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    Amino acid derivatives
    3.
    发明授权
    Amino acid derivatives 失效
    氨基酸衍生物

    公开(公告)号：US4113715A

    公开(公告)日：1978-09-12

    申请号：US759685

    申请日：1977-01-17

    申请人： Miguel Angel Ondetti ,  Michael Edward Condon

    发明人： Miguel Angel Ondetti ,  Michael Edward Condon

    IPC分类号： A61K31/19 ,  A61K31/195 ,  A61K31/215 ,  A61K31/22 ,  A61K31/395 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K38/00 ,  A61P9/12 ,  A61P43/00 ,  C07C67/00 ,  C07C313/00 ,  C07C323/60 ,  C07C327/20 ,  C07C327/22 ,  C07C327/34 ,  C07D207/08 ,  C07D207/10 ,  C07D207/16 ,  C07D207/46 ,  C07D209/20 ,  C07D211/60 ,  C07D211/86 ,  C07D233/64 ,  C07K5/02 ,  C07K5/06 ,  C07K5/062 ,  C07C103/52 ,  A61K37/00

    CPC分类号： C07K5/0606 ,  C07C327/00 ,  C07D207/16 ,  C07D207/46 ,  C07D209/20 ,  C07D211/60 ,  C07D211/86 ,  A61K38/00 ,  Y10S514/929 ,  Y10S530/80

    摘要： New substituted acyl derivatives of amino acids which have the general formula ##STR1## are useful as angiotensin converting enzyme inhibitors.SUMMARY OF THE INVENTIONThis invention relates to new substituted acyl derivatives of amino acids which have the general formula ##STR2## and salts thereof,WHEREIN R is hydroxy or lower alkoxy;R.sub.1 is hydrogen, lower alkanoyl or amino(imino)methyl;R.sub.2 is hydrogen, lower alkyl or phenyl-lower alkylene;R.sub.3 is hydrogen, lower alkanoyl, benzoyl or ##STR3##A is hydrogen, lower alkyl or hydroxy-lower alkylene;B is hydrogen, lower alkyl, phenyl, phenyl-lower alkylene, hydroxy-lower alkylene, hydroxyphenyl-lower alkylene, amino-lower alkylene, guanidino-lower alkylene, mercapto-lower alkylene, lower alkyl-thio-lower alkylene, imidazolyl-lower alkylene, indolyl-lower alkylene, carbamoyl-lower alkylene or carboxy-lower alkylene;OR A and B together form a (CH.sub.2).sub.p bridge which completes a ring of 5 or 6 atoms with the nitrogen and carbon to which they are joined, one carbon optionally bearing a hydroxy group;N IS 0 OR 1;M IS 0, 1, 2, 3 OR 4; AT LEAST ONE OF M AND N IS OTHER THAN 0; ANDP IS 3 OR 4.The asterisks denote centers of asymmetry.DETAILED DESCRIPTION OF THE INVENTION phenylglycineThe invention in its broad aspects includes substituted acyl derivatives of amino acids having formula I above. The substituted acyl groups refer to the side chains on the carbon beta to the nitrogen atom. The one side chain has one or two sulfur containing groups and the second side chain has one nitrogen containing group. Within the class defined by formula I, because of their properties, certain subgroups are preferred.Compounds in the group represented by formula I which are derived from or include the structure of the amino acids glycine, alanine, leucine, threonine, phenylalanine, lysine, arginine, glutamine, histidine, methionine, serine, cysteine, tyrosine, valine, asparagine, glutamic acid, proline, hydroxyproline, pheylglycine or tryptophane are broadly preferred. Preferred modifications are compounds of formula I wherein R is hydroxy; R.sub.1 is hydrogen, lower alkanoyl or amino(imino)-methyl [particularly hydrogen, methyl, acetyl or amino(imino)-methyl]; R.sub.2 is hydrogen, lower alkyl (particularly hydrogen or methyl) or phenyl-lower alkylene (particularly benzyl), most particularly R.sub.2 is hydrogen; R.sub.3 is hydrogen, lower alkanoyl or benzoyl (particularly hydrogen, or acetyl); A is hydrogen; B is lower alkyl, guanidino-lower alkylene (particularly guanidinopropyl), amino-lower alkylene (particularly amino-C.sub.3 -C.sub.4 -lower alkylene) or phenyl-lower alkylene (particularly phenylmethyl); or A and B complete a 5- or 6-membered ring; m is 0, 3 or 4 and n is 0 or 1, but not both m and n are 0.Especially preferred are those compounds of formula I which are derived from proline and have the formula ##STR4## The symbols have the same preferred meanings described above.The lower alkyl groups represented by any of the variables include straight and branched chain hydrocarbon radicals from methyl to heptyl, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl and the like. The lower alkylene groups are of the same kind also having 1 to 7 carbons. Similarly, the lower alkoxy groups are of the same kind with a link to oxygen, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and the like. The C.sub.1 -C.sub.4 members, especially C.sub.1 and C.sub.2 members, of all types are preferred. Phenylmethyl is the preferred phenyl-lower alkylene group and methoxy and t-butoxy the preferred lower alkoxy groups. The lower alkanoyl groups are the acyl radicals of the lower (up to 7 carbons) fatty acids, e.g., acetyl, propionyl, butyryl and the like, acetyl being preferred.The amino(imino)methyl group represented by R.sub.1 is the residue of the guanidino radical ##STR5##The products of formula I and the preferred subgroups can be produced by various methods of synthesis. According to a preferred method, the amino acid of the formula ##STR6## wherein A, B and R are defined as above, and R is hydroxy is acylated with an acid of the formula ##STR7## wherein R.sub.1 is an acyl group, and R.sub.2, R.sub.3, m and n have the meaning defined above, by one of the known procedures in which the acid IV is activated, prior to reaction with the amino acid III, involving formation of a mixed anhydride, symmetrical anhydride, acid chloride, active ester, Woodward reagent K, N,N'-carbonylbisimidazole, EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) or the like. When R is lower alkoxy, this or other known methods of coupling such moieties can be used [For a review of these methods, see Methoden der Organischen Chemie (Houben-Weyl) Vol. XV, parts 1 and 2 (1974)].When the product obtained is an ester, e.g., R is t-butoxy, the ester can be converted to the free carboxy group (R is hydroxy) by cleavage with acids, e.g., trifluoroacetic acid. Conversely the free acid can be esterified by conventional procedures.Starting materials of formula IV wherein m is 0 are derivatives of the amino acid cysteine which can be produced by known procedures.The acids of formula IV wherein m is 2, 3 or 4 can be synthesized, according to a preferred method, by the addition of a thiol acid to the substituted acrylic acid of the formula ##STR8##The latter are obtained by hydrolysis, e.g., with 6N hydrochloric acid, of the methylene lactams of the formula ##STR9## [J. Org. Chem. 39, 893 (1974)]The compounds of formula I wherein m is 1 are obtained by the Curtius rearrangement of an acid of the formula ##STR10##The preferred method for producing compounds of formula I wherein n is 0 is by displacement of the halo derivative of the formula ##STR11## wherein X is halogen, preferably chlorine or bromine, with the thiol acid R.sub.3 --COSH.The disulfides of formula I, wherein R.sub.3 is ##STR12## are obtained by oxidation of the compound of the formula ##STR13## e.g., with an alcoholic solution of iodine.The compounds of formula I wherein R.sub.1 is amino(imino)-methyl are obtained by reacting a compound of formula I wherein R.sub.1 or R.sub.2 is hydrogen with a guanyl-forming reagent e.g., guanyl-3,5-dimethylpyrazole nitrate, S-methylisothiourea, or O-methylisourea.Products of formula I have two asymmetric carbon atoms. These carbon atoms are indicated by an asterisk in formula I. The compounds accordingly exist in diastereoisomeric forms or in racemic mixtures thereof. All of these are within the scope of the invention. The above described syntheses can utilize the racemate or one of the enantiomers as starting material. When the racemic starting material is used in the synthetic procedure, the stereoisomers obtained in the product can be separated by conventional chromatographic or fractional crystallization methods. In general, the L-isomer with respect to the carbon of the amino acid constitutes the preferred isomeric form.The compounds of formula I form salts which are also part of this invention. The salts include acid-addition salts which are formed by reaction with a variety of inorganic and organic acids providing acid addition salts including, for example, hydrohalides (especially hydrochloride and hydrobromide), sulfate, nitrate, borate, phosphate, oxalate, tartrate, maleate, citrate, acetate, ascorbate, succinate, benzenesulfonate, methanesulfonate, cyclohexanesulfamate and toluenesulfonateThe salts are formed in conventional manner by reacting the free form of the product with one or more equivalents of the appropriate acid or base providing the desired anion or cation in a solvent or medium in which the salt is insoluble, or in water and removing the water by freezing drying. By neutralizing the salt with an insoluble acid like a cation exchange resin in the hydrogen form [e.g., polystyrene sulfonic acid resin -- Dowex 50 (Mikes, Laboratory Handbook of Chromatographic Methods (Van Nostrand, 1961) page 256] eluting with a volatile buffer (e.g. pyridine-acetic acid) extraction with an organic solvent, the free form can be obtained, and if, desired, another salt formed.Additional experimental details are found in the examples which are preferred embodiments and also serve as models for the preparation of other members of the group.The compounds of this invention inhibit the conversion of the decapeptide angiotensin I to angiotensin II and therefore are useful in reducing or relieving angiotensin related hypertension. The action of the enzyme renin on angiotensinogen, a pseudoglobulin in blood plasma, produces angiotensin I. Angiotensin I is converted by angiotensin converting enzyme (ACE) to angiotensin II. The latter is an active pressor substance which has been implicated as the causative agent in various forms of hypertension in various mammalian species, e.g., rats, dogs, etc. The compounds of this invention intervene in the angiotensingen .fwdarw. angiotensin I .fwdarw. angiotensin II sequence by inhibiting angiotensin converting enzyme and reducing or eliminating the formation of the pressor substance angiotensin II.The inhibition of the angiotensin converting enzyme by compounds of formula I can be measured in vitro with isolated angiotensin converting enzyme from rabbit lungs following the procedure described by Cushman and Cheung [Biochem. Pharmacol., 20, 1637 (1971)], and with an excised smooth muscle assay [E. O'Keefe, et al., Federation Proc. 31, 511 (1972)] in which these compounds have been shown to be powerful inhibitors of the contractile activity of angiotensin I and potentiators of the contractile activity of bradykinin.The administration of a composition containing one or a combination of compounds of formula I or physiologically acceptable salt thereof to the species of hypertensive mammal alleviates or reduces hypertension. A single dose, or preferably two to four divided daily doses, provided on a basis of about 5 to 1000 mg. per kilogram per day, preferably about 10 to 500 mg. per kilogram per day is appropriate to reduce blood pressure. The animal model experiments described by S. L. Engel, T. R. SChaeffer, M. H. Waugh and B. Rubin, Proc. Soc. Exp. Biol. Med. 143, 483 (1973) serve as a useful guide.The substance is preferably administered orally, but parenteral routes such as subcutaneously, intramuscularly, intravenously or intraperitoneally can also be employed.The compounds of this invention can be utilized to achieve the reduction of blood pressure by formulating in compositions such as tablets, capsules or elixirs for oral administration or in sterile solution or suspensions for parenteral administration. About 10 to 500 mg. of a compound or mixture of compounds of formula I or physiologically acceptable salt is compounded with a physiologically acceptable vehicle, carrier, excipient, binder, preservative, stabilizer, flavor, etc., in a unit dosage form as called for by accepted pharmaceutical practice. The amount of active substance in these compositions or preparations is such that a suitable dosage in the range indicated is obtained.

    摘要翻译： 具有通式“IMAGE”的氨基酸的新取代的酰基衍生物可用作血管紧张素转换酶抑制剂。

    Cleaning cards
    4.
    发明授权
    Cleaning cards 有权
    清洁卡

    公开(公告)号：US08323779B2

    公开(公告)日：2012-12-04

    申请号：US10957830

    申请日：2004-10-04

    申请人： Glen Alan Bailey ,  John Edward Condon

    发明人： Glen Alan Bailey ,  John Edward Condon

    IPC分类号： B32B3/28

    CPC分类号： B32B27/12 ,  B32B3/263 ,  B32B3/28 ,  B32B3/30 ,  B32B5/02 ,  B32B5/022 ,  B32B27/32 ,  B32B2307/726 ,  B32B2432/00 ,  G06K7/0021 ,  G06K13/0893 ,  G06K19/02 ,  Y10T428/24628 ,  Y10T428/24669

    摘要： A cleaning card for use in cleaning internal surfaces of a machine-reading mechanism includes a substrate having plurality of discrete raised areas in opposed surfaces thereof. The discrete raised areas each include a peak and a peripheral wall having an edge remote from the peak, and the peak of each raised area is farther from a central plane of the card than the edge of the peripheral wall remote from the peak. Relief means are provided in the substrate for preventing the peaks of at least some of the discrete raised areas from flattening toward the central plane to an extent that such peaks will not effectively engage and clean desired internal surfaces of a machine-reading mechanism when the cleaning card moves in the machine direction in other than a single, substantially linear plane.

    摘要翻译： 用于清洁机器读取机构的内表面的清洁卡包括在其相对表面中具有多个离散的凸起区域的基板。 离散的凸起区域各自包括峰和具有远离峰的边缘的周壁，并且每个凸起区域的峰距离远离峰的周边壁的边缘比卡的中心平面更远。 在衬底中设置有缓解装置，用于防止至少一些离散的凸起部分的峰部朝向中心平面平坦化，使得当清洁时这些峰值将不能有效地接合和清洁机器读取机构的所需内表面 卡除了单个基本线性的平面之外沿机器方向移动。

    Stiffened cleaning cards
    5.
    发明授权
    Stiffened cleaning cards 有权
    加固清洁卡

    公开(公告)号：US07631390B1

    公开(公告)日：2009-12-15

    申请号：US11156514

    申请日：2005-06-20

    申请人： Peter Klein ,  John Edward Condon ,  Stephen Anthony Bouchard

    发明人： Peter Klein ,  John Edward Condon ,  Stephen Anthony Bouchard

    IPC分类号： B32B3/02

    CPC分类号： B32B3/00

    摘要： A cleaning card for use in cleaning internal surfaces of machine components includes a substrate having a central plane between opposed outer surfaces, a machine direction dimension defined between opposed end edges and a transverse direction dimension defined between opposed side edges. The opposed surfaces have a plurality of discrete raised working areas for engaging and cleaning internal surfaces of the machine components. The working areas each include a peak and a peripheral wall having an edge remote from the peak and the peak of each raised working area is further from the central plane than the edge of the peripheral wall remote from the peak. The cleaning card substrate has an effective working thickness that is greater than the nominal thickness between the opposed surfaces. The substrate also has a plurality of raised, rigidifying areas that extend continuously over a majority of the machine direction dimension of the cleaning card and at least one of the rigidifying areas extends outwardly on each side of the central plane of the substrate.

    摘要翻译： 用于清洁机器部件的内表面的清洁卡包括：基板，其具有在相对的外表面之间的中心平面，在相对的端部边缘之间限定的纵向尺寸和在相对的侧边缘之间限定的横向尺寸。 相对的表面具有用于接合和清洁机器部件的内表面的多个离散的凸起工作区域。 工作区域各自包括具有远离峰的边缘的峰和周壁，并且每个凸起工作区的峰距离远离峰的周边壁的边缘的中心平面更远。 清洁卡衬底具有大于相对表面之间的标称厚度的有效工作厚度。 衬底还具有多个凸起的刚性区域，其在清洁卡的机器方向尺寸的大部分上连续延伸，并且至少一个刚性区域在衬底的中心平面的每一侧向外延伸。

    Pin fin ground plane for a patch antenna
    6.
    发明申请
    Pin fin ground plane for a patch antenna 有权
    贴片天线的接地平面

    公开(公告)号：US20060071859A1

    公开(公告)日：2006-04-06

    申请号：US11003255

    申请日：2004-12-03

    申请人： Edward Condon ,  Richard Smith ,  John Grabner

    发明人： Edward Condon ,  Richard Smith ,  John Grabner

    IPC分类号： H01Q1/38 ,  H01Q9/04 ,  H01Q5/00

    CPC分类号： H01Q1/02 ,  H01Q1/2258 ,  H01Q1/48 ,  H01Q9/0407 ,  H01Q21/28 ,  H01Q25/005

    摘要： A system and method improves linearly-polarized microstrip patch antenna performance and fabrication through the incorporation of a pin fin ground plane and an integral antenna feed assembly. In one embodiment, a patch antenna system includes an antenna area with a patch antenna that provides radio communications. A heat dissipation member is coupled to the antenna area and includes a plurality of pins that provide for both the dissipation of heat from the antenna area and a ground plane for the antenna area. An antenna feed line is further coupled with the antenna patch for providing an electrical connection from the antenna patch to other electronic circuitries, such as a wireless device that may be mechanically coupled to the heat dissipation member. Heat generated during the operation of the wireless device is directed to ambient air by way of the heat dissipation member.

    摘要翻译： 一种系统和方法通过引入鳍鳍接地平面和整体天线馈电组件来提高线性极化微带贴片天线的性能和制造。 在一个实施例中，贴片天线系统包括具有提供无线电通信的贴片天线的天线区域。 散热构件耦合到天线区域并且包括多个引脚，其提供来自天线区域的热量的散发和用于天线区域的接地平面。 天线馈线还与天线贴片耦合，以提供从天线贴片到其它电子电路的电连接，例如可机械耦合到散热构件的无线装置。 在无线设备的操作期间产生的热量通过散热构件被引导到环境空气。

    Combined radial and thrust bearing
    9.
    发明授权
    Combined radial and thrust bearing 失效
    组合径向和推力轴承

    公开(公告)号：US3930692A

    公开(公告)日：1976-01-06

    申请号：US542112

    申请日：1975-01-20

    申请人： Charles Edward Condon, Jr. ,  Charles Warrell Shattuck

    发明人： Charles Edward Condon, Jr. ,  Charles Warrell Shattuck

    IPC分类号： F16C19/30 ,  F16C19/38 ,  F16C19/54 ,  F16C33/58 ,  F16C43/04 ,  F16C19/04

    CPC分类号： F16C33/588 ,  F16C19/381 ,  F16C33/60 ,  F16C43/04 ,  F16C19/30 ,  F16C19/44

    摘要： An annular shoulder on the radial bearing is contacted by the thrust bearing raceway radially inwardly from the inside periphery of the thrust bearing cage. Either the thrust race or the annular shoulder on the radial bearing, or both, may have an integral axial extension with the thrust race and the radial bearing interlocking radially inwardly from the inner periphery of the thrust bearing cage.The bearing is pressed in to the bore of the housing by pushing against the thrust race with the force against the thrust race being transmitted by way of the annular shoulder to the radial raceway. Thus, it is not necessary to push the bearing into the housing bore by pressing against the thrust rollers which often results in critical damage to the thrust race.

    摘要翻译： 径向轴承上的环形肩部由推力轴承座圈从推力轴承保持架的内周向内径向向内接触。 推力座圈或径向轴承上的环形肩部或两者都可以具有与推力座圈和径向轴承从推力轴承保持架的内周径向向内互锁的整体轴向延伸。