermediates therefore
The present invention provides an industrially advantageous process for preparing a 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo[4,5-b]pyridine derivative represented by the following formula (II) which is a precursor of an antagonist against an angiotensin II receptor useful as an antihypertensive drug, a biphenyl derivative which is a precursor of the substituent of the pyridine derivative, a process for the preparation thereof, and an intermediate useful for the preparation of the biphenyl derivative: STR1 The 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo-[4,5-b]pyridine derivative can be prepared in a high yield according to the present invention from a 2-amino-5-halogeno-3-nitropyridine derivative through amidation, N-alkylation and reductive cyclization. The halogen atom introduced at the 5-position as a protective group against nitration can be eliminated simultaneously in the step which is conducted thereafter. Thus, this process is industrially advantageous.Further, the biphenyl derivative of the present invention is excellent in reactivity and purity of the product, thus being an intermediate suitable for the industrial production.
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(2008/06/13)

QUINOLINE DERIVATIVES AND USE THEREOF AS ANGIOTENSIN II ANTAGONISTS
The invention concerns pharmaceutically useful novel compounds of the formula I, in which R 1, R 2, R 3, R 4, R 5, Ra, A, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment. STR1
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(2008/06/13)

Imidazo[1,2-a](pyrrolo, thieno or furano) [3,2a-d]azepine derivatives, compositions and methods of use
The present invention is concerned with novel imidazo[1,2-a](pyrrolo, thieno or furano)[3,2-d]azepines of formula STR1 the pharmaceutically acceptable addition salts and stereochemically isomefic forms thereof, wherein each of the dotted lines independently represents an optional bond; R1 represents hydrogen, C1-4 alkyl, halo, ethenyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, hydroxy C1-4 alkyl, formyl, hydroxycarbonyl or hydroxycarbonyl C1-4 alkyl; R2 represents hydrogen, C1-4 alkyl, ethenyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, C1-4 alkyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, hydroxy C1-4 alkyl, formyl or hydroxycarbonyl; R3 represents hydrogen, C1-4 alkyl, hydroxy C1-4 alkyl, phenyl or halo; L represents hydrogen; C1-6 alkyl; C1-6 alkyl substituted with one substituent selected from the group consisting of hydroxy, halo, C1-4 alkyloxy, hydroxycarbonyl, C1-4 alkyloxycarbonyl, C1-4 alkyloxycarbonyl C1-4 alkyloxy, hydroxycarbonyl C1-4 alkyloxy, C1-4 alkyloxycarbonylamino, C1-4 alkylaminocarbonyl, C1-4 alkylaminocarbonylamino, C1-4 alkylaminothiocarbonylamino, aryl, aryloxy and arylcarbonyl; C1-6 alkyl substituted with both hydroxy and aryloxy; C3-6 alkenyl; C3-6 alkenyl substituted with aryl; L represents a radical of formula --Alk--Y--Het1 (a-1), --Alk--NH--CO--Het2 (a-2) or --Alk--Het3 (a-3); which are useful antiallergic compounds. Compositions comprising said compounds, methods of using, and processes for preparing the same.
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(2008/06/13)

Imidazo[2,1-b]benzazepine derivatives, compositions and method of use
The present invention is concerned with novel imidazo[2, 1-b][3]benzazepines of formula STR1 the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein each of the dotted lines independently represents an optional bond; R1 represents hydrogen, halo, C1-4 alkyl or C1-4 alkyloxy; R2 represents hydrogen, halo, C1-4 alkyl or C1-4 alkyloxy; R3 represents hydrogen, C1-4 alkyl, ethenyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, C1-4 alkyl substituted with hydroxycarbonyl or C1-4 alkyloxycarbonyl, hydroxyC1-4 alkyl, formyl or hydroxycarbonyl; R4 represents hydrogen, C1-4 alkyl, hydroxyC1-4 alkyl, phenyl or halo; R5 represents hydrogen, C1-4 alkyl or halo; L represents hydrogen; C1-6 alkyl; C1-6 alkyl substituted with one substituent selected from the group consisting of hydroxy, halo, C1-4 alkyloxy, hydroxycarbonyl, C1-4 alkyloxycarbonyl, C1-4 alkyloxycarbonyl-C1-4 alkyloxy, hydroxycarbonylC1-4 alkyloxy, C1-4 alkyloxycarbonylamino, C1-4 alkylaminocarbonyl, C1-4 alkylaminocarbonylamino, C1-4 alkylaminothiocarbonylamino, aryl, aryloxy and arylcarbonyl; C1-6 alkyl substituted with both hydroxy and aryloxy; C3-6 alkenyl; C3-6 alkenyl substituted with aryl; or, L represents a radical of formula --Alk--Y--Het1 (a-1),--Alk--NH--CO--Het2 (a-2)or --Alk--Het3 (a-3); provided that 6,11-dihydro-11-(4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine is ecxluded, which are useful antiallergic compounds. Compositions comprising said compounds, methods of using and processes for preparing the same.
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(2008/06/13)

Biphenylmethane derivative and pharmacological use
The biphenylmethane derivative having the formula (I) is useful to prevent and treat hypertension and cardiac failure. STR1 in which R1 is hydrogen, an alkyl, a cycloalkyl, a halogenated alkyl, --S--R7, --SO2--R7, --C C--R7 or --(CH2)--OR7, R7 being hydrogen, an alkyl, a cycloalkyl or a halogenated alkyl, p being zero or 1, --A1=A2--A3=A4-- is CH=CH--CH=CH--, --N=CH--CH=CH--, --CH=N--CH=CH--, --CH=CH--N=CH--, --CH=CH--CH=N-- or --CH=N--CH=N--, R2 and R3 are each hydrogen, a halogen, a lower alkyl, a lower alkoxy, a carbamoyl or cyano, R4 is hydrogen or a lower alkyl, R5 is 1H-tetrazol-5-yl, carboxyl (--COOH) or a carboxylic ester and R6 is hydrogen, a halogen, hydroxyl or a lower alkoxy, or a pharmacologically acceptable salt thereof.
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(2008/06/13)

PYRIDINYL COMPOUNDS WHICH ARE USEFUL AS ANGIOTENSIN II ANTAGONISTS
The invention concerns pharmaceutically useful compounds of the formula I, in which R 1, R 2, R 3, R 4, R 5, R. sup.6, R 7, Rz, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment. STR1
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(2008/06/13)

RENAL-SELECTIVE BIPHENYLALKYL 1H-SUBSTITUTED-1,2,4-TRIAZOLE ANGIOTENSIN II ANTAGONISTS FOR TREATMENT OF HYPERTENSION
Renal-selective compounds are described which, in one embodiment, are prodrugs preferentially converted in the kidney to compounds capable of blocking angiotensin II (AII) receptors. These prodrugs are conjugates formed from two components, namely, a first component provided by an AII antagonist compound and a second component which is capable of being cleaved from the first component when both components are chemically linked within the conjugate. The two components are chemically linked by a bond which is cleaved selectively in the kidney, for example, by an enzyme. The liberated AII antagonist compound is then available to block AII receptors within the kidney. Conjugates of particular interest are glutamyl derivatives of biphenylmethyl 1H-substituted-1,2,4-triazole compounds, of which N-acetylglutamic acid, 5-[[4'-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl][1,1'-biphenyl]-2-yl]] car bonylhydrazide, (shown below) is an example: STR1
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(2008/06/13)

Diazine derivatives and pharmaceutical use
The invention concerns pharmaceutically useful novel compounds of the formula I, in which ring B, R1, R2, R3, R4, R5, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.
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(2008/06/13)

Benz[4,5]imidazole-containing angiotensin antagonists
The invention concerns novel heterocyclic compounds of the formula I as defined herein and their physiologically acceptable salts, together with pharmaceutical compositions containing them. The heterocyclic compounds antagonize the actions of angiotensin II and are of value in treating diseases or medical conditions such as hypertension and congestive heart failure in warm-blooded animals. The invention further includes processes for the manufacture of the novel compounds and their use in medical treatment.
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(2008/06/13)

Angiotensin II antagonizers which are condensed pyridine derivatives
The invention concerns pharmaceutically useful novel compounds of the formula I, in which R1, R2, R3, R4, R5, R6, R7, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.
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(2008/06/13)

1H-substituted-1,2,4-triazole compounds and methods of use thereof for treatment of cardiovascular disorders
A class of 1H-substituted-1,2,4-triazole compounds is described for use in treatment of cardiovascular disorders. Compounds of particular interest are angiotensin II antagonists of the formula STR1 wherein R1 is selected from hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, n-pentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, 1-oxoethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl, 1,1-dimethoxypropyl, 1,1-dimethoxy-butyl, 1,1-dimethoxypentyl, hydroxyalkyl, halo, difluoro-methyl, 1,1-difluoroethyl, 1,1-difluoropropyl, 1,1-di-fluorobotyl and 1,1-difluoropentyl; wherein R2 is selected from ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, 4-methylbutyl, tert-butyl, n-pentyl and neo-pentyl; wherein each of R3 through R11 is hydrido with the provision that at least one of R5 and R9 must be selected from COOH, SH, PO3 H2, SO3 H, CONHNH2, CONHNHSO2 CF3, OH, STR2 wherein each of R40 and R41 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.
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(2008/06/13)

Nonpeptide Angiotensin II Receptor Antagonists: The Discovery of a Series of N-(Biphenylylmethyl)imidazoles as Potent, Orally Active Antihypertensives
A new series of nonpeptide angiotensin II (AII) receptor antagonists has been prepared.These N-(biphenylylmethyl)imidazoles, e.g. 2-butyl-1--4-chloro-5-(hydroxymethyl)imidazole, differ from the previously reported N-(benzamidobenzyl)imidazoles and related compounds in that they produce a potent antihypertensive effect upon oral administration; the earlier series generally were active only when administered intravenously.It has been found that the acidic group at the 2'-position of the biphenyl is essential.Only ortho-substituted acids possess both high affinity for the AII receptor and good oral antihypertensive potency.The carboxylic acid group has been replaced with a variety of acidic isosteres, and the tetrazole ring has been found to be the most effective.The tetrazole derivative, DuP 753, is currently in development for the treatment of hypertension.
Carini, David J.,Duncia, John V.,Aldrich, Paul E.,Chiu, Andrew T.,Johnson, Alexander L.,et al.
p. 2525 - 2547
(2007/10/02)