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    • 7. 发明授权
    • Vitronectin receptor antagonists
    • Vitronectin受体拮抗剂
    • US6159964A
    • 2000-12-12
    • US91937
    • 1999-07-27
    • Fadia E. AliWilliam E. BondinellRichard M. KeenanThomas Wen-Fu KuWilliam H. MillerJames Samanen
    • Fadia E. AliWilliam E. BondinellRichard M. KeenanThomas Wen-Fu KuWilliam H. MillerJames Samanen
    • A61K31/00A61K31/44A61K31/4427A61K31/443A61K31/4439A61K31/445A61K31/4465A61K31/4523A61K31/4545A61K31/47A61K31/472A61K31/4725A61K31/495A61K31/4965A61K31/497A61K31/55A61K31/551A61K31/5513A61K31/5517A61P7/02A61P9/00A61P9/10A61P19/00A61P19/08A61P29/00A61P35/00A61P43/00C07D213/73C07D213/74C07D401/12C07D403/12C07D405/12C07D413/12C07D487/04
    • C07D213/74C07D401/12C07D403/12C07D405/12C07D487/04
    • Compounds of formula (I) are disclosed, wherein: A is a fibrinogen antagonist template; W is a linking moiety of the form --(CHR.sup.g).sub.a --U--(CHR.sup.g).sub.b --V--; Q.sup.1, Q.sup.2, Q.sup.3 and Q.sup.4 are independently N or C--R.sup.y, provided that no more than one Q.sup.1, Q.sup.2, Q.sup.3 and Q.sup.4 is N; R' is H or C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 -alkyl or Ar--C.sub.0-6 alkyl; R.sup.g is H or C.sub.1-6 alkyl, Het-C.sub.0-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 alkyl or Ar--C.sub.0-6 alkyl; R.sup.k is R.sup.g, --C(O)R.sup.g or --C(O)OR.sup.g R.sup.i is H, C.sub.1-6 alkyl, Het-C.sub.0-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 alkyl, Ar--C.sub.0-6 alkyl, Het-C.sub.0-6 alkyl--U'--C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 alkyl--U'--C.sub.1-6 alkyl or Ar--C.sub.0-6 alkyl--U'--C.sub.1-6 alkyl; R.sup.y is H, halo, --OR.sup.g, --SR.sup.g, --CN, --NR.sup.g R.sup.k, --NO.sub.2, --CF.sub.3, CF.sub.3 S(O).sub.r, --CO.sub.2 R.sup.g, --COR.sup.g or --CONR.sup.g.sub.2, or C.sub.1-6 alkyl optionally substituted by halo, --OR.sup.g, --SR.sup.g, --CN, --NR.sup.8 R", --NO.sub.2, --CF.sub.3, R'S(O).sub.3 --, --CO.sub.2 R.sup.g, --COR.sup.g or --CONR.sup.g.sub.2 ; U and V are absent or CO, CR.sup.g.sub.2, C(.dbd.CR.sup.g.sub.2), S(O).sub.c, O, NR.sup.g, CR.sup.g OR.sup.g, CR.sup.g (OR.sup.k)CR.sup.g.sub.2, CR.sup.g.sub.7 CR.sup.g (OR.sup.k), C(O)CR.sup.g.sub.2, CR.sup.g.sub.2 C(O), CONR.sup.i, NR.sup.i CO, OC(O), C(O)O, OC(S), C(S)NR.sup.g, NR.sup.8 C(S), S(O.sub..sub.2 NR.sup.g, NR.sup.g S(O).sub.2 N.dbd.N, NR.sup.g NR.sup.g, NR.sup.g CR.sup.g.sub.2, NR.sup.g CR.sup.g.sub.2, CR.sup.g.sub.2 O, OCR.sup.g.sub.2, CR.sup.g .dbd.CR.sup.g, C.ident.C, Ar or Het; a is 0, 1 or 2; c is 0, 1 or 2; r is 0, 1 or 2; and u is 0 or 1; or pharmaceutically acceptable salts thereof, which are vitronectin receptor antagonists useful in the treatment of osteoporosis. ##STR1##
    • PCT No.PCT / US96 / 20327 Sec。 371日期:1999年7月27日 102(e)日期1999年7月27日PCT 1996年12月20日PCT PCT。 公开号WO97 / 24124 日期1999年7月10日公开了式(I)的化合物,其中:A是纤维蛋白原拮抗剂模板; W是 - (CHRg)a-U-(CHRg)b-V-的形式的连接部分; Q1,Q2,Q3和Q4独立为N或C-Ry,条件是不超过一个Q1,Q2,Q3和Q4为N; R'是H或C 1-6烷基,C 3-7环烷基-C 0-6 - 烷基或Ar-C 0-6烷基; R g是H或C 1-6烷基,Het-C 0-6烷基,C 3-7环烷基-C 0-6烷基或Ar-C 0-6烷基; R k是R g,-C(O)R g或-C(O)OR g R 1是H,C 1-6烷基,Het-C 0-6烷基,C 3-7环烷基-C 0-6烷基,Ar-C 0-6烷基,Het-C 0-6烷基 -N''-C 1-6烷基,C 3-7环烷基-C 0-6烷基-U'-C 1-6烷基或Ar-C 0-6烷基-U'-C 1-6烷基; R y是H,卤素,-OR g,-SR g,-CN,-NR g R k,-NO 2,-CF 3,CF 3 S(O)r,-CO 2 R g,-COR g或-CONRg 2,或任选被卤素取代的C 1-6烷基,-OR g ,-SRg,-CN,-NR 8 R“,-NO 2,-CF 3,R'(O)3 - ,-CO 2 R g,-COR g或-CONRg 2; U和V不存在或CO,CRg2,C(= CRg2),S(O)c,O,NRg,CRgORg,CRg(ORk)CRg2,CRg7CRg(ORk),C(O)CRg2,CRg2C(O) C(O)O,OC(S),C(S)NR g,NR 8 C(S),S(O 2 NRR,NR g S(O)2 N = N,NR g NRR,NR g CR 2,NR g CR 2, ,OCRg2,CRg = CRg,C = C,Ar或Het; a为0,1或2; c为0,1或2; r为0,1或2; u为0或1;或药学上可接受的盐 它们是可用于治疗骨质疏松症的玻连蛋白受体拮抗剂。
    • 9. 发明授权
    • Automatic weight application machine
    • 自动重量应用机
    • US5134766A
    • 1992-08-04
    • US681885
    • 1991-04-08
    • William H. Miller
    • William H. Miller
    • F16F15/32G01M1/32
    • G01M1/326F16F15/32Y10T29/4987Y10T29/49876Y10T29/49945Y10T29/53391Y10T29/53657Y10T29/53783Y10T29/53991Y10T29/53996
    • A machine for automatically applying a balance correcting weight (44)-and-clip (46) assembly to vehicle wheel-and-tire assembly (12). The machine includes a conveyor (20) portion for conveying the wheel-and-tire assembly (12) to a weight (44) application station, orienting the wheel-and-tire assembly (12) properly to receive at the correct location the balance-correcting weight (44), and conveying the wheel-and-tire assembly (12) to which the balance-correcting weight (44) has been applied away from the weight (44) application station. The machine includes a hammer (22, 24) having a storage orientation out of operating position permitting conveying of the wheel-and-tire assembly (12) to and from the weight (44) application station and a use orientation in operating position adjacent the wheel-and-tire assembly (12) to which balance correcting weight (44) is to be applied, and means for moving the hammer (22, 24) selectively between its storage and use orientations. The hammer (22, 24) includes a jaw (40) with a contour conforming to the shape of the clip (46) and a shank (50) portion of ferromagnetic material, said shank (50) being surrounded by an electrically conductive coil (94).
    • 一种用于自动将平衡校正重物(44)和夹子(46)组件应用于车轮和轮胎组件(12)的机器。 机器包括用于将轮胎和轮胎组件(12)输送到重物(44)施加工位的输送机(20)部分,适当地使轮胎和轮胎组件(12)定向以在正确位置处接收平衡 - 修正重量(44),并且将已经施加有平衡校正重块(44)的轮胎和轮胎组件(12)输送到配重(44)施加站。 该机器包括具有不在操作位置的存储方向的锤子(22,24),允许轮胎和轮胎组件(12)运送到重物(44)施加工位和从重物(44)施加工位移动,并且在与 要施加平衡矫正重量(44)的轮胎和轮胎组件(12),以及用于在其存储和使用取向之间选择性地移动锤(22,24)的装置。 锤子(22,24)包括具有与夹子(46)的形状相符的轮廓和铁磁材料的柄(50)部分的钳口(40),所述杆(50)被导电线圈 94)。
    • 10. 发明授权
    • Automatic weight application machine
    • US5048173A
    • 1991-09-17
    • US435483
    • 1989-04-24
    • William H. Miller
    • William H. Miller
    • F16F15/32G01M1/32
    • F16F15/32G01M1/326Y10T29/4987Y10T29/49876Y10T29/49945Y10T29/53391Y10T29/53657Y10T29/53783Y10T29/53991Y10T29/53996
    • A machine is provided for automatically applying a balance correcting weight (44)-and-clip (46) assembly to a vehicle wheel-and-tire assembly (12). The machine includes a conveyor (20) portion for conveying the wheel-and-tire assembly (12) to which the balance-correcting weight (44) is to be applied to a weight (44) application station, orienting the wheel-and-tire assembly (12) properly to receive at the correct location the balance-correcting weight (44), and conveying the wheel-and-tire assembly (12) to which the balance-correcting weight (44) has been applied away from the weight (44) application station. The machine includes a hammer (22, 24) having a storage orientation permitting conveying of the wheel-and-tire assembly (12) to and from the weight (44) application station and a use orientation adjacent the wheel-and-tire assembly (12) to which balance correcting weight (44) is to be applied, and means for moving the hammer (22, 24) selectively between its storage and use orientations to permit conveying of the wheel-and-tire assembly (12) to the weight (44) application station, application of the balance-correcting weight (44) to the wheel-and-tire assembly (12), and conveying of the wheel-and-tire assembly (12) to which a balance correcting weight (44) has been attached away from the weight (44) application station. The hammer (22, 24) includes a jaw (40) with a contour conforming to the shape of the clip (46) and a shank (50) portion. The shank (50) portion and jaw (40) comprise ferromagnetic material. An electrically conductive coil (94) surrounds the shank (50) portion of the hammer (22, 24). The hammer (22, 24) is driven through operating cycles to hammer (22, 24) the weight (44)-and-clip (46) assembly onto the wheel.