Abstract:
Compounds of the formula ##STR1## wherein the variables are defined in the specification. The compounds and their salts are soft anticholinergic/antisecretory agents especially useful as mydriatics and as antiperspirants.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of application Ser. No. 08/104,650, filed Aug. 11, 1993, now U.S. Pat. No. 5,418,244, which is a divisional of application Ser. No. 07/931,320, filed Aug. 18, 1992, now U.S. Pat. No. 5,258,388, which is a divisional of application Ser. No. 07/558,823, filed Jul. 27, 1990, now U.S. Pat. No. 5,223,528, which is a continuation of application Ser. No. 07/245,333, filed Sep. 16, 1988, now abandoned, which is a continuation-in-part of application Ser. No. 07/189,709, filed May 3, 1988, now abandoned, which is a continuation-in-part of application Ser. No. 07/130,454, filed Nov. 17, 1987, now abandoned, which is the U.S. national phase of PCT/US87/00533, filed Mar. 17, 1987 and a continuation-in-part of application Ser. No. 06/839,941, filed Mar. 17, 1986, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to certain novel anticholinergic, mydriatic and antisecretory compounds as well as pharmaceutical and anti perspirant compositions containing the novel compounds and methods of treatment of animals and humans in need thereof. 
     2. Prior Art 
     Commercially available anticholinergic drugs such as atropine and scopolamine and their synthetic analogs all share a variety of undesirable side effects. In the elderly, excitement, agitation and drowsiness are frequently observed even in small doses. Dangerous central nervous system mediated psychotic reactions and behavioral disturbances have occurred in children after topical ocular administration. Ophthalmic use may also induce local side effects such as transient stinging, allergic lid reactions, follicular conjunctivitis, edema and photophobia. See Toxicology of Commercial Products, R. E. Gosselin et al, Eds. (Williams &amp; Wilkins, Balt., 4th Ed., 1976) Sec. III, pp. 43-46. 
     Mydriatic agents are an important class of compounds that are used to dilate the pupil. Mydriasis is required during ophthatmic examinations, in order to provide for a more complete examination of the fundus, the vitreous and the periphery of the lens, and in various surgical procedures such as those reported by Freeman et al, American Intra-Ocular Society Journal 7:17214 173 (1981) (e.g., vitrectomy, lens extraction, and intraocular lens implantation). Commercially available mydriatic drugs such as atropine, scopolamine, homatropine and their synthetic analogs all suffer from several disadvantages. Because the mydriasis induced by these agents causes blurred vision and is of a relatively long duration, i.e., several hours, it is necessary to virtually immobilize the patient after the ophthalmic examination until the mydriasis subsides and the patient can resume normal activities. Ophthalmic use of these agents may also induce local side effects such as transient stinging, allergic lid reactions, follicular conjunctivitis, edema and photophobia. See R. E. Gossel in et al supra. 
     One of the commonly known effects of antisecretory agents is inhibition of eccrine sweating and compensatory cutaneous flush. Systemically administered anticholinergics do generally decrease the secretion of the sweat glands, as well as saliva and that of other secretory glands. Based on these properties, it has been long investigated how one could safely use an antimuscarinic agent to inhibit local hyperhydration by topical application. Although a wide range of compounds have proved to be highly effective as antiperspirants when applied topically, it was concluded that they are in general not safe to use because of the well-known systemic effects of these drugs at a possible over-exposure. Side effects appear even at very low concentrations when highly potent anticsolinergics are used. 
     It would be desirable to obtain practically exclusively locally acting agents, which is possible if the rate of penetration-absorption and the rate of in vivo destruction are well-balanced: if the latter is faster, no buildup and consequently no systemic effects due to the drug would be observed. 
     New drug design approaches can lead to novel, safer anticholinergic drugs with fewer side effects. One new approach that has shown promise is the soft drug design proposed by Bodor (Bodor, Chemtech, Jan. 28, 1984, pp. 28-38, and Bodor, in Design of Biopharmaceutical Properties Through Products and Analogs, ed. E. B. Roche, Washington, D.C., Academy of Pharmaceutical Sciences, 1977, pp. 98-135) and used to design and synthesize anticholinergic agents and other pharmacologically active classes of drugs. Previous soft ester analogs of anticholinergics were synthesized from cyclopentylpheny lacetic acid, pnenylacetic acid and branched aliphatic carboxylic acids. These soft drugs, also known as soft analogs, are described in U.K. Patent Application No. 7848850, filed Dec. 18, 1978 and published under U.K. Patent Application Publication No. 2010270A on Jun. 27, 1979, and in a related publication by Bodor et al, J. Med. Chem. 23, pp. 474-480 (1980). Nevertheless, it would be desirable to design yet other soft anticholinergic drugs, especially to design such drugs using the &#34;inactive roetab olite approach&#34;. According to this approach, an inactive metabolite (which could be hypothetical) is selected and reactivated by synthesizing an agent resembling the parent drug. The soft drug is designed with a molecular soft spot which should predictably metabolize back to the inactive starting metabolite in vivo in one step and without going through toxic intermediates. 
     It is an object of the present invention to provide such novel anticholinergic compounds which exhibit anticholinergic properties, which induce mydriasis and which also exhibit local antisecretory, especially antiperspirant, properties as well as pharmaceutical and antiperspirant compositions and methods of treatment embodying those compounds which are more effective and less toxic than those presently available. 
     SUMMARY OF THE INVENTION 
     The foregoing and other objects are realizeal by the present invention which provides novel compounds having the formula: ##STR2## wherein: R 1  is C 1  -C 8  straight or branched alkyl; C 2  -C 8  straight or branched alkenyl; (C 3  -C 8  cycloalkyl)-C p  H 2p  -- wherein p is an integer from 0 to 4, and wherein the 3- to 8-membered ring portion may optionally bear 1 to 4 C 1  -C 4  straight or branched alkyl substituents; (C 3  -C 8  cycloalkenyl)-C p  H 2p  -- wherein p is an integer from 0 to 4 and wherein the 3- to 8-membered ring portion may optionally bear 1 to 4 C 1  -C 4  straight or branched alkyl substituents; C 6  H 5  --C q  H 2q  -- wherein q is an integer from 1 to 4; or (C 6  -C 18  polycarbocyclic)-C p  H 2p  -- wherein p is an integer from 0 to 4, the 6- to 18-membered ring portion consisting of 2 to 4 rings which may be bridged or fused, which may be saturated or unsaturated and which may optionally bear one or more C 1  -C 8  straight branched alkyl substituents, the total carbon atom content of all such optional alkyl substituents being from 1 to 10; 
     R 2  is any radical defined by R 1  above, or R 2  is phenyl optionally bearing 1 to 3 C 1  -C 4  straight or branched alkyl substituents; 
     R 3  is H, 2- , 3- or 4-pyridyl , phenyl optionally bearing 1 to 3 C 1  -C 8  straight or branched alkyl substituents, C 1  -C 8  straight or branched alkyl or (C 3  -C 8  cycloalkyl)-C p  H 2p  -- wherein p is an integer from 0 to and wherein the 3- to 8-membered ring portion may optionally bear 1 to 4 C 1  -C 4  straight or branched alkyl substituents; 
     n is an integer from 0 to 4; 
     X is ##STR3## wherein R 8  is H or C 1  -C 5  or branched alkyl; ##STR4## wherein each of R 9  and 9 10 , which may be the same or different, is H or C 1  -C 5  straight or branched alkyl; .brket open-st.S(CH 2 ) x  .brket close-st. wherein x is 0 or 1; .brket open-st.O(CH 2 ) x  .brket close-st. wherein x is 0 or 1; or ##STR5## wherein x is 0 or 1 and R 11  is H or C 1  -C 5  straight or branched alkyl; 
     m is an integer from 0 to 4; and 
     R 4  is ##STR6## wherein R 5  is C 1  -C 5  straight or branched alkyl; or R 4  is ##STR7## wherein each of R 6  and R 7 , which may be the same or different, is selected from the group consisting of C 1  -C 5  straight or branched alkyl, C 6  H 5  --C q  H 2q  -- wherein q is an integer from 1 to 4, phenyl optionally bearing 1 to 3 C 1  -C 4  straight or branched alkyl substituents, and (C 3  -C 8  cycloalkyl)-C p  H 2p  -- wherein p is an integer from 0 to 4 and wherein the 3- to 8-membered ring portion may optionally bear 1 to 4 C 1  -C 4  straight or branched alkyl substituents, or wherein R 6  and R 7  are combined such that --NR 6  R 7  represents the residue of a saturated monocyclic secondary amine; or R 4  is a radical of the formula ##STR8## wherein formula z is an integer from 0 to 3; the acid additions salts of the compounds of formula (I) with acids of the formula HY wherein Y is a pharmaceutically acceptable anion; and the quaternary ammonium salts of the compounds of formula (I) with compound of the formula R 12  Y wherein Y is above and R 12  is C 1  -C 4  straight or branched alkyl or benzyl. 
     The compounds of formula (I) and their salts are designed such that the ester group, --COOR 1 , is metabolically hydrolyzable to the free alcohol (R 1  --OH) and a non-toxic metabolite of an anticholinergic agent following administration to a human or non-human animal. 
     The invention further provides pharmaceutical compositions in unit dosage form comprising an anticholinergic or mydriasis-inducing effective amount of a compound of the above formula or an acid addition salt or quaternary ammonium salt thereof and a pharmaceutically acceptable carrier therefor; and antiperspirant compositions comprising an antiperspirant effective amount of said compound or salt and a non-toxic carrier therefor. 
     Finally, the invention also provides methods of treatment comprising administering to an animal or human in need thereof an anticholinergic or mydriasis-inducing or an antisecretory/antiperspirant effective amount of a compound of the above formula or salt thereof. 
    
    
     BRIEF DESCRIPTION OF THE DRAWING 
     FIG. 1 depicts the mydriati cactivity of a representative compound of the invention (0.05% and 0.1%) in rabbits compared with tropicamide (0.1%). 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The invention is predicared on the discovery that certain esters of in active polar acidic metabolites of atropine, scopolamine and other known anticholinergic compounds, as well as synthetic analogs thereof, are active anticnolinergic compounds which are significantly less toxic than their parent free alcohols. Several have also been found to be active mydriatic agents which induce a much shorter duration of mydriasis than the parent free alcohols. 
     For example, the free acids having the structural formula: ##STR9## are anticholinergically inactive metabolites of atropine and scopolamine, respectively. Certain esters of these acids possess anticholinergic, mydriatic and antisecretory/antiperspirant properties equivalent to atropine and scopolamine but are far less toxic. The esters are metabolically hydrolyzed to the above inactive acidic metabolites (II) and (III) and nontoxic alcohols when administered to animals or humans. 
     The structural variables R 2 , R 3 , R 4  and m in formula (I) are selected such that those portions of the compound of formula (I) closely resemble the corresponding portions of a known anticholinergic agent. The R 1  substituent is selected such that it is metabolically hydrolyzable to the free alcohol and the inactive metabolite. All of the groups are selected such that they do not detrimentally affect the anticholinergic mydriatic/antisecretory/antiperspirant properties of the compound or adversely affect the nontoxic nature of the compound. Preferably, when it is desired th at the compound not enter the central nervous system, th e compound of formula (I) is utilized in its quaternary salt form. The quaternary salts are also preferred in that they frequently possess higher anticholinergic/mydriatic/antisecretory/antiperspirant activity than the corresponding non-quaternized compounds. 
     With respect to the various groups encompassed by the generic terms used in this specification, the following definitions and explanations are applicable: 
     The alkyl groupings encompassed by the R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11  and R 12  structural variables in formula (I) include some or all of the following, depending on the specific carbon atom limitations expressed with formula (I) for the particular alkyl group involved: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl and octyl, and their branched-chain isomers such as isopropyl, isobutyl and the like. 
     The alkenyl groupings encompassed by R 1  and R 2  in formula (I) can be exemplified by vinyl, propenyl and butenyl. 
     The optionally substituted C 3  -C 8  cycloalkyl portion of the (C 3  -C 8  cycloalkyl)-C p  H 2p  -- radicals encompassed by R 1 ,R 2 , R 3 , R 6  and R 7  in formula (I) can be exemplified by cyclopropyl , 2-methylcyclopropyl, 3-ethylcyclopropyl, 2-butylcyclopropyl, 3-pentylcyclopropyl, 2-hexylcyclopropyl, cyclobutyl, 2-methylcyclobutyl, 2,3-dimethylcyclobutyl, 3-butylcyclobutyl, 4-hexylcyclobutyl, 2,3,3-trimethylcyclobutyl, 3,3,4,4-tetramethylcyclobutyl, cyclopentyl, 2-methylcyclopentyl, 3-ethylcyclopentyl, 4-butylcyclopentyl, 5-methylcyclopentyl, 3-pentylcyclopentyl, 4-hexylcyclopentyl, 2,3-dimethylcyclopentyl, 2,2,5,5-tetramethylcyclopentyl, 2,3,4-trimethylcyclopentyl, 2,4-dimetnyl-3-ethylcyclopentyl, 2,2,3,4,4-pentamethylcyclopentyl, 2,3-dimethyl-3-propylcyclopentyl, cyclohexyl, 4-metnylcyclohexyl, 4-tert-butylcyclohexyl, 2,6-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 3,3,5,5-tetramethylcyclohexyl, 2-methylcyclohexyl, 2-ethylcyclohexyl, 4-propylcyclohexyl, 5-butylcyclohexyl, 2,3-dimethylcyclohexyl, 2,4-dimethylcyclohexyl, 2,5-dimethylcyclohexyl, 2,3,4-trimethylcyclohexyl, 2,3-dimethyl-5-ethylcyclohexyl, 2,5-dimethyl-6-propylcyclohexyl, 2,4-dimethyl-3-butylcyclohexyl, 2,2,4,4-tetramethylcyclohexyl, 3,3,6,6-tetramethylcyclohexyl, 3,3,4,5,5-pentamethylcyclohexyl, 3,3,4,5,5,6-hexamethylcyclohexyl, 3,3,5-trimethyl-4-ethylcyclohexyl, 3,4,4-trimethyl-5-propylcyclohexyl, cycloheptyl, 3-methylcycloheptyl, 5-propylcycloheptyl, 6-butylcycloheptyl, 7-methylcycloheptyl, cyclooctyl, 2-methylcyclooctyl, 3-ethylcyclooctyl, 3,3,4-trimethylcyclooctyl, 3,3,5,5-tetralnethylcyclooctyl and the like. 
     The optionally substituted C 3  -C 8  cycloalkenyl portion of the (C 3  -C 8  cycloalkenyl)-C p  H 2p  -- radicals encompassed by R 1  and R 2  in formula (I) can be exemplified by cyclopentenyl and cyclohexenyl and the like. 
     The (C 6  -C 18  polycarbocyclic)-C p  H 2p  -- radicals encompassed by R 1  and R 2  in formula (I) have a total of 6 to 28 carbon atoms in t he optionally substituted (C 6  -C 18  polycarbocyclic) portion, i.e. 6 to 18 in the ring and 0 to 10 in the optional alkyl substituents. The (C 6  -C 18  polycarbocyclic)-C p  H 2p  -- radicals can be exemplified by adamantyl (especially 1- or 2-adamantyl), adamantylmethyl (especially 1-adamantylmethyl-methyl), adamantylethyl (especially 1-adamantylethyl), bornyl [especially (1S)-endo-bornyl], norbonyl, (e.g. exo-norbornyl or endo-norbornyl), isopinocamphyl, norbornenyl (e.g. 5-norbornen-2-yl ), norbornylmethyl (e.g. 2-norbornylmethyl), and norbornylethyl (e.g. 2-norbornylethyl), and by radicals of the type 
     
         --C.sub.p H.sub.2p -- (sterol residue) 
    
     wherein p is defined as above and the sterol residue is the portion of a steroidal alcohol which remains after removal of a hydrogen atom from a hydroxy group therein. The sterol residue may be that of a pharmacologically inactive steroid, e.g. cholesterol, a bile acid (cholicacid or related compound), 5α-androstan-3β-ol, epiandrosterone, androstenol, dehydroepiandrosterone, epicholestanol or the like. 
     When R 6  and R 7  in formula (I) are combined such that --NR 6  R 7  represents the residue of a saturated monocyclic secondary amine, such monocycles preferably have 5 to 7 ring atoms optionally containing another hereto atom (--O--, --S--or --N--) in addition to the indicated nitrogen atom, and optionally bear one or more, preferably 1 or 2, substituents such as phenyl, benzyl and methyl. Illustrative of residues of saturated monocyclic secondary amines which are encompassed by the --NR 6  R 7  term are morpholino, 1-pyrrolidinyl, 4-benzyl-1-piperazinyl, perhydro-1,2,4-oxathiazin-4-yl, 1- or 4-piperazinyl, 4-methyl-1-piperazinyl, piperidino, hexamethyleneimino, 4-phenylpiperidino, 2-methyl-1-pyrazolidinyl, 1- or 2-pyrazolidinyl, 3-methyl-1-imidazolidinyl, 1- or 3-iraidazolidinyl, 4-benzylpiperidino and 4-phenyl-1-piperazinyl. 
     The pharmaceutically acceptable acids HY with which the compounds of formula (I) can form pharmaceutically acceptable acid addition salts can be illustrated by inorganic acids such as hydrochloric acid, sulfuric acid, hydrobromic acid and the like; and by organic acids such as acetic acid, oxalic acid, succinic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, malonic acid, methanesulfonic acid, benzoic acid and the like. 
     The compounds of the formula R 12  Y with which the compounds of formula (I) can form pharmaceutically acceptable quaternary ammonium salts can be illustrated by alkyl and benzyl halides (iodides, chlorides and bromides, especially CH 3  Br, CH 3  I and CH 3  Cl) and the corresponding dialkylsulfates, e.g. dimethylsulfate. However, Y can be any pharmaceutically acceptable anion, e.g. halogen, sulfate, alkylsulfate or alkylsulfonate, as in the case of the acid addition salts. 
     Preferred compounds of formula (I) include those in which the structural variables are as follows: 
     R 1  is alkyl (especially methyl, ethyl, isopropyl, n-propyl, isobutyl, n-butyl, n-pentyl, n-hexyl, n-heptyl or n-octyl), cycloalkyl-C p  H 2p  -- (especially cyclohexyl, cyclopentyl, cyclopropylmethyl, 2-methylcyclohexyl, 4-methylcyclohexyl, 4-tert-butylcyclohexyl, 3,5-dimethylcyclohexyl, 2,6 -dimethylcyclonexyl, cyclohexylmethyl or cyclohexylethyl) or polycarbocyclic-C p  H 2p  -- [especially adamantylmethyl, adamantylethyl, norbornylmethyl, norbornylethyl, isopinocamphyl, endonorbornyl, exo-norbornyl or (1S)-endo-bornyl]; 
     R 2  is phenyl, cyclopentyl or cyclohexyl; 
     R 3  is H, phenyl, cyclopentyl or cyclonexyl; 
     n is 0 or 1; 
     X is ##STR10## where R 8  is H, CH 3  or C 2  H 5 , or X is --CH 2  --; m is 0, 1 or 2; and 
     R 4  is ##STR11## wherein R 5  is --CH 3  or ##STR12## or R 4  is ##STR13## or (CH 3 ) 2  N--. The quaternary ammonium salts of these compounds are particularly preferred. 
     The compounds of the present invention can be referred to as &#34;soft drug&#34; analogs or derivatives of the corresponding active alcohols. 
     Soft drug mydriatic/antiperspirant agents according to the present invention are illustrated in the following Table A which exemplifies several drugs based upon the above structural formula I. 
     
                                           TABLE A__________________________________________________________________________1. Tropicamide Soft Drug ##STR14##                           ##STR15## ##STR16##                           ##STR17##2. Isopropamide Soft Drug ##STR18##                           ##STR19## ##STR20##                           ##STR21##3. Ipratropium Soft Drug ##STR22##                           ##STR23## ##STR24##                           ##STR25##4. Cyclopentolate Soft Drug ##STR26##                           ##STR27## ##STR28##                           ##STR29##                          where R.sup.6, R.sup.7, R.sup.12 = lower                          alkyl                          (1 to 5 carbon atoms), preferably methyl                          and Y.sup.-  = anion, preferably halogen,                          alkysulfate, sulfate, alkylsulfonate.__________________________________________________________________________ 
    
     The compounds of the present invention can be synthesized in a variety of ways, the method of choice depending upon the particular compound involved, particularly on the identity of the X and n groupings. Typical synthetic routes are illustrated below for each of the categories of X values encompassed by formula (I). In the reaction schemes which follow, structural variables are as defined with formula (I) except as otherwise specified. ##STR30## 
     The esters and amides are thus prepared in two stages to the tertiary compounds and in three stages to the quaternary compounds from the starting diacid. When R 2  is phenyl and R 3  is hydrogen, the starting acid is phenylmalonic acid. A typical reaction is depicted below: ##STR31## Thus, use of tropine as the alcohol reactant in the second esterification generates an atropine soft drug. Selection of other alcohol or amine reactants in the second esterification/amidation affords soft drugs corresponding to other anticholinergic agents, e.g. use of the alcohol (CH 3 ) 2  NCH 2  CH 2  OH generates a cyclopentolate soft drug, use of the amine ##STR32## generates a tropicamide soft drug, use of the alcohol ##STR33## generates a tropicamide ester analog soft drug and so forth. ##STR34## 
     In this sequence, the anticholinergic ester or amide grouping is added prior to the R 1  OH reactant, which completes the soft portion of the molecule. In the first esterification/amidation, use of tropine ultimately affords an attopine soft drug, use of (CH 3 ) 2  NCH 2  CH 2  OH generates a cyclopentolate soft drug, use of ##STR35## gives a tropicamide soft drug and so forth. Typical starting acids include phenylsuccinic acid (n=1) and phenyladipic acid (n=2). ##STR36## 
     In a specific embodiment, the starting acid can have the formula ##STR37## the alcohol reactant in the second esterification can be tropine, the amine reactant can be ##STR38## and the thiol reactant can be ##STR39## 
     In one embodiment of this method, the starting amide is isopropamide iodide, which has the structure ##STR40## 
     In a specific embodiment of Method B, the starting acid has the structure ##STR41## and the amine reactant R 6  R 7  NH is diisopropylamine. ##STR42## 
     In a specific embodiment of Method C, the starting acid has the same structure as in the preceding Method B and the ketone reactant in the fourth step is tropinone, which has the structure ##STR43## 
     Again, in a specific illustration of the method, the same starting acid as employed in Methods B and C can be used. To obtain a soft drug isosteric with tropicamide, the ketone reactant in the fourth step can be ##STR44## The length of the alkylene chain --(CH 2 ) r  CH 2  --(CH 2 ) m  -- in the final product can be adjusted by selection of (CH 2 ) m  in the acid starting material as well as by selection of the ketone reactant. When X in formula (I) is ##STR45## and R 4  is ##STR46## then m and z are not simultaneously zero. ##STR47## 
     Preferred starting acids are those in which n=0 or 1, especially phenylmalonic acid and phenylsuccinic acid. In the case of phenylsuccinic acid, the product of the cyclizaion step, phenylsuccinic anhydride, is commercially available and can be employed in the racemic form or as a pure isomer (preferably the d, 1 or 1 form). When X in formula (I) is ##STR48## and R 4  is ##STR49## then m is greater than or equal to 1, i.e. m=1 to 4. ##STR50## 
     Preferred embodiments are derived from phenylmalonic acid and phenylsuccinic acid/phenylsuccinic anhydride, as described in the preceding Method A. When X in formula (I) is ##STR51## and R 4  is ##STR52## then m and z are not simultaneously zero. ##STR53## 
     In preferred embodiments of Method C, n=0 or 1, i.e. the compounds are derived from phenylmalonic acid and phenylsuccinic acid/phenylsuccinic anhydride, as described in the preceding Method A. The preferred alcohol reactant in the first step is tropine ##STR54## is ##STR55## R 5  is CH 3  and m is zero) or scopine ##STR56## is ##STR57## R 5  is CH 3  and m is zero. 
     Soft drug anticholinergic, mydriatic and anti-secretory agents according to the present invention are illustrated in the following Table B which shows several drugs based upon above structural formula I. These derivatives can be prepared according to the one or more of the reaction schemes depicted above, utilizing the appropriate reactants: 
     
         TABLE B  - R.sup.1 R.sup.2 R.sup.3 R.sup.4 or R.sup.4 /R.sup.12 m (0 to 4) n (0 to 4) X Y.sup.-  ##STR58##  ##STR59##  H  ##STR60##  0 0  ##STR61##  ##STR62## CH.sub.3  ##STR63##  ##STR64##  ##STR65##  1 0 CH.sub.2 Br.sup.- CH.sub.3  CH.sub.2 ##STR66##  H  ##STR67##  0 0  ##STR68##  I.sup.- CH.sub.3 CH.sub.2  CH.sub.2 ##STR69##  H  ##STR70##  2 0  ##STR71##  --  ##STR72##  ##STR73##  ##STR74##  ##STR75##  0 0  ##STR76##  ##STR77## CH.sub.3 (CH.sub.2).sub.2  CH.sub.2 ##STR78##  ##STR79##  ##STR80##  0 0  ##STR81##  ##STR82## CH.sub.3  (CH.sub.2).sub.3CH.sub.2 ##STR83##  H  ##STR84##  0 1  ##STR85##  ##STR86## CH.sub.3 (CH.sub.2).sub.4  CH.sub.2 ##STR87##  H  ##STR88##  0 2  ##STR89##  Cl.sup.- CH.sub.3 (CH.sub.2).sub.5  CH.sub.2 ##STR90##  H  ##STR91##  0 3  ##STR92##  ##STR93## CH.sub.3 (CH.sub.2).sub.6  CH.sub.2 ##STR94##  ##STR95##  ##STR96##  1 4 O --  ##STR97##  CH.sub.2 CH.sub.2  CH.sub.3 H ##STR98##  0 2  ##STR99##  I.sup.-  ##STR100##  ##STR101##  ##STR102##  ##STR103##  3 0  ##STR104##  ##STR105## Lower alkyl, cyclic, straight       Any pharmaceutically  or branched chain alcohols       acceptable anion, halogen,  (1 to 8 carbon atoms)       sulfate, alkylsulfate or    alkyl sulfonate  ##STR106##  ##STR107##  ##STR108##  ##STR109##  2 0 O --  ##STR110##  CH.sub.3(CH.sub.2).sub.3CH.sub.2 CH.sub.3(CH.sub.2).sub.4CH.sub.2  ##STR111##  2 0 NH Br.sup.-  ##STR112##  ##STR113##  H  ##STR114##  4 0 S  ##STR115##  ##STR116##  ##STR117##  ##STR118##  ##STR119##  1 0 CH.sub.2 --  ##STR120##  ##STR121##  ##STR122##  ##STR123##  0 0  ##STR124##  ##STR125##  ##STR126##  ##STR127##  ##STR128##  ##STR129##  0 1 CH.sub.2 I.sup.-  ##STR130##  ##STR131##  ##STR132##  ##STR133##  1 0  ##STR134##  --  ##STR135##  ##STR136##  ##STR137##  ##STR138##  2 0 O Cl.sup.- 
    
     The rates of metabolic hydrolysis of the active esters may be controlled by selection of the esterifying alcohol. 
     The invention is illustrated by the following nonlimiting examples. 
     EXAMPLE 1 
     Methyl hydrogen phenylmalonate 
     A mixture of phenylmalonic acid (3.6 g, 0.02 mol), boron trifluoride etherate (2.4 mL, 0.02 mol) and 0.8 mL of anhydrous methanol (0.02 mol) was refluxed and stirred for 24 hours. After cooling to room temperature, the reaction mixture was filtered and 20 mL of water was added. 
     The precipitated oil was extracted with CHCl 3  (30 mL×3). The combined extracts were washed with water and dried over anhydrous MgSO 4  and evaporated under reduced pressure. The oily liquid obtained showed NMR spectra consistent with its structure. 
     R f  of the acid: 0.52 yield: 57% 
     R f  of the ester: 0.72. 
     Preparation of methyl phenylmalonyl chloride 
     To the oily liquid obtained above was added 5 mL of thionyl chloride. The reaction mixture was heated on an oil bath for one hour under anhydrous conditions. The excess thionyl chloride was removed by the addition and the in vacuo distillation of 10 mL of anhydrous benzene. The product was oily and was reacted immediately with tropine base. 
     Esterification of methyl phenylmalonyl chloride and tropine 
     Thoroughly dried tropine (1.4 g, 0.01 mol) was added to the freshly prepared methyl hydrogen phenylmalonyl chloride. The mixture was heated for 5 hrs at 100° C., with stirring, under anhydrous conditions. The mixture turned brown and gas evolved. After cooling to room temperature and filtration, the mixture was treated with 10 mL of water. The clear solution was adjusted to pH 9 with saturated Na 2  CO 3  solution, extracted with ethyl ether and dried over anhydrous MgSO 4 . The ethereal solution was filtered and distilled under reduced pressure to produce an oily product. 
     EXAMPLE 2 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-ethoxycarbonyl-α-phenyl)acetate 
     a) Preparation of ethyl hydrogen phenylmalonate: 
     Phenylmalonic acid (13.5 g, 0.07 mol) in dry ether (40 mL) was treated with thionyl chloride (8.92 g, 5.4 mL, 0.07 mol) and one drop of N,N-dimethylformamide. The mixture was heated at 40°-50° C. for 3 hours. The clear solution was evaporated under reduced pressure to remove any residual thionyl chloride. The oily residue was redissolved in dry ether (40 mL), the solution was treated with ethanol (0.075 mol, 4.1 mL) and refluxed for 2 hours. The reaction mixture was cooled to room temperature and washed with water. The organic layer was extracted with saturated solution of sodium bicarbonate until alkaline. The combined extracts were washed with ether and the aqueous layer was acidified with 5N HCl to pH 1. The precipitated oil was extracted with CH 2  Cl 2  (50 mL×3). The combined extracts were washed with water (50 mL×4) and dried over anhydrous MgSO 4 . The oily product crystallized on standing. 
     Yield: 7.2 g (49.4%) 
     M.p.: 78°-9° C. (as reported). 
     b) Preparation of ethyl phenylmalonyl chloride 
     Ethyl hydrogen phenylmalonate (2.08 g, 0.01 mol) was mixed with thionyl chloride (5 mL) and heated at 70° C. for one hour under anhydrous conditions. The liquid thus obtained was evaporated under reduced pressure. Anhydrous benzene (10 mL) was added to the residue and redistilled to remove any residual thionyl chloride. 
     c) Esterification of ethyl phenylmalonyl chloride and tropine 
     The previously obtained acid chloride (0.01 mol) dissolved in 10 mL of dry benzene was added dropwise with stirring for half an hour to a solution of dry tropine (2.8 g, 0.02 mol) in dry benzene. The mixture was stirred at room temperature for 24 hours and filtered. The filtrate was washed with water until neutral. The organic layer was dried over anhydrous MgSO 4  and the solvent was evaporated. The obtained oily base was converted into the oxalate salt by adding an ether solution of oxalic acid to a solution of the base in ether. By scratching the mixture, a white solid product was obtained. When cooled in a deep freezer, then washed with cold ether and dried for 24 hours in a desiccator over CaCl 2 , the crystalline product represented 78% conversion to oxalate. 
     Recrystallization was carried out from a methanol-ether mixture. 
     R f  of the free base: 0.4 
     Yield of the free base: 75% 
     Yield of the oxalate: 78% 
     M.p. 135°-7° C. 
     
         ______________________________________Anal for C.sub.19 H.sub.25 O.sub.4 N.(COOH).sub.2    C %         H %    N %______________________________________Theoretical      59.85         6.45   3.32Found      59.88         6.52   3.30______________________________________ 
    
     According to the microanalytical data and NMR spectra, the compound obtained has the following structure: ##STR139## 
     EXAMPLE 3 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-methoxycarbonyl-α-phenyl)acetate 
     a) Synthesis of methyl hydrogen phenylmalonate (new method) 
     Phenylmalonic acid (13.5 g, 0.07 mol) in dry ether (40 mL) was treated with thionyl chloride (8.92 g, 5.4 mL, 0.071 mol) and one drop of N,N-dimethylformamide. The mixture was heated at 40°-50° C. for 3 hours. The clear solution was evaporated under reduced pressure to remove any residual thionyl chloride. The oily residue was redissolved in dry ether (40 mL) and the solution was treated with methyl alcohol (0.075. mol, 3 mL) and refluxed for 2 hours. The reaction mixture was cooled to room temperature and washed with water. The organic layer was extracted with saturated solution of sodium bicarbonate until alkaline. The combined extracts were washed with ether and the aqueous layer acidified with 5N HCl to pH 1. The precipitated oil was extracted with CH 2  Cl 2  (50 ml×3). The combined extracts were washed with water (50 mL×4) and dried over anhydrous MgSO 4 . The oily product crystallized on standing. 
     Yield: 6 g (41.2%) 
     M.p.: 86°-88° C. as reported. 
     b) Synthesis of methyl phenylmalonyl chloride 
     The previously prepared ester (2.94 g, 0.01 mol) was mixed with thionyl chloride (5 mL) and heated at 70° C. for one hour under anhydrous conditions. The liquid obtained was evaporated under reduced pressure. Anhydrous benzene (10 mL) was added to the residue and redistilled to remove any residual thionyl chloride. 
     c) Esterification of methyl phenylmalonyl chloride and tropine 
     The previously prepared acid chloride was discolored in 10 mL of dry benzene and was added dropwise with stirring for half an hour to a solution of dry tropine (2.8 g, 0.02 mol) in dry benzene. The mixture was stirred at room temperature for 24, hours and filtered. The filtrate was washed with water until neutral. The organic layer was dried over anhydrous MgSO 4  and the solvent was evaporated. The oily base thus obtained was purified by conversion into the oxalate salt by adding an ether solution of oxalic acid to a solution of the base in ether. By scratching the mixture and keeping in a refrigerator overnight, a white solid product was separated. Rapid filtration and drying in a vacuum desiccator over anhydrous CaCl 2  were carried out. 
     Recrystallization from methanol-ether mixture gave white crystalline product. 
     R f  of the free base: 0.4 
     Yield of the free base: 1 g (64.5%) 
     Yield of the oxalate: 1.5 g (35.7%) 
     M.p.: 89°-91° C. 
     
         ______________________________________Anal. for C.sub.18 H.sub.23 O.sub.4 N.(COOH).sub.2.H.sub.2 O:    C %         H %    N %______________________________________Theoretical      56.47         6.39   3.29Found      56.48         6.2    2.94______________________________________ 
    
     According to the microanalytical data and NMR spectra, the compound has the following structure: ##STR140## 
     EXAMPLE 4 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-isopropoxycarbonyl-α-phenyl)acetate 
     a) Synthesis of isopropyl hydrogen phenylmalonate 
     Phenylmalonic acid (13.5 g, 0.07 mol) in dry ether (40 mL) was treated with thionyl chloride (8.92 g, 5.4 mL, 0.07 mol) and one drop of N,N-dimethylformamide. The mixture was heated at 40°-50° C. for 3 hours. The clear solution was evaporated under reduced pressure to remove any residual thionyl chloride. The oily residue was redissolved in dry ether (40 mL), and the solution was treated with isopropyl alcohol (0.075 mol, 5.76 mL), refluxed for 2 hours and worked up as before to give the titled compound. 
     Yield=60% (as reported) 
     M.p.: 64°-66° C. (as reported). 
     b) Synthesis of isopropyl phenylmalonyl chloride 
     The previously prepared monoester (2.22 g, 0.01 mol) was mixed with thionyl chloride (5 mL) and heated at 70° C. for one hour under anhydrous conditions. The liquid thus obtained was evaporated under reduced pressure. Anhydrous benzene (10 mL) was added and the mixture was redistilled. 
     c) Esterification of isopropyl phenylmalonyl chloride and tropine 
     The previously prepared acid chloride was dissolved in 10 mL of dry benzene and added dropwise with stirring for half an hour to a solution of dry tropine (2.8 g, 0.02 mol) in dry benzene. The mixture was stirred at room temperature for 24 hours and filtered. The filtrate was washed with water until neutral. The organic layer was dried over anhydrous MgSO 4  and the solvent was evaporated. The oily base thus obtained was purified by formation of the oxalate salt. An ether solution of oxalic acid was added to an ether solutfon of the base. By scratching the mixture and keeping in a deep freezer for 24 hours, a white solid product was obtained. Filtration followed by drying in a vacuum desiccator over CaCl 2  was carried out. 
     Recrystallization from methanol-ether mixture gave a white crystalline product. 
     R f  of the base: 0.3 
     Yield of the base: 2.5 G (72.4%) 
     Yield of the oxalate: 3 g (58.9%) 
     M.p.: 73°-80° C. 
     
         ______________________________________Anal. for C.sub.20 H.sub.27 O.sub.4 N.(COOH).sub.2.    C %         H %    N %______________________________________Theoretical      60.68         6.71   3.21Found      60.41         6.77   3.13______________________________________ 
    
     According to both microanalytical data and NMR spectra, the compound obtained has the following structure: ##STR141## 
     EXAMPLE 5 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-cyclohexyloxycarbonyl-α-phenyl)acetate 
     a) Preparation of cyclohexyl hydrogen phenylmalonate 
     Phenylmalonic acid (13.5 g, 0.07 mol) in dry ether (40 mL) was treated with thionyl chloride (8.92 g, 5.4 mL, 0.07 mol) and one drop of N,N-dimethylformamide. The mixture was heated at 40°-5° C. for 3 hours. The clear solution was distilled under vacuum. The oily residue was redissolved in dry ether (40 mL), the solution was treated with cyclohexyl alcohol (0.075 mol, 7.9 mL) and refluxed for 2 hours. The mixture was worked up as before to give an oily product which crystallized on standing. Recrystallization was carried out from a benzene-petroleum ether (40°-60°) mixture to give a white crystalline product. 
     R f  : 0.76 
     M.p.: 80°-2° C. 
     Yield: 12.5 g (64.14%) 
     
         ______________________________________Anal. for C.sub.15 H.sub.18 O.sub.4          C %  H %______________________________________Theoretical      68.69  6.9Found            68.79  6.92______________________________________ 
    
     According to microanalytical and NMR data, the synthesized compound has the following structure: ##STR142## Synthesis of cyclohexyl phenylmalonyl chloride 
     The cyclohexyl ester prepared above (2.6 g, 0.01 mol) was mixed with thionyl chloride (5 mL) and heated at 70° C. for one hour under anhydrous conditions, The liquid obtained was evaporated under reduced pressure. Anhydrous benzene (10 mL) was added to the residue and redistilled again to remove any residual thionyl chloride. The oily product was soildified on standing and was used for the next step without further purification. 
     c) Esterification of cyclohexyl phenylmaonyl chloride and tropine 
     The acid chloride was dissolved in 10 mL of dry benzene and added dropwise with stirring for half an hour to a solution of dry tropine (2.8 g, 0.02 mol) in dry benzene. The mixture was stirred at room temperature for 24 hours and filtered. The filtrate was washed with water until neutral. The organic layer was dried over anhydrous MgSO 4  and the solvent was evaporated. The obtained oily base was converted into its oxalate salt by adding an ether solution of oxalic acid to a solution of the base in ether. By scratching the mixture and cooling in a refrigerator, a white solid product was separated. Filtration and drying over CaCl 2  in a vacuum desiccator was carried out. On recrystallization from a methanol-ether mixture, white crystalline product was obtained. 
     R f  : 0.22 
     Yield of the base: 3 g, 77% 
     Yield of the oxalate: 3.1 g, 63% 
     M.p.: 160°-2° C. 
     
         ______________________________________Anal. for C.sub.23 H.sub.31 NO.sub.4.(COOH).sub.2    C %         H %    N %______________________________________Theoretical      63.15         6.99   2.94Found      63.05         7.26   2.78______________________________________ 
    
     Based on the microanalytical data and NMR spectra, the compound obtained has the following structure: ##STR143## 
     EXAMPLE 6 
     Preparation of Tropanyl hydrogen phenylmalonate or (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-carboxy-α-phenyl)acetate 
     Phenylmalonic acid (2.5 g, 0.014 mol) in dry ether (10 mL) was treated with thionyl chloride (1.78 g, 1.09 mL, 0.01 mol), and N,N-dimethylformamide (two drops). The mixture was heated at 50°-60° C. for 2 hr. Ether and excess thionyl chloride were removed and three separate portions of dry benzene were added and removed the same way. The residue (1.9 gm, 0.01 mol) was dissolved in 20 mL dry benzene and added dropwise over a period of 0.5 hr to a stirred solution of dry tropine (2.82 g, 0.02 mol) in 10 mL dry benzene. The mixture was stirred at ambient temperature for 24 hr and filtered. The filtrate was washed with water until neutral and the organic layer was dried over anhydrous MgSO 4  and evaporated. The oily product was transformed to the corresponding oxalate by addition of an ethereal solution of oxalic acid to the solution of the compound in ether. A white solid product was obtained by scratching the ethereal solution and keeping it in a refrigerator overnight. 
     The white solid was isolated by filtration and thoroughly washed with ether and dried to give 0.7 gm (23%). R f  (CHCl 3  : MeOH 3:1)=0.23, m.p. 112°-115° C. 
     
         ______________________________________Anal. for C.sub.17 H.sub.21 O.sub.4 N.(COOH).sub.2.0.5H.sub.2 O    C %         H %    N %______________________________________Theoretical      56.71         6.01   3.48Found      56.94         6.26   3.32______________________________________ 
    
     According to microanalytical and NMR data, the compound obtained has the following structure: ##STR144## 
     EXAMPLE 7 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-cyclohexyloxycarbonyl-α-phenyl)acetate methiodide 
     A solution of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-cyclohexyloxycarbonyl-α-phenyl)acetate (3.85 g, 0.01 mol) and 10 mL of methyl iodide in 30 mL of dry benzene was stirred at room temperature for 6 hr. The mixture was filtered and the solid was dried and recrystallized from methanol-ether mixture to give a yellowish-white product. 
     R f  : 0.35 
     Yield: 55.9% 
     M.p.: 228°-230° C. 
     
         ______________________________________Anal. for C.sub.24 H.sub.34 INO.sub.4.0.25H.sub.2 O    C %         H %    N %______________________________________Theoretical      54.19         6.53   2.63Found      54.00         6.48   2.50______________________________________ 
    
     Based on microanalytical and NMR data, the obtained compound has the following structure: ##STR145## 
     EXAMPLE 8 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-ethoxycarbonyl-α-phenyl)acetate methiodide 
     A solution of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-ethoxycarbonyl-α-phenyl)acetate (3.31 g, 0.01 mol) and 10 mL of methyl iodide in 25 mL of dry benzene was stirred at room temperature for 6 hr. The mixture was filtered and the solid was dried and recrystallized from an alcohol-ether mixture. 
     R f  : 0.41 
     M.p.: 232°-234° C. (dec.). 
     
         ______________________________________Anal. for C.sub.20 H.sub.28 INO.sub.4    C %         H %    N %______________________________________Theoretical      50.75         5.92   2.96Found      50.55         5.97   2.97______________________________________ 
    
     According to microanalytical and NMR data, the compound has the following structure: ##STR146## 
     EXAMPLE 9 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct 3-yl (α-methoxycarbonyl-α-phenyl)acetate dimethylsulfate 
     A solution of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-methoxycarbonyl-α-phenyl)acetate in dry ethyl ether and dimethylsulfate (2×moles of the ester), was stirred at room temperature overnight. The white solid was filtered, dried, and recrystallized from methanolether. 
     M.p.: 138°-140° C. 
     
         ______________________________________Anal. for C.sub.20 H.sub.29 NO.sub.8 S.1/2H.sub.2 O.     C %  H %         N %    S %______________________________________Theoretical 53.08  6.68        3.09 7.08Found       53.06  6.65        3.01 7.14______________________________________ 
    
     According to microanalytical and NMR data, the compound has the following structure: ##STR147## 
     EXAMPLE 10 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-ethoxycarbonyl-α-phenyl)acetate dimethylsulfate 
     A solution of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-ethoxycarbonyl-α-phenyl)acetate in dry ethyl and dimethylsulfate (2×moles of the ester) was stirred at room temperature overnight. The white solid was filtered, dried and recrystallized from methanolether. 
     M.p.: 165°-167° C. 
     
         ______________________________________Anal. for C.sub.21 H.sub.31 NO.sub.8 S.     C %  H %         N %    S %______________________________________Theoretical 55.13  6.83        3.06 7.01Found       55.10  6.87        2.96 7.02______________________________________ 
    
     Based on microanalytical and NMR data, the compound has the following structure: ##STR148## 
     EXAMPLE 11 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-isopropoxycarbonyl-α-phenyl)acetate dimethylsulfate 
     A solution of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-isopropoxycarbonyl-α-phenyl)acetate in dry ethyl ether and dimethylsulfate (2×moles of the ester) was stirred at room temperature overnight. The white solid was filtered, dried, and recrystallized from methanol-ether. 
     M.p.: 128°-130° C. 
     
         ______________________________________Anal. for C.sub.22 H.sub.33 NO.sub.8 S     C %  H %         N %    S %______________________________________Theoretical 56.03  7.05        2.97 6.80Found       55.91  7.08        2.96 6.78______________________________________ 
    
     According to microanalytical and NMR data, the compound has the following structure: ##STR149## 
     EXAMPLE 12 
     Preparation of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-cyclohexyloxycarbonyl-α-phenyl)acetate dimethylsulfate 
     A solution of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-cyclohexyloxycarbonyl-α-phenyl)acetate in dry ethyl ether and dimethylsulfate (2×moles of the ester) was stirred at room temperature overnight. The white solid was filtered, dried, and recrystallized from methanol-ether. 
     M.p.: 196°-198° C. 
     
         ______________________________________Anal. for C.sub.25 H.sub.37 NO.sub.8 S.1/2H.sub.2 O     C %  H %         N %    S %______________________________________Theoretical 57.67  7.36        2.69 6.16Found       57.91  7.15        2.68 6.17______________________________________ 
    
     According to microanalytical and NMR data, the compound has the following structure: ##STR150## 
     In the examples which follow, compounds which were tested are numbered as follows: 
     
         ______________________________________ ##STR151##Compound No.   R______________________________________1              CH.sub.32              CH.sub.2 CH.sub.33              CH(CH.sub.3).sub.2           ##STR152##5              CH.sub.2 CH.sub.3                     (methiodide salt)6           ##STR153##                     (methiodide salt)7              H______________________________________ 
    
     EXAMPLE 13 
     Kinetic Studies of the New Tropanyl Esters 
     A high pressure liquid chromatography (HPLC) method was used for the determination of rates of hydrolysis of the newly prepared tropanyl esters aqueous buffered solution at pH 12.0 and in human plasma. 
     The chromatographic analysis was performed in a system consisting of LCD/Milton Roy Consta Metric III metering pump and LCD UV III Monitor Detector operated at 254 nm. A 30 cm×3.9 mm (internal diameter) reverse phase ASI/U Bondpak C18 column operated at ambient temperature was used for the analysis. The mobile phase consisted of 32% acetonitrile in 0.01M potassium dihydrogen phosphate, 0.004M 1-octane-sulfonic acid sodium salt in 0.1% acetic acid at a flow rate of 2.3 mL/min. 
     Determination of the hydrolytic rate constants in aqueous buffered solution at pH 12 at 37° C. 
     Sodium hydroxide and sodium dibasic phosphate were used to prepare the buffer at pH 12. The ionic strength was maintained at 0.1M with sodium chloride. 
     One hundred microLiters of a freshly prepared solution of the compound in methanol was added to 10 mL buffered solution, previously equilibrated to 37° C. in a water bath and mixed thoroughly to make an initial concentration of 6×10 -3  mol. Liter -1 . Samples of 100 μL were injected into the column at various time intervals. The rate constants, half-lives and standard errors were calculated and the results are listed in Table 1. The following retention times at a flow rate of 2.3 mL/min. using 32% acetonitrile are: 
     Compound (1) had a retention time of 3.0 minutes. 
     Compound (2) had a retention time of 7.3 minutes. 
     Compound (3) had a retention time of 9.3 minutes. 
     Compound (5) had a retention time of 4.7 minutes. 
     Compound (7) had a retention time of 3.5 minutes. 
     At a flow rate of 2.0 mL/min, compound 7 had a retention time of 4.0 min. A mobile phase or 40% acetonitrile was used to separate compounds 4 and 6 at a flow rate of 2.0 mL/min. 
     Compound (4) had a retention time of 8.0 minutes. 
     Compound (6) had a retention time of 6.6 minutes. 
     
                       TABLE 1______________________________________ ##STR154##The observed First Order Hydrolytic Rate Constants (K),the standard error (S.E.) and half-life (t  1/2) in 0.01N sodium hydroxide at pH 12.0, at 37° C.CompoundNo.     R           K.sup.a ± S.E. (min.sup.-1)                             t  1/2 (min)______________________________________1       CH.sub.3    1.43 ± 0.12 × 10.sup.-1                             4.802       CH.sub.2 CH.sub.3               16.9 ± 0.15 × 10.sup.-2                             4.08    ##STR155## 30 ± 0.77 × 10.sup.-3                             22.81______________________________________ .sup.a Average of three runs ± S.E.M. Compound (5) ##STR156## K ± S.E. (min.sup.-1) = 80.8 ± 0.75 × 10.sup.-2 t  1/2 (min) = 0.85. 
    
     The kinetic studies for the hydrolysis of the new tropines in aqueous buffer solution at pH 12.0 and in human plasma was carried out using HPLC method. 
     EXAMPLE 14 
     Determination of the hydrolytic rate constants in aqueous buffer at pH 12.0 
     The previous method adapted for the hydrolysis of compounds 1, 2, 3 and 5 was used for the determination of rate of hydrolysis of compounds 4, 6 and 7. In case of compounds 4 an d 6, the mobile phase was 40% acetonitrile, 0.01M KH 2  PO 4 , 0.04M 1-octanesulfonic acid sodium salt and 0.1% acetic acid, at a flow rate 2 mL/min. Compounds 4 and 6 had retention time of 8.0 and 6.6 min, respectively, as shown in Table 2. Compound 7 had a retention time of 3.1 min at a flow rate of 2.3 mL/min and 3.5 min at 2.0 mL/min. 
     
                       TABLE 2______________________________________ ##STR157##The observed pseudo first order hydrolytic rateconstants (K) and half lives (t  1/2) in 0.01 M sodiumhydroxide at pH 12 and 37° C.CompoundNo.     R           K (min.sup.-1).sup.a S.E.M.                             t  1/2 (min)______________________________________    ##STR158## 379 ± 0.8 × 10.sup.-5                             182.sup. 6.sup.b    ##STR159## 5.43 ± 0.1 × 10.sup.-1                             1.287       H           19.8 ± 0.3 × 10.sup.-4                             350______________________________________ .sup.a Average of three runs. .sup.b The quaternary iodide salt of the ester 4. 
    
     EXAMPLE 15 
     Determination of the enzymatic hydrolytic cleavage rates in human plasma at 37° C. 
     Freshly collected plasma was used which contained about 80% plasma diluted with anticoagulant citrate phosphate dextrose solution, U.S.P. 
     A 100 μL volume of a freshly prepared solution of the compound in methanol was added to 10 mL plasma, previously equilibrated at 37° C. in a water bath, and mixed thoroughly to result in an initial concentration of 6×10 -3  mol. Liter -1 . One mL samples of plasma were withdrawn from the test medium, mixed immediately with 3 mL ice cold acetonitrile, centrifuged and the supernatant analyzed by HPLC. The first order hydrolytic rate constant was determined by following the disappearance of the compound as a function of time. The results are given in Table 3. 
     
                       TABLE 3______________________________________The observed first order hydrolytic rate constants (K)and half lives (t  1/2) in human plasma at 37° C.CompoundNo.     R           K (min.sup.-1) ± S.E.M.                              t  1/2 (hr)______________________________________2       CH.sub.2 CH.sub.3.sup.a               15.0 ± 0.3 × 10.sup.-5                              77.4    ##STR160## 6.27 ± 0.3 × 10.sup.-5                              185.54    ##STR161## 4.44 ± 0.4 × 10.sup.-5                              269.85       CH.sub.2 CH.sub.3.sup.b               14.1 ± 0.6 × 10.sup.-5                              82.26    ##STR162## 6.31 ± 0.8 × 10.sup.-5                              183.2______________________________________ .sup.a Average of 4 runs, the rest of data are average of 3 runs. .sup.b The quaternary iodide salt of the ester 2. .sup.c The quaternary iodide salt of the ester 4. 
    
     EXAMPLE 16 
     Determination of the rate of hydrolysis of tertiary ethyl ester (2) and rate of formation of its degradation product (7) in 0.01M NaOH at pH 12 and 37° C. 
     The mobile phase used for the separation of compound (2) and its degradation product, the half ester (7), consisted of 32% CH 3  CN, 0.01M KH 2  PO 4 , 0.004M 1-octanesulfonic acid sodium salt and 0.1% acetic acid. At a flow rate of 1.5 mL/min, (2) and (7) have retention times of 9 min and 4.6 min, respectively. 
     Procedure 
     100 microLiters of a freshly prepared solution of compound (2) in methanol was added to 10 mL buffered solution (pH 12), previously equilibrated to 37° C. in a water bath to result in an initial concentration of 6×10 -3  mol Liter -1 . Samples of 1 mL were taken at time intervals and mixed with 3 mL of acetonitrile. 100 microLiters of the collected samples were injected and disappearance of (2) and formation of (7) was followed by HPLC. 
     The results are given in Table 4. 
     
                       TABLE 4______________________________________Rate of hydrolysis of tertiary ethyl ester (2) to thehalf ester (7) in 0.01 N NaOH, pH at 37° C.CompoundNo.        K.sub.obsd (min.sup.-1) ± S.E.M.                      t  1/2 (min)______________________________________2          16.5 ± 0.58 × 10.sup.-2                      4.19 ± 0.147          1.68 ± 0.34 × 10.sup.-1                      3.79 ± 0.66______________________________________ 
    
     EXAMPLE 17 
     Rate of hydrolysis of tropanyl hydrogen phenyl malonate (7) to the dibasic acid (phenylmalonic acid) in 0.01N sodium hydroxide, pH 12 at 37° C. 
     The previously described method for the determination of rate of hydrolysis of compound (2) was followed for the determination of hydrolysis of compound (7). 
     The disappearance of compound (7) was followed by HPLC. 
     The concentration of the formed dibasic acid was determined by HPLC. 15% acetonitrile, 0.01M KH 2  PO 4  and 0.1% acetic acid were used as a mobile phase. At a flow rate of 2 mL/min, the product has a retention time of 4 min. 
     The collected samples, after determination of rate of disappearance of compound (7), were used for the determination of rate of formation of the hydrolysis product (8). 100 microLiters of the sample was injected and the formation of the product was followed by HPLC. 
     The results are given in Table 5. 
     
                       TABLE 5______________________________________CompoundNo.        K.sub.obsd (min.sup.-1) ± S.E.M.                      t  1/2 (min)______________________________________7          20.9 ± 0.27 × 10.sup.-4                      331.25 ± 4.318          21.7 ± 0.95 × 10.sup.-4                      316.01 ± 33.5______________________________________ 
    
     EXAMPLE 18 
     Determination of the Enzymatic Hydrolysis of the New Esters in Rat Liver Homogenate at 37° C. 
     The liver homogenate was prepared by the following method. Two Sprague-Dawley rats were killed by decapitation and the livers were removed, weighed and homogenized in a tissue homogenizer in 0.11M aqueous phosphate buffer, pH 7.4, to make 20% liver homogenate. The homogenate was centrifuged and the supernatant was used for the test. 100 μL of 0.6M solution of the ester in methanol was mixed with 10 mL of the homogenate, previously equilibrated to 37° C. in a water bath, to result in an initial concentration of 6×10 -3  mol. Liter -1 . Samples of 1.0 mL were withdrawn at time intervals from the medium, added immediately to 3 mL ice-cold acetonitrile, shaken vigorously, and placed in a freezer. When all samples had been collected, they were centrifuged and each supernatant was analyzed by HPLC. 
     The results are shown in Table 6. 
     
                       TABLE 6______________________________________Rates of hydrolysis in liver homogenate of selectedtropanyl esters.CompoundNo.     R          K (min.sup.-1) ± S.E.                             t  1/2 (min)______________________________________2       CH.sub.2 CH.sub.3.sup.a              1.99 ± 0.996 × 10.sup.-1                             3.48    ##STR163##              97.2 ± 0.76 × 10.sup.-3                             7.124    ##STR164##              37.0 ± 0.3 × 30.sup.-3                             18.735       CH.sub.2 CH.sub.3.sup.b              10.5 ± 0.28 × 10.sup.-2                             6.66    ##STR165##              10.4 ± 0.23 × 10.sup.-3                             66.8______________________________________ .sup.a Mobile phase used for Compounds 2, 3 and 5 was 32% acetonitrile, 0.01 M KH.sub.2 PO.sub.4, 0.004 M 1octane sulfonic acid sodium salt and 0.1% acetic acid. Mobile phase used for compounds 4 and 6 was 40% acetonitrile, 0.01 M KH.sub.2 PO.sub.4, 0.004 M 1octane-sulfonic acid sodium salt and 0.1% acetic acid. .sup.b It is the methiodide of Compound 2. .sup.c It is the methiodide of Compound 4. 
    
     EXAMPLE 19 
     Pharmaceutical Study of the New Tropanyl Esters 
     The anticholinergic activity of all the new compounds was investigated in vitro by studying the inhibitory action of the drugs on carbachol-induced spasms of strips of ileum from freshly killed guinea pigs. The terminal ileum from guinea pig (200-500 g) was cut into 2-3 cm strips and suspended in freshly prepared Tyrode&#39;s solution in 40 mL organ bath. The solution was aerated with 95% oxygen and 5% carbon dioxide at 37° C. A tension of 1 g was applied to the tissue, and cumulative-response curves were recorded with carbachol until constant responses were obtained. A concentration of the antagonist was then added to the bath and after 10 seconds, further concentration response curves to carbachol were established. This procedure was then repeated using increasing concentrations of the antagonist. EC 50  was calculated for carbachol alone and for carbachol in the presence of the various antagonist concentrations. PA 2  value for each tested compound is listed in Table 7. Atropine was used as a standard for comparison. The PA 2  was calculated as follows: ##EQU1## A=EC 50  or carbachol in presence of the antagonist a=EC 50  for carbachol alone before adding antagonist 
     
                       TABLE 7______________________________________CompoundNo..sup.a       R          PA.sub.2______________________________________Atropine                   8.291               CH.sub.3   6.55.sup.b2               CH.sub.2 CH.sub.3                      6.72            ##STR166##                      7.554            ##STR167##                      6.59.sup.b.sup. 5.sup.c   CH.sub.2 CH.sub.3                      7.86.sup. 6.sup.d            ##STR168##                      7.357               H          6.20______________________________________ .sup.a Results were the average of two experiments, except as otherwise noted. .sup.b Average of three experiments. .sup.c Quaternary iodide salt of tertiary ethyl ester. .sup.d Quaternary iodide salt of cyclohexyl ester. 
    
     EXAMPLE 20 
     Synthesis of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-isopropoxycarbonyl-α-phenyl)acetate methiodide ##STR169## 
     To a solution of 2.07 g (0.006 mol) of (±)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (α-isopropoxycarbonyl-α-phenyl)acetate in 20 mL of dry benzene was added 6 mL methyl iodide and the mixture was stirred at room temperature for 6 hr. The yellowish white solid product was filtered, dried and crystallized from ethanol-ether mixture to yield 1.8 g (61.56%) of the title compound, m.p. 251-254° C. 
     
         ______________________________________Anal. for C.sub.21 H.sub.30 INO.sub.4.0.5H.sub.2 O.    C %         H %    N %______________________________________Theoretical      50.81         6.29   2.82Found      50.67         6.25   2.95______________________________________ 
    
     The pharmacological result: PA 2  =7.61. 
     EXAMPLE 21 
     The mydriatic activity of the compounds is illustrated by the following procedure. 
     The mydriatic activity of the soft ester drug (Compound 5) was evaluated in 0.9% saline solution at concentrations of 0.05: and 0.1% compared to 0.1% tropicamide (Mydriacyl®). Normal New Zealand albino rabbits of either sex weighing about 2 kg were employed. The animals were placed in wooden restraining boxes. Standard doses of 50 uL were applied to the rabbits&#39; eyes and pupillary changes were measured in a light and temperature controlled room. The degree of pupil dilation, in millimeters, was measured with a Starrett micrometer held at a constant distance at time intervals of 15, 30, 60, 90, 120, 180, 240, 300 and 360 minutes. The differences in the same animals between the pupil diameter of the eye with drug versus the other eye with saline was recorded. Each point on the graph is the average obtained on 3-6 animals. The recovery time is defined as that time required for the pupil diameter to return to 1.0 millimeter in diameter. 
     The results are set forth in FIG. 1 which depicts mydriasis as a function of time. Tropicamide is typical of the shortest acting of the commercially available anticholinergic mydriatic agents. The active agent therein is tropicamide--chemical name=Benzeneacetamide N-ethyl-α-(hydroxymethyl)-N-(4-pyridinylmethyl)-. As is apparent from the results depicted in FIG. 1, the &#34;recovery time&#34;, i.e., recovery from mydriasis, is much shorter with the compositions and methods of the invention than with the commercially available products. 
     Tables 8, 9 and 10 below set forth yield and analysis data for compounds depicted therein prepared according to the above-described procedures. Table 11 below sets forth hydrolysis kinetic data in various media for several compounds according to the invention. Table 12 below sets forth anticholinergic activities for various of the compounds according to the present invention. See Table 11 for the identities of the compounds identified by Roman numerals. The activities were determined according to the method described in Example 19. 
     
                                           TABLE 8__________________________________________________________________________OXALATE SALTS OF SOFT ANTICHOLINERGIC AGENTS ##STR170##       m.p..sup.a            Yield             Calculated                                       FoundCompound R     °C.            %   Formula       C %                                 H %                                    N %                                       C %                                          H %                                             N %__________________________________________________________________________II    H     112-115            23  C.sub.17 H.sub.21 NO.sub.4.C.sub.2 H.sub.2 O.sub.4.0.                5H.sub.2 O    56.71                                 6.01                                    3.48                                       56.94                                          6.26                                             3.32Va    CH.sub.3       89-91            64.5                C.sub.18 H.sub.23 NO.sub.4.C.sub.2 H.sub.2 O.sub.4.H.                sub.2 O       56.47                                 6.39                                    3.29                                       56.48                                          6.2                                             2.94Vb    CH.sub.2 CH.sub.3       135-137            75  C.sub.19 H.sub.25 NO.sub.4.C.sub.2 H.sub.2 O.sub.4                              59.85                                 6.45                                    3.32                                       59.88                                          6.52                                             3.3Vc    CH(CH.sub.3).sub.2       78-80            72.4                C.sub.20 H.sub.27 NO.sub.4.C.sub.2 H.sub.2 O.sub.4                              60.68                                 6.71                                    3.21                                       60.41                                          6.77                                             3.13Vd    C.sub.6 H.sub.11       160-162            77.91                C.sub.23 H.sub.31 NO.sub.4.C.sub.2 H.sub.2 O.sub.4                              63.15                                 6.99                                    2.94                                       63.05                                          7.26                                             2.78__________________________________________________________________________ .sup.a All compounds were recrystallized from methanolether. 
    
     
                                           TABLE 9__________________________________________________________________________QUATERNARY IODIDES ##STR171##        m.p.           Yield          Calculated                                               FoundCompound R      °C.               Cryst. Solvent                       %   Formula    C  H  N  C   H  N__________________________________________________________________________VIb   CH.sub.2 CH.sub.3        232-234 (dec)               methanol-ether                       50.9                           C.sub.20 H.sub.28 INO.sub.4                                      50.75                                         5.92                                            2.96                                               50.55                                                   5.97                                                      2.97VIc   CH(CH.sub.3).sub.2        251-254               ethanol-ether                       61.56                           C.sub.21 H.sub.30 INO.sub.4.0.5H.sub.2                                      50.81                                         6.29                                            2.82                                               50.67                                                   6.26                                                      2.95VId   C.sub.6 H.sub.11        228-230               methanol-ether                       55.9                           C.sub.24 H.sub.34 INO.sub.4.0.25H.sub.2                                      54.19                                         6.53                                            2.63                                               54.00                                                   6.48                                                      2.50__________________________________________________________________________ 
    
     
                                           TABLE 10__________________________________________________________________________QUATERNARY DIMETHYLSULFATES ##STR172##       m.p. Cryst.                  Yield          Calculated  FoundCompound R     °C.            Solvent                  %   Formula    C  H  N  S  C  H  N  S__________________________________________________________________________VIIa  CH.sub.3       138-140            Methanol/                  22  C.sub.20 H.sub.29 NO.sub.8 S.H.sub.2 O                                 53.08                                    6.68                                       3.09                                          7.08                                             53.06                                                6.65                                                   3.01                                                      7.14            EtherVIIb  C.sub.2 H.sub.5       165-167            Methanol/                  62  C.sub.21 H.sub.31 NO.sub.8 S                                 55.13                                    6.83                                       3.06                                          7.01                                             55.10                                                6.87                                                   2.96                                                      7.02            EtherVIIc  CH(CH.sub.3).sub.2       128-130            Methanol/                  48  C.sub.22 H.sub.33 NO.sub.8 S                                 56.03                                    7.05                                       2.97                                          6.80                                             55.91                                                7.08                                                   2.96                                                      6.78            EtherVIId  C.sub.6 H.sub.11       196-198            Methanol/                  36  C.sub.25 H.sub.37 NO.sub.8 S. 1/2H.sub.2                                 57.67                                    7.36                                       2.69                                          6.16                                             57.91                                                7.15                                                   2.68                                                      6.17            Ether__________________________________________________________________________ 
    
     
                                           TABLE 11__________________________________________________________________________HYDROLYSIS KINETICS IN AQUEOUS SOLUTION (pH 12), HUMAN PLASMA (37°C.)AND RAT LIVER HOMOGENATE (37° C.) ##STR173##         t  1/2 (Min)   t  1/2 (h)  t  1/2 (Min)         Aqueous Soln, pH 12.sup.a, 37° C.                        Human Plasma, 37° C..sup.a                                    Rat Liver Homogenate, 37°                                    C..sup.aCompound R       (k.sub.obsd min.sup.-1)                        (k.sub.obsd min.sup.-1)                                    (k.sub.obsd min.sup.-1)__________________________________________________________________________II    H       350                        --         (19.8 ± 0.3 × 10.sup.-4)Va    Me      4.80           --          --         (1.43 ± 0.12 × 10.sup.-1)Vb    Et      4.08           77.4        3.48         (16.9 ± 0.15 × 10.sup.-2)                        (15.0 ± 0.3 × 10.sup.-5)                                    (1.99 ± 0.996 ×                                    10.sup.-1)Vc    i-Pr    22.8           185.5       7.12         (30 ± 0.77 × 10.sup.-3)                        (6.27 ± 0.3 × 10.sup.-5)                                    (97.2 ± 0.76                                    × 10.sup.-3)Vd    c-Hexyl 182            269.8       18.7         (379 ± 0.8 × 10.sup.-5)                        (4.44 ± 0.4 × 10.sup.-5)                                    (37.0 ± 0.3                                    × 10.sup.-3)VIb   Et (N.sup.+).sup.b         0.85           82.2        6.6         (80.8 ± 0.75 × 10.sup.-2)                        (14.1 ± 0.6 × 10.sup.-5)                                    (10.5 ± 0.28                                    × 10.sup.-2)VId   c-Hexyl (H.sup.+).sup.b         1.28           183.2       66.8         (5.43 ± 0.1 × 10.sup.-1)                        (6.31 ± 0.8 × 10.sup.-5)                                    (10.4 ± 0.23                                    × 10.sup.-3)__________________________________________________________________________ .sup.a Average of three runs ± SEM. .sup.b Tests were performed with the quaternary methiodide salts. 
    
     
                       TABLE 12______________________________________ANTICHOLINERGIC ACTIVITY OF SOFT ATROPINEAGENTS ##STR174##    PA.sub.2SOFT DRUG                 QUATERNARYR          TERTIARY AMINE AMINE.sup.a______________________________________H          6.20 (II)      --Me         6.55 (Va)      --Et         6.72 (Vb)      7.85 (VIb)i-Pr       7.55 (Vc)      7.61 (VIc)c-Hexyl    6.59 (Vd)      7.35 (VId)Atropine   8.29           --______________________________________ .sup.a Tests were carried out with the quaternary methiodide soft esters. 
    
     EXAMPLE 22 
     The antiperspirant/antisecretory activity of the compounds of the invention is illustrated by the following procedure. 
     Forearm Antiperspirant Test 
     Ref.: F. S. K. MacMillan, H. H. Reller and F. H. Snyder, J. Investig. Dermatol., 43, 363-377 (1964); R. B. Stoughton, F. Chiu, W. Fritsch, and D. Nurse, ibid 42, 151-155 (1964). 
     Circles, 4.5 cm 2  in area, were marked on the inner aspect of the forearm about  3/4 inch apart. The antiperspirant solution was applied with a cotton-tipped swab and allowed to dry. This was done three times for each area. A total of 0.1-0.2 mL was applied in this manner. After an appropriate time interval, often about 5 hours, the forearm was washed with soap and water and rinsed thoroughly to remove any excess of the material and the areas were treated with 3% iodine in alcohol until the skin was an orange/yellow color when dry, then covered with a fine slurry of 50% starch in castor oil. Subjects were placed in a room at 88°-94° F. and a relative humidity of 70-80%. Degree of inhibition of sweating was determined after 30 minutes. 
     The ethyl and cyclohexyl soft diester analogs of attopine (the quaternary salts, Compounds 5 and 6) showed inhibition of eccrine sweat glands using this method and serve as soft drug examples of antiperspirant spitant activity (Tables A and B). The soft agents are designed to be less toxic than atropine, scopolamine and other anticholinergic, antisecretory agents if absorbed into the systemic circulation due to their chemical and/or enzymatic deactivation to an inactive metabolite. Passage of any intact molecules across the blood-brain barrier into the central nervous system and their resultant toxic effects would also be prevented when the quaternary ammonium feature is incorporated in the soft antisecretory molecular structure. 
     EXAMPLE 23 
     The general procedure of Example 2 is repeated, except that the ethanol reactant employed in step (a) is replaced with an equivalent quantity of a different alcohol reactant, as specified below. Atropine soft drugs of the formula ##STR175## are thus obtained. 
     
         __________________________________________________________________________Alcohol Reactantfor Step (a) R in Product__________________________________________________________________________n-butanol    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.32-cyclohexylethanol         ##STR176##cyclohexylmethanol         ##STR177##2,6-dimethylcyclohexanol         ##STR178##1-adamantanemethanol         ##STR179##1-adamantaneethanol         ##STR180##2-norbornanemethanol         ##STR181##cholesterol         ##STR182##n-propanol   CH.sub.2 CH.sub.2 CH.sub.3n-pentanol   (CH.sub.2).sub.4 CH.sub.3n-hexanol    (CH.sub.2).sub.5 CH.sub.3n-heptanol   (CH.sub.2).sub.6 CH.sub.3n-octanol    (CH.sub.2).sub.7 CH.sub.33,5-dimethylcyclohexanol         ##STR183##4-methylcyclohexanol         ##STR184##4-tert-butylcyclohexanol         ##STR185##epiandrosterone         ##STR186##isopinocampheol         ##STR187##endo-norborneol         ##STR188##exo-norborneol         ##STR189##(1S)-endo-(-)-borneol         ##STR190##__________________________________________________________________________ 
    
     When these products are quaternized according to the process of Examples 8 and 9, the corresponding methiodides and dimethylsulfates, respectively, are obtained. 
     EXAMPLE 24 
     The general procedure of Example 2 is repeated, except that the ethanol reactant utilized in step (a) is replaced with an equivalent quantity of the alcohol reactant specified below, and the tropine reactant employed in step (c) is replaced with an equivalent quantity of 6,7-epoxytropine (scopine). Scopolamine soft drugs of the formula ##STR191## are thus obtained. 
     
         __________________________________________________________________________Alcohol Reactantfor Step (a) R in Product__________________________________________________________________________n-butanol    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.32-cyclohexylethanol         ##STR192##cyclohexylmethanol         ##STR193##2,6-dimethylcyclohexanol         ##STR194##1-adamantanemethanol         ##STR195##1-adamantaneethanol         ##STR196##2-norbornanemethanol         ##STR197##cholesterol         ##STR198##cyclohexanol         ##STR199##ethanol      CH.sub.2 CH.sub.3isopropanol  CH(CH.sub.3).sub.2methanol     CH.sub.3n-propanol   CH.sub.2 CH.sub.2 CH.sub.3n-pentanol   (CH.sub.2).sub.4 CH.sub.3n-hexanol    (CH.sub.2).sub.5 CH.sub.3n-heptanol   (CH.sub.2).sub.6 CH.sub.3n-octanol    (CH.sub.2).sub.7 CH.sub.33,5-dimethylcyclohexanol         ##STR200##4-methylcyclohexanol         ##STR201##4-tert-butylcyclohexanol         ##STR202##epiandrosterone         ##STR203##isopinocampheol         ##STR204##endo-norborneol         ##STR205##exo-norborneol         ##STR206##(1S)-endo-(-)-borneol         ##STR207##__________________________________________________________________________ 
    
     When these products are quaternized according to the process of Examples 8 and 9, the corresponding methiodides and dimethylsulfates, respectively, are obtained. 
     EXAMPLE 25 
     When the general procedure of Example 2 is followed, substituting an equivalent quantity of the alcohol reactant specified below in place of the ethanol reactant employed in step (a) and substituting an equivalent quantity of N-ethyl-N-(4-pyridylmethyl)amine for the tropine reactant employed in step (c), tropicamide soft drugs of the formula ##STR208## are obtained. 
     
         __________________________________________________________________________Alcohol Reactantfor Step (a) R in Product__________________________________________________________________________n-butanol    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.32-cyclohexylethanol         ##STR209##cyclohexylmethanol         ##STR210##2,6-dimethylcyclohexanol         ##STR211##1-adamantanemethanol         ##STR212##1-adamantaneethanol         ##STR213##2-norbornanemethanol         ##STR214##cholesterol         ##STR215##cyclohexanol         ##STR216##ethanol      CH.sub.2 CH.sub.3isopropanol  CH(CH.sub.3).sub.2methanol     CH.sub.3n-propanol   CH.sub.2 CH.sub.2 CH.sub.3n-pentanol   (CH.sub.2).sub.4 CH.sub.3n-hexanol    (CH.sub.2).sub.5 CH.sub.3n-heptanol   (CH.sub.2).sub.6 CH.sub.3n-octanol    (CH.sub.2).sub.7 CH.sub.33,5-dimethylcyclohexanol         ##STR217##4-methylcyclohexanol         ##STR218##4-tert-butylcyclohexanol         ##STR219##epiandrosterone         ##STR220##isopinocampheol         ##STR221##endo-norborneol         ##STR222##exo-norborneol         ##STR223##(1S)-endo-(-)-borneol         ##STR224##__________________________________________________________________________ 
    
     When these products are quaternized according to the process of Examples 8 and 9, the corresponding methiodides and dimethylsulfates, respectively, are obtained. 
     EXAMPLE 26 
     d, 1 or 1-Phenylsuccinic anhydride (0.1 mol) is dissolved in benzene (30-50 fold), and a solution of 0.1 mol of alcohol or amine reactant as specified below in an equal volume of benzene is introduced gradually, with stirring. In the case of the amine reactant, 0.1 mol of triethylamine is included as an acid scavenger. At the end of the addition, the reaction mixture is warmed to gentle reflux and maintained at that temperature for 1 hour. Th e reaction mixture is washed twice with water, then with 5% aqueous sodium bicarbonate solution until neutral, then twice more with water. The solvent is evaporated and the crude monoester or amide thus obtained is then reacted with thionyl chloride according to the general procedure of Example 2(b) to afford the monoester acid chloride or amide acid chloride, which is then esterified with an alcohol R 1  OH as specified below according to the procedure of Example 2(c) to afford the corresponding oxalate salts of the free bases shown below. 
     Using tropine as the alcohol reactant in the first step: 
     
         __________________________________________________________________________ ##STR225##Alcohol reactantin final step        R in product__________________________________________________________________________n-butanol    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.32-cyclohexylethanol         ##STR226##cyclohexylmethanol         ##STR227##2,6-dimethylcyclohexanol         ##STR228##1-adamantanemethanol         ##STR229##1-adamantaneethanol         ##STR230##2-norbornanemethanol         ##STR231##cholesterol         ##STR232##cyclohexanol         ##STR233##ethanol      CH.sub.2 CH.sub.3isopropanol  CH(CH.sub.3).sub.2methanol     CH.sub.3n-propanol   CH.sub.2 CH.sub.2 CH.sub.3n-pentanol   (CH.sub.2).sub.4 CH.sub.3n-hexanol    (CH.sub.2).sub.5 CH.sub.3n-heptanol   (CH.sub.2).sub.6 CH.sub.3n-octanol    (CH.sub.2).sub.7 CH.sub.33,5-dimethylcyclohexanol         ##STR234##4-methylcyclohexanol         ##STR235##4-tert-butylcyclohexanol         ##STR236##epiandrosterone         ##STR237##isopinocampheol         ##STR238##endo-norborneol         ##STR239##exo-norborneol         ##STR240##(1S)-endo-(-)-borneol         ##STR241##__________________________________________________________________________ 
    
     Using scopine as the alcohol reactant in the first step: 
     
         __________________________________________________________________________ ##STR242##Alcohol reactantin final step        R in product__________________________________________________________________________n-butanol    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.32-cyclohexylethanol         ##STR243##cyclohexylmethanol         ##STR244##2,6-dimethylcyclohexanol         ##STR245##1-adamantanemethanol         ##STR246##1-adamantaneethanol         ##STR247##2-norbornanemethanol         ##STR248##cholesterol         ##STR249##cyclohexanol         ##STR250##ethanol      CH.sub.2 CH.sub.3isopropanol  CH(CH.sub.3).sub.2methanol     CH.sub.3n-propanol   CH.sub.2 CH.sub.2 CH.sub.3n-pentanol   (CH.sub.2).sub.4 CH.sub.3n-hexanol    (CH.sub.2).sub.5 CH.sub.3n-heptanol   (CH.sub.2).sub.6 CH.sub.3n-octanol    (CH.sub.2).sub.7 CH.sub.33,5-dimethylcyclohexanol         ##STR251##4-methylcyclohexanol         ##STR252##4-tert-butylcyclohexanol         ##STR253##epiandrosterone         ##STR254##isopinocampheol         ##STR255##endo-norborneol         ##STR256##exo-norborneol         ##STR257##(1S)-endo-(-)-borneol         ##STR258##__________________________________________________________________________ 
    
     Using N-ethyl-N-(4-pyridylmethyl)amine the amine reactant in the first step: 
     
         __________________________________________________________________________ ##STR259##Alcohol reactantin final step        R in product__________________________________________________________________________n-butanol    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.32-cyclohexylethanol         ##STR260##cyclohexylmethanol         ##STR261##2,6-dimethylcyclohexanol         ##STR262##1-adamantanemethanol         ##STR263##1-adamantaneethanol         ##STR264##2-norbornanemethanol         ##STR265##cholesterol         ##STR266##cyclohexanol         ##STR267##ethanol      CH.sub.2 CH.sub.3isopropanol  CH(CH.sub.3).sub.2methanol     CH.sub.3n-propanol   CH.sub.2 CH.sub.2 CH.sub.3n-pentanol   (CH.sub.2).sub.4 CH.sub.3n-hexanol    (CH.sub.2).sub.5 CH.sub.3n-heptanol   (CH.sub.2).sub.6 CH.sub.3n-octanol    (CH.sub.2).sub.7 CH.sub.33,5-dimethylcyclohexanol         ##STR268##4-methylcyclohexanol         ##STR269##4-tert-butylcyclohexanol         ##STR270##epiandrosterone         ##STR271##isopinocampheol         ##STR272##endo-norborneol         ##STR273##exo-norborneol         ##STR274##(1S)-endo-(-)-borneol         ##STR275##__________________________________________________________________________ 
    
     When the products of this Example are quaternized according to the process of Examples 8 and 9, the corresponding methiodides and dimethylsulfates, respectively, are obtained. 
     For therapeutic use as an anticholinergic agent or as a mydriatic agent, a compound of formula (I) or its acid addition or quaternary ammonium salt can be conveniently administered in the form of a pharmaceutical composition containing the formula (I) compound or its salt and a pharmaceutically acceptable carrier therefor. Suitable carriers vary with the desired form of the pharmaceutical composition and may include diluents or excipients such as fillers, binders, wetting agents, disintegrators, surface-active agents, lubricants and the like. 
     The compound of the invention or its salt, in an effective anticholinergic or mydriasis-inducing amount, may be formulated together with the carrier into any desired unit dosage form, the dosage form of choice depending upon the ultimate use of the selected compound. Typical unit dosage forms include tablets, pills, powders, solutions, suspensions, emulsions, gels, ointments, granules, capsules and suppositories. 
     In the preparation of tablets, carriers which are widely used in this field can be employed, e.g. excipients such as lactose, sucrose, sodium chloride, glucose solution, urea, starch, calcium carbonate, kaolin, crystalline cellulose and silicic acid; binding agents such as water, ethanol, propanol, simple syrup, glucose, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose; calcium phosphate and polyvinylpyrrolidone; disintegrators such as dried starch, sodium algihate, agar-agar powder, laminalia powder, sodium bicarbonate, calcium carbonate, Tweens, sodium lauryl sulfate, stearic acid monoglyceride, starch and lactose; disintegration inhibitors such as sucrose, stearin, coconut butter and hydrogenated oil; absorption accelerators such as quaternary ammonium bases an d sodium lauryl sulfate; wetting agents such as glycetin and starch; adsorbing agents such as starch, lactose, kaolin, bentonite and colloidal silicic acid; and lubricants such as purified talc, stearic acid salts, boric acid powder, Macrogol and solid polyethylene glycol. 
     In the preparation of pills, carriers which are known and widely used in this field can also be used, for example, excipients such as glucose, lactose, starch, coconut butter, hydrogenated vegetable oils, kaolin and talc; binders such as powdered gum arabic, powdered tragacanth, gelatin and ethanol; and disintegrators such as laminaria and agar-agar. In the case of tablets, they can be further coated with the usual coating materials to make sugar-coated tablets, gelatin film-coated tablets, tablets coated with enteric coatings, tablets coated with films or double-layered tablets and multi-layered tablets. 
     In order to form suppositories, carriers which are known and widely used in this field can also be used, for example, polyethylene glycols, coconut butter, higher alcohols, esters of higher alcohols, gelatin and semi-synthesized glycerides. 
     Furthermore, the usual dissolving agents, buffers, analgesic agents and preservatives can be added, as well as coloring materials, perfumes, seasoning agents, sweetening agents and other medicines, to the pharmaceutical compositions, if necessary or if desired. 
     The amount of a compound of formula (I) or its salt to be present in the pharmaceutical composition can be suitably be selected from a wide range, but usually 1 to 70% by weight of the total composition is preferable when the composition is a solid dosage form. 
     As to the route of administration, same will vary with the particular composition used. For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules can be administered orally; suppositories can be administered rectally. 
     The dosage of the compound of the present invention or its salt and frequency of administration is selected according to the usage, purpose and conditions of symptoms, as well as the size and species of the recipient. For example, when the compound or salt is administered therapeutically as an anticholinergic, usually 0.006 mg to 6.0 mg per kg of body weight per day will suffice. 
     The compounds of the present invention and their acid addition and quaternary ammonium salts induce mydriasis when applied topically/locally to the eye, thus are of particular use in dilating the pupils during ophthalmic examinations, for eye surgery and in the treatment of certain eye conditions. The instant compounds and their salts can be conveniently administered for these purposes by formulating the selected compound or salt, in an effective mydriasis-inducing amount, together with a non-toxic ophthalmically acceptable carrier therefor. Suitable carriers will be apparent to those skilled in the art of ophthalmic formulations. Obviously, the choice of suitable carriers will depend on the exact nature of the particular dosage form desired, e.g. whether the soft mydriatic agent of the invention is to be formulated into an ophthalmic solution or suspension (typically for use as eye drops), an ophthalmic ointment or cream or an ophthalmic gel. Preferred dosage forms are solutions, which contain a major amount of water addition to the active ingredient. Minor amounts other ingredients such as pH adjusters (e.g. a base such as NaOH), emulsifiers or dispersing agents, buffering agents, preservatives, wetting agents and jelling agents (e.g. methylcellulose) may also be present. Most preferably, the ophthalmic composition is a sterile, isotonic, buffered aqueous solution. Generally speaking, the ophthalmic composition containing the instant mydriatic may be prepared and may contain the various inert ingredients or carriers as previously described in the patent or non-patent literature as being suitable for ophthalmic compositions comprising known anticholinergic-type mydriatic agents such as tropine, scopolamine, homatropine and the like. The amount of the soft mydriatic of this invention which will be present in the ophthalmic composition will of course vary with the particular soft mydriatic employed and the type of formulation selected. Generally speaking, the composition will contain 0.01 to 5% of a compound of formula (I), preferably 0.25 to 2.5%; in other words, each mL of solution will contain 0.1 to 50 mg, preferably 2.5 to 25 mg, of the free base. The dose administered ophthalmically will be selected according to the particular compound employed, the size and condition of the patient and the effect desired, but in any event will be a quantity sufficient to cause mydriasis. To dilate the pupils for ophthalmic examination, 1 or 2 drops per eye of the solution will generally suffice. 
     Similarly, in a typical topical formulation for topical application as an antiperspirant, any one of the compounds or salts of the instant invention can be combined with any suitable topical vehicle safe for underarm application. The vehicle may be solid, liquid or aerosol. Vehicles serving the aforementioned purpose are readily found in Remindton&#39;s Pharmaceutical Sciences (Fourteenth Edition) 1970 and the text entitled, Cosmetics, Science and Technology, H. D. Goulden, et al, Interscience Publishers (1957), pp. 5, 717-31, 826-9, 1016, 1211, 1255 and 1266, respectively. When topically administered to inhibit perspiration a 0.01% to 25% by weight composition applied in the usual manner will normally be sufficient. Generally speaking, a usual application would consist of approximately 1 mL of a lotion composition (e.g. a roll-on formulation) or 1 gram of a dry (e.g. stick) composition, applied daily. 
     From the foregoing description, one of ordinary skill in the art can easily ascertain the essential characteristics of the instant invention, and without departing from the spirit and scope thereof, can make various changes and/or modifications of same to adapt it to various usages and conditions. Consequently, these changes and/or modifications are properly, of equitably and intended to be, within the full range equivalence of the following claims.