公开(公告)号：US5744461A

公开(公告)日：1998-04-28

申请号：US451221

申请日：1995-05-26

Applicant: Karl Y. Hostetler ,  Raj Kumar

Inventor： Karl Y. Hostetler ,  Raj Kumar

IPC: A61K38/00 ,  A61K9/127 ,  A61K31/70 ,  A61P31/12 ,  A61P31/16 ,  A61P31/22 ,  C07F9/38 ,  C07F9/40 ,  C07H15/04 ,  C07H19/16 ,  A01N57/18

CPC classification number: B82Y5/00 ,  A61K47/48053 ,  A61K9/127 ,  C07F9/3891 ,  C07F9/4006 ,  C07F9/4065 ,  C07H15/04 ,  C07H19/16 ,  Y10S514/885

Abstract: Lipid-containing prodrugs are provided for treating viral infections due to herpes, influenza, hepatitis B, Epstein-Barr, and varicella zoster viruses, as well as cytomegalovirus and derivatives of antiviral agents. The compounds comprise phosphonoacids having antiviral activity which are linked, either through the phosphate group or carboxyl group of the phosphonoacid, to one of a selected group of lipids. Phosphonoacetic acid and phosphonoformic acid are thus linked to phospholipids, glycerolipids, sphingolipids, glycolipids, or fatty acids. The compounds persist, after intracellular hydrolysis, as the antiviral phosphonoacids. The lipid prodrugs are effective in improving the efficacy of antiviral phosphonoacids by prolonging their antiviral activity following administration.

Abstract translation: 提供含脂质的前药用于治疗由于疱疹，流感，乙型肝炎，爱泼斯坦巴尔和水痘带状疱疹病毒引起的病毒感染，以及巨细胞病毒和抗病毒剂的衍生物。 这些化合物包含具有抗病毒活性的膦酰基酸，其通过磷酸酯基或膦酰基酸的羧基与所选择的脂质组之一连接。 因此，膦酰基乙酸和膦酰基甲酸与磷脂，甘油脂，鞘脂，糖脂或脂肪酸相连。 化合物在细胞内水解后持续存在，作为抗病毒膦酰基酸。 脂质前药通过在施用后延长其抗病毒活性，有效地改善抗病毒膦酰基苷的功效。

公开(公告)号：US5704422A

公开(公告)日：1998-01-06

申请号：US445041

申请日：1995-05-19

Applicant: David Durham Chess ,  Mark Elliott Taylor ,  Raj Kumar Khanna ,  William Dale Henderson ,  Ronald William Hill

Inventor： David Durham Chess ,  Mark Elliott Taylor ,  Raj Kumar Khanna ,  William Dale Henderson ,  Ronald William Hill

IPC: F28D7/16 ,  F28F9/00 ,  F28F9/22

CPC classification number: F28F9/00 ,  F28D7/163 ,  Y10S165/402 ,  Y10S165/407

Abstract: A heat exchanger is provided, including a tubular shell having an opening in one end thereof, an open-topped, side-slotted shroud mounted inside the shell, a bundle of tubes extending through the opening into the shroud, means for circulating a hot fluid through the bundle of tubes, means for charging a heat-exchange fluid to the space between the shell and the shroud for flow through slots into the shroud and into indirect heat exchange contact with the bundle of tubes for cooling the hot fluid, and means for removing heated exchange fluid from the top of said shell.

Abstract translation: 提供了一种热交换器，其包括在其一端具有开口的管状壳体，安装在壳体内部的敞开的侧面开口的护罩，穿过开口延伸到护罩中的一束管，用于使热流体循环的装置 通过一束管，用于将热交换流体加载到壳体和护罩之间的空间的装置，用于通过狭槽进入护罩并与用于冷却热流体的管束间接热交换接触，以及用于 从所述壳的顶部移除加热的交换流体。

公开(公告)号：US5463092A

公开(公告)日：1995-10-31

申请号：US993133

申请日：1992-12-18

Applicant: Karl Y. Hostetler ,  Raj Kumar

Inventor： Karl Y. Hostetler ,  Raj Kumar

IPC: A61K38/00 ,  A61K9/127 ,  A61K31/70 ,  A61P31/12 ,  A61P31/16 ,  A61P31/22 ,  C07F9/38 ,  C07F9/40 ,  C07H15/04 ,  C07H19/16 ,  C07C233/00

CPC classification number: B82Y5/00 ,  A61K47/48053 ,  A61K9/127 ,  C07F9/3891 ,  C07F9/4006 ,  C07F9/4065 ,  C07H15/04 ,  C07H19/16 ,  Y10S514/885

Abstract: Lipid-containing prodrugs are provided for treating viral infections due to herpes, influenza, hepatitis B, Epstein-Barr, and varicella zoster viruses, as well as cytomegalovirus and derivatives of antiviral agents. The compounds comprise phosphonoacids having antiviral activity which are linked, either through the phosphate group or carboxyl group of the phosphonoacid, to one of a selected group of lipids. Phosphonoacetic acid and phosphonoformic acid are thus linked to phospholipids, glycerolipids, sphingolipids, glycolipids, or fatty acids. The compounds persist, after intracellular hydrolysis, as the antiviral phosphonoacids. The lipid prodrugs are effective in improving the efficacy of antiviral phosphonoacids by prolonging their antiviral activity following administration.

Abstract translation: 提供含脂质的前药用于治疗由于疱疹，流感，乙型肝炎，爱泼斯坦巴尔和水痘带状疱疹病毒引起的病毒感染，以及巨细胞病毒和抗病毒剂的衍生物。 这些化合物包含具有抗病毒活性的膦酰基酸，其通过磷酸酯基或膦酰基酸的羧基与所选择的脂质组之一连接。 因此，膦酰基乙酸和膦酰基甲酸与磷脂，甘油脂，鞘脂，糖脂或脂肪酸相连。 化合物在细胞内水解后持续存在，作为抗病毒膦酰基酸。 脂质前药通过在施用后延长其抗病毒活性，有效地改善抗病毒膦酰基苷的功效。

公开(公告)号：US5411947A

公开(公告)日：1995-05-02

申请号：US991166

申请日：1992-12-16

Applicant: Karl Y. Hostetler ,  Raj Kumar

Inventor： Karl Y. Hostetler ,  Raj Kumar

IPC: A61K47/48 ,  A61K9/127 ,  A61K31/337 ,  A61P35/00 ,  C07F9/38 ,  C07F9/40 ,  C07F9/655 ,  C07H15/04 ,  C07H19/06 ,  C07H19/16 ,  A01N43/04 ,  A01N37/18 ,  A61K31/43 ,  A61K38/00

CPC classification number: C07H15/04 ,  A61K47/48023 ,  A61K47/48038 ,  A61K47/48053 ,  A61K47/48084 ,  A61K9/127 ,  B82Y5/00 ,  C07F9/3891 ,  C07F9/4006 ,  C07F9/4065 ,  C07F9/65512 ,  C07H19/06 ,  C07H19/16 ,  Y10S514/885

Abstract: The oral delivery of many classes of drugs is facilitated by converting drugs having suitable functional groups to 1-O-alkyl-, 1-O-acyl-, 1-S-acyl, and 1-S-alkyl-sn-glycero-3-phosphate derivatives. The method confers the ability to be absorbed through the digestive tract to drugs that are not orally bioavailable in the non-derivatized state, and enhances the effectiveness of drugs that are poorly absorbed or rapidly eliminated. The method provides orally bioavailable lipid prodrugs of pharmaceutical compounds having diverse physiological activities, including anticancer and antiviral agents, anti-inflammatory agents, antihypertensives and antibiotics. Potency of the lipid prodrugs is comparable to that of the corresponding non-derivatized drugs.

Abstract translation: 通过将具有合适的官能团的药物转化为1-O-烷基 - ，1-O-酰基 - ，1-S-酰基和1-S-烷基-sn-甘油基-3，可促进许多类药物的口服递送 磷酸酯衍生物。 该方法赋予了在非衍生化状态下不经口服生物利用的药物通过消化道吸收的能力，并提高吸收不良或快速消除的药物的有效性。 该方法提供具有不同生理活性的药物化合物的口服生物可利用的脂前药，包括抗癌和抗病毒剂，抗炎药，抗高血压药和抗生素。 脂质前药的效力与相应的非衍生化药物的效力相当。

公开(公告)号：US5223263A

公开(公告)日：1993-06-29

申请号：US373088

申请日：1989-06-28

Applicant: Karl Y. Hostetler ,  Raj Kumar ,  Louise M. Stuhmiller

Inventor： Karl Y. Hostetler ,  Raj Kumar ,  Louise M. Stuhmiller

IPC: C07D213/24 ,  A01N43/40 ,  A61K9/127 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61P31/12 ,  C07C17/093 ,  C07C25/13 ,  C07D213/61 ,  C07D213/64 ,  C07D213/70 ,  C07H15/04 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/207

CPC classification number: C07H15/04 ,  A01N43/40 ,  A61K47/48038 ,  A61K47/48053 ,  A61K47/48084 ,  A61K9/127 ,  C07C17/093 ,  C07C25/13 ,  C07D213/61 ,  C07D213/64 ,  C07D213/70 ,  C07H19/04 ,  C07H19/06 ,  C07H19/16

Abstract: Compounds are disclosed for treating AIDS, herpes, and other viral infections by means of lipid derivatives of antiviral agents. The compounds consist of nucleoside analogues having antiviral activity which are linked, commonly through a phosphate group at the 5' position of the pentose residue, to one of a selected group of lipids. The lipophilic nature of these compounds provide advantages over the use of the nucleoside analogue alone. It also makes it possible to incorporate them into the lamellar structure of liposomes, either alone or combined with similar molecules. In the form of liposomes, these antiviral agents are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target HIV virus. Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins. Effective nucleoside analogues are dideoxynucleosides, azidothymine (AZT), and acyclovir; lipid groups may be glycolipids, sphingolipids, phospholipids or fatty acids. The compounds persist, after intracellular hydrolysis, as phosphorylated or non-phosphorylated antiviral nucleosides. The compounds are effective in improving the efficacy of antiviral nucleoside analogues by prolonging the antiviral activity after the administration of the drug has ended, and in preventing retroviral replication in HIV infections which have become resistant to therapy with conventional forms of the antiretroviral agents.

公开(公告)号：US4042694A

公开(公告)日：1977-08-16

申请号：US664907

申请日：1976-03-08

Applicant: Louis Selig Harris ,  Harry George Pars ,  John Clark Sheehan ,  Raj Kumar Razdan

Inventor： Louis Selig Harris ,  Harry George Pars ,  John Clark Sheehan ,  Raj Kumar Razdan

IPC: C07D211/14 ,  C07D491/052 ,  C07D491/04

CPC classification number: C07D211/14

Abstract: Novel heterocyclic esters of benzopyranopyridines represented by the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, lower alkanoyl, cycloalkyl-lower alkyl, cycloalkyl-lower alkanoyl, lower alkenyl, lower alkynyl, halo-loweralkenyl, phenyl-lower alkyl, phenyl-lower alkenyl or phenyl-lower alkynyl; R.sub.2 is lower alkyl; R.sub.3 is an alkyl having one to twenty carbon atoms or a cycloalkyl-lower alkyl, Y is a straight or branched chain alkylene having one to eight carbon atoms, and R.sub.4 is a group of the formula ##STR2## a is an integer from 1 to 4, b is an integer from 1 to 4 and X is CH.sub.2, O, S or N--R.sub.5 with R.sub.5 being hydrogen or lower alkyl, with the limitation that when X is O, S or N--R.sub.5, a and b each must be 2 and R.sub.6 is hydrogen or a lower alkyl group bonded to a carbon in the ring; and the acid addition salts thereof.

Abstract translation: 其中R 1为氢，低级烷基，低级烷酰基，环烷基 - 低级烷基，环烷基 - 低级烷酰基，低级烯基，低级炔基，卤代低级烯基，苯基 - 低级烷基，苯基 - 低级烷基， 低级烯基或苯基 - 低级炔基; R2是低级烷基; R3是具有1-20个碳原子的烷基或环烷基 - 低级烷基，Y是具有1-8个碳原子的直链或支链亚烷基，R4是下式的基团：a是从1到 4，b为1〜4的整数，X为CH 2，O，S或N-R 5，其中R 5为氢或低级烷基，限制在X为O，S或N-R 5时，a和b各自为 是2，R6是氢或与环中的碳键合的低级烷基; 及其酸加成盐。

公开(公告)号：US4007207A

公开(公告)日：1977-02-08

申请号：US594534

申请日：1975-07-09

Applicant: Martin Winn ,  Raj Kumar Razdan ,  Haldean Cloyce Dalzell ,  Joyce Ruth Krei

Inventor： Martin Winn ,  Raj Kumar Razdan ,  Haldean Cloyce Dalzell ,  Joyce Ruth Krei

IPC: C07D311/78

CPC classification number: Y10S514/96

Abstract: 1,2,3,4-Tetrahydrocyclopenta[c][1]benzopyrans of the formulae ##STR1## wherein R is a lower alkyl group having 1 to 5 carbons, R.sub.1 is hydrogen or a lower alkyl group having 1 to 5 carbons, R.sub.2 is a lower alkyl group and R.sub.3 is an alkyl group having 1 to 20 carbon atoms, a phenyl-lower alkyl group or a cycloalkyl-lower alkyl group. The compounds have anti-hypertensive, antidepressant, analgesic, anticonvulsant, anti-anxiety, sedative-hypnotic and tranquilizing activity in animals.

Abstract translation: 其中R为具有1至5个碳原子的低级烷基，R 1为氢或低级烷基，具有1至5个碳原子的低级烷基， 5个碳，R2为低级烷基，R3为碳原子数1〜20的烷基，苯基 - 低级烷基或环烷基 - 低级烷基。 该化合物在动物体内具有抗高血压，抗抑郁，镇痛，抗惊厥，抗焦虑，镇静催眠和镇静作用。

公开(公告)号：US3992550A

公开(公告)日：1976-11-16

申请号：US594533

申请日：1975-07-09

Applicant: Martin Winn ,  Raj Kumar Razdan ,  Haldean Cloyce Dalzell ,  Joyce Ruth Krei

Inventor： Martin Winn ,  Raj Kumar Razdan ,  Haldean Cloyce Dalzell ,  Joyce Ruth Krei

IPC: A61K31/335

Abstract: 1,2,3,4-Tetrahydrocyclopenta[c] [1]benzopyrans of the formulae ##SPC1##Wherein R is a lower alkyl group having 1 to 5 carbons, R.sub.1 is hydrogen or a lower alkyl group having 1 to 5 carbons, R.sub.2 is a lower alkyl group and R.sub.3 is an alkyl group having 1 to 20 carbon atoms, a phenyl-lower alkyl group or a cycloalkyl-lower alkyl group. The compounds have anti-hypertensive, antidepressant, analgesic, anticonvulsant, anti-anxiety and tranquilizing activity in animals.

Abstract translation: 1,2,3,4-四氢环戊二烯并[c] [1]苯并吡喃，式为WHEREIN R为碳原子数1〜5的低级烷基，R1为氢或碳原子数为1〜5的低级烷基，R2为低级 烷基，R 3为碳原子数1〜20的烷基，苯基 - 低级烷基或环烷基 - 低级烷基。 该化合物在动物中具有抗高血压，抗抑郁，止痛，抗惊厥，抗焦虑和镇静作用。

公开(公告)号：US3987190A

公开(公告)日：1976-10-19

申请号：US550292

申请日：1975-02-18

Applicant: Raj Kumar Razdan ,  Harry George Pars

Inventor： Raj Kumar Razdan ,  Harry George Pars

IPC: A61K31/35 ,  C07D495/02 ,  C07D495/04 ,  A61K31/38

CPC classification number: C07D495/04 ,  A61K31/35 ,  C07D495/02

Abstract: A method of reducing blood pressure in a hypertensive mammalian patient by administering 1,2-dihydro-4,4-dimethyl-9-hydroxy-7-(3-methyl-2-octyl)-4H-thieno[2,3-c][1]benzopyran or 1,2-dihydro-5,5-dimethyl-10-hydroxy-8-(3-methyl-2-octyl)-3H,5H-thiopyrano-8 2,3-c][1]benzopyran. Pharmaceutical compositions containing 1,2-dihydro-4,4-dimethyl-9-hydroxy-7-(3-methyl-2-octyl)-4H-thieno[2,3-c][1]benzopyran or 1,2-dihydro-5,5-dimethyl-10-hydroxy-8-(3-methyl-2-octyl)-3H,5H-thiopyrano[2,3-c][1]benzopyran dispersed in a pharmaceutical carrier.

公开(公告)号：US3972880A

公开(公告)日：1976-08-03

申请号：US558640

申请日：1975-03-17

Applicant: Louis Selig Harris ,  Harry George Pars ,  Raj Kumar Razdan ,  John Clark Sheehan

Inventor： Louis Selig Harris ,  Harry George Pars ,  Raj Kumar Razdan ,  John Clark Sheehan

IPC: C07D495/04

CPC classification number: C07D495/04

Abstract: Novel thienobenzopyran and thiopyranobenzopyran esters represented by the formula ##SPC1##Wherein n is 0 to 3 and m is 0 to 3 and m + n = 2 or 3, R.sub.1 is lower alkyl, R.sub.2 is alkyl or cycloalkyl-lower alkyl, R.sub.4 is hydrogen or lower alkyl, R.sub.5 is hydrogen or lower alkyl, and R.sub.3 is ##EQU1## wherein Y is a straight or branched chain C.sub.1 to C.sub.8 alkylene, R.sub.6 is hydrogen or a lower alkyl, a is an integer from 1 to 4, b is an integer from 1 to 4, X is CH.sub.2, O, S or NR.sub.7 wherein R.sub.7 is hydrogen or lower alkyl, with the limitation that when X is O, S or NR.sub.7, a and b each must be 2; and the acid addition salts thereof.

Abstract translation: 新型的噻吩并苯并吡喃和噻喃并吡喃并吡喃酮，由下式表示：其中N为0至3且M为0至3，M + N = 2或3，R1为低级烷基，R2为烷基或环烷基 - 低级烷基，R4为氢或低级烷基 R 5是氢或低级烷基，R 3是O（CH 2）a并环-CYN角度X（CH 2）b R 6其中Y是直链或支链C1至C8亚烷基，R6是氢或低级烷基， 是1至4的整数，b是1至4的整数，X是CH 2，O，S或NR 7，其中R 7是氢或低级烷基，但是当X是O，S或NR 7时，a和b 每个必须是2; 及其酸加成盐。