US3816457A - Lactamimide derivatives - Google Patents

Lactamimide derivatives Download PDF

Info

Publication number
US3816457A
US3816457A US00321160A US32116073A US3816457A US 3816457 A US3816457 A US 3816457A US 00321160 A US00321160 A US 00321160A US 32116073 A US32116073 A US 32116073A US 3816457 A US3816457 A US 3816457A
Authority
US
United States
Prior art keywords
carbon atoms
hydrochloride
straight
formula
imino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US00321160A
Other languages
English (en)
Inventor
J Grisar
G Claxton
T Blohm
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Richardson Vicks Inc
Original Assignee
Richardson Merrell Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Richardson Merrell Inc filed Critical Richardson Merrell Inc
Priority to US00321160A priority Critical patent/US3816457A/en
Priority to ZA738704A priority patent/ZA738704B/xx
Priority to AU62509/73A priority patent/AU469726B2/en
Priority to CA186,439A priority patent/CA1018170A/en
Priority to IL43704A priority patent/IL43704A/en
Priority to GB5521173A priority patent/GB1417030A/en
Priority to JP14481073A priority patent/JPS5647186B2/ja
Priority to DE2365006A priority patent/DE2365006A1/de
Priority to FR7400315A priority patent/FR2213063B1/fr
Priority to US453566A priority patent/US3890445A/en
Application granted granted Critical
Publication of US3816457A publication Critical patent/US3816457A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis

Definitions

  • Novel compounds useful as hypoglycemic agents are represented by the formula wherein X represents oxygen or sulfur; A represents a bond, or a straight or branched alkylene chain of from 1 to 3 carbon atoms; R represents hydrogen, a straight or branched lower alkyl group of from 1 to 4 carbon atoms, a straight or branched lower alkenyl group of from 3 to 6 carbon atoms, a cycloalkyl group of from 3 t 6 carbon atoms or phenyl; R represents hydrogen or a straight or branched lower alkyl group of from 1 to 4 carbon atoms; n is an integer of from 3 to 11; and pharmaceutically acceptable acid addition salts and individual optical isomers of the compounds where applicable.
  • This invention relates to novel lactamimide derivatives useful as hypoglycemic agents and to methods of using the compounds either alone or in the form of pharmaceutical preparations.
  • Lactamimide derivatives of the following Formula I and pharmaceutically acceptable acid addition salts and individual optical isomers where applicable are useful as hypoglycemic agents.
  • X represents oxygen or sulfur
  • A represents a bond or a straight or branched alkylene chain of from 1 to 3 carbon atoms
  • R represents hydrogen, or a straight or branched lower alkyl group from 1 to 4 carbon atoms, a straight or branched lower alkenyl group of from 3 to 6 carbon atoms, cycloalkyl of from 3 to 6 carbon atoms or phenyl
  • R represents hydrogen or a straight or branched lower alkyl group of from 1 to 4 carbon atoms
  • n is an integer of from 3 to 11.
  • Pharmaceutically acceptable acid addition salts and individual optical isomers of the compounds where applicable are also included within the scope of this invention.
  • R and R may represent in the above Formulas I to I11 there may be mentioned methyl, ethyl, propyl, isopropyl, butyl, tertbutyl, and the like.
  • alkenyl groups of from 3 to 6 carbon bon atoms which R may represent in the above Formulas I to HI there may be mentioned cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • alkenyl groups of from 3 to 6 carbon atoms which R may represent in the above Formulas I to III there may be mentioned allyl, Z-butenyl, 3-butenyl, 3-pentenyl, and the like.
  • Pharmaceutically acceptable acid addition salts of the base compounds of this invention are those of any suitable inorganic or organic acids.
  • Suitable inorganic acids are for example, hydrochloric, hydrobromic, sulfuric or phosphoric acids, and the like.
  • Suitable organic acids are, for example, carboxylic acids such as acetic, propionic, glycolic, lactic, pyruvic, rnalonic, succinic, fumaric, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, benzoic, hydroxybenzoic, phenylacetic, cinnamic, salicylic, 2- phenoxybenzoic, and the like, or sulfonic acids such as methane sulfonic, Z-hydroxyethane sulfonic acid and the like.
  • the compounds of this invention are useful as hypoglycemic agents and may be used to control hyperglycemic conditions, such as occur for example in diabetic patients, by inducing a hypoglycemic response in the patient.
  • hypoglycemic agents male rats of the Charles River C.D. strain each weighing from 120 to 140 grams were fastened for 15 hours then injected subcutaneously with 1 g./kg. of body weight of glucose in 0.5 ml. of 0.9% sodium chloride solution. Immediately following the glucose injection the animals were administered by oral intubation a compound of this invention in 0.5 ml. of carboxymethyl cellulose.
  • novel compounds can be administered to animals, warm blooded animals and particularly mammals, either alone or in the form of pharmaceutical preparations which contain the novel compounds suitable for oral or parenteral administration.
  • Pharmaceutical preparations containing novel compounds of this invention and conventional pharmaceutical carriers can be employed in unit dosage forms such as solids, for example, tablets and capsules, or liquid solutions, suspensions or elixirs for oral administration, or liquid solutions, suspensions, emulsions, and the like for parenteral administration.
  • the quantity of compound administered can vary over a wide range to provide from about 0.1 mg./kg. (milligram per kilogram) to about 100 mg./kg. of body weight of the patient per day to achieve the desired efiect.
  • Unit doses of these compounds can contain from about to 500 mg. of the compound and may be administered, for example, from 1 to 4 times daily. Specific Examples 25 to 28 are illustrative of pharmaceutical preparations containing as active ingredients compounds of this invention.
  • the compounds of this invention may be prepared by reacting an excess of a lactim ether of the formula N lower alkyl 0- 0 (CH R Formula IV with a primary amine of the following formula II X/ A CH NH: Formula V in a manner similar to that reported by R. E. Benson and T. L. Cairns in J. Am. Chem. Soc. 70, 2115-8 (1948).
  • the various symbols X, A, R, R and n have the meanings defined hereinbefore.
  • This reaction may be carried out with or without a solvent.
  • a solvent that preferred is a lower alcohol, such as methanol, ethanol, isopropyl alcohol, butanol and the like.
  • solvents such as, aromatic hydrocarbons, for example, benzene and toluene may also be used as suitable solvents for this reaction.
  • a basic or an acidic catalyst such as a tertiary amine or hydrogen chloride may be added to the reaction mixture.
  • the hydrochloride salt of the amine be used in the reaction.
  • the temperature of the reaction varies from 40 C. to C., and the preferred temperature is about 1525 C.
  • the reaction time varies from 1 hour to about 60 days being dependent upon the temperature of the reaction, the reactant primary amine, and more particularly on the degree of steric hindrance of the amine since highly sterically hindered amines react very slowly.
  • lactim others as represented by Formula IV which find use in this reaction may be prepared from commercially available corresponding lactams by methods known in the art. For example, by reaction of an appropriate lactam with dirnethyl sulfate in a solvent such as benzene, toluene, xylene or the like at the reflux temperature of the solvent for 2-24 hours the corresponding o-methyl lactim ether is obtained.
  • a solvent such as benzene, toluene, xylene or the like
  • the amines as represented by Formula V which find use in this reaction may be prepared by several methods known to the art.
  • a nitrile of the formula H HA-CN X Formula VI may be reacted with an alkylor phenylmagnesium halide compound followed by reduction of the resulting ketimine complex in situ with lithium aluminum hydride.
  • nitriles of the formula RCN Formula VII via Hoffman or Curtius degradation, such as described by F. J. McCarty et al., J. Med. Chem. 11, 534 (1968), or as described by Van Zoeren in U.S. 2,367,702.
  • the compounds of this invention may also be prepared using a complex of an appropriate lactam of the formula Formula VIII R Formula IX wherein n and R have the meaning defined above, with phosphorus oxychloride, phosgene, borontrifluoride etherate, dimethylsulfate, hydrogenjhalide or a combination of two or more such reagents.
  • phosphorus oxychloride, phosgene, borontrifluoride etherate, dimethylsulfate, hydrogenjhalide or a combination of two or more such reagents Several attempts have been made to formulate the structure of these complexes, and one formulation includes the imino halide, that is, 2- chloro-4,5,6,7-tetrahydro-3g-azepine. However, none of the formulations have been unambiguously established. This reaction has been studied by H. Bredereck in a series of articles in Chem. Ber., 1953-1968, particularly in vol.
  • the complex formed is reacted with an appropriate primary amine describedhereinabove in an aromatic hydrocarbon solvent such as benzene, toluene or xylene or an alkyl polyhalide solvent such as carbon tetrachloride, chloroform, methylene chloride, dichloroethane, tetrachloroethylene or the like.
  • aromatic hydrocarbon solvent such as benzene, toluene or xylene
  • an alkyl polyhalide solvent such as carbon tetrachloride, chloroform, methylene chloride, dichloroethane, tetrachloroethylene or the like.
  • the reaction temperature is limited by the boiling point of the solvent, however, in some cases it is advantageous to carry out the reaction at room temperature or with cooling 'at 0 to'40 C. depending on the reactants.
  • the above reaction may be carried out by using known thiolactim ethers such as S-methylthiocaprolactim [H. Behringer and H. Meier, Ann. 607, 73-91 (1957)], or by using thiolactams'wherein the latter case it may be advantageous to employ a catalyst such as mercury or silver oxide or cyanide [1. Gautier and J. Renault, C. 'R. Acad. Sci. 234, (1952)].
  • thiolactim ethers such as S-methylthiocaprolactim [H. Behringer and H. Meier, Ann. 607, 73-91 (1957)]
  • thiolactams'wherein the latter case it may be advantageous to employ a catalyst such as mercury or silver oxide or cyanide [1. Gautier and J. Renault, C. 'R. Acad. Sci. 234, (1952)].
  • a-(Z-thienyDbenZylamine hydrochloride is added. Stirring is continued at room temperature for 1 hour then at reflux temperature for 4 hours. The resulting solution is allowed to cool to room temperature and stand over night after which it is washed with 2 N h ydrochloric acid. The organiclayer is separated and. washed with a saturated sodium chloride solution and dried over sodium sulfate.
  • EXAMPLE 25 An illustrative composition for tablets is as follows:
  • a granulation obtained upon mixing lactose with the starch and granulated starch paste is dried, screened and mixed with the active ingredient (a) and magnesium stearate. The mixture is compressed in tablets weighing 150 mg. each.
  • EXAMPLE 26 An illustrative composition for hard gelatin capsules is as follows:
  • EXAMPLE 27 An illustrative composition for pills is as follows:
  • composition is prepared by dissolving the active ingredient and suflicient sodium chloride in water for injection to render the solution isotonic.
  • the composition may be dispensed in a single ampule containing 100 mg. of the active ingredient for multiple dosage or in 10 ampules for a single dosage.
  • a compound selected from a base of the formula H R N K A-( 3H-N C (CH1) wherein X is selected from oxygen or sulfur; A is selected from the group representing a bond or a straight or branched alkylene chain of from 1 to 3 carbon atoms; R is selected from the group consisting of hydrogen or a straight or branched lower alkyl group of from 1 to 4 carbon atoms, a straight or branched lower alkenyl group of from 3 to 6 carbon atoms, a cycloalkyl group of from 3 to 6 carbon atoms and phenyl; R is selected from the group consisting of hydrogen or a straight or branched lower alkyl group of from 1 to 4 carbon atoms; 11 is an integer of from 3 to 11; and pharmaceutically acceptable acid addition salts thereof.
  • a compound of claim 2 which is 2-[(a-[2-furyl] benzyl)imino]hexahydroazepine and pharmaceutically acceptable acid addition salts thereof.
  • a compound of claim 2 which is 2[[a-(2furyl)- benzyl1imino]octahydroazocine and pharmaceutically acceptable acid addition salts thereof.
  • a compound of claim 5 which is octahydro-Z-[l-(Z- thienyl) 2 butylimino]azonine and pharmaceutically acceptable acid addition salts thereof.
  • a compound of claim 5 which is hexahydro-2-[2-(1- [2-thienyl1pent 4 enyl)imino1azepine and pharmaceutically acceptable acid addition salts thereof.
  • a compound of claim 5 which is heXahydro-Z-Ha- (2- thienyl)benzyl]imino]azepine and pharmaceutically acceptable acid addition salts thereof.
  • a compound of claim 5 which is 2-[a-cyclopropyl- 2-thenyl)imino]hexahydroazepine and pharmaceutically acceptable acid addition salts thereof.

Landscapes

  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Furan Compounds (AREA)
US00321160A 1973-01-05 1973-01-05 Lactamimide derivatives Expired - Lifetime US3816457A (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
US00321160A US3816457A (en) 1973-01-05 1973-01-05 Lactamimide derivatives
ZA738704A ZA738704B (en) 1973-01-05 1973-11-13 Lactamimide derivatives
AU62509/73A AU469726B2 (en) 1973-01-05 1973-11-15 Lactam imide derivatives
CA186,439A CA1018170A (en) 1973-01-05 1973-11-22 Lactamimide derivatives
IL43704A IL43704A (en) 1973-01-05 1973-11-26 Lactamimide derivatives
GB5521173A GB1417030A (en) 1973-01-05 1973-11-28 Lactamimide derivatives
JP14481073A JPS5647186B2 (enExample) 1973-01-05 1973-12-28
DE2365006A DE2365006A1 (de) 1973-01-05 1973-12-28 Neue lactamimid-derivate und diese enthaltende pharmazeutische zusammensetzungen
FR7400315A FR2213063B1 (enExample) 1973-01-05 1974-01-04
US453566A US3890445A (en) 1973-01-05 1974-03-22 Lactamimide derivatives useful as hypoglycemic agents

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US00321160A US3816457A (en) 1973-01-05 1973-01-05 Lactamimide derivatives

Publications (1)

Publication Number Publication Date
US3816457A true US3816457A (en) 1974-06-11

Family

ID=23249450

Family Applications (1)

Application Number Title Priority Date Filing Date
US00321160A Expired - Lifetime US3816457A (en) 1973-01-05 1973-01-05 Lactamimide derivatives

Country Status (9)

Country Link
US (1) US3816457A (enExample)
JP (1) JPS5647186B2 (enExample)
AU (1) AU469726B2 (enExample)
CA (1) CA1018170A (enExample)
DE (1) DE2365006A1 (enExample)
FR (1) FR2213063B1 (enExample)
GB (1) GB1417030A (enExample)
IL (1) IL43704A (enExample)
ZA (1) ZA738704B (enExample)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4126621A (en) * 1973-08-09 1978-11-21 Richardson-Merrell Inc. Substituted cycloalkyl lactamimides
US4252819A (en) * 1977-08-29 1981-02-24 Yamanouchi Pharmaceutical Co., Ltd. Antisecretory heterocyclic amidine compounds
US5010072A (en) * 1988-06-28 1991-04-23 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists
US5082837A (en) * 1988-06-28 1992-01-21 Merrell Dow Pharmaceuticals Lactamimides as calcium antagonists
US5198433A (en) * 1988-06-28 1993-03-30 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists
US5854234A (en) * 1993-10-21 1998-12-29 G. D. Searle & Co. Amidino dervatives useful as nitric oxide synthase inhibitors
US5883251A (en) * 1995-04-20 1999-03-16 G. D. Searle & Co. Azepine derivatives useful as nitric oxide synthase inhibitors
US5958958A (en) * 1997-07-22 1999-09-28 G.D. Searle & Co. 1,2,4-oxa diazolino and 1,24-oxa diazolidion heterocycles as useful nitric oxide synthase inhibitors
US6344473B1 (en) 2000-08-07 2002-02-05 G.D. Searle & Co. Imidazoles useful as nitric oxide synthase inhibitors
WO2002094802A1 (de) * 2001-05-22 2002-11-28 Grünenthal GmbH Substituierte c-furan-2-yl-methylamin- und c-thiophen-2-yl-methylamin-derivate
US6489323B1 (en) 1998-06-10 2002-12-03 G.D. Searle & Co. Heterobicyclic and tricyclic nitric oxide synthase inhibitors

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2192631A (en) * 1986-07-16 1988-01-20 Ici Plc Fungicidal heterocyclic tertiary amine compounds containing a cyclopropane ring
USD825997S1 (en) 2018-03-22 2018-08-21 Remson Concepts, Inc Stackable serving tray
USD835467S1 (en) 2018-07-23 2018-12-11 Remson Concepts, Inc. Stackable serving tray

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA722407B (en) * 1971-05-13 1973-01-31 Richardson Merrell Inc Substituted cycloalkyl lactamimides

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4126621A (en) * 1973-08-09 1978-11-21 Richardson-Merrell Inc. Substituted cycloalkyl lactamimides
US4252819A (en) * 1977-08-29 1981-02-24 Yamanouchi Pharmaceutical Co., Ltd. Antisecretory heterocyclic amidine compounds
US5010072A (en) * 1988-06-28 1991-04-23 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists
US5082837A (en) * 1988-06-28 1992-01-21 Merrell Dow Pharmaceuticals Lactamimides as calcium antagonists
US5198433A (en) * 1988-06-28 1993-03-30 Merrell Dow Pharmaceuticals Inc. Lactamimides as calcium antagonists
US6071906A (en) * 1993-10-21 2000-06-06 G. D. Searle & Co. Imidino piperidine derivatives useful as nitric oxide synthase inhibitors
US6046211A (en) * 1993-10-21 2000-04-04 G.D. Searle & Co. Amidino derivatives useful as nitric oxide synthase inhibitors
US5854234A (en) * 1993-10-21 1998-12-29 G. D. Searle & Co. Amidino dervatives useful as nitric oxide synthase inhibitors
US6448286B1 (en) 1993-10-21 2002-09-10 G.D. Searle & Co. Imino pyrrolidine derivatives useful as nitric oxide synthase inhibitors
US5883251A (en) * 1995-04-20 1999-03-16 G. D. Searle & Co. Azepine derivatives useful as nitric oxide synthase inhibitors
US5958958A (en) * 1997-07-22 1999-09-28 G.D. Searle & Co. 1,2,4-oxa diazolino and 1,24-oxa diazolidion heterocycles as useful nitric oxide synthase inhibitors
US5981556A (en) * 1997-07-22 1999-11-09 G.D. Searle & Co. 1,3-diazolino and 1,3-diazolidino heterocycles as useful nitric oxide synthase inhibitors
US6136829A (en) * 1997-07-22 2000-10-24 G.D. Searle & Co. Oxathiadiazole derivatives usful as iNOS inhibitors
US6489323B1 (en) 1998-06-10 2002-12-03 G.D. Searle & Co. Heterobicyclic and tricyclic nitric oxide synthase inhibitors
US6344473B1 (en) 2000-08-07 2002-02-05 G.D. Searle & Co. Imidazoles useful as nitric oxide synthase inhibitors
DE10125145A1 (de) * 2001-05-22 2002-11-28 Gruenenthal Gmbh Substituierte C-Furan-2-yl-methylamin- und C-Thiophen-2-yl-methylamin-Derivate
WO2002094802A1 (de) * 2001-05-22 2002-11-28 Grünenthal GmbH Substituierte c-furan-2-yl-methylamin- und c-thiophen-2-yl-methylamin-derivate
US20040152734A1 (en) * 2001-05-22 2004-08-05 Gruenenthal Gmbh Substituted C-furan-2-yl-methylamine and C-thiophen-2-yl-methylamine compounds
US6878740B2 (en) 2001-05-22 2005-04-12 Gruenenthal Gmbh Substituted C-furan-2-yl-methylamine and C-thiophen-2-yl-methylamine compounds
US20050148550A1 (en) * 2001-05-22 2005-07-07 Gruenenthal Gmbh Substituted C-furan-2-yl-methylamine and C-thiophen-2-yl-methylamine compounds
US7317034B2 (en) 2001-05-22 2008-01-08 Gruenenthal Gmbh Substituted C-furan-2-yl-methylamine and C-thiophen-2-yl-methylamine compounds

Also Published As

Publication number Publication date
ZA738704B (en) 1974-09-25
JPS4995966A (enExample) 1974-09-11
DE2365006A1 (de) 1974-07-18
FR2213063A1 (enExample) 1974-08-02
IL43704A0 (en) 1974-03-14
GB1417030A (en) 1975-12-10
JPS5647186B2 (enExample) 1981-11-07
FR2213063B1 (enExample) 1977-03-11
IL43704A (en) 1976-11-30
CA1018170A (en) 1977-09-27
AU6250973A (en) 1975-05-15
AU469726B2 (en) 1976-02-19

Similar Documents

Publication Publication Date Title
US3816457A (en) Lactamimide derivatives
CA1315793C (en) Method for controlling emesis caused by chemotherapeutic agents and antiemetic carboxamides useful therein
US3900565A (en) Hypoglycemic compositions containing benzhydryllactamimide derivatives
US3783162A (en) Hypoglycemic compositions containing benzhydryl-lactamimide derivatives
US4061746A (en) Lactamimide inhibitors of gastrointestinal hypersecretion
US3890445A (en) Lactamimide derivatives useful as hypoglycemic agents
US4126613A (en) Substituted cycloalkyl lactamimides
US3840524A (en) Alpha-cycloalkylbenzyl lactamimides
US3991194A (en) Heterocyclic esters of benzopyranopyridines
US3881006A (en) Hypoglycemic compositions containing benzhydryllactamimide derivatives
US4126612A (en) Substituted cycloalkyl lactamimides
US3444181A (en) Isoindoles
US3963701A (en) Substituted benzhydryl lactamimide derivatives
US3840523A (en) Tricyclic arylalkylene lactamimides
US3803170A (en) 2-((1-benzylcyclopentyl)imino)pyrrolidine
GB2055818A (en) 3-methyleneazetidine derivatives
US3838151A (en) Cycloalkyllactamimides
US3984557A (en) Antiarrhythmia compositions and methods
US3247222A (en) Alpha (nu-hydrocarbonpyrrolidyl-3-) alpha, alpha carbocyclic arylacetamides
US3845071A (en) Imidazo(1,2-a)azacycloalkanes
US3833559A (en) Dibenzocycloheptenyl lactamimides
US3562281A (en) Bis-piperidyl-alkanes
US4130652A (en) 2-(Iminoethylidene)-pyrrolidines and tautomeric 2-(aminoethenyl)-1-pyrrolines
US3470189A (en) Heterocyclic substituted acetic acid derivatives,intermediates therefor,and production and use thereof
US3725419A (en) Quinuclidylalkyl esters