公开(公告)号：US06300330B1

公开(公告)日：2001-10-09

申请号：US09297768

申请日：1999-05-07

Applicant: Andrew Stocker ,  John Preston ,  John Wall Rayner ,  Michael James Smithers ,  Paul Turner

Inventor： Andrew Stocker ,  John Preston ,  John Wall Rayner ,  Michael James Smithers ,  Paul Turner

IPC: A61K31496

CPC classification number: C07D213/73 ,  A61K31/44 ,  A61K31/505 ,  C07D213/56 ,  C07D213/61 ,  C07D213/84 ,  C07D213/89 ,  C07D237/08 ,  C07D239/26

Abstract: The invention relates to heterocyclic derivatives of the formula (I): A—B—X1—T1(R2)—L1—T2(R3)—X2—Q or pharmaceutically acceptable salts thereof, which possess antithrombotic and anticoagulant properties due to their inhibition of Factor Xa and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

Abstract translation: 本发明涉及式（I）的杂环衍生物：AB-X1-T1（R2）-L1-T2（R3）-X2-Q或其药学上可接受的盐，由于它们抑制因子而具有抗血栓形成和抗凝血性质 因此，可用于治疗人或动物的方法。 本发明还涉及制备杂环衍生物的方法，含有它们的药物组合物及其在制备用于产生抗血栓形成或抗凝血作用的药物中的用途。

公开(公告)号：US06486154B1

公开(公告)日：2002-11-26

申请号：US09463446

申请日：2000-01-27

Applicant: Andrew Stocker ,  John Preston

Inventor： Andrew Stocker ,  John Preston

IPC: A61K3154

CPC classification number: C07D401/04

Abstract: A compound of formula (I), or a pharmaceutically-acceptable salt thereof, wherein A is an optionally substituted 5- or 6-membered monocyclic aromatic ring containing 1, 2 or 3 ring heteroatoms; B is optionally substituted phenylene or a 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen heteroatoms; R and R1 are hydrogen or (1-4C)alkyl; n is 1 or 2; R2 and R3 are hydrogen, (1-6C)alkyl, (4-7C)cycloalkyl, or (2-6C)alkenyl, or R2 and R3 may form along with the nitrogen to which they are attached a 5-, 6- or 7-membered heterocyclic ring, wherein each R2 or R3 group or any heterocyclic ring formed from R2 and R3 may be optionally substituted with various substituent groups, and wherein Q may be optionally substituted by various substituent groups, which posseses antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention relates to processes for the preparation of the compounds represented by formula (I), to pharmaceutical compositions containing them, and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

Abstract translation: 式（I）化合物或其药学上可接受的盐，其中A是含有1,2或3个环杂原子的任选取代的5元或6元单环芳环; B是任选取代的亚苯基或含有1,2或3个氮杂原子的6元杂环; R和R 1是氢或（1-4C）烷基; n为1或2; R2和R3是氢，（1-6C）烷基，（4-7C）环烷基或（2-6C）烯基，或R2和R3可以与它们所连接的氮一起形成5-，6-或 7元杂环，其中每个R 2或R 3基团或由R 2和R 3形成的任何杂环可以任选被各种取代基取代，并且其中Q可任选地被各种取代基取代，这些取代基具有抗血栓形成和抗凝血性质， 因此在治疗人或动物的方法中有用。 本发明涉及制备由式（I）表示的化合物的方法，含有它们的药物组合物及其在制备用于产生抗血栓形成或抗凝血作用的药物中的用途。

公开(公告)号：US06395731B1

公开(公告)日：2002-05-28

申请号：US09674563

申请日：2000-12-20

Applicant: Nowak Thorsten ,  John Preston ,  John W Rayner ,  Michael J Smithers ,  Andrew Stocker

Inventor： Nowak Thorsten ,  John Preston ,  John W Rayner ,  Michael J Smithers ,  Andrew Stocker

IPC: A61K31541

CPC classification number: C07D233/64 ,  C07D213/56 ,  C07D233/88 ,  C07D237/12 ,  C07D237/14 ,  C07D237/20 ,  C07D239/26 ,  C07D239/34 ,  C07D239/36 ,  C07D239/42 ,  C07D295/26

Abstract: The invention relates to heterocyclic derivatives of formula (I) and (Ia), or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

Abstract translation: 本发明涉及具有抗血栓形成和抗凝血性质的式（I）和（Ia）的杂环衍生物或其药学上可接受的盐，因此可用于治疗人或动物的方法。 本发明还涉及制备杂环衍生物的方法，含有它们的药物组合物及其在制备用于产生抗血栓形成或抗凝血作用的药物中的用途。

公开(公告)号：US07173025B1

公开(公告)日：2007-02-06

申请号：US09117436

申请日：1997-01-31

Applicant: Andrew Stocker ,  John Preston ,  Michael James Smithers

Inventor： Andrew Stocker ,  John Preston ,  Michael James Smithers

IPC: A61K31/55 ,  A61K31/495 ,  C07D401/00 ,  C07D223/00

CPC classification number: C07D401/14 ,  C07D213/74 ,  C07D237/20 ,  C07D239/42 ,  C07D401/04 ,  C07D401/12

Abstract: Compounds of formula (I), wherein G1 is CH or N; G2 is CH or N; R1 is a variety of optional substituents; L1 is (1-4C)alkylene; T1 is CH or N; R2 and R3 are independently hydrogen or (1-4C)alkyl or are joined to form a ring; X1 and X2 represent various linking groups; Ar is phenylene or certain heteroaryl rings and Q represents a variety of aromatic or heterocyclic rings systems, and pharmaceutically acceptable salts thereof are described as useful antithrombotic and anticoagulant agents, and are selective Factor Xa inhibitors. Processes for their preparation and pharmaceutical compositions containing them are also described.

Abstract translation: 式（I）的化合物，其中G 1是CH或N; G 是CH或N; R 1是各种任选的取代基; L 1是（1-4C）亚烷基; T 1是CH或N; R 2和R 3独立地是氢或（1-4C）烷基或连接形成环; X 1和X 2代表各种连接基团; Ar是亚苯基或某些杂芳基环，Q表示各种芳族或杂环体系，其药学上可接受的盐被描述为有用的抗血栓形成和抗凝血剂，并且是选择性因子Xa抑制剂。 还描述了其制备方法和含有它们的药物组合物。

公开(公告)号：US06936610B2

公开(公告)日：2005-08-30

申请号：US09963686

申请日：2001-09-27

Applicant: Andrew Stocker ,  John Preston ,  John Wall Rayner ,  Michael James Smithers ,  Paul Turner

Inventor： Andrew Stocker ,  John Preston ,  John Wall Rayner ,  Michael James Smithers ,  Paul Turner

IPC: A61K31/44 ,  A61K31/444 ,  A61K31/496 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61P7/02 ,  C07D213/00 ,  C07D213/56 ,  C07D213/61 ,  C07D213/73 ,  C07D213/84 ,  C07D213/89 ,  C07D237/08 ,  C07D239/26 ,  C07D241/00 ,  C07D307/77 ,  C07D401/10 ,  C07D405/12

CPC classification number: C07D213/73 ,  A61K31/44 ,  A61K31/505 ,  C07D213/56 ,  C07D213/61 ,  C07D213/84 ,  C07D213/89 ,  C07D237/08 ,  C07D239/26

Abstract: The invention relates to heterocyclic derivatives of formula (I) A—B—X1—T1(R2)—L1—T2(R3)—X2—Q  (I) or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

Abstract translation: 本发明涉及式（I）的杂环衍生物<？in-line-formula description =“In-line Formulas”end =“lead”？> ABX

（R 2） - L 1 - （R 2） - X 2（R 3） - X 2 -Q（I）<？in-line-formula description =“In-line Formulas”end =“tail”？>或其药学上可接受的盐，其具有抗血栓形成和抗凝血性质，因此可用于方法 治疗人或动物。 本发明还涉及制备杂环衍生物的方法，含有它们的药物组合物及其在制备用于产生抗血栓形成或抗凝血作用的药物中的用途。

公开(公告)号：US06730672B2

公开(公告)日：2004-05-04

申请号：US09800745

申请日：2001-03-08

Applicant: Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

Inventor： Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

IPC: C07D40114

CPC classification number: C07D213/74 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

Abstract: The invention concerns compounds of formula (I) wherein each of G1, G2 and G3 is CH or N; m is 1 or 2; R1 includes hydrogen, halogeno and (1-4C)alkyl; M1 is a group of the formula: NR2—L1—T1R3 in which R2 and R3 together form a (1-4C)alkylene group, L1 includes (1-4C)alkylene, and T1 is CH or N; A may be a direct link; M2 is a group of the formula: (T2R4)r—L2—T3R5 in which r is 0 or 1, each of T2 and T3 is CH or N, each of R4 and R5 is hydrogen or (1-4C)alkyl, or R4 and R5 together form a (1-4C)alkylene group, and L2 includes (1-4C)alkylene; M3 may be a direct link to X; X includes sulphonyl; and Q includes naphthyl and a heterocyclic moiety; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use as antithrombotic or anticoagulant agents.

Abstract translation: 本发明涉及式（I）化合物，其中G 1，G 2和G 3各自为CH或N; m为1或2; R 1包括氢，卤素和（1-4C）烷基; M 1是下式的基团：其中R 2和R 3一起形成（1-4C）亚烷基，其中R 2，R 2，R 3，R 3， ，L 1包括（1-4C）亚烷基，T 1是CH或N; A可能是直接链接; M 2是下式的基团：（T 2 R 4）r L 2 -T 3 R 5，其中r是0或1，每个T 2和T R 3和R 5分别是氢或（1-4C）烷基，或者R 4和R 5一起形成（1-4C）亚烷基， 和L 2包括（1-4C）亚烷基; M 3可以直接连接到X; X包括磺酰基; 且Q包括萘基和杂环部分; 或其药学上可接受的盐; 其制备方法，含有它们的药物组合物及其作为抗血栓形成或抗凝血剂的用途。

公开(公告)号：US06225309B1

公开(公告)日：2001-05-01

申请号：US09369857

申请日：1999-08-09

Applicant: Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

Inventor： Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

IPC: C07D40114

CPC classification number: C07D213/74 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

Abstract: The invention concerns compounds of formula (I), wherein each of G1, G2 and G3 is CH or N; m is 1 or 2; R1 includes hydrogen, halogeno and 1-C)alkyl; M1 is a group of formula: NR2—L1—T1R3, in which R2 and R3 together form a (1-4C)alylene group, L1 includes (1-4C)alkylene, and T1 is CH or N; A may be a direct link; M2 is a group of the formula: (T2R4)rL2—T3R5 in which R is 0 or 1, each of T2 and T3 is CH or N, each of R4 and R5 is hydrogen or (1-4C)alkyl, or R4 and R5 together form a (1-4C)alkylene group, and L2 includes (1-4C)alkylene; M3 may be a direct link to X; X includes sulphonyl; and Q includes naphthyl and a heterocyclic moiety; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use as antithrombotic or anticoagulant agents.

Abstract translation: 本发明涉及式（I）化合物，其中G1，G2和G3各自为CH或N; m为1或2; R1包括氢，卤代和1-C）烷基; M1是下式的基团：NR2-L1-T1R3，其中R2和R3一起形成（1-4C）亚甲基，L1包括（1-4C）亚烷基，并且T1是CH或N; A可能是直接链接; M2是下式的基团：（T2R4）rL2-T3R5其中R是0或1，每个T2和T3是CH或N，每个R4和R5分别是氢或（1-4C）烷基，或R4和 R5一起形成（1-4C）亚烷基，L2包括（1-4C）亚烷基; M3可能直接连接到X; X包括磺酰基; Q包括萘基和杂环部分; 或其药学上可接受的盐; 其制备方法，含有它们的药物组合物及其作为抗血栓形成或抗凝血剂的用途。

公开(公告)号：US5965559A

公开(公告)日：1999-10-12

申请号：US817031

申请日：1997-03-26

Applicant: Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

Inventor： Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

IPC: A61K31/44 ,  A61K31/4409 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/495 ,  A61K31/505 ,  A61K31/53 ,  A61K31/535 ,  A61P7/02 ,  C07D213/74 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  A61K31/435

CPC classification number: C07D213/74 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

Abstract: The invention concerns compounds of formula (I), wherein each of G.sup.1, G.sup.2 and G.sup.6 is CH or n; m is 1 or 2; R.sup.1 includes hydrogen, halogeno and (1-4C)alkyl; M.sup.1 is a group of formula: NR.sup.2 -L.sup.1 -T.sup.1 R.sup.3, in which R.sup.2 and R.sup.3 together form a (1-4C)alkylene group, L.sup.1 includes (1-4C)alkylene, and T.sup.1 is CH or N; A may be a direct link; M.sup.2 is a group of the formula: (T.sup.2 R.sup.4).sub.r -L.sup.2 T.sup.3 R.sup.5 in which R is 0 or 1, each of T.sup.2 and T.sup.3 is CH or N, each of R.sup.4 and R.sup.5 is hydrogen or (1-4C)alkyl, or R.sup.4 and R.sup.5 together form a (1-4C)alkylene group, and L.sup.2 includes (1-4C)alkylene; M.sup.3 may be a direct link to X; X includes sulphonyl; and Q includes naphthyl and a heterocycle moiety; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use as antithrombotic or anticoagulant agents.

Abstract translation: PCT No.PCT / GB95 / 02285第 371日期1997年3月26日 102（e）1997年3月26日PCT PCT 1995年9月25日PCT公布。 WO96 / 10022 PCT出版物 日期：1996年4月4日本发明涉及式（I）化合物，其中，G1，G2和G6各自为CH或n; m为1或2; R1包括氢，卤代和（1-4C）烷基; M1为式（Ⅱ）所示的基团，其中R2和R3一起形成（1-4C）亚烷基，L1包括（1-4C）亚烷基，且T1为CH或N; A可能是直接链接; M2是下式的基团：（T2R4）r-L2T3R5其中R是0或1，每个T2和T3是CH或N，每个R4和R5分别是氢或（1-4C）烷基，或R4和 R5一起形成（1-4C）亚烷基，L2包括（1-4C）亚烷基; M3可能直接连接到X; X包括磺酰基; Q包括萘基和杂环部分; 或其药学上可接受的盐; 其制备方法，含有它们的药物组合物及其作为抗血栓形成或抗凝血剂的用途。

公开(公告)号：US5110808A

公开(公告)日：1992-05-05

申请号：US738436

申请日：1991-07-31

Applicant: David R. Brittain ,  Steven P. Brown ,  Anthony L. Cooper ,  Jethro L. Longridge ,  Jeffrey J. Morris ,  John Preston ,  Linda Slater

Inventor： David R. Brittain ,  Steven P. Brown ,  Anthony L. Cooper ,  Jethro L. Longridge ,  Jeffrey J. Morris ,  John Preston ,  Linda Slater

IPC: A61K31/255 ,  A61P3/08 ,  A61P3/10 ,  A61P43/00 ,  C07C317/40 ,  C07C317/42 ,  C07D295/14 ,  C07D295/185

CPC classification number: C07D295/185 ,  C07C317/40 ,  C07C317/42

Abstract: The invention concerns novel (oxamido- and ureido-phenylsulfonyl)nitromethane derivatives and pharmaceutically acceptable salts thereof which are inhibitors of the enzyme aldose reductase and are of value, for example, in the treatment of certain peripheral effects of diabetes and galactosemia. Also disclosed are pharmaceutical compositions containing one of the derivatives and processes for the manufacture and use of the derivatives.

公开(公告)号：US4528282A

公开(公告)日：1985-07-09

申请号：US459143

申请日：1983-01-19

Applicant: John Preston ,  William R. Carling

Inventor： John Preston ,  William R. Carling

IPC: C07D317/30 ,  A61K38/00 ,  A61K45/06 ,  A61P9/12 ,  C07D207/16 ,  C07D307/54 ,  C07D333/24 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07K5/02 ,  A61K37/00 ,  C07C103/52

CPC classification number: C07K5/0222 ,  A61K38/00 ,  Y10S530/80

Abstract: Amide derivatives of the formula: ##STR1## wherein either R.sup.1 is aryl or heterocyclic and A.sup.1 is a direct link, or R.sup.1 is aryl or heterocyclic, or hydrogen, or halogeno, hydroxy, amino, guanidino, mercapto, carboxy, carbamoyl, or a substituted derivative thereof, and A.sup.1 is alkylene, alkenylene, cycloalkylene or cycloalkenylene; wherein X is carbonyl or hydroxymethylene or substituted derivatives thereof; wherein A.sup.2 is alkylene, alkenylene or alkylidene; wherein R.sup.2 is hydrogen or alkyl which is unsubstituted or which bears an aryl substituent, or R.sup.2 has the formula --Q.sup.2 --R.sup.20 as defined below; wherein R.sup.3 is hydrogen, alkyl or a carbonyl-containing group; wherein R.sup.4 is hydrogen or alkyl which is unsubstituted or which bears a halogeno, hydroxy, amino, guanidino, carboxy, carbamoyl, mercapto, alkoxy, alkylamino, dialkylamino, cyclic amino, alkylthio, alkanoylamino, alkoxycarbonylamino, alkoxycarbonyl, alkoxycarbonyl, aryl or heterocyclyl substituent;wherein --NR.sup.5 --CR.sup.6 R.sup.16 --Q.sup.1 --R.sup.10 is an amino acid residue, R.sup.5, R.sup.6 and R.sup.16 being defined in claim 1, wherein Q.sup.1 and Q.sup.2, which may be the same or different, each is carbonyl (--CO--) or methylene (--CH.sub.2 --); and wherein R.sup.10 and R.sup.20, which may be the same or different, is hydroxy, amino or a substituted derivative thereof or hydroxyamino or arylthio; or a salt thereof where appropriate; processes for their manufacture and pharmaceutical compositions containing them. The compounds are inhibitors of angiotensin converting enzyme and may be used in the treatment of hypertension.

Abstract translation: 下式的酰胺衍生物：其中R 1为芳基或杂环，且A 1为直链，或R 1为芳基或杂环，或氢或卤素，羟基，氨基，胍基，巯基，羧基，氨基甲酰基或 取代衍生物，A1为亚烷基，亚烯基，亚环烷基或环亚烯基; 其中X是羰基或羟基亚甲基或其取代的衍生物; 其中A2是亚烷基，亚烯基或亚烷基; 其中R 2是氢或未被取代或带有芳基取代基的烷基，或R 2具有如下定义的式-Q 2 -R 20; 其中R3是氢，烷基或含羰基的基团; 羟基，氨基，胍基，羧基，氨基甲酰基，巯基，烷氧基，烷基氨基，二烷基氨基，环状氨基，烷硫基，烷酰基氨基，烷氧基羰基氨基，烷氧基羰基，烷氧基羰基，芳基或杂环基取代基 ; 其中-NR5-CR6R16-Q1-R10是氨基酸残基，R5，R6和R16如权利要求1所定义，其中Q1和Q2可以相同或不同，分别为羰基（-CO-）或亚甲基（-CO-） -CH2-）; 并且其中R10和R20可以相同或不同，为羟基，氨基或其取代的衍生物或羟基氨基或芳硫基; 或其盐; 其制造方法和含有它们的药物组合物。 该化合物是血管紧张素转换酶的抑制剂，可用于治疗高血压。