公开(公告)号：US20100168176A1

公开(公告)日：2010-07-01

申请号：US12513888

申请日：2007-11-08

申请人： Craig Townsend ,  Francis Kuhajda ,  Kandasamy Subburaj ,  Jill Marie Sturdivant

发明人： Craig Townsend ,  Francis Kuhajda ,  Kandasamy Subburaj ,  Jill Marie Sturdivant

IPC分类号： A61K31/4436 ,  C07D333/34 ,  C07D277/82 ,  C07D409/12 ,  A61K31/381 ,  A61K31/427 ,  A61P31/04

CPC分类号： C07D409/12 ,  C07D333/32 ,  C07D417/12

摘要： Compounds having the following general formula, pharmaceutical compositions comprising the compounds, and methods of treating cancer, obesity, and microbial infections using such compositions: wherein: R1=H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, cyanomethyl, —OCH3, OC(O)CH3 or OC(O)CF3 R2=-OCH2C(O)NHNH—R5, where R5 is (a) phenyl, optionally substituted with one or more of halogen, C1-C8 alkyl, optionally substituted with halogen, —OH, —OR6, where R6 is C1-C8 alkyl, optionally substituted with halogen, or (b) 2-, 3-, or 4-pyridyl, optionally substituted with halogen, —OH, —OR6, where R6 is C1-C8 alkyl, optionally substituted with halogen, or (c) a heterocycle selected from the group consisting of imidazole, thiazole, benzimidazole, benzoxazole, benzthiazole, tetrazole, triazole, and aminothiazole; or (d) —C(O)R7, where R7 is a C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, or a heterocycle selected from the group consisting of pyridyl, imidazole, thiazole, benzimidizole, benzoxazole, benzthiazole, tetrazole, triazole, and aminothiazole; and R3 and R4, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl.

摘要翻译： 具有以下通式的化合物，包含该化合物的药物组合物，以及使用这些组合物治疗癌症，肥胖和微生物感染的方法：其中：R1 = H，C1-C20烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基， 氰基甲基，-OCH 3，OC（O）CH 3或OC（O）CF 3 R 2 = -OCH 2 C（O）NHNH-R 5，其中R 5是（a）苯基，任选地被一个或多个卤素， -OH，-OR 6，其中R 6是任选被卤素取代的C 1 -C 8烷基，或（b）任选被卤素，-OH，-OR 6取代的2-，3-或4-吡啶基，其中 R6是任选被卤素取代的C1-C8烷基，或（c）选自咪唑，噻唑，苯并咪唑，苯并恶唑，苯并噻唑，四唑，三唑和氨基噻唑的杂环; 或（d）-C（O）R 7，其中R 7是C 1 -C 20烷基，环烷基，烯基，芳基，芳烷基或烷基芳基，或选自吡啶基，咪唑，噻唑，苯并咪唑，苯并恶唑， 苯并噻唑，四唑，三唑和氨基噻唑; 和R 3和R 4彼此相同或不同的是C 1 -C 20烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基。

公开(公告)号：US20070197638A1

公开(公告)日：2007-08-23

申请号：US11657536

申请日：2007-01-25

申请人： Thomas Loftus ,  Craig Townsend ,  Gabrielle Ronnett ,  M. Lane ,  Francis Kuhajda

发明人： Thomas Loftus ,  Craig Townsend ,  Gabrielle Ronnett ,  M. Lane ,  Francis Kuhajda

IPC分类号： A61K31/365 ,  C12Q1/68

CPC分类号： C12Q1/6883 ,  A61K31/365 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/158

摘要： This invention provides a method for inducing weight loss in an animal by administering to the animal a compound which reduces the expression and/or secretion of neuropeptide Y (NPY). The effect may be accomplished directly, indirectly, or humorally. Preferably, administration of this compound has the effect of increasing malonyl CoA levels in the animal. Compounds administered according to this invention may be inhibitors of fatty acid synthase (FAS), including substituted α-methylene-β-carboxyl-γ-butyrolactones, or inhibitors of malonyl Coenzyme A decarboxylase (MCD). Preferably, the compound is administered in an amount sufficient to reduce the amount and/or duration of expression and/or secretion of NPY to levels at or below those observed for lean animals. In another preferred embodiment, the administration will reduce expression and/or secretion to levels observed for fed or satiated animals; more preferably, administration will reduce the level of NPY below that of fed animals. In a particular embodiment, this invention provides a method for inducing weight loss in an animal by administering a compound which inhibits feeding behavior in the animal. The method is particularly useful for inducing weight loss in animals deficient in expression of the hormone leptin or animals resistant to the action of leptin.

摘要翻译： 本发明提供一种通过向动物施用降低神经肽Y（NPY）的表达和/或分泌的化合物来诱导动物体内的体重减轻的方法。 效果可以直接，间接或幽默地完成。 优选地，该化合物的给药具有增加动物中丙二酰辅酶A水平的作用。 根据本发明施用的化合物可以是脂肪酸合酶（FAS）的抑制剂，包括取代的α-亚甲基-β-羧基-γ-丁内酯或丙二酰辅酶A脱羧酶（MCD）的抑制剂。 优选地，化合物以足以将NPY的表达和/或分泌的量和/或持续时间降低至对于瘦动物观察到的水平或以下的量施用。 在另一个优选的实施方案中，施用将将表达和/或分泌降低至饲喂或饱食动物观察到的水平; 更优选地，施用将降低NPY的水平低于饲养动物的水平。 在一个具体实施方案中，本发明提供了通过施用抑制动物中的进食行为的化合物来诱导动物体重减轻的方法。 该方法特别可用于诱导缺乏激素瘦素或对瘦素作用的动物的表达的动物的体重减轻。

公开(公告)号：US20070142456A1

公开(公告)日：2007-06-21

申请号：US10533311

申请日：2003-10-31

申请人： Francis Kuhajda ,  Elizabeth Jaffee ,  Craig Townsend

发明人： Francis Kuhajda ,  Elizabeth Jaffee ,  Craig Townsend

IPC分类号： A61K31/381 ,  A61K31/365

CPC分类号： A61K31/365 ,  A61K31/00 ,  A61K31/34 ,  A61K31/381

摘要： A method for inhibiting or preventing cancer development by the administration of fatty acid synthase (FAS) inhibitors. In particular, the present invention prohibits or delays the development of invasive cancer from pre-malignant (non-invasive) lesions that express FAS. Compositions containing FAS inhibitors also are provided, as well as methods for administering the FAS inhibitors and compositions to patients in need thereof.

摘要翻译： 通过施用脂肪酸合成酶（FAS）抑制剂抑制或预防癌症发展的方法。 特别地，本发明禁止或延迟侵入性癌症从表达FAS的恶性前（非侵入性）损伤的发展。 还提供了含有FAS抑制剂的组合物，以及用于将FAS抑制剂和组合物给予有此需要的患者的方法。

公开(公告)号：US20060241177A1

公开(公告)日：2006-10-26

申请号：US10519804

申请日：2003-07-01

申请人： Francis Kuhadja ,  Susan Medghalchi ,  Jagan Thupari ,  Craig Townsend ,  Jill McFadden

发明人： Francis Kuhadja ,  Susan Medghalchi ,  Jagan Thupari ,  Craig Townsend ,  Jill McFadden

IPC分类号： A61K31/365 ,  C07D305/12

CPC分类号： C07D307/33 ,  C07D307/58 ,  C07D307/68

摘要： Pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula IX: R29═H, or C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, ═CHR31, —C(O)OR31, —C(O)R31, —CH2C(O)OR31, CH2C(O)NHR31, where R31 is H or C1-C10 alkyl, cycloalkyl, or alkenyl; R30═C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl; X5═—OR32, or NHR32, Where R32 is H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, the R32 group optionally containing a carbonyl group, a carboxyl group, a carboxyamide group, an alcohol group, or an ether group, the R32 group further optionally containing one or more halogen atoms; with the proviso that when R29 is ═CH2, then X5 is not OH. Also disclosed are compounds within the scope of the formula IX, as well as uses of the pharmaceutical compositions for weight loss, anti-microbial and anti-cancer applications, inhibition of fatty acid synthase and neuropeptide-Y, and the stimulation of the activity of carnitine palmitoyl transferase-1.

摘要翻译： 包含药物稀释剂和式IX化合物的药物组合物：R 29 -H或C 1 -C 20烷基，环烷基，烯基 ，芳基，芳烷基或烷基芳基，-CHR 31，-C（O）OR 31，-C（O）R 31， - CH 2 C（O）OR 31，CH 2 C（O）NHR 31，其中R SUP > 31是H或C 1 -C 10烷基，环烷基或链烯基; 烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基;其中R 1，R 2，R 2，R 3， 其中R 32为H，C 1〜S 12，或其中R 32为H，C 1〜 烷基，环烷基，烯基，芳基，芳烷基或烷基芳基，任选含有羰基，羧基，羧酰胺的R 32基团 基团，醇基团或醚基团，R 32基团还任选地含有一个或多个卤素原子; 条件是当R 29为-CH 2时，则X 5不是OH。 还公开了式IX范围内的化合物，以及药物组合物用于体重减轻，抗微生物和抗癌应用，抑制脂肪酸合酶和神经肽Y的用途以及刺激活性 肉碱棕榈酰转移酶-1。

公开(公告)号：US20090005435A1

公开(公告)日：2009-01-01

申请号：US11597538

申请日：2005-05-25

申请人： Jill M. Sturdivant ,  Craig Townsend ,  Susan Medghalchi

发明人： Jill M. Sturdivant ,  Craig Townsend ,  Susan Medghalchi

IPC分类号： A61K31/381 ,  C07D333/32 ,  A61P35/00 ,  A61P3/04

CPC分类号： C07D333/32

摘要： A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula (II), wherein R1 and R2, the same or different from each other, are H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH2CORS, —CH2C(O)NRS, —C(O)R5, or —CH2OR5, and can optionally contain halogen atoms, where R5 is a C1-C12 alkyl group. R3 and R4, the same or different from each other, are H, C1-C20 alkyl cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl.

摘要翻译： 一种药物组合物，其包含药物稀释剂和式（II）化合物，其中R 1和R 2彼此相同或不同，为H，C 1 -C 20烷基，环烷基，烯基，芳基，芳烷基或烷芳基，-CH 2 CORS ，-CH 2 C（O）NRS，-C（O）R 5或-CH 2 OR 5，并且可任选地含有卤素原子，其中R 5是C 1 -C 12烷基。 R 3和R 4彼此相同或不同，为H，C 1 -C 20烷基环烷基，烯基，芳基，芳基烷基或烷基芳基。

公开(公告)号：US20050089974A1

公开(公告)日：2005-04-28

申请号：US10399693

申请日：2001-10-22

申请人： Craig Townsend ,  Michele Gunsior ,  Ulrike Muller ,  Friso Assema Van ,  Theodorus Sonke

发明人： Craig Townsend ,  Michele Gunsior ,  Ulrike Muller ,  Friso Assema Van ,  Theodorus Sonke

IPC分类号： C12N1/21 ,  C12N9/10 ,  C12N15/52 ,  C12N15/53 ,  C12N15/54 ,  C12P21/02 ,  C12P13/22

CPC分类号： C12N15/52 ,  C12N9/1096 ,  C12P21/02

摘要： A new fermentative process for the preparation of D-p-hydroxyphenylglycine (D-HPG) or D-henylglycine (D-pG) in enantiomerically pure form is disclosed. Precursors for the formation of D-HPG and D-pG are withdrawn form the common aromatic amino acid pathway, converted to p-hydroxyphenylglyoxylate or phenylglyoxylate, and are finally converted to D-HPG or D-pG by the action of a stero-inverting D-aminotransferase.

摘要翻译： 公开了以对映异构纯的形式制备D-对羟基苯基甘氨酸（D-HPG）或D-丁二酰甘氨酸（D-pG）的新的发酵方法。 用于形成D-HPG和D-pG的前体从共同的芳香族氨基酸途径中排出，转化为对羟基苯基乙醛酸或苯基乙醛酸，并最终通过反相转化为D-HPG或D-pG D-氨基转移酶。

公开(公告)号：US20070161092A1

公开(公告)日：2007-07-12

申请号：US11530118

申请日：2006-09-08

申请人： Craig Townsend ,  Rong-feng Li

发明人： Craig Townsend ,  Rong-feng Li

IPC分类号： C12P17/00 ,  C12N1/21

CPC分类号： C12P17/188

摘要： Genetically engineered Streptomyces clavuligerus strains with improved capabilities to produce clavulanic acid are provided. The strains are genetically engineered by disrupting newly identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes. This results in an increased intracelluar pool of the clavulanic acid precursor D-glyceraldehyde-3-phosphate (D-G3P), and increased clavulanic acid production. Clavulanic acid production may be further increased by supplying arginine to the medium in which the S. clavuligerus is grown.

摘要翻译： 提供了具有改进的克拉维酸能力的遗传工程链霉菌（Streptomyces clavuligerus）菌株。 通过破坏新鉴定的甘油醛-3-磷酸脱氢酶（GAPDH）基因，遗传工程菌株。 这导致克拉维酸前体D-甘油醛-3-磷酸（D-G3P）的增加的胞内池，并且增加了克拉维酸的产生。 通过将精氨酸供给到其中生长S.clavuligerus的培养基可以进一步增加克拉维酸生产。

公开(公告)号：US20060135568A1

公开(公告)日：2006-06-22

申请号：US10520506

申请日：2003-07-09

申请人： Craig Townsend ,  James Dick ,  Nicole Parrish ,  Minerva Hughes

发明人： Craig Townsend ,  James Dick ,  Nicole Parrish ,  Minerva Hughes

IPC分类号： A61K31/455 ,  A61K31/421 ,  A61K31/381 ,  A61K31/365 ,  A61K31/16 ,  A61K31/22

CPC分类号： A61K31/4409 ,  A61K31/16 ,  A61K31/165 ,  A61K31/22 ,  A61K31/221 ,  A61K31/341 ,  A61K31/365 ,  A61K31/381 ,  A61K31/421 ,  A61K31/455

摘要： A method of treating a subject with a microbially-based infection, comprising the administration of a compound to the subject. The compound is able to decrease ATP levels in the microbe by at least 10% compared to controls after 24 hours in an in vitro test, without killing mammalian cells during the same time period. The decrease in ATP levels is measured by: (1) removing the cells from the testing location and putting them on ice; (2) harvesting the cells at 4 degrees C. by centrifugation and disrupting it with bead-beating in an ATP extraction buffer; (3) removing cellular debris by centrifugation at 4 degrees C., leaving an ATP-containing supernatant; (4) measuring the amount of ATP present in the supernatant by a bioluminescence assay at 4 degrees C.

摘要翻译： 一种用基于微生物的感染治疗受试者的方法，包括向受试者施用化合物。 该化合物能够在体外试验中在24小时后将微生物中的ATP水平降低至少10％，而不会在同一时间段内杀死哺乳动物细胞。 ATP水平的降低通过以下方法测量：（1）从测试位置移除细胞并将其放在冰上; （2）通过离心在4℃收获细胞，并在ATP提取缓冲液中用珠珠打浆破坏细胞; （3）通过在4℃离心除去细胞碎片，留下含ATP的上清液; （4）通过4℃下的生物发光测定法测定上清液中存在的ATP的量。