LV12208B - Hiv proteāzes inhibitora pielietojums aids ārstēšanai - Google Patents

Hiv proteāzes inhibitora pielietojums aids ārstēšanai Download PDF

Info

Publication number
LV12208B
LV12208B LVP-98-235A LV980235A LV12208B LV 12208 B LV12208 B LV 12208B LV 980235 A LV980235 A LV 980235A LV 12208 B LV12208 B LV 12208B
Authority
LV
Latvia
Prior art keywords
hydroxy
compound
alkyl
aryl
group
Prior art date
Application number
LVP-98-235A
Other languages
English (en)
Other versions
LV12208A (lv
Inventor
Joseph P. Vacca
Katharine M. Holloway
Bruce D. Dorsey
Randall W. Hungate
James P. Guare
Original Assignee
Merck & Co., Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.
Publication of LV12208A publication Critical patent/LV12208A/lv
Publication of LV12208B publication Critical patent/LV12208B/lv

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • AIDS & HIV (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyrrole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Claims (17)

  1. Izgudrojuma formula 1. Savienojums un tā farmaceitiski pieņemamās sālis ar formulu (I)
    T* I kurā: R ir ūdeņraža atoms vai CMalkilgrupa; R1 un R2 var abi kopā ar slāpekļa atomu, pie kura pievienots R1, veidot 3-10 locekļu piesātinātu monociklisku vai biciklisku sistēmu, kurā ietilpst slāpekļa atoms, kam pievienots R1, un 2 - 9 oglekļa atomi, pie tam tas var būt aizvietots ar: 1) -VV-arilgrupa, vai 2) -W-C=0 I arilgrupa, kur W ir —O-, -S- vai -NH-; vai arī R1 un R2 var abi kopā ar slāpekļa atomu, pie kura pievienots R1, veidot 3-10 locekļu piesātinātu monociklisku vai biciklisku sistēmu, kurā ietilpst slāpekļa atoms, kam pievienots R1, un 1 - 8 oglekļa atomi, kā arī grupa -N- V-R1*, kurā -V- ir vienkāršā saite, vai grupa -OO, I Q vai arī grupa -SO2-C)-; 2 Μ uti .! R1* ir: 1) ūdeņraža atoms, 2) Ci^alkilgrupa, neobligāti aizvietota ar vienu vai vairākiem aizvietotājiem no rindas: a) halogēna atoms, b) hidroksilgrupa, c) Ci.3alkoksigrupa, d) arilgrupa, neobligāti aizvietota ar vienu vai vairākiem aizvietotājiem no rindas: Ci^alkilgrupa, hidroksilgrupa un arilgrupa, e) -W-arilgrupa vai -W-benzilgrupa, kur W ir -O-, -S- vai -NH-, f) 5 - 7 locekju cikloalkilgrupa, neobligāti aizvietota ar vienu vai vairākiem aizvietotājiem no rindas: i) halogēna atoms, ii) hidroksilgrupa, iii) Ci-3alkoksigrupa, iv) arilgrupa, g) heterocikls, neobligāti aizvietots ar vienu vai vairākiem aizvietotājiem no rindas: hidroksilgrupa, C1.4 alkilgrupa, kas var būt aizvietota ar hidroksilgrupu, BOC grupa, h) -NH-C-0-Ci.3alkilgrupa, i 0 i) NH-C-Cļ-salkilgrupa, O j) -NH-S02-Ci-3alkilgrupa, k) -NR2, l) -COOR, m) -[(CH2)mO]-R, kur m ir 2 - 5, n ir 0, 1, 2 vai 3; 3) arilgrupa, neobligāti aizvietota ar vienu vai vairākiem aizvietotājiem no rindas: a) halogēna atoms, b) hidroksilgrupa, c) —N02 vai -NR2, d) C-Malkilgrupa, e) Ci.3alkoksigrupa, neobligāti aizvietota ar vienu vai vairākām hidroksilgrupām vai C1.3 alkoksigrupām, f) -COOR, g) grupa -C=0 , I nr2 h) -CH2NR2i 3 LV 12208 i) grupa -CH2NHC=0, R j) -CN, k) -CF3l l) grupa -NHC=0, R m) aril-Ci.3alkoksigrupa, n) arilgrupa, o) -NHSO2R, p) -0P(0)(0Rx)2l kur -Q- ir vienkāršā saite vai -O-, -NR- vai heterocikls, neobligāti aizvietots ar Ci^alkilgrupu; ir benzilgrupa, neobligāti aizvietota ar vienu vai vairākiem aizvietotājiem no rindas: (1) hidroksilgrupa, (2) Ci^alkoksigrupa, kas aizvietota ar vienu vai vairākām hidroksilgrupām, (3) grupa -o
    ir ūdeņraža atoms vaii arilgrupa ir: 1) -W-(CH2)m-N R6R7, kurā W ir jau minētā nozīme, m ir 2 - 5 un R6 un R7, neatkarīgi viens no otra, ir: a) ūdeņraža atoms, b) Ci^alkilgrupa, neobligāti aizvietota ar vienu vai vairākiem aizvietotājiem no rindas: i) Ci-3alkoksigrupa, ii) hidroksilgrupa, iii) -NR2, c) vienādi vai dažādi aizvietotāji, kas savienoti, veidojot 5-7 locekļu heterociklu, piemēram, morfolīna grupu, un var papildus saturēt vēl līdz diviem heteroatomiem no rindas: >N-R, -O-, >S=0, -S-, >S02, pie kam heterocikls ir neobligāti aizvietots ar Ci^alkilgrupu, d) aromātisks heterocikls, neobligāti aizvietots ar vienu vai vairākiem aizvietotājiem no rindas: i) Ci-4alkilgrupa, ii) -NR2, 2) -(CH2)q-R6R7, kurā q ir 1 - 5, R6 un R7 nozīmes ir jau minētās, izņemot to, ka, R6 un R7 nevar būt ūdeņraža atoms vai Ci^alkilgrupa, 4 3) benzofuranilgrupa, indolilgrupa, azacikloalkilgrupa, azabicikloalkil-C7.iidkloalkilgrupa vai benzopiperidinilgrupa, neobligāti aizvietotas ar Ci^alkilgrupu; J1 ir-NH-Ci-4alkilgrupa;
    R1
  2. 2. Savienojums pēc 1. punkta ar formulu (27) un tā farmaceitiski pieņemamās sālis, .
    kur R1*, R3 un R12 ir 1. punktā minētie, izņemot to, ka tad, kad -V- ir vienkāršā saite vai -SC>2-Q-, R1* nevar būt ūdeņraža atoms vai cita grupa, kā vienīgi ar brīvu hidroksilgrupu aizvietota arilgrupa,
  3. 3. Savienojums no rindas: N-(2(R)-hidroksi-1(S)-indanil)-2(R)-fenilmetil-4(S)-hidroksi-5-{2-[3(S)-N’-(t-butil- karboksamido)-(4aS,8aS)-dekahidroizohinolin]il}pentānamīds, N-(2(R)-hidroksi-1(S)-indanil)-2(R)-fenilmetil-4(S)-hidroksi-5-{1-[4- karbobenziloksi-2(S)-N’-(t-butil-karboksamido)-piperazinil]}pentānamīds, N-(2(R)-hidroksi-1(S)-indanil)-2(R)-({4-[2-(4-morfolinil)etoksi]fenil}metil)-4(S)- hidroksi-5-[2-(3(S)-N’'(t-butil-karboksamido)-(4aS,8aS)-dekahidroizohinolin)ii]- pentānamīds, N-(2(R)-hidroksi-1(S)-indanil)-2(R)-({4-[2-(4-morfolinil)etoksi]fenil}metil)-4(S)- hidroksi-5-{1-[4-karbobenziloksi-2(S)-N’-(t-butil-karboksamido)-piperazinil]}- pentānamīds, 5 I» 1(1 I i LV 12208 N-(2(R)-hidroksi-1(S)-indanil)-2(R)-({4-[(2-hidroksi)etoksi]fenil}metil)-4(S)- hidroksi-5-[2-(3(S)-N,-(t-butil-karboksamido)-(4aS,8aS)-dekahidroizohinolin)il]- pentānamīds, N-(2(R)-hidroksi-1(S)-indanil)-2(R)-({4-[(2-hidroksi)etoksi]fenil}metil)-4(S)- hidroksi-S-il-^-karbobenziloksi^CSJ-N’-it-butil-karboksamidoj-piperazinil]}- pentānamīds, N-(4(S)-3,4-dihidro-1H-2,2-dioksobenzotiopiranil)-2(R)-fenilmetil-4(S)-hidroksi- S-ļŽ-^isj-N’-it-butil-karboksamidoļ-^aS.eaSJ-dekahidroizohinolinJilj-pentān- amīds, N-(4(S)-3,4-dihidro-1H-2,2-dioksobenzotiopiranil)-2(R)-fenilmetil-4(S)-hidroksi- 5^-l-[4-karbobenziloksi-2(S)-N’-(t-butil-karboksamido)-piperazinil]}-pentān- amīds, N-(2(R)-hidroksi-1(S)-indanil)-2(R)-fenilmetil-4(S)-hidroksi-5-{1-[4-(3- piridinilmetil)-2(S)-N’-(t-butilkarboksamido)piperazinii]}pentānamīds> vai ŠT savienojuma farmaceitiski pieņemamā sāls.
  4. 4. Savienojums ar formulu
    vai šī savienojuma farmaceitiski pieņemamā sāls.
  5. 5. Farmaceitiskā kompozīcija, kas ietver savienojumu pēc jebkura no 1. līdz 3. punktam kopā ar farmaceitiski pieņemamu nesēju.
  6. 6. Kompozīcija pēc 5. punkta orāli lietojamas gatavās zāļu formas veidā.
  7. 7. Kompozīcija pēc 5. punkta, kas ietver savienojumu pēc 3. punkta.
  8. 8. Savienojuma pēc jebkura no 1. līdz 4. punktam pielietojums tāda medikamenta ražošanai, kas piemērots AIDS ārstēšanai.
  9. 9. Savienojuma pēc jebkura no 1. līdz 4. punktam pielietojums tāda medikamenta ražošanai, kas piemērots HIV infekcijas profilaksei vai ārstēšanai. 6 i l Ulli il
  10. 10. Savienojuma pēc jebkura no 1. līdz 4. punktam pielietojums tāda medikamenta ražošanai, kas piemērots HIV proteāzes inhibēšanai.
  11. 11. Paņēmiens savienojuma ar formulu (27) OH R3
    CONH-f 27 R kurā R1*, R3 un R12 nozīmes ir 1. punktā minētās, izņemot to, ka tad, kad -V- ir vienkāršā saite vai -S02-Q-, R1* nevar būt ūdeņraža atoms vai cita grupa, kā vienīgi ar brīvu hidroksilgrupu aizvietota arilgrupa, iegūšanai, kas paredz to, ka savienojumu ar formulu (28),
    28 kurā R3 un R12 ir ar jau minētām nozīmēm, apstrādā standartapstākjos ar savienojumu R1*-X vai R1*S02CI, kur R1* nozīme ir jau minētā, un X ir Cl, Br vai
  12. 12. Paņēmiens pēc 11. punkta, kas atšķiras arto, ka savienojumu ar formulu (28) apstrādā ar savienojumu R1*.
  13. 13. Paņēmiens pēc 11. vai 12. punkta, kas atšķiras ar to, ka R3 ir (R)-benzilgrupa un R12 ir 2(R)-hidroksi-1(S)-indanilgrupa.
  14. 14. Paņēmiens pēc 11., 12. vai 13. punkta, kas atšķiras ar to, ka savienojums ar formulu (28) ir N-(2-(2(R)-hidroksi-1(S)-indanil)-2(R)-feniimetil-4(S)-hidroksi-5-{1-[2(S)~N-(t-butilkarboksamido)-piperazinil]}pentānamīds.
  15. 15. Paņēmiens savienojuma pēc 4. punkta iegūšanai, kas paredz pikolilhlorīda, bromīda vai jodīda reakciju ar N-[2-(2(R)-hidroksi-1(S)-indanil)-2(R)-fenilmetil-4(S)-hidroksi-5-{1-[2(S)-N-(t-butilkarboksamido)-piperazinil]}-pentānamīdu šķīdinātājā.
  16. 16. Paņēmiens pēc 15. punkta, kurā šķīdinātājs ir dimetilformamīds. LV 12208 7
  17. 17. N-[2-(2(R)-hidroksi-1(S)-indanil)-2(R)-fenilmeti!-4(S)-hidroksi-5-{1-[2(S)-N-(t-butilkarboksamido)-piperazinil]}pentānamīds.
LVP-98-235A 1991-11-08 1998-10-26 Hiv proteāzes inhibitora pielietojums aids ārstēšanai LV12208B (lv)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US78950891A 1991-11-08 1991-11-08
US88382592A 1992-05-15 1992-05-15

Publications (2)

Publication Number Publication Date
LV12208A LV12208A (lv) 1999-01-20
LV12208B true LV12208B (lv) 1999-03-20

Family

ID=27120923

Family Applications (1)

Application Number Title Priority Date Filing Date
LVP-98-235A LV12208B (lv) 1991-11-08 1998-10-26 Hiv proteāzes inhibitora pielietojums aids ārstēšanai

Country Status (27)

Country Link
EP (1) EP0541168B1 (lv)
JP (1) JPH0733373B2 (lv)
KR (1) KR100273623B1 (lv)
AT (1) ATE163926T1 (lv)
AU (1) AU659234B2 (lv)
BG (1) BG61725B1 (lv)
CA (2) CA2081970C (lv)
CY (1) CY2090B1 (lv)
CZ (1) CZ287610B6 (lv)
DE (1) DE69224703T2 (lv)
DK (1) DK0541168T3 (lv)
ES (1) ES2112880T3 (lv)
FI (2) FI106025B (lv)
GR (1) GR3026334T3 (lv)
HK (1) HK1006060A1 (lv)
HU (1) HU220866B1 (lv)
IL (1) IL103613A (lv)
LV (1) LV12208B (lv)
NO (1) NO303383B1 (lv)
NZ (1) NZ244986A (lv)
PL (1) PL171340B1 (lv)
RO (1) RO115726B1 (lv)
RU (1) RU2131416C1 (lv)
SG (1) SG52731A1 (lv)
SK (1) SK281864B6 (lv)
UA (1) UA45945C2 (lv)
WO (1) WO1993009096A1 (lv)

Families Citing this family (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040122000A1 (en) 1981-01-07 2004-06-24 Vertex Pharmaceuticals Incorporated. Inhibitors of aspartyl protease
US6878728B1 (en) 1999-06-11 2005-04-12 Vertex Pharmaceutical Incorporated Inhibitors of aspartyl protease
USH1649H (en) 1987-07-31 1997-05-06 Barrish; Joel C. HIV protease inhibitor combinations
US5413999A (en) * 1991-11-08 1995-05-09 Merck & Co., Inc. HIV protease inhibitors useful for the treatment of AIDS
US5888992A (en) 1992-03-11 1999-03-30 Narhex Limited Polar substituted hydrocarbons
DE69333270T2 (de) 1992-03-11 2004-08-05 Narhex Ltd. Aminderivate von oxo- und hydroxy- substituierten kohlenwasserstoffen
US6071895A (en) 1992-03-11 2000-06-06 Narhex Limited Polar-substituted hydrocarbons
NZ249789A (en) * 1992-03-11 1997-07-27 Narhex Ltd Hydrazine, carbazate and 1,2-diazacyclic derivatives and pharmaceutical compositions
US5559256A (en) * 1992-07-20 1996-09-24 E. R. Squibb & Sons, Inc. Aminediol protease inhibitors
KR100336699B1 (ko) 1992-08-25 2002-05-13 윌리암스 로저 에이 레트로바이러스 프로테아제 저해제로서 유용한히드록시에틸아미노 술폰아미드
US7141609B2 (en) 1992-08-25 2006-11-28 G.D. Searle & Co. α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
US5783701A (en) 1992-09-08 1998-07-21 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
IS2334B (is) 1992-09-08 2008-02-15 Vertex Pharmaceuticals Inc., (A Massachusetts Corporation) Aspartyl próteasi hemjari af nýjum flokki súlfonamíða
US5723490A (en) * 1992-09-08 1998-03-03 Vertex Pharmaceuticals Incorporated THF-containing sulfonamide inhibitors of aspartyl protease
US5430150A (en) * 1992-12-16 1995-07-04 American Cyanamid Company Retroviral protease inhibitors
IL110255A (en) * 1993-07-16 1998-12-06 Merck & Co Inc Creation and resolution of 2 tert-butylcarboxamidopiprazine
US5463067A (en) * 1993-07-16 1995-10-31 Merck & Co., Inc. Process for making HIV protease inhibitors
IL110752A (en) * 1993-09-13 2000-07-26 Abbott Lab Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor
US5559158A (en) * 1993-10-01 1996-09-24 Abbott Laboratories Pharmaceutical composition
IL111584A0 (en) * 1993-11-18 1995-01-24 Merck & Co Inc Prodrugs of an inhibitor of hiv protease and pharmaceutical compositions containing them
US5455351A (en) * 1993-12-13 1995-10-03 Abbott Laboratories Retroviral protease inhibiting piperazine compounds
AU692509B2 (en) * 1993-12-15 1998-06-11 Merck & Co., Inc. HIV protease inhibitors
US5428167A (en) * 1994-01-14 1995-06-27 American Cyanamid Company Asymmetric synthesis of intermediates for retroviral protease inhibitor compounds
US5733882A (en) * 1994-01-17 1998-03-31 Smithkline Beecham Corporation Retroviral protease inhibitors
TW472047B (en) * 1994-02-04 2002-01-11 Merck & Co Inc Process for making HIV protease inhibitors
TW380137B (en) * 1994-03-04 2000-01-21 Merck & Co Inc Process for making an epoxide
US5728840A (en) * 1994-03-04 1998-03-17 Merck & Co., Inc. Process for making an epoxide
US6127372A (en) * 1994-03-07 2000-10-03 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
US5420353A (en) * 1994-03-11 1995-05-30 Merck & Co., Inc. Regiospecific process to make cis-1-amino-2-alkanol from epoxide
US5449830A (en) * 1994-03-11 1995-09-12 Marck & Co., Inc. Regiospecific processes to make CIS-1-Amino-2-Alkanol from Diol or Halohydrin
EP0756593B1 (de) * 1994-04-20 2000-09-20 Lonza Ag Verfahren zur herstellung von 2-piperazincarbonsäurederivaten
EP0705824B1 (en) * 1994-04-22 2002-08-07 Koei Chemical Co., Ltd. Process for producing optically active n-tert-butyl- 2-piperazine- carboxamide
UA49803C2 (uk) * 1994-06-03 2002-10-15 Дж.Д. Сьорль Енд Ко Спосіб лікування ретровірусних інфекцій
US5476874A (en) * 1994-06-22 1995-12-19 Merck & Co., Inc. New HIV protease inhibitors
IL114808A (en) * 1994-08-11 1999-10-28 Merck & Co Inc Combinations of protease inhibitors for the treatment of hiv infection and aids
GB2292146A (en) * 1994-08-11 1996-02-14 Merck & Co Inc HIV protease inhibitors useful for the treatment of AIDS
WO1996012492A1 (en) * 1994-10-25 1996-05-02 Merck & Co., Inc. Microbial synthesis of hiv protease inhibitors
US5612217A (en) * 1994-10-25 1997-03-18 Merck & Co., Inc. Streptomyces sp. MA 7074 (ATCC 55605) used for microbial synthesis of HIV protease inhibitors
DE4446025A1 (de) * 1994-12-22 1996-06-27 Basf Ag 2-Caroxamido-1,4,5,6-tetrahydropyrazine
JPH11500425A (ja) * 1995-01-23 1999-01-12 ロンザ アーゲー １，４，５，６−テトラヒドロピラジン−２−カルボキサミドの製造方法
US5508404A (en) * 1995-03-15 1996-04-16 Merck & Co., Inc. Reductive amination process
US5618937A (en) * 1995-03-15 1997-04-08 Merck & Co., Inc. Process to make HIV protease inhibitor from (2S)-4-picolyl-2-piperazine-t-butylcarboxamide
US5691372A (en) * 1995-04-19 1997-11-25 Vertex Pharmaceuticals Incorporated Oxygenated-Heterocycle containing sulfonamide inhibitors of aspartyl protease
US5612484A (en) * 1995-05-18 1997-03-18 Merck & Co., Inc. Process for making HIV protease inhibitors
US5605819A (en) * 1995-05-19 1997-02-25 Merck & Co., Inc. Quantitative conversion of indene to (1S,2R) indene oxide and (1S,2R)-indandiol by combination of haloperoxidase bioconversion and chemical steps
ES2164187T3 (es) * 1995-05-23 2002-02-16 Lonza Ag Procedimiento para la preparacion de derivados de acidos 2-piperazina-carboxilicos opticamente activos.
US6004957A (en) * 1995-06-07 1999-12-21 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
US6037157A (en) 1995-06-29 2000-03-14 Abbott Laboratories Method for improving pharmacokinetics
DE69634959T2 (de) 1995-11-13 2006-05-24 Vitaleech Bioscience N.V. Antivirale isolate von blutegeln
US5883252A (en) * 1996-01-26 1999-03-16 Vertex Pharmaceuticals Incorporated Aspartyl protease inhibitors
MY126358A (en) * 1996-03-22 2006-09-29 Glaxo Group Ltd Compositions comprising vx478 and a water soluble tocopherol derivative such as vitamin e-tpgs
CA2201218C (en) * 1996-04-23 2004-09-28 Rudolf Fuchs Process for the preparation of optically active piperazine-2-carboxylic acid derivatives
DE19620494A1 (de) * 1996-05-21 1997-11-27 Basf Ag 1-(Halogenalkanoyl)-2-carboxamido-1,4,5,6-tetrahydropyrazine
US5747540A (en) * 1996-10-21 1998-05-05 Merck & Co., Inc. HIV protease inhibitors useful for the treatment of AIDS
ZA9710071B (en) * 1996-11-21 1998-05-25 Abbott Lab Pharmaceutical composition.
US6232333B1 (en) 1996-11-21 2001-05-15 Abbott Laboratories Pharmaceutical composition
US6645961B1 (en) 1997-03-07 2003-11-11 Merck & Co., Inc. Dry granulation formulation for an HIV protease inhibitor
US6436989B1 (en) 1997-12-24 2002-08-20 Vertex Pharmaceuticals, Incorporated Prodrugs of aspartyl protease inhibitors
CA2331756A1 (en) * 1998-05-15 1999-11-25 Abbott Laboratories Retroviral protease inhibiting compounds
US6251906B1 (en) 1998-05-15 2001-06-26 Abbott Laboratories Retroviral protease inhibiting compounds
OA11573A (en) 1998-06-19 2004-07-01 Vertex Pharma Sulfonamide inhibitors of aspartyl protease.
EP1095022A1 (en) 1998-07-08 2001-05-02 G.D. Searle & Co. Retroviral protease inhibitors
WO2000048466A2 (en) * 1999-02-19 2000-08-24 Oklahoma Medical Research Foundation Protease inhibitors that overcome drug resistance
ES2295068T3 (es) 1999-11-24 2008-04-16 MERCK & CO., INC. Gamma-hidroxi-2-(fluoroalquilaminocarbonil)-1-piperazinpentanamidas como inhibidores de la proteasa del vih.
DE60038899D1 (de) * 2000-01-19 2008-06-26 Abbott Lab Hiv-proteasehemmern
BR0213138A (pt) * 2001-10-05 2004-08-24 Elan Pharm Inc Métodos de tratar ou prevenir mal de alzheimer e uma doença distinguida por depósito de beta-amilóide no cérebro, de tratar um paciente que tenha, ou de prevenir um paciente de contrair uma doença ou condição, de produzir um complexo de beta-secretase e de inibir a produção de placa beta-amilóide em um animal, composição e uso de um composto
IL163666A0 (en) 2002-02-22 2005-12-18 New River Pharmaceuticals Inc Active agent delivery systems and methods for protecting and administering active agents
US7037913B2 (en) * 2002-05-01 2006-05-02 Bristol-Myers Squibb Company Bicyclo 4.4.0 antiviral derivatives
JP5448854B2 (ja) 2007-03-12 2014-03-19 ウェルズ ファーゴ バンク ナショナル アソシエイション オリゴマー−プロテアーゼ阻害剤複合体
US9095620B2 (en) 2008-03-12 2015-08-04 Nektar Therapeutics Reagents
US20120108501A1 (en) 2009-06-12 2012-05-03 Nektar Therapeutics Protease Inhibitors
WO2015013835A1 (en) 2013-07-31 2015-02-05 Merck Sharp & Dohme Corp. Piperazine derivatives as hiv protease inhibitors
CN107074904B (zh) 2014-10-23 2022-12-23 深圳华大智造科技股份有限公司 信号约束测序(scs)和用于信号约束测序的核苷酸类似物
WO2021209563A1 (en) 2020-04-16 2021-10-21 Som Innovation Biotech, S.A. Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8927913D0 (en) * 1989-12-11 1990-02-14 Hoffmann La Roche Amino acid derivatives
CA2032259A1 (en) * 1989-12-18 1991-06-19 Wayne J. Thompson Hiv protease inhibitors useful for the treatment of aids

Also Published As

Publication number Publication date
HK1006060A1 (en) 2003-07-10
NO941696D0 (no) 1994-05-06
SK52394A3 (en) 1995-02-08
GR3026334T3 (en) 1998-06-30
HU220866B1 (en) 2002-06-29
CA2195027A1 (en) 1993-05-09
CY2090B1 (en) 2002-04-05
DE69224703T2 (de) 1998-10-15
BG98745A (bg) 1995-03-31
RO115726B1 (ro) 2000-05-30
CA2195027C (en) 2000-01-11
LV12208A (lv) 1999-01-20
FI106025B (fi) 2000-11-15
AU2819992A (en) 1993-05-13
FI981591A (fi) 1998-07-10
AU659234B2 (en) 1995-05-11
HU9401424D0 (en) 1994-08-29
NO941696L (lv) 1994-06-24
EP0541168A1 (en) 1993-05-12
EP0541168B1 (en) 1998-03-11
UA45945C2 (uk) 2002-05-15
CZ287610B6 (cs) 2001-01-17
WO1993009096A1 (en) 1993-05-13
JPH0733373B2 (ja) 1995-04-12
JPH05279337A (ja) 1993-10-26
FI981591A0 (fi) 1992-11-03
PL171340B1 (pl) 1997-04-30
ATE163926T1 (de) 1998-03-15
HUT70519A (en) 1995-10-30
SG52731A1 (en) 1998-09-28
NZ244986A (en) 1995-10-26
ES2112880T3 (es) 1998-04-16
BG61725B1 (bg) 1998-04-30
CA2081970A1 (en) 1993-05-09
CZ111094A3 (en) 1995-03-15
IL103613A (en) 1999-05-09
CA2081970C (en) 1997-07-08
FI942112A0 (fi) 1994-05-06
FI942112A (fi) 1994-05-06
NO303383B1 (no) 1998-07-06
DE69224703D1 (de) 1998-04-16
KR100273623B1 (ko) 2000-12-15
IL103613A0 (en) 1993-04-04
SK281864B6 (sk) 2001-08-06
RU2131416C1 (ru) 1999-06-10
DK0541168T3 (da) 1998-05-11

Similar Documents

Publication Publication Date Title
EP0541168B1 (en) HIV protease inhibitors useful for the treatment of aids
EP0539192B1 (en) HIV Protease inhibitors
AU676563B2 (en) HIV protease inhibitors useful for the treatment of AIDS
WO1994022480A1 (en) Hiv protease inhibitors in pharmaceutical combinations for the treatment of aids
AU691941B2 (en) New HIV protease inhibitors
EP0550924A1 (en) 2-Pyrrolidinone derivatives as HIV protease inhibitors
NZ269904A (en) 1,3-oxazole derivatives; preparative process; intermediate compounds
RU2171254C2 (ru) Способ получения производных пиперазинилпентанамида и производное пиперазинилпентанамида
GB2288801A (en) HIV protease inhibitors useful for the treatment of aids
JPH05271187A (ja) ピロリジン誘導体又はその薬学的に許容される塩