1,4-DIHYDROPYRIDINE DERIVATIVES USEFUL IN THE TREATMENT OF CARDIOVASCULAR DISORDERS, AND A PROCESS FOR PRODUCING THE DERIVATIVES

Abstract: The present invention relates to novel 1,4-dihydro­ pyridine derivatives of the following formulae. The compounds have activity as calcium antagonists useful for the treatment of cardiovascular disorders. More particularly, the invention includes preferred compounds which in addition to the usefulness associated with calcium antagonism also exhibit positive inotropic effect without the usual accompanying negative inotropic effect. Thus, the preferred compounds additionally provide beneficial increased myocardial activity.

Description: 1,4-DIHYDROPYRIDINE DERIVATIVES USEFUL IN THE TREATMENT OF CARDIOVASCULAR DISORDERS, AND A PROCESS FOR PRODUCING THE DERIVATIVES. More specifically, 1,4-dihydropyridine derivatives substituted in the two position are said to be distin guished by a powerful vessel-influencing action in US Patent Number 4,188,395 by Bossert, et al. No mention is made of inotropic effect. British Patent Number 2,112,782 discloses various dihydropyridines not teaching the compounds of the present invention but having increased myocardial contractility. None of the above references teaches the combina tion of substituents on a dihydropyridine moiety of the present invention. More particularly, the 1,4-dihydropyridine derivatives of the present inven tion having Formula I or II are distinguished from Bossert, et al, by the differences in the sulfur containing substituent on the dihydropyridine moiety and, therefore, are not taught by Bossert, et al. Dihydropyridine polyesters have been described in the literature as antihypertensive and antianginal agents. For example, British Patent Number 1,389,509 describes 1,4-dihydropyridine polyesters as coronary agents. Further, disclosure for cardiovascular activity used as antihypertensives, vasodilators, antifibrillatory agents, and also having marked smooth muscle effect is made for 1,2,3,4-tetrahydropyridine-3,5-dicarboxylic acid derivatives in West German Application Number 3,239,273A. Other dihydropyridines are shown to be calcium agonists or cardiotonics in Belgian Patent 893,984. Additional disclosure for various dihydropyridine polyesters having usefulness as cardiovascular agents is found in West German Application 2,248,150 and Belgian Patents 804,160, 803,474, 861,964, 843,576, and 817,540. Thus, the present novel dihydropyridine derivatives of Formula I or Formula II each as defined hereinafter having valuable calcium antagonist and cardiotonic properties useful for the treatment of cardiovascular disorders are not within the teachings of the prior art. Accordingly, the present invention provides a compound of Formula I and a pharmaceutically acceptable salt thereof; wherein R is (1) hydrogen; (2) lower alkyl of from one to four carbons, inclusive; which is optionally substituted with an amino group such as NR7R8 where tri and R8 are independently hydrogen or lower alkyl, or taken together form a five- or six-membered ring; and (3) aralkyl wherein (a) ar is phenyl optionally substituted with one or more of halo, nitro, amino, mono- or di- alkylamino wherein the alkyls when taken together are of from one to six carbons, inclusive, cyano, lower alkoxy of from one to four carbons, inclusive, lower alkyl of from one to four carbons, inclusive, lower thioalkyl of from one to four carbons, inclusive, and (b) alkyl is alkylene of from one to four carbons, inclusive. R2 and R3 are the same or different and are hydrogen, lower alkyl of from one to four carbons, inclusive, cyano, nitro, R wherein R4 is hydrogen CO24 or lower alkyl of from one to four carbons, inclusive, optionally substituted with amino, mono- or dialkylamino wherein the alkyls when taken together are of from one to six carbons, inclusive. R1, R5, and R6 are the same or different and are (1) lower alkyl of from one to four carbons, inclusive, which is optionally substituted with a) an amino group, such as N bN where b and R8 are independently hydrogen and lower alkyl which may also be taken together to form a five- or sixmembered ring; or (b) ON where R9 is H or lower alkyl of from one to four carbons, inclusive, or c) CO2R4, where R4 has same definition as stated above; 2) cycloalkyl of from four to seven carbons; 3) phenyl optionally substituted with one or more of alkyl of from one to four carbons, inclusive, halo, nitro, amino, mono- or di- alkylamino wherein the alkyls when taken together are of from one to six carbons, inclusive, cyano, lower alkoxy of from one to four carbons, inclusive, lower thioalkyl of from one to four carbons, inclusive; (4) alkyl wherein ar is phenyl optionally substituted with one or more of alkyl of from one to four carbons, inclusive, halo, nitro, amino, mono- or di- alkylamino wherein the alkyls when together have of from one to six carbons, inclusive, cyano, lower alkoxy of from one to four carbons, inclusive, lower thioalkyl of from one to four carbons, inclusive; or (5) heteroaryls. Additionally, h and R5 may also be taken together to form a five- or six-membered ring having as a member of the ring a C(O)- or C(O)O- group. n is a number of from zero to two, inclusive; m is a number of from one to six, inclusive; and with the proviso that when n is 0 then R1 cannot be lower alkyl or cycloalkyl. Additionally, the present invention is a compound of the Formula II and a pharmaceutically acceptable salt thereof where possible, e.g., when a basic nitrogen is present, wherein n, R, R1, R2' R3, R5, and R6 are as defined above but where n is 0, then R1 can also be lower alkyl of from one to four carbons, inclusive, and cycloalkyl. The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I or II as each is defined above with a pharmaceutically acceptable carrier. A therapeutically effective amount comprises a therapeutic cardiovascular effective amount. The compounds of this invention are useful in a method of treating cardiovascular disorders in a mammal, including man, suffering therefrom,which method rrnpri6es administering to such mammals a therapeutically effective--amsunt of a compound of Formula I or a compound of Formula II. The preferred compounds of the present invention are (1) the compounds of Formula I and II wherein R2 is CN and n is one or two; (2) the compounds of Formula I and II wherein R2 and R5 may also be taken together to form a five- or six-membered ring having as a' member of the ring a -C(O)- or sC < O)O group and n is one or two. The preferred compounds provide increased myocardial contractility giving the compounds greater value as cardiotonic agents for treatment of cardiovascular disorders. These compounds demonstrate only positive inotropic activity in in vitro tests which activity is associated with increased myocardial contractility (PCSI). That is, these compounds do not demonstrate undesirable negative inotropic activity usually associated with these types of compounds. The most preferred compounds of the present invention are the compounds of Formula I wherein R2 is CN, R5 is lower alkyl, R3 is CO2R4, m is one, n is one or two, R4 is same as defined above and R1 is phenyl or heteroaryl as defined herein. Also included in the invention are methods using novel compounds of the present invention wherein n is zero having the disclosed utility recited herein as intermediates for the preparation of the 1,4dihydropyridine derivatives of the invention therefrom having sulfinyl or sulfonyl moieties. The salts of the compounds of Formula I or Formula II; possible when a basic nitrogen is present, are prepared in a manner which is in itself known by reacting the compounds obtained according to the processes of the invention with suitable acids. For example, the appropriate compounds of Formula I or II are dissolved in ethanol, then suitable acids are added to the solution. Examples of inorganic and organic acids which form physiologically acceptable acid addition salts with the dihydropyridines of the present invention are hydrogen halide acids, such as hydrochlqric acid and hydrobromic acid, particularly hydrochloric, phosphoric, sulfuric, nitric, monofunctional and bifunctional carboxylic acids and hydroxycarboxylic acids, such as acetic, maleic, succinic, fumaric, tartaric, citric, salicylic, lactic, and l,5-naphthalenedicarboxylic and naphthalenedicarboxylic and naphthalenedisulphonic acids. Lower alkyl or alkyl of from one to four carbons, inclusive, is meant to include a straight or branched chain alkyl group such as methyl, ethyl, propyl, butyl, and isomers thereof. Halogen or halo means fluorine, chlorine, bromine, or trifluoromethyl. Lower alkoxy and lower thioalkyl of from one to four carbons, inclusive is also meant to include methyl, ethyl, propyl, butyl, and isomers thereof. Mono- or di- alkylamino is meant to include methylamino, dimetbylamino, ethylamino, N-methyl N-ethylamino, propylamino, diisopropylamino, butylamino, N-ethyl-N-ethylamino, N-butyl-N-ethylamino and the like. A heteroaryl means thienyl, furanyl, pyryl, pyridinyl, quinolyl, isoquinolyl, pyrimidyl, pyridazinyl, quinazolyl, quinoxalyl, benzothienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, pyrazinyl, oxazinyl, thiazinyl, indolizinyl, indolyl, benzofuranyl, indazolyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzioxazolyl, benzthiazolyl, benztriazolyl, benzoxadiazolyl, cinnolinyl, phthalaxinyl, naphthyridinyl, or benzothiazinyl. Alkylene of from one to four carbons, inclusive, are methylene, ethylene, propylene, butylene, or isomers thereof. The compounds of Formula I are useful as salts derived from physiologically acceptable acids The acids may be mineral acids such as hydrochloric acid, sulfuric acid, and the like, or organic acids, such as ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like; giving the hydrochloride, sulfamate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and the like, respectively. The compound of Formula I and II of the present invention wherein at least R2 and R3 are not just the same as each other, includes stereoisomers due to the presence of at least one asymmetric carbon atom at the four position of the 1,4-dihydropyridine nucleus and can exist as each opticÅal isomer or a racemic mixture. Further, some of the compounds of Formula I and II which have not less than two asymmetric carbon atoms in its molecule may exist as each diastereomer(s) or the mixture thereof. The mixture of the diastereomers can be resolved to each racemic compound by conventional resolution methods such as chromatography or fractional recrystallization and the like and the racemic compound can be resolved into each optical isomer by a conventional method for racemic resoaution by fractional recrystallization of a salt of the racemic compound with an optically active acid, e.g., tartaric acid or camphor sulfonic acid. The terms wstereoisomersw and a stereoisomerismw as used throughout this specification and the appended claims are to be given the meaning usually ascribed to them by practitioners of the organic chemical arts, and specifically as defined by Eliel ip."Stereo- chemistry of Carbon Compounds," pp 1-6, McGraw-'Hill, New York, 1962. Generally, the compounds of Formula I and Formula II wherein n is one or two may be conveniently synthesized by oxidation of the compounds of Formula I and Formula II wherein n is 0, respectively. Such oxidation is accomplished in a manner analogous to those known in the art. See, for example, wOxida- tion of Sulfides to Sulfoxides and Sulfonesw in Advanced Organic Chemistry, Ed. Jerry, March, p. 1089, 3rd Edition, John Wiley & Sons (1985). See Scheme I. The compounds of Formula I and II wherein n is zero are generally prepared by the following procedures. A compound having the Formula III wherein R2 and Rg are as defined above, a compound of the Formula IV wherein R6 is as defined above and a compound of Formula V wherein R1 and R3 are as defined above is contacted in the presence of an inert organic solvent such as ethanol, 1-butanol, or dioxane under reflux condition. The products of the reaction are a mixture of the compounds of Formula 10 and IIo. Such products are recovered and/or separated by conventional means such as extraction, distillation, chromatography, and the like. See Scheme II. The compounds of Formula 10 and 11o may optionally be reacted with a compound of Formula RX wherein R is as defined above and X is halogen by conventional methods to further obtain the compounds having a definition of R other than hydrogen. See Scheme III The desired compound of Formula I or Formula II is isolated and purified by conventional methods. Such isolation and purification do not neceqsÅatate any methods not within the skill of the ordinary artisan. Representative novel compounds of Formula I and of Formula II are found to possess inotropic and vasodilatory activity in vitro and as such, these are useful for the treatment of congestive heart failure, coronary heart disease, myocardial ischemia, angina, and hypertension. These are, thus, the cardiovascular disorders noted above to be within the meaning of the present invention. Representative compounds of Formula I and II inhibit niterendipine (a reference calcium antagonist) binding with an IC50 of 1 x 10 6N to 1 x 10 9M range. These data predict calcium modulator activity beneficial for the utility of the present invention. It is now additionally found that some of the above named preferred compounds advantageously demonstrate positive inotropic effect in vitro. For the preferred compounds of the present invention as defined above, the compounds also produce effects that include increases in contractility and decreases in vascular resistance, with only moderate increases in heart rate in anesthetized dogs. These effects are further complemented by a direct stimulatory effect on the myocardium (ire., a positive inotropic effect). The complementary effects-are observed in isolated atrial tissue and the effects are not subject to negative inotropic effect. Thus, compounds having the combined activity may provide support to a failing heart without offsetting negative effects usually associated with previously known calcium blocking agents. Additionally, the compounds of the present invention generally exhibit an advantageous vasodilatory effect resulting in the after load reduction associated with calcium antagonists. Test for In Vitro Myocardial Inotropic Activity in Isolated Guinea Pig Atria Adult male guinea pigs weighing 300-400 g are reserpinized 12000 units i.p.) and, after ten minutes, are killed by cervical dislocation. The hearts are quickly removed and placed in a physiological salt solution (PSS) containing: 118 mM NaCl, 4.8 mM KC1, 2.4 mM CaCl, 1.2 mM Mug604, 1.0 mM NaH2PO4, 11.1 in dextrose, and 27.2 mM NaHCO3, maintained at pH 7.4 and 3O0C. After removing all superficial blood, the hearts are perfused via the aorta to remove any blood from the coronary arteries. After five to ten minutes of perfusion, the left atria are dissected and mounted vertically in a 50 ml, water-jacketed bather containing PSS at 300C and continuously oxygenated with 95% 02/5% CO2. The left atria are electrically stimulated at 1.5 Hz. The tissues are equilibrated for 30 minutes and washed with fresh PSS. The stimulation voltage is adjusted to 20% above the threshold and tension adjusted to Lmax (the muscle length at which tension development is maximal). The tissues are then equilibrated for an additional 30 minutes, after which the compounds to be examined are added to the tissue bather. The compounds are initially dissolved in DMSO and dilutions made with normal saline, such that the final concentration of DMSO does not exceed 0.5%. The compounds are added in full or half-log concentration increments, usually over a concentration range of 1 x 1018 to 1 x 10-4M. The muscles are generally allowed to assume a new steady-state contractile response before each subsequent additiqn.of drug. Using this procedure the inotropic activity of preferred compounds of the present invention is shown as found in the following Table 1. The reference calcium antagonist has also been tested for comparison. TABLE 1 % Change in Mvocardial Contractilitv (PSCI) Example &commat; e io 5M 2 +33 2 +53 10 +30 13 +26 16 +26 18 +33 19 +33 The present invention includes a method for treating mammals, including humans, suffering from the diseases noted above by administering to such mammals a corresponding pharmaceutical composition containing a compound of the Formula I as defiled above in appropriate unit dosage form. A physician or veterinarian of ordinary skill readily determines a subject exhibiting symptoms of the diseases. The routes of administration and the dosage forms therefor are from among those conventional to the pharmaceutical art. Regardless of the route of administration selected the invention provides a compound of Formula I, in unit dosage form comprising the compound either alone or in admixture with a pharmaceutically acceptable carrier appropriately selected from those known. An effective but nontoxic quantity of the compound I is employed in treatment. The dosage regimen is selected in accordance with a variety of factors including the type, age, weight, sex, and medical condition of the mammal, the severity of symptoms of the disease being treated, the route of administration and particular compound of Formula I employed. An ordinarily skilled physician or veterinarian will readily determine and prescribe the effective amount of the compound I to prevent or arrest the progress of the disease condition. In so proceeding, the physician or veterinarian could employ relatively low dosages at first, subsequently increasing the dose until a maximum response is obtained. For convenience, the total daily dosage may be divided and administered in portions during the day if-desired. It is understood that the compositions and methods of treatment of the present invention as described above also include the pharmacologically acceptable acid addition salts of the compounds of Formula I and Formula IIx The following Examples further merely illustrate the invention and, therefore, are not meant to be limiting. EXAMPLE 1A Ethyl S-coano-1.4-dihodro-6-methYl-2-[(phenslthiol- methyl)-4-[2-(trifluoromethylphenyl]-3-pyridinecarboxylate A solution of 2-trifluoromethyl benzaldehyde (3.48 g, 0.02 mole), 3-aminocrotononitrile (1.6 g, 0.02 mole) and ethyl 3-oxo-4-(phenylthio)butanoate (4.76 g, 0.02 mole) in ethanol (50 ml) is refluxed for 24 hours. The solution is concentrated to a brown oil from which the above product is isolated by chromatography on silica gel with isopropyl ether as eluent. The crude product was crystallized from ethyl acetate to give analytically pure material; mp 122-1230C. Anal. calcd. for C24H21F3O2N2S; C, 62.88; H, 4.58; N, 6.11 Found: C, 62.85; H, 4.73; N, 6.01 EXAMPLE 1B The chromatographic separation also provides the isomeric compound 3-pyridinecarboxylic acid, 5-cyano-1,2,3,4-tetrahydro-2-[(phenylthio)methylene]6-methyl-4-[(2-trifluoromethyl)phenyl]-, ethyl ester; mp 146-1480C. Anal. calcd. for C24H21F3O2N2S; C, 62.87; H, 4.61; N, 6.1; S, 6.99 Found: C, 63.40;"H, 4.83; N, 6.31; S, 6.91 Similarly, by substituting amino cyclohexen3-one for the 3-aminocrotononitrile in Example 1A one obtains: EXAMPLE 1C 3-Quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro 5-oxo-2-l(phenylthio)methyl]-4-t2-(trifluoromethyl)- phenyl]-, ethyl ester; mp 176-1770C. Chromatographic separation also provides the isomeric compound as follows: EXAMPLE 1D 3-Quinolinecarboxylic acid, 1,2,3,4,5,6,7,8-octahydro- 5-oxo-2-[(phenylthio)methylenel-4-12-(trifluoromethyl)- phenyl]-, ethyl ester; mp 204-2050C. EXAMPLE 1E Ethyl s-cyano-1,4-dihydro-6-methyl-2-1[(2-methylphenyl)- thioamethyl]-4-[2-(trifluoromethyl)phenyll-3-pyridine- carboxylate; mp 146-1480C. EXAMPLE 1F Ethyl 5-cyano-1,4-dihydro-6 -methyl-2-l(phenylthio) - methyl]-4-(3-nitrophenyl)-3-pyridinecarboxylate; mp 122-123 0C. EXAMPLE 1G Ethyl 4-(2-chlorophenyl)-5-cyanol-1,4-dihydro-6-methyl2-[(phenylthio)methyl]-3-pyridinecarboxylate; mp 161-162 C. EXAMPLE 1H Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4-pyridinylthio) methyl] -4-12- (trifluoromethyl) phenyl] -3-pyridinecarboxylate; mp 229-230 0C Also, similarly, by using appropriate corresponding starting materials in the procedure described in Example ZA, the following compounds are obtained. EXAMPLE 1I 3-Pyridinecarboxylic acid, 5-cyano-2-[ ethyl)-2-methylphenyl] thioamethyll-1,4-dihydro-6- methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 126-128 C. EXAMPLE 1J Ethyl 3-cyano-1,4-dihydro-6-methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-5-pyridinecarboxylate; mp 144-145 C. EXAMPLE 1K 3,-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2- t[(4-methoxyphenyl) thio] methyl] 6-methyl-4- [2- (tri- fluromethylphenyl]-, ethy ester; mp 108-109 C EXAMPLE 1L 3-Pyridinecarboxylic acid, 2-[[(2-chlorophenylthio] methyl3-5-cyano-1,4-dihydro-6-methyl-4-12-(trifluoro- methyl)phenyl]-, ethyl ester; mp 172-1730C. EXAMPLE 1M 3-Pyridinecarboxylic acid, 5-cyano-2-[[(2-fluoro phenyl)thioZmethylJ-1,4-dihydro-6-methyl-4-[2-(tri- fluoromethyl)phenyl]-, ethyl ester; mp 121-122 C. EXAMPLE 1N 3-Pyridinecarboxylic acid, 2-[[[4-(acetyl- amino)phenyl]thio]methyl]-5-cyano-1,4-dihydro-6methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 187-189 C. EXAMPLE 10 3-Pyridinecarboxylic acid, 2-[[84-chlorophenyl)thio]- methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)phenyl9-, ethyl ester; mp 107-109 C. EXAMPLE 1P 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-4-phenyl-2-[(phenylthio)methyl]-, ethyl ester; (Isomer A); mp 168-170 0C. EXAMPLE 1Q 3-Pyridinecarboxylic acid, 5-cyano-4-(2-furanyl)1,4-dihydro-6-methyl-2-[(phenylthio)methyl]-, ethyl ester; mp 109-110 C. EXAMPLE 1R 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-4-(2-phenyl-lH-imidazol-4-yl)-2-l(phenylthio) methyl, ethyl ester; mp 198-199 0C. EXAMPLE 1S 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylthio)methyl]-4-(2-pyridinyl)-, ethyl ester; mp 164-167 C. EXAMPLE 1T 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6- methyl-2-[(2-pyridinylthio)methyl]-4-[2-(trifluoro méthyl)phenyl-, ethyl ester; mp 179-180 0C. EXAMPLE 1U 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2-cyanoethyl ester; mp 158-160 C. EXAMPLE 1V 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6 methyl-2-[(phenylthio)methyl]-4-t2-(trifluoromethyl)- phenyl]-; mp 204-2060C. EXAMPLE 1W 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6 methyl-2-t(phenylthio)methyl]-4-12-(trifluoromethyl)- phenyl]-, l-methylethyl ester; mp l23-1250C. EXAMPLE 1X 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-, methyl ester; mp 117-118 C. EXAMPLE 1Y 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2-propenyl ester; mp 113-114 0C. EXAMPLE 1Z Following the procedure of Example 1A and by substituting ethyl 3-aminocrotonate in place of 3-aminocrotononitrile, one obtains 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-methyl-6-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; mp 129-130 0C. Anal. calcd. for C26H26F304NS; C, 61.72; H, 5.14; N, 2.76; S, 6.33 Found: C, 61.98; H, 5.31; N, 2.74; S, 6.37 EXAMPLE IAA 3,5-Pyridinecarboxylic acid, 1,4-dihydro-6-methyl2-[[(2-methylphenyl)thio]methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; mp 117-119 C. Similarly by using appropriate starting materials in the procedure described in Example 1Z, the following additional analogs are obtained. EXAMPLE 1BB 3, 5-Pyridinedicarboxylic acid, l,4-dihydro-2-methyl- 6-[(2-pyridinylthio)methyll-4-t2-(trifluoromethyl)- phenyl]-, diethyl ester; mp 118-119 C. EXAMPLE lCC 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2-methyl 6-[(4-pyridinylthio)methyl]-4-[2-(trifluoromethyl)- phenyll-, diethyl ester; mp 146-148 0C. EXAMPLE 1DD 3 ,5-Pyridinedicarboxylic acid, 1,4-dihydro-2-methyl4-(2-phenyl-1H-imidazol-4-yl)-6-[(phenylthio)methyl]-, diethyl ester; mp 179-1800C. EXAMPLE 1EE [3,4'-Bipyridine]-3',5'-dicarboxylic acid, 1',4'dihydro-2'-methyl-6'-[(phenylthio)methyl]-, diethyl ester; mp 116-118 0C. EXAMPLE 1FF 3,5-Pyridinedicarboxylic acid, 2-[[(2-chlorophenyl) thio]methyl]-1,4-dihydro-6-methyl-4-12-(trifluoro- methyl)phenyl]-, 3-ethyl 5-methyl ester; mp 123 125 0C. EXAMPLE 2 Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-3-pyridine carboxvlate m-Chloroperbenzoic acid (0.43 g, 0.002 mole) is added to a solution of ethyl-5-cyano-1,4-dihydro6-methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethylphenyl]-3-pyridinecarboxylate as prepared above in Example 1 (0.96 g, 0.002 mole) in 20 ml of dichloro- methane with stirring at 0 0C. The solution is stirred for two hours at 0 0C to complete the reaction. The solution is washed with 10% aqueous potassium carbonate solution followed by water, dried, and stripped to give a semisolid product. This is purified by chromatography to give two isomers of ethyl 5-cyano-1,4-dihydro-6methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylate. Isomer A, mp 120-122 C Anal. calcd. for C24H21F3N203S; C, 60.75; H, 4,40t N, 5.90 Found: C, 60.35; H, 4.38; N, 5.89 Isomer B, mp 183-185 0C Anal. calcd. for C24H21F3N203S; C, 60.75; H, 4.40; N, 5.90 Found: C, 60.72; H, 4.59; N, 5.83 By following the procedure described in the Example 2 and using substrates selected from among Examples 1 the following additional sulfinyl derivatives are obtained. EXAMPLE 2A Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(2-methylphenyl)sulfinyl]methyl]-4-[2-(trifluoromethyl)phenyl]3-pyridinecarboxylate; mp 176-180 C. EXAMPLE 2B Ethyl 5-cyano-l, 4-dihydro-6-methyl-4- (3-nitrophenyl) 2-[(phenylsulfinyl)methyl]-3-pyridinecarboxylate; mp 194-195 C Isomer A]; mp 168-1700C isomer fl]. EXAMPLE 2C Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(4-methoxy phenyl)sulfinyllmethyl]-4-t2-(trifluoromethyl)phenyl]- 3-pyridinecarboxylate; mp 151-154 0C [diastereoisomers]. EXAMPLE 2D Ethyl 4-(2-chlorophenyl)-5-cyano-1,4-dihydro-6-methyl 2-[(phenylsulfiny1)methyl]-3-pyridinecarboxylatei mp 198-202 0C [diastereoisomers]. EXAMPLE 2E Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4-pyridinylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-3pyridinecarboxylate; mp 202-2030C (dec) (Isomer A]. EXAMPLE 2F 3 ,5-Pyridinedicarboxylic acid, 1,4-dihydro-2-methyl6-[(4-pyridinylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; mp 202-203 C. EXAMPLE 2G Ethyl 2-[[(2-chlorophenyl)sulfinyl]methyl]-5-cyano 1,4-dihydro-6-methyl-4-[(2-trifluoromethyl)phenyl]- 3-pyridinecarboxylate; mp 174-1840C. EXAMPLE 2H 5-Cyano-2-ttt2-(dimethylamino)ethyl]sulfinyl]methyl]- 1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)phenyl]- 3-pyridinecarboxylic acid, ethyl ester. EXAMPLE 21 Ethyl 4-(2-chlorophenyl) -5-cyano-1,4-dihydro-6 -methyl- 2-[(4-pyridinylsulfinyl)methyl]-3-pyridinecarboxylate; mp. 236-237 C. EXAMPLE 2J Ethyl 5-cyano-4- (2, 3-dichlorophenyl) -1, 4-dihydro- 6-methyl-2[4-pyridinylsulfinyl)methyl]-3-pyridinecarboxylate; mp. EXAMPLE 2K 5-Cyano-1,4-dihydro-6-methyl-2-[(2-pyrimidinylsulfinyl)methyl]-4-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, ethyl ester; mp 15l-l540C (dec). EXAMPLE 2L 5-Cyano-1,4-dihydro-6-methyl-2-[[(1-methyl-1H-imidazol 2-yl)sulfinyl]methyll-4-[2-(trifluoromethyl)phenyll- 3-pyridinecarboxylic acid, ethyl ester. EXAMPLE 2M Ethyl 5-cyano-1,4-dihydro-6-methyl-2-l(phenylsulfinyl) methyl] -4-phenyl-3-pyridinecarboxylate. EXAMPLE 2N 3,5-Pyridinecarboxylic acid, 2-[[(2-chlorophenyl)sulfinyl]methylene]-6-methyl-1,2,3,4-tetrahydro4-[(2-trifluoromethyl)phenyl]-3-ethyl-5-methyl ester; mp 153-154 0C. EXAMPLE 20 3-Pyridinecarboxylic acid, 5-cyano-4-cyclohexyl l,4-dihydro-6-methyl-2- [ (phenylsulfinyl)methyl] -, ethyl ester; mp 144-146 OC EXAMPLE 2P 3-Pyridinecarboxylic acid, 5-cyano-4-[2-(difluoro methoxy)phenyl]-1,4-dihydro-6-metfi91-2-[(phenyl- sulfinyl)methyl]-, ethyl ester, mp 122-124 C. EXAMPLE 2Q 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, methyl ester; mp 207-210 C. EXAMPLE 2R 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoro methyl)phenyl]-, 1-methylethyl ester; Isomer A; mp 189-1910C. EXAMPLE 2S 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2-hydroxyethyl ester; mp 172-173 0C. EXAMPLE 2T 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-4-(2-phenyl-1H-imidazol-4-yl)-2-[(phenyl sulfinyl)methyl]-, ethyl ester, (diastereoisomers); mp 211-212 0C. EXAMPLE 2U 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6 methyl-2-[(2-pyridinylsulfinyl)methyl]-4-12-(tri- fluoromethyl)phenyl]-, ethyl ester; mp l55-l740C (dec). EXAMPLE 2V 3-Pyridinecarboxylic acid, 5-cyano-2- [ [(2-fluoro- phenyl)sulfinyl]methyl]-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl)phenyl]-, ethyl ester, (diastereoisomers); mp 186-187 C. EXAMPLE 2W 3-Pyridinecarboxylic acid, 2-[[[4-(acetylamino)phenyl] sulfinyl]methyl]-5-cyano-1,4-dihydro-6-methyl-a- [2-(trifluoromethyl)phenyl]-, ethyl ester, (mixture of isomers); mp 228-2300C. EXAMPLE 2X 3-Pyridinecarboxylic acid, 2-[[(4-chlorophenyl)sulfinyl)methyl]-5-cyano-1,4-dihydro-6-methyl-4 [2-(trifluoromethyl)phenyl]-, ethyl ester; mp 207 210 0C. EXAMPLE 2Y 3-Pyridinecarboxylic acid, 5-cyano-2-[1(3,4-dichlorophenyl)sulfinyl]methyl]-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl)phenyl]-, ethyl ester, (diastereoisomers); mp 173-176 C. EXAMPLE 2Z 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-; mp 209-211 C. EXAMPLE 2AA 3-Quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydromethyl-5-oxo-2-l(phenylsulfinyl)methyll -4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 177-178 C. EXAMPLE 2BB 3-Quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro5-oxo-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester, (t)-; mp 223-2240C. EXAMPLE 2CC Ethyl 3-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-5-pyridinecarboxylate. EXAMPLE 2DD 3-Pyridinecarboxylic acid, 5-cyano-l- (2-(diethyl- amino)ethyl]-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; (mixture of isomers); mp 128-1310C. EXAMPLE 2EE 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2 [[83-methoxy-3-oxopropyl]sulfonyl]methyl]-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 135-137 C. EXAMPLE 2FF 3-Pyridinecarboxylic acid, 5-cyano-2- ( ( (2-ethoxy- 2-oxoethyl)sulfinyl]methyl]-1,4-dihydro-6-methyl 4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 127-130 0C. EXAMPLE 2GG [2,4'-bipyridine]-3'-carboxylic acid, 5'-cyano-1',4'dihydro-6'-methyl-2'-[(phenylsulfinyl)methyl]-, ethyl ester; mp 167-170 0C. By following the procedure described in the Example 2 and using substrates from Example 1Z, the following additional sulfinyl derivatives are obtained. EXAMPLE 2HH 3, 5-Pyridinedicarboxylic acid, 1,4-dihydro-6-methyl 2-t[(2-methylphenyl)sulfinyl]methyl] -4-12-(trifluoro- methyl)phenyl], diethyl ester; mp 143-1470C [Isomer A], mp 140-1440C [Isomer B]. EXAMPLE 211 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2-methyl- 6-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; mp 142-143 C. EXAMPLE 2JJ 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2-methyl6-[(2-pyridinylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; mp 182-183 C. EXAMPLE 2KK 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2-[[(4 methoxyphenyl)sulfinyl]methyl] -6-methyl-4-12-(tri- fluoromethyl)phenyl]-, diethyl ester; Isomer A, mp 190-1910C; Isomer B, mp 159-160 C. EXAMPLE 3 3 ,5-Pvridinedicarboxvlic acid, l,4-dibvdro-2-methvl- 6-[(phenylsulfonyl)methyl]-4-[2-(trimethyl)phenyl]diethyl ester m-Chloropenbenzoic acid (0.4 g, 0.002 mole) is added with stirring to a solution of 0.5 g (0.001 mole) of 3,5-pyridinedicarboxylic acid, 1,4-dihydro6-methyl-2-[(2-phenylthio)methyl]-4-[2-(trifluoro methyl)phenylidiethyl ester in 20 ml of dichloromethane at room temperature. The reaction mixture is stirred for four hours at room temperature to complete the reaction. The solution is washed successively with dilute sodium bicarbonate solution followed by water, dried, and stripped to give a solid. This is purified by chromatography to give pure 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-methyl-6-[(phenylsulfonyl)methyl]4-[2-(trifluoromethyl)phenyl]diethyl ester; mp 194 1950c. Anal. calcd. for C26H26NF3O6S; C, 58.04; H, 4.83; N, 2.60* Found: C, 58.36; H, 5.14; N, 2.58 Following the procedure of Example 3 and using substrates selected from among Examples 1, additional sulfonyl derivatives were obtained. EXAMPLE 3A Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylate; mp 209-211 C. EXAMPLE 3B Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(4-methoxyphenyl)sulfonyl]methyl]-4-[2-(trifluorophenyl)-3pyridinecarboxylate; mp 205-208 0C EXAMPLE 3C Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(2-meth phenyl)sulfonyl]methyl]-4-[2-(trifluorophenyl)-3pyridinecarboxylate; mp 223-225 C (dec). EXAMPLE 3D Ethyl 2-[[(2-chlorophenyl)sulfonyl]methyl]-5-cyano 1,4-dihydro-6-methyl-4-t(2-trifluoromethyl)phenyl] - 3-pyridinecarboxylate: EXAMPLE 3E 3,5-Pyridinecarboxylic acid, 2-[[(2-chlorophenyl)sulfonyl]methyl]-1,4-dihydro-6-methyl-4-[2-(tri fluoromethyl)phenylj-3-ethyl, 5-methyl ester; mp 155-1570C. EXAMPLE 3F Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4-pyridinylsulfonyl)methyl]-4-[2-(trifluorophenyl)phenyl]-3pyridinecarboxylate; mp 219-220 C (dec). EXAMPLE 3G 5-Cyano-1,4-dihydro-6-methyl-2-[(2-pyridinylsulfonyl)methyl]-4-[2-(trifluorophenyl)phenyl]-3-pyridinecarboxylic acid, ethyl ester, N-oxide; mp 233-2350C. EXAMPLE 3H Ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4-phenyl-3-pyridinecarboxylate. EXAMPLE 3I [2,4'-Bipyridine]-3'-carboxylic acid, 5'-cyano-1',4' dihydro-6'-methyl-2'-[(phenylsulfonyl)methyl] -, ethyl ester, l-oxide EXAMPLE 3J [3,4'-Bipyridine]-3'-carboxylic acid, 5'-cyano-1',4' dihydro-6'-methyl-2'-[(phenylsulfonylEmethyl]-, ethyl ester, (mixture of isomers); mp 201-202 C. EXAMPLE 3K Ethyl 3-cyano-1,4-dihydro-6-methyl-2-[(phenylsufonyl) methyl] -4-12-(trifluoromethyl)phenyl-5 carboxylate. EXAMPLE 3L 3-Pyridinecarboxylic acid, 2-tl(4-aminophenyl)sulfonyll- methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 237-240 C. EXAMPLE 3M [2,4'-Bipyridine]-3'-carboxylic acid, 5'-cyano-1',4' dihydro-6'-methyl-2'-[(phenylsulfonyl)methyl]-, ethyl ester; mp 196-198 C. EXAMPLE 3N 3-Pyridinecarboxylic acid, 5-cyano-4-cyclohexyl6-methyl-1,4-dihydro-2-[(phenylsulfonyl)methyl]-, ethyl ester; mp 150-152 C. EXAMPLE 30 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6methyl-2-[(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 1-methylethyl ester; mp 205-207 C. EXAMPLE 3P 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6 methyl-2-[(phenylsulfonyl)methyl] -4-12-(trifluoro- methyl)phenyl]-, 2-propenyl ester; mp 187-1890C. EXAMPLE 3Q 3-Pyridinecarboxylic acid, 5-cyano-2-[[[4-(1,1-dimethylethyl)-2-methylphenyl)sulfonyl]methyl]-1,4-dihydro6-methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 155-159 C. EXAMPLE 3R 3-Pyridinecarboxylic acid, 5-cyano-2-[[(2-fluorophenyl) sulfonyl] methyl]-1,4-dihydro-6-methyl-4-12-(trifluoro- methyl)phenyl]-, ethyl ester; mp 212-213 C. EXAMPLE 3S 3-Pyridinecarboxylic acid, 2-[[(4-chlorophenyl)sulfonyl] methyll -5-cyano-1,4-dihydro-6-methyl-4-12-(trifluoro- methyl)phenyl]-, ethyl ester; mp 230-233 C. EXAMPLE 3T 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6 methyl-4-(3-nitrophenyl)-2-r(phenylsulfonyl)methyll-t ethyl ester; mp 175-176 C. EXAMPLE 3U 3-Pyridinecarboxylic acid, 5-cyano-l,4-dihydro-6- methyl-2-[(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2,3-dihydroxypropyl ester; mp 102 103 0C EXAMPLE 3V 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2 tft3-methoxy-3-oxopropyl) sulfonyl] methyll -6-methyl- 4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 119 120 0C EXAMPLE 3W 3-Quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro l-methyl-5-oxo-2-[(phenylsulfonylAmethyl]-4-[2-(tri- fluoromethyl)phenyl]-, ethyl ester; mp 214-215 C. EXAMPLE 3X 3-Quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro5-oxo-2-[(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; mp 235-2360C. EXAMPLE 4 3-Quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro1-methyl-5-oxo-2-[8phenylthio)methyl)-4-[2-(trifluoromethyl)phenyl]-, ethyl ester To a stirred solution of sodium hydride (40 mg, 60% oil dispersion) in 5 ml of tetrahydrofuran is added dropwise a solution of 480 mg of 3-quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro-5-oxo-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]- ethyl ester, in 15 ml of tetrahydrofurÅan. Hydrogen is evolved and a bright orange color develops. Methyl iodide (0.9 g) is added and the reaction mixture is stirred at room temperature for 2 hours. ShNe solvent is distilled, the residue is treated with water and the organic material is extracted with methylene chloride. The organic extract is separated, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is crystallized from ether to give 250 mg of the title compound; mp 129-130 0C. Anal. calcd. for C27H26F3NO3S; C, 64.67; H, 5.19; N, 2.79 Found: C, 64.75; H, 5.38; N, 2.74 Starting materials for use in preparation of compounds of the present invention are known or may be prepared according to methods analogous to those described below. PREPARATIVE EXAMPLES Ethyl 3-oxo-4-(4-pyridylthio)butanoate (see compound of the Formula V in Scheme II, wherein R3 is COVET and R1 is 4-psridvl) Ethyl 4-chloroacetoacetate (12.4 g, 0.075 mole) is added dropwise with stirring to a suspension of 4-mercaptopyridine (8.3 g, 0.075 mole) in a mixture of tetrahydrofuran (80 ml) and N,N-dimethylformamide (40 ml). Extherm is observed and precipitate begins to appear. The reaction mixture is stirred at ambient temperature for three hours and filtered. The filtrate is stripped to remove solvent and used as is without further purification. Ethyl 3-oxo-4-(phenylthio)butanoate (see compound of the Formula V in Scheme II, wherein R3 is CO2Et and R1 is phenyl Ethyl 4-chloroacetoacetate (15 g, 0.09 mole) is added dropwise with stirring to a solution of benzenethiol (10 g, 0.09 mole) in pyridine (15 ml), The reaction mixture is stirred for an additional two hours at ambient temperature. The reaction mixture is poured into water and the oil is extracted with ether. The ether extract is washed successively with 1 N HC1, water, dried over anhydrous MgSO4 and evaporated. This material is used as is for the next step without further purification. Anal. calcd. for C12Hl403S; C, 60.48; H, 5.92; S, 13.45 Found: C, 60.18; H, 5.59; S, 14.02 Similarly, by substituting 4-bromo-3-oxo-butanenitrile (Chem. Ber 115(1), 355-80) in place of ethyl 4-chloroacetoacetate one obtains 3-oxo-4-(phenylthio)butanenitrile. (Formula V in Scheme II, wherein R3 is CN and R1 is phenyl.) FORMULA EMI33.1 SCHEME I EMI34.1 where in n is 1 or 2 where in n is 1 or 2 SCHEME II EMI35.1 SCHEME III EMI36.1

Claims: CLAIMS (for the Contracting States BE, CH, DE, FR, GB, IT, LI, LU, NL, SE): 1. A compound having the following general formula (I) EMI37.1 and a pharmaceutically acceptable salt thereof; wherein R is (1) hydrogen; (2) lower alkyl of from one to four carbon atoms, optionally substituted with an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl of from one to four carbon atoms, or R7 and Rg, when taken together with the nitrogen atom to which they are attached form a fiveor six-membered ring having four or five CH2 groups; or (3) an arylalkylene radical in which the aryl part is phenyl optionally substituted with ode or more of (i) halo, (ii) trifluoromethyl, (iii) nitro, (iv) amino (v) mono- or di-alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together represent an alkylene of from one to six carbon atoms, (vi) cyano, (vii) lower alkoxy of from one to four carbon atoms, (viii) lower alkyl of from one to four carbon atoms, (ix) lower thioalkyl of from one to four carbon atoms; and in which the alkylene part has from one to four carbon atoms; R2 and R3, which may be the same or different, are each hydrogen, lower alkyl of from one to four carbon atoms, cyano, nitro, -CO2R4 in which R4 is hydrogen or lower alkyl of from one to four carbon atoms, optionally substituted with amino, mono-, or dialkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; ; R11 R5, and R6, which may be the same or different, are each (1) lower alkyl of from one to four carbon atoms, optionally substituted with (a) an amino group having the formula NR7R8 in which R7 and Rug are independently hydrogen or lower alkyl, or R7 and Rg, when taken together with the nitrogen atom to which they are attacked form a five- or six-membered ring having four or five carbon atoms, (b) -ORg in which Rg is hydrogen or lower alkyl of from one to four carbon atoms, or (c)-CO2R4 in which R4 is as defined above; (2) cycloalkyl of from four to seven carbon atoms; ; (3) phenyl optionally substituted with On'e, or more of (i) alkyl having from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; (vii) cyano, (viii) 'lower alkoxy of from one to four carbon atoms, and (ix) lower thioalkyl of from one to four carbon atoms; (4) arylalkylene in which the aryl part is phenyl optionally substituted with one or more of (i) alkyl of from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of'from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, and (ix) lower thioalkyl of from one to four carbon atoms; and the alkylene part has from one to four carbon atoms; or (5) heteroaryls; and wherein R2 and R5 may also be taken together to form a five- or six-membered ring having, as a member of the ring, a EMI39.1 group; n is zero or an integer of one o; two; m is zero or an integer of from one to six; and with the proviso that when n is 0, then R1 cannot be lower alkyl or cycloalkyl. 2. A compound of the formula (II) EMI39.2 and a pharmaceutically acceptable salt thereof; wherein R is (1) hydrogen; (2) lower alkyl of from one to four carbon atoms, optionally substituted with an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl of from dne to four carbons, or R7 and R8, when taken together with the nitrogen atom to which they are attached form a five- or six-membered ring having four or five CH2 groups; or (3) an arylalkylene radical in which the aryl part is phenyl optionally substituted with one or more of (i) halo, (ii) trifluoromethyl, (iii) nitro, (iv) amino, (iv) mono- or di-alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together represent an alkylene of from one to six carbon atoms, (vi) cyano, (vii) lower alkoxy of from one to four carbon atoms, (viii) lower alkyl of from one to four carbon atoms, (ix) lower thioalkyl of from one to four carbon atoms; and the alkylene part has from one four carbon atoms; R2 and R3, which may be the sameFor different, are each hydrogen, lower alkyl of from one to four carbon atoms, cyano, nitro, -CO2R4 in which R4 is hydrogen or lower alkyl of from one to four carbon atoms, optionally substituted with amino, mono-, or dialkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; ; R1, R5, and R6, which may be the same or different, are each (1) lower alkyl of from one to four carbon atoms, optionally substituted with (a) an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl, or R7 and Rg, when taken together with the nitrogen atom to which they are attacked form a five- or six-membered ring having four or five carbon atoms, (b) -ORg in which Rg is hydrogen or lower alkyl of from one to four carbon atoms, or (c)-CO2R4 in which R4 is as defined above; (2) cycloalkyl of from four to seven carbon atoms; ; (3) phenyl optionally substituted with one or more of li) alkyl having from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, and (ix) lower thioalkyl of from one to four carbon atoms; (4) arylalkylene in which the aryl part is phenyl optionally substituted with one or more of (i) alkyl of from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent at alkylene of from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, (xi) lower thioalkyl of from one to four carbon atoms; and the alkylene part has from one to four carbon atoms; or (5) heteroaryls; and wherein R2 and R5 may also be taken together to form a five- or six-membered ring having, as a member of the ring, a EMI41.1 group; n is zero or an integer of one or two; and m is zero or an integer of from one to six 3. A compound according to Claim 1 or 2, wherein R2 is cyano and n is one or two. 4. A compound according to Claim 1 or 2, and beina of the formula EMI42.1 wherein X is > CH2 or an oxygen atom. 5. A compound according to Claim 1 or 2, wherein R is hydrogen, R2 is cyano, R3 is -C02R4, R5 is methyl and m is one. 6. A compound according to Claim 1 or 2, wherein R is hydrogen, R2 and R3 are independently -C02R4, R5 is methyl and m is one. 7. A compound according to Claim 4, 5 or 6, wherein n is zero. 8. A compound according to Claim 1 or 2 having one of the following names: ethyl 5-cyano-1,4-dihydro-6-methyl-2-{(phen ylthio)methyl]-4-[2-(trifluoromethyl)phenyl] 3-pyridinecarboxylate; 3-pyridinecarboxylic acid, 5-cyano-1,2,3,4 tetrahydro-2-[(phenylthio)methylene]-6-methyl 4-[(2-trifluoromethyl)phenyl]-, ethy ester; 3-quinolinecarboxylic acid, 1,4,5,6,7,8- hexahydro-5-oxo-2- [ (phenylthio) methyl] -4- [2- (trifluoromethyl)phenyl]-, ethyl ester 3-quinolinecarboxylic acid, 1,2,3,4,5,6,7,8- octahydro-5-oxo-2-[(phenylthio)methylene] 4-[2-(trifluoromethyI)phenyll-, ethyl ester; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(2methylphenyl)thio]methyl]-4-[2-(trifluoromethyl) phenyll-3-pyridinecarboxylate; ; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylylthio)methyl]-4-(3-nitrophenyl-3-pyridinecarboxylate; ethyl 4-(2-chlorophenyl)-5-cyano-1,4-dihydro6-methyl-2-[(phenylthio)methyl]-3-pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4pyridinylthio)methyl]-4-[2-(trifluoromethyl) phenyl]-3-pyridinecarboxylatei 3-pyridinecarboxylic acid, 5-cyano-2-[[[4 (1,1-dimethylethyl)-2-methylphenyl]thio]methyl] 1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylthio)methyl]-4-82-(trifluoromethyl)phenyl]5-pyridinecarboxylate; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-2-[[(4-methoxyphenyl)thio]methyl] 6-methyl-4-[2-(trifluoromethylphenyl]-, ethyl ester; ; 3-pyridinecarboxylic acid, 2-[[(2-chlorophenylthio]methyl]-5-cyano-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-2-[[(2fluorophenyl)thio]methyl]-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 2-[[[4-(acetylamino)phenyl]thio]methyl]-5-cyano-1,4-dihydro6-methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester,' 3-pyridinecarboxylic acid, 2-[[(4-chlorophenyl)thio]methyl]-5-cyano-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-4-phenyl-2-[(phenylthio)methyl]-, ethyl ester; (Isomer A); 3-pyridinecarboxylic acid, 5-cyano-4-(2furanyl)-1,4-dihydro-6-methyl-2-[(phenythio) methyl, , ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-4-(2-phenyl-1H-imidazol-4yl)-2-[(phenylthio)methyl]-, ethyl ester 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-2-[(phenylthio)methyl]-4 (2-pyridinyl)-, ethyl ester, 3-pyridinecarboxylic acid, 5- cyano-1,4dihydro-6-methyl-2-[(2-pyridinylthio)methyl]4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-6-2-8(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, 2-cyanoethyl ester' 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-6-2-8(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-; ; 3-pyridinecarboxylic acid, 5-cyano-l,4- dihydro-6-methyl-6-2-8(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, 1-methylethyl ester7 3-pyridinecarboxylic acid, 5-cyano-1,4 dihydro-6-methyl-6-2-8(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, methyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-6-2-8(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, 2-propenyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro2-methyl-6-[(phenylthio)methyl]-4-[2-(trifluoro methyl)phenyl]-, diethyl ester3 3,5-pyridinecarboxylic acid, 1,4-dihydro6-methyl-2-[[(2-methylphenyl)thio]methyl]4-[2-(trifluoromethyl)phenyl]diethyl ester; 3,5-pyridinecarboxylic acid, 1,4-dihydro2-methyl-6-[(2-pyridinylthio)methyl]-4-[2 (trifluoromethyl)phenyl]-, diethyl ester; ; 3,5-pyridinecarboxylic acid, 1,4-dihydro 2-methyl-6- [ (4-pyridinylthio) methyl] -4- [2- (trifluoromethyl)phenyl]-, diethyl ester; - 3,5-pyridinedicarboxylic acid, 1,4-dihydro2-methyl-4-(2-phenyl-1H-imidazol-4-yl)-6-[(phenylthio)methyll-, diethyl ester; [3,4'-bipyridine]-3',5'-dicarboxylic acid, 1',4'-dihydro-2'-methyl-6'-[(phenylthio)methyl]-, diethyl esterj 3,5-pyridinedicarboxylic acid, 2-[[(2-chlorophenyl)thio]methyl]-1,4-dihydro-6-methyl-4 [2-(trifluoromethyl)phenyll-, 3-ethyl 5-methyl ester ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]3-pyridinecarboxylate3 ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(2- methylphenyl)sulfinyl]methyl]-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylate, ethyl 5-cyano-1,4-dihydro-6methyl-4-(3- nitrophenyl)-2-[(phenylsulfinyl)methyl]-3pyridinecarboxylate, ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(4- methoxyphenyl)sulfinyl]methyl]-4-[2-(trifluoromethy)phenyl]-3-pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfinyl) methyll -4- [2- (chlorophenyl) -3-pyridinecarboxylate; ; ethyl 5-cyano-1,4-dihydro-6-methyl-2-1(4- pyridinesulfinyl)methyl]-4-[2-trifluoromethyl) phenyl] -3 -pyridinecarboxylate5 3 ,5-pyridinedicarboxylic acid, 1,4-dihydro2-methyl-6-[(4-pyridinylsulfinyl)methyl]-4 [2-(trifluoromethyl)phenyl]-, diethyl ester; is ethyl 2-[[(2-chlorophenyl)sulfinyl]methyl]5-cyano-1,4-dihydro-6-methyl-4-[(2-trifluoromethyl)phenyl]-3-pyridinecarboxylate; 5-cyano-2-[[[2-(dimethylamino)ethyl]sulfinyl]methyl]-1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, ethyl ester; ethyl 4-(2-chlorophenyl) -5-cyano-1,4-dihydro- 6-methyl-2-[(4-pyridinylsulfinyl)methyl]-3 pyriainecarboxyiate; ethyl 5-cyano-4-(2,3-dichlorophenyl)-1,4dihydro-6-methyl-2-[4-pyridinylsulfinyl)methyl3-pyridinecarboxylate; 5-cyano-1,4-dihydro-6-methyl-2-[(2-pyrimi dinylsulfinyl)methyl]-4-[2-(trifluoromethyl) phenyl] -3-pyridinecarboxylic acid, ethyl ester 5-cyano-1,4-dihydro-6-methyl-2-[[(1-methyl1H-imidazol-2-yl)sulfinyl]methyl]-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, ethyl ester; ; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-4-phenyl-3-pyridinecarboxylate 3,5-pyridinedicarboxylic acid, 2-11(2-chlo:ophenyl)sulfinyll- methylene]-6-methyl-1,2,3,4-tetrahydro-4-t(2- trifluoromethyl)phenyl]-3-ethyl-5-methyl ester; 3-pyridine- carboxylic acid, 5-cyano-4-cyclohexyl-1,4dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-, ethyl ester 3-pyridinecarboxylic acid, 5-cyano-4-[2-(difluoromethoxy) phenyl]-1,4-dihydro-6-methyl-2-t(phenylsulfinyl)- methyl]-, ethyl ester; - 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, methyl ester; (53.47 mixture of isomers); 3-pyridinecarboxylic acid, 5-cyano-I,4-dihydro-6-methyl- 2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 1-methylethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2-hydroxyethyl ester, 3-pyridine- carboxylic acid, 5-cyano-1,4-dihydro-6-methyl4-(2-phenyl-1H-imidazol-4-yl)-2-[(phenylsulfinyl)methyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl 2- [ (2-pyridinylsulfinyl) methyl] -4- [2- (trifluoro- methyl)phenyl]-, ethyl ester, (+)-j 3-pyridine-. carboxylic acid, 5-cyano-2-[[(2-fluorophenyl)sulfinyl]methyl]-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl) phenyl] -, ethyl ester 3-pyr idine- carboxylic acid, 2-[[[4-(acetylamino)phenyl]sulfinyl]methyl]-5-cyano-1,4-dihydro-6-methyl 4- [2-(trifluoromethyl) phenyl] -, ethyl ester 3-pyridinecarboxylic acid, 2-[[(4-chlorophenyl)sulfinyl]methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl)phenyll-, ethyl ester, (+)-S 3-pyridinecarboxylic acid, 5-cyano-2-[[(3,4-dichlorophenyl)sulfinyl]methyl]-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl- 2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-; ; 3-quinoline- carboxylic acid, 1,4,5,6 7,8-hexahydro-1-methyl- 5-oxo-2-[(phenylsulfinyl]methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-quinolinecarboxylic acid, 1,4,5,6,7,8-hexahydro-5-oxo2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester, (+)-; ethyl 3-cyano1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]4-[2-(trifluormethyl)phenyl]-5-pyridinecarboxylate; 3-pyridine- carboxylic acid, 5-cyano-1-[2-(diethylamino) ethyll-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)- methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester1 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2-[[(3methoxy-3-oxoprpyl]sulfinyl]methyl]-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; ; 3-pyridinecarboxylic acid, 5-cyano-2-[[(2-ethoxy-2-oxoethyl)sulfinyl]methyl]-1,4-dihydro-6-methyl4-[2-(sulfluoromethyl)phenyl]-, ethyl ester7' [2,4'-bipyridine]-3'-carboxylic acid, 5'-cyano-1',4'-dihydro6'-methyl-2-'[(phenylsulfinyl)methyl]-,ethyl ester, 3,5-pyridine- dicarboxylic acid,1,4-dihydro-6-methyl-2 [[(2-methylphenyl)sulfinyl]methyl]-4-[2-(trifloromethyl)phenyl], diethyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-methyl-6 [(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl) phenyl)-, diethyl ester; 3,5-pyridinedicarboxylic acid, 1, 4-dihydro-2-methyl-6- [(2-pyridinylsulfinyl)methyl]-4-[2-(trifloromethyl)phenyl]-, diethyl ester; ; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-[[(4-methoxyphenyl)sulfinyl]methyl]-6-methyl-4-[2-(tri fluoromethyl) phenyl) -, diethyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-methyl-6 [(phenylsulfonyl)methyl]-4-[2-(trifloromethyl)phenyl]-, diethyl ester; ethyl 5-cyano-1,4dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4 [2-(trifluoromethyl)phenyl]-3-pyridinecarboxylate; ethyl 5-cyano-1,4dihydro-6-methyl-2-[[(4-methoxyphenyl)sulfonyl]methyl]-4-[2-(triflorophenyl)-3-pyridinecarboxylate; ethyl 5-cyano-1,4dihydro-6-methyl-2-[[(2-methylphenyl)sulfonyl]methyl]-4-[2-(triflorophenyl)-3-pyridinecarboxylate; ethyl 2-(((2- clorophenyl)sulfonyl]methyl]-5-cyano-1,4dihydro-6-methyl-4-[(2-trifluoromethyl)phenyl]3-pyridinecarboxylate; ; 3,5-pyridinecarboxylic acid, 2-[E(2-chlorophenyl)sulfonyl]- methyl]-1,4-dihydro-6-methyl-4-[2-(trifloromethyl)-phenyll-3-ethyl, 5-methyl ester ethyl 5-cyano-1,4dihydro-6-methyl-2-[(4-pyridinlsulfonyl)methyl] 4-[2-(tri fluoromethyl) phenyl-3-pyridinecarboxylatej 5-cyano-1,4dihydro-6-methyl-2-[(2-pyridinylsulfonyl)methyl] 4-[2-(trifluoromethylOphenyll-3-pyridinecarboxylic acid, ethyl ester, N-oxidej ethyl 5-cyano l,4-dihydro-6-methyl-2- [ (phenylsulfonyl) methyl] - 4-phenyl-3-pyridinecarboxylatei [2,4'-bipyridine]-3'-carboxylic acid, 5'-cyano-1',4'-dihydro6'-methyl-2'-[(phenylsulfonyl)methyl]-, ethyl ester, l-oxide; [3,4'-bipyridine]-3'-carboxylic acid, 5'-cyano-1',4'-dihydro6'-methyl-2'-[(phenylsulfonyl)methyl]-, ethyl ester; ; ethyl 3-cyano1,4-dihydro-6-methyl-2-[(phenylsulfoxyl)methyl]4-[2-(trifloromethyl)phenyl-5-carboxylate; -pyridine- carboxylic acid, 2-[[(4-aminophenyl)sulfonyl]methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl) phenyl) -, ethyl esther; [2,4' -bipyri- dine]-3'-carboxylic acid, 5'-cyano-1',4'-dihydro6'-methyl-2'-[(phenylsulfonyl)methyl]-, ethyl esterj 3-pyridinecarboxylic acid, 5-cyano-4-cyclohexyl-6-methyl1,4-dihydro-2-[(phenylsulfonyl)methyl]-, ethyl esterj 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl 2-l(phenylsulfonyl)methyl]-4-12- (trifluoromethyl)- phenyl]-, l-methylethyl ester; ; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl- 2- [ (phenylsulfonyl)methyl] -4- [2-(trifluoromethyl) - phenyl]-, 2-propenyl ester; 3-pyridinecarboxylic acid, 5-cyano-2-[[[4-(1,1-dimethylethyl)-2-methylphenyl]sulfonyl]methyl]-1,4 dihydro-6-methyl-4-12-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridine- carboxylic acid, 5-cyano-2-11(2-fluorophenyl)- sulfonyl]methyl]-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl)phenyl] -, ethyl ester; ; 3-pyridinecarboxylic acid, 2-[[(4-chlordophenyl)sulfonyl] methyl] -5-cyano-l, 4-dihydro-6 -methyl-4 - C2- (trifluoromethyl)phenyl)-, ethyl ester 3-pyridine- carboxylic acid, 5-cyano-1,4-dihydro-6-methyl4-(3-nitrophenyl)-2-[(phenylsulfonyl)methyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl 2- ( (phenylsulfonyl)methyl) -4- (2-(trifluoromethyl) - phenyl]-, 2,3-dihydroxypropyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2-f [(3- methoxy-3-oxopropyl)sulfonyl]methyl]-6-methyl4-[2(trifloromethyl)phenyl]-, ethyl ester; ; 3 -gu inol ine- carboxylic acid, 1,4,5,6,7,8-hexahydro-l-methyl- 5-oxo-2-[(phenylsulfonyl)methyl]-4-[2-(trifloro methyl)phenyl]-, ethyl ester; 3-quinoline carboxylic acid, 1,4,5,6.,7,8-hexahydro-5-oxo- 2-[(phenylsulfonyl)methyl]-4-[2-(trifloromethyl) phenyl]-, ethyl ester, 3-quinoline carboxylic acid,1,4,5,6,7,8-hexahydro-1-methyl 5-oxo-2-[(phenylthio)methyl]-4-[2-(trifloro methyl)phenyl]-, ethyl ester. 9. A pharmaceutical composition comprising an effective amount of a compound as claimed in any preceding claim in admixture with a pharmaceutically acceptable carrier or diluent. 10. For use in a method of treating a mammal suffering from a cardiovascular disorder, a compound as claimed in any one of Claims 1 to 8 or a pharmaceutical composition as claimed in Claim 9 11. A process for preparing a compound of the formula (I) or (II) as defined in Claims 1 and 2 respectively, which process comprises: contacting the compounds EMI56.1 wherein R1, R2, R4, R5 and R6 are as defined in Claims 1 or 2 in an organic solvent to form a compound of formula (Io) or (IIo) EMI57.1 and, if desired, further reacting the product in one or more of the following steps: (1) oxygenating the sulphur atom (2) alkylating the nitrogen atom; and (3) reacting the -C02R4 group to obtain an R3 group other than -CO2R4; and optionally forming a pharmaceutically acceptable salt thereof. CLAIMS (for the Contracting State AT): 1. A process for preparing a compound having the following general formula (I) EMI58.1 and a pharmaceutically acceptable salt thereof; wherein R is (1) hydrogen; (2) lower alkyl of from one to four carbon atoms, optionally substituted with an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl of from one to four carbon atoms, or R7 and Rg, when taken together with the nitrogen atom to which they are attached form a fiveor six-membered ringhaving four or five CH2 groups; or (3) an arylalkylene radical in which the aryl part is phenyl optionally substituted with one or more of (i) halo, (ii) trifluoromethyl, (iii) nitro;, (iv) amino; (v) mono- or di-alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together represent an alkylene of from one to six carbon atoms, (vi) cyano, (vii) lower alkoxy of from one to four carbon atoms, (viii) lower alkyl of from one to four carbon atoms, (ix) lower thioalkyl of from one to four carbon atoms; and in which the alkylene part has from one to four carbon atoms; R2 and R3, which may be the same or different, are each hydrogen, lower alkyl of from one to four carbon atoms, cyano, nitro, -CO2R4 in which R4 is hydrogen or lower alkyl of from one to four carbon atoms, optionally substituted with amino, mono-, or dialkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; ; R1, Rg, and R6, which may be the same or different, are each (1) lower alkyl of from one to four carbon atoms, optionally substituted with (a) an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl, or R7 and R81 when taken together with the nitrogen atom to which they are attacked form a five- or six-membered ring having four or five carbon atoms, (b) -ORg in which Rg is hydrogen or lower alkyl of from one to four carbon atoms, or (c)-C02R4 in which R4 is as defined above; (2) cycloalkyl of from four to seven carbon atoms; ; (3) phenyl optionally substituted with one or more of (i) alkyl having from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, and (ix) lower thioalkyl of from one to four carbon atoms; (4) arylalkylene in which the aryl part is phenyl optionally substituted with one or more of (i) alkyl of from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, and (ix) lower thioalkyl of from one to four carbon atoms; and the alkylene part has from one to four carbon atoms; or (5) heteroaryls; and wherein R2 and R5 may also be taken together to form a five- or six-membered ring having, as a member of the ring, a EMI60.1 group; n is zero or an integer of one or two; m is zero or an integer of from one to six; and with the proviso that when n is 0, then R1 cannot be lower alkyl or cycloalkyl; which process comprises: contacting the compounds EMI60.2 wherein R1, R2, R4, R5 and R6 are as defined above in an organic solvent to form a compound of formula (Io) EMI61.1 and, if desired, further reacting the product in one or more of the following steps: (1) oxygenating the sulphur atom (2) alkylating the nitrogen atom; and (3) reacting the -C02R4 group to obtain an R3 group other than -C02Rq; and optionally forming a pharmaceutically acceptable salt thereof. 2. A process for preparing a compound of the formula (II) EMI61.2 and a pharmaceutically acceptable salt thereof; wherein R is (1) hydrogen; (2) lower alkyl of from one to four carbon atoms, optionally substituted with an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl of from one to four carbons, or R7 and Rg, when taken together with the nitrogen atom to which they are attached form a five- or six-membered ring having four or five CH2 groups; or (3) an arylalkylene radical in which the aryl part is phenyl optionally substituted with one or more of (i) halo, (ii) trifluoromethyl, (iii) nitro, (iv) amino, (iv) mono- or di-alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken-together represent an alkylene of from one to six carbon atoms, (vi) cyano, (vii) lower alkoxy of from one to four carbon atoms, (viii) lower alkyl of from one to four carbon atoms, (ix) lower thioalkyl of from one to four carbon atoms; and the alkylene part has from one to four carbon atoms; R2 and R3, which may be the same or different, are each hydrogen, lower alkyl of from one to four carbon atoms, cyano, nitro, -CO2R4 in which R4 is hydrogen or lower alkyl of from one to four carbon atoms, optionally substituted with amino, moao-, or dialkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; ; R1, R5, and R6, which may be the same or different, are each (1) lower alkyl of from one to four carbon atoms, optionally substituted with (a) an amino group having the formula NR7R8 in which R7 and R8 are independently hydrogen or lower alkyl, or R7 and R8, when taken together with the nitrogen atom to which they are attacked form a five- or six-membered ring having four or five carbon atoms, (b) -ORg in which Rg is hydrogen or lower alkyl of from one to four carbon atoms, or (c)-C02R4 in which R4 is as defined above; (2) cycloalkyl of from four to seven carbon atoms; ; (3) phenyl optionally substituted with one or more of (i) alkyl having from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamino, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, and (ix) lower thioalkyl of from one to four carbon atoms; (4) arylalkylene in which the aryl part is phenyl optionally substituted with one or more of (i) alkyl of from one to four carbon atoms, (ii) halo, (iii) trifluoromethyl, (iv) nitro, (v) amino, (vi) mono- or di- alkylamino in which the or each alkyl is independently a lower alkyl of from one to six carbon atoms or, in the case of a dialkylamiAo, in which the two alkyls, when taken together, represent an alkylene of from one to six carbon atoms; (vii) cyano, (viii) lower alkoxy of from one to four carbon atoms, (ix) lower thioalkyl of from one to four carbon atoms; and the alkylene part has from one to four carboniaztoms; or (5) heteroaryls; and wherein R2 and R5 may also be taken together to form a five- or six-membered ring having, as a member of the ring, a EMI63.1 group; n is zero or an integer of one or two; and m is zero or an integer of from one to six. which process comprises: contacting the compounds EMI64.1 wherein R1, R2, R4, R5 and R6 are as defined above in an organic solvent to form a compound of formula fIo) EMI64.2 and, if desired, further reacting the product in one or more of the following steps: (1) oxygenating the sulphur atom (2) alkylating the nitrogen atom; and (3) reacting the -CO2R4 group to obtain an R3 group other than -dd2R4; and optionally forming a pharmaceutically acceptable salt thereof. 3. A process according to Claim 1 or 2, wherein R2 is cyano and n is one or two. 4. A process according to Claim 1 or 2, for preparing a compound of the EMI65.1 EMI65.2 wherein X is > CH2 or an oxygen atom. 5. A process according to Claim 1 or 2, wherein R is hydrogen, R2 is cyano, R3 is -CO2 R4, R5 is methyl and m is one. 6. A process according to Claim 1 or 2, wherein R is hydrogen, R2 and R3 are independently -CO2 R4, R5 is methyl and m is one. 7. A process according to Claim 4, 5 or 6, wherein n is zero. 8. A process according to Claim 1 or 2 for preparing a compound having one of the following names: ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phen ylthio) methyll -4- [2-(trifluorometh:l)phenyl]- 3-pyridinecarboxylate3 3-pyridinecarboxylic acid, 5-cyano-1,2,3,4 tetrahydro-2-[(phenylthio)methylene]-6-methyl 4-[(2-trifloromethyl)phenyl]-, ethyl ester; 3-quinolinecarboxylic acid, 1,4,5,6,7,8 hexahydro-5-oxo-2-[(phenylthhio)methyl]-4-[2 (trifluoromethyl) phenyl) -, ethyl ester; 3-quinolinecarboxylic acid, 1,2,3,4,5,6,7,8- octahydro-5-oxo-2-[(phenylthio)methylene] 4-[2-(trifloromethyl)phenyl]-, ethyl ester; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(2methylphenyl)thio]methyl]-4-[2-(trifloromethyl)phenyl]-3-pyridinecarboxylate; ; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[)phenylthio)methyl]-4-(3-nitrophenyl)-3-pyridinecarboxylate; ethyl 4-(2-chlorophenyl)-5-cyano-1,4-dihydro6-methyl-2-[(phenylthio)methyl]-3-pyridinecarboxylate: ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4 pyridinylthio) methyl -4- I2- (trifluoromethyl)- phenyl]-3-pyridinecarboxylate; 3-pyridinecarboxylic acid, 5-cyano-2- (([4- (1,1-dimethylethyl)-2-methylphenyl]thiho]methyl]1,4-dihydro-6-methyl-4-[2-(trioifluoromethyl)phenyl]ethyl ester; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]5-pyridinecarboxylate; ; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-2-[[(4-methoxyphenyl)thio]methyl] 6-methyl-4-[2-(trifluoromethylphenyl]-, ethyl ester' 3-pyridinecarboxylic acid, 2- [ ( (2-chlorophen- ylthio]methyl]-5-cyano-1,4-dihydro-6-methyl4-[2-(triflluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-2-[[(2fluorophenyl)thio]]methyl]-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 2-[[[4-(acetylamino)phenyl]thio]methyl]-5-cyano-1,4-dihydro6-methyl-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 2-[[(4-chlorophenyl)thio]methyl]-5-cyano-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-l,4- dihydro-6-methyl-4-phenyl-2- r (phenylthio) methyl)-, ethyl ester; (Isomer A); 3-pyridinecarboxylic acid, 5-cyano-4-(2furanyl)-1,4-dihydro-6-methyl-2-[(phenylthio) methyll-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-4-(2-phenyl-1H-imidzol-4yl)-2-[(phenylthio)methyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-l,4- dihydro-6-methyl-2- ( (phenylthio) methyl] -4- (2-pyridinyl)-, ethyl ester; 3-pyridinecarboxylic acid, - 5-cyano-1,4 dihydro-6-methyl-2-[(2-pyridinylthio)methyl]4[2-(trifluoromethyl)phenyl-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-2-[(phenykthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, 2-cyanoethyhl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4 dihydro-6-methyl-2- ((phenylthio) methyl] -4- [2-(trifluoromethyl)phenyl]-; ; 3-pyridinecarboxylic acid, 5rcyano-l,4- dihydro-6-methyl-2-[(phenylthio)methyl]-4 [2-(triflluoromethyl)phenyl]-, 1-methylethyl ester. 3-pyridinecarboxylic acid, 5-cyano-1,4 dihydro-6-methyl-2-[(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, methyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4dihydro-6-methyl-2-[(phenylthio)methyl]-4 [2-(trifluoromethyl)phenyl]-, 2-propenyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro2-methyl-6-[(phenylthio)methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; 3 3,5-pyridinecarboxylic acid, 1,4-dihydro6-methyl-2-[[(2-methylphenyl)thio]methyl]4-[2-(trifluoromethyl)phenyl]diethyl ester; 3,5-pyridinecarboxylic acid, 1,4-dihydro2-methyl-6-[(2-pyridinylthio)methyl]-4-[2 (trifluoromethyl)phenyl]-, diethyl ester; 3 ,5-pyridinecarboxylic acid, 1,4-dihydro2-methyl-6-[(4-pyridinylthio)methyl]-4-[2 (trifluoromethyl)phenyl]-, diethyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro2-methyl-4-(2-phenyl-1H-imidazol-4-yl)-6-[(phenylthio)methyll-, diethyl ester; [3,4'-bipyridine]-3',5'-dicarboxylic acid, lE,4'-dihdro-2'-methyl-6'-l(phenylthio)methyl]-, diethyl esterj 3,5-pyridinedicarboxylic acid, 2-[t(2-chloro- phenyl)thio]methyl]-1,4-dihydro-6-methyl-4 t2-(trifluoromethyl)phenyll-r 3-ethyl 5-methyl ester; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phenylsulfinyl) methyl] -4-12- (trifluoromethyl) phenyl] 3-pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[[(2 methylphenyl) sulfinyl] methyl] -4- [2-(trifluoro- methyl)phenyl]-3-pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro-6-methyl-4-(3nitrophenyl)-2-[(phenylsulfinyl)methyl]-3pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro-6-methyl-2-1[(4- methoxvphenyl) sulfinyll methyl] -4- I2-(trifluoro- methyl)phenyll-3-pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro--methyl-2-[(phen- ylsulfinyl)methyl]-4-[2-(chlorophenyl)-3-pyridinecarboxylate; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(4pyridinylsulfinyl) methyl] -4- [2- (trifluoromethyl) phenyl]-3-pyridinecarboxylate) 3,5-pyridinedicarboxylic acid, 1,4-dihydro2-methyl-6-[(4-pyridinylsulfinyl)methyl]-4 [2-(trifluoromethyl)phenyl]-, diethyl ester; is ethyl 2-[[(2-chlorophenyl)sulfinyl)methyl]5-cyano-1,4-dihydro-6-methyl-4-[(2-trifluoromethyl)phenyll-3-pyridinecarboxylatej S-cyana-a-[[ [2-(dimethylamino) ethlrll sul- finyl]methyl]-1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)phenyl9-3-pyridinecaarboxylic acid, ethyl ester; t ethyl 4-(2-chlorophepnyl)-5-cyano-1,4-dihydro6-methyl-2-[(4-pyridinylsulfinyl)methyl]-3pyridinecarboxylate; ethyl 5-cyano-4-(2,3-dichlorophenyl)-1,4dihydro-6-methyl-2-[4-pyridinylsulfinyl)methyl 3-pyridinecarboxylatej 5-cyano-1,4-dihydro-6-methyl-2-[(2-pyrimi dinylsulfinyl)methyl]-4-[2-(triflluoromethyl)phenyl]-3-pyridinecarboxylic acid, ethyl ester; 5-cyano-1,4-dihydro-6-methyl-2-[[(1-methyl1H-imidazol-2-yl)aulfinyl]methyl]-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, ethyl ester; ethyl 5-cyano-1,4-dihydro-6-methyl-2-[(phen ylsulfinyl)methyl]-4-phenyl-3-pyridinecarbo-xylateX 3 ,5-pyridinedicarboxylic acid, 2-I1 (a-chlorophenyl) sulfinyll- methylene]-6-methyl-1,2,3,4-tetrahydro-4-[(2trifluoromethyl)phpenyl]-3-ethyl-5-methyl ester; ; - - - 3-pyridinecarboxylic acid, 5-cyano-4-cyclohexyl-1,4dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-, ethyl ester 3-pyridinecarboxyllllic acid, 5-cyano-4-[2-(difluoromethoxy)phenyl]-1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]-, methyl]-, ethyl ester; - 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfinyl)methyl]-4-[2-(trifluoro methyl)phenyli-, methyl ester; (53.47 mixture of isomers); 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromthyl)phenyl]-, 1-methylethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2-hydroxyethyl esterj - .- 3-pyridine- carboxylic acid, 5-cyano-1,4-dihydro-6-methyl4-(2-phenyl-1H-imidazol-4-yl)-2-[(phenylsulfinyl)methyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(2-pyridinylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester, #-; 3-pyridine'-- carboxylic acid, 5-cyano-2-[[(2-fluorophenyl)sulfinyl]methyl]-1,4,dihydro-6-methyl-4-[2 (trifluoromethyl)phenyl]-, ethyl ester; ; 3-pyridinecarboxylic acid, 2-[[[4-(acetylamino)phenyl]sulfinyl]methyl]-5-cyano-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 2-[[(4-chlorophenyl)sulfinyl]methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl)phenyli-, ethyl ester, (+ 3-pyridinecarboxylic acid, 5-cyano-2-[[(3,4-dichlorophenyl)sulfinyl]methyl]-1,4-dihydro-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl) phenyl] -, 3-quinolinecarboxylic acid, 1,4,5,6,7 ,8-bexahydro-l-methyl- 5-oxo-2-[(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, ethyl ester; ; -¯¯ 7 3-quinoline- carboxylic acid, - 1,4,5,6,7,8-hexahydro-5-oxo- 2-[(phenylsulfinyl)methyl]-4-] 2-(trifluoromethyl)phenyl-, ethyl ester, (t)-; ethyl 3-cyano1,4-dihydro-6-methyl-2-[(phenylsulfinyl)methyl]4-[2-(trifluoromethyl)phenyl]-5-pyridinecarboxylate; 3-pyridine- carboxylic acid, 5-cyano-1-E2-(diethylamino)- ethyl]-1,4-dihydro-6-methyl-2-[(phenylsulfinyl) methyl]-4-f2-(trifluoramethyl)phenyll-, ethyl ester 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2-[[(3methoxy-3-oxopropyl]sulfinyl]methyl]-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-2-[[(2-ethoxy-2-oxoethyl)sulfinyl]methyl]-1,4-dihydro-6-methyl4-12-(sulfluoromethyl)phenyll-, ethyl ester; ; * 12,4'-bipyri- dine]-3'-carboxylic acid, 5'-cyano-1',4'-dihydro6'-methyl-2'-[(phenylsulfinyl)methyl]-, ethyl ester' 3,5-pyridinedicarboxylic acid, 1,4-dihydro-6-methyl-2 [[(2-methylphenyl)sulfinyl]methyl]-4-[2-(trifluoromethyl)phenyll, diethyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-methyl-6 [(phenylsulfinyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, diethyl ester; 3 ,5-pyridinedicarboxylic acid, 1, 4-dihydro-2-methyl-6 - [(2-pyridinylsulfinyl)methyl]-4-[2-(trifloro methyi)phenyl]-, diethyl ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-[[(4-methoxyphenyl)sulfinyl]methyl]-6-methyl-4-[2-(tri fluoromethyl)phenyl] -, diethyl ester; ; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2-methyl-6 [(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl) phenyl] -, diethyl ester; ethyl 5-cyano-1,4dihydro-6-methyl-2-[(phenylsulfonyl)methyl]-4 [2-(trifloromethyl)phenyl]-3-pyridinecarboxylate; ethyl 5-cyano-1,4dihydro-6-methyl-2-[[(4-methoxyphenyl)sulfonyl]methyl]-4-[2-(trifluorophpenyl)-3-pyridinecarboxylate ethyl 5-cyano-1,4dihydro-6-methyl-2-[[(2-methylphenyl)sulfonyl]methyl]-4-[2-(trifluorophenyl)-3-pyridinecarboxylate ethyl 2-I[(2- chlorophenyl)sulfonyl]methyl]-5-cyano-1,4dihydro-6-methyl-4-[(2-trifluoromethyl)phenyl] 3 -pyridinecarboxylate; ; 3,5-pyridinecarboxylic acid, 2-[[(2-chlorophenyl)sulfonyl]methyl]-1,4-dihydro-6-methyl-4-[2-(trifluoromethyl)-phenyl]-3-ethyl, 5-methyl ester) - ethyl 5-cyano-1,4dihydro-6-methyl-2-[(4-pyridinylsulfonyl)methyl] 4-12-(trifluoromethyl)phenyl]-3-pyridinecarboxylate; 5-cyano-1,4dihydro-6-methyl-2-[(2-pyridinylsulfonyl)methyl] 4-12- (trifluoromethyl) phenyli -3-pyridinecarboxylic acid, ethyl ester, N-oxidej ethyl 5-cyano1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl] 4-phenyl-3-pyridinecarboxylate; I2,4'-bipyri- dine] -3' -carboxylic acid, 5'-cyano-1',4'-dihydro6'-methyl-2'-[(phenylsulfonyl)methyl]-, ethyl ester, l-oxide; ; [3,4'-bipyridine]-3'-carboxylic acid, 5-cyano-1',4'-dihydro6'-methyl-2'-[(phenylsulfonyl)methyl]-, ethyl ester; ethyl 3-cyano1,4-dihydro-6-methyl-2-[(phenylsulfonyl)methyl]4-[2-(trifluoromethyl)phenyl-5-carboxylate; &num;-pyridine- carboxylic acid, 2-[[(4-aminophenyl)sulfonyl]methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl)phenyl]-, ethyl ester; [2,4'-bipyridine]-3'-carboxylic acid, 5-cyano-1',4'-dihydro 6'-methyl-2'-C(phenyIsulfonyl)methyl]-, ethyl esterj 3-pyridinecarboxylic acid, 5-cyano-4-cyclohexyl-6-methyl 1,4-dihydro-2-[(phenylsulfonyl)methyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl 2-1 (phenylsulfonyl) methyl] -4- [2-(trifluoromethyl) phenyl]-, 1-methylehyl ester; ; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl 2-t(phenylsulfonyl)methyll-4-12-(trifluoromethyl)- phenyl]-, 2-propenyl ester; 3-pyridinecarboxylic acid, 5-cyano-2-[[[4-(1,1-dimethylethyl)-2-methylphenyl]sulfonyl]methyl]-1,4 dihydro-6-methyl-4-t2-(trifluoromethyl)phenyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-2-[[(2-flluorophenyl)sulfonyl]methyl]-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl) phenyl] -, ethyl ester 3-pyridine- 1 carboxylic acid, 2-[[(4-chlorophenyl)sulfonyl]methyl]-5-cyano-1,4-dihydro-6-methyl-4-[2 (trifluoromethyl) phenyl] -, ethyl ester. - 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl4-(3-nitrophenyl)-2-[(phenylsulfonyl)methyl]-, ethyl ester; 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-6-methyl2-[(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl)phenyl]-, 2,3-dihydroxypropyl ester 3-pyridinecarboxylic acid, 5-cyano-1,4-dihydro-2-I1(3- methoxy-3-oxopropyl)sulfonyl]methyl]-6-methyl4-[2-(trifluoromethyl)phenyl]-, ethyl ester; 3-guinoline- casrboxylic acid, 1,4,5,6,7,8-hexahydro-1-methyl 5-oxo-2-[(phenylsulfonyl)methyl]-4-[2-(trifluoro methyl)phenyl]-, ethyl ester; ; 3-guinoline carboxylic acid, 1,4,5,6-,7,8-hexahydro-5-oxo- 2-[(phenylsulfonyl)methyl]-4-[2-(trifluoromethyl) phenyll-, ethyl ester, - 3-quinoline carboxylic acid, 1,4,5,6,7 ,8-hexahydro-l-methyl- 5-oxo-2-[(phenylthio)methyl]-4-[2-(triiofluoro methyl)phenyl]-, ethyl ester. 9. A process for preparing a pharmaceutical composition which process comprises cdmbining an effective amount of a compound prepared by a process as claimed in any preceding claim together with a pharmaceutically acceptable carrier or diluent. 10. For use in a method of treating a mammal suffering from a cardiovascular disorder, a compound prepared by a process as claimed in any one of Claims 1 to 8 or a pharmaceutical composition prepared by a process as claimed in Claim 9.

Inventors: SIRCAR, ILA
Applicants: WARNER-LAMBERT COMPANY
Application year: 1986
Main classification: C07D211
IPC codes: C07D211, C07D215, C07D405, C07D401