ZA200106592B - Functionalized heterocycles as chemokine receptor modulators. - Google Patents
Functionalized heterocycles as chemokine receptor modulators. Download PDFInfo
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- ZA200106592B ZA200106592B ZA200106592A ZA200106592A ZA200106592B ZA 200106592 B ZA200106592 B ZA 200106592B ZA 200106592 A ZA200106592 A ZA 200106592A ZA 200106592 A ZA200106592 A ZA 200106592A ZA 200106592 B ZA200106592 B ZA 200106592B
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- South Africa
- Prior art keywords
- methyl
- decahydro
- quinolizine
- pyrrolo
- carboxylic acid
- Prior art date
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- 102000009410 Chemokine receptor Human genes 0.000 title claims description 10
- 108050000299 Chemokine receptor Proteins 0.000 title claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 title description 4
- -1 2-methylpropyl ester Chemical class 0.000 claims description 184
- 150000002148 esters Chemical class 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000004494 ethyl ester group Chemical group 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 10
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 10
- QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 150000004702 methyl esters Chemical class 0.000 claims description 10
- 229950004354 phosphorylcholine Drugs 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
- 208000030507 AIDS Diseases 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- WQJFIWXYPKYBTO-UHFFFAOYSA-N indole-1-acetic acid Chemical compound C1=CC=C2N(CC(=O)O)C=CC2=C1 WQJFIWXYPKYBTO-UHFFFAOYSA-N 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 5
- GUOHRXPYGSKUGT-UHFFFAOYSA-N quinolizinium Chemical compound C1=CC=CC2=CC=CC=[N+]21 GUOHRXPYGSKUGT-UHFFFAOYSA-N 0.000 claims description 5
- WBVHKJQWPYVDGG-UHFFFAOYSA-N 2-oxa-7,17-diazapentacyclo[11.8.0.01,17.03,11.06,10]henicosa-3,5,7,9,11,13,15,18,20-nonaene-9-carboxylic acid Chemical compound C1=CC=CN2C=CC=C(C=C34)C21OC4=CC=C1C3=C(C(=O)O)C=N1 WBVHKJQWPYVDGG-UHFFFAOYSA-N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- NFGMWAKGHQALBE-KVGGNSOTSA-N (4-nitrophenyl)methyl (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-3-[(3s,5s)-1-[(4-nitrophenyl)methoxycarbonyl]-5-[(sulfamoylamino)methyl]pyrrolidin-3-yl]sulfanyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound N1([C@H](CNS(N)(=O)=O)C[C@@H](C1)SC=1[C@H](C)[C@@H]2[C@H](C(N2C=1C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)=O)[C@H](O)C)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 NFGMWAKGHQALBE-KVGGNSOTSA-N 0.000 claims description 2
- WXAVSTZWKNIWCN-UHFFFAOYSA-N 1-(1-phenylethoxy)ethylbenzene Chemical compound C=1C=CC=CC=1C(C)OC(C)C1=CC=CC=C1 WXAVSTZWKNIWCN-UHFFFAOYSA-N 0.000 claims description 2
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims description 2
- UQDJZUOBEZNCRM-UHFFFAOYSA-N C(C)OC(=O)C1=C(NC=2C1=C1CC3CCCN(C3(OC1=CC2)C)CC2=CC=CC=C2)C Chemical compound C(C)OC(=O)C1=C(NC=2C1=C1CC3CCCN(C3(OC1=CC2)C)CC2=CC=CC=C2)C UQDJZUOBEZNCRM-UHFFFAOYSA-N 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- QSSJZLPUHJDYKF-UHFFFAOYSA-N methyl 4-methylbenzoate Chemical group COC(=O)C1=CC=C(C)C=C1 QSSJZLPUHJDYKF-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- MDHYEMXUFSJLGV-UHFFFAOYSA-N phenethyl acetate Chemical compound CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 claims description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- SERVTOXIOYSDQO-UHFFFAOYSA-N 2h-chromen-2-ol Chemical compound C1=CC=C2C=CC(O)OC2=C1 SERVTOXIOYSDQO-UHFFFAOYSA-N 0.000 claims 1
- 125000002471 4H-quinolizinyl group Chemical class C=1(C=CCN2C=CC=CC12)* 0.000 claims 1
- 239000005711 Benzoic acid Substances 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 101150047356 dec-1 gene Proteins 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- QXOKHIVHFRAHMT-UHFFFAOYSA-N ethyl 2-oxa-4,14-diazatetracyclo[8.7.0.03,8.011,15]heptadeca-1(17),3(8),4,6,9,11,13,15-octaene-12-carboxylate Chemical compound C(C)OC(=O)C=1C=NC=2C=1C1=CC3=CC=CN=C3OC1=CC=2 QXOKHIVHFRAHMT-UHFFFAOYSA-N 0.000 claims 1
- XBMIIVQPAWWEQI-UHFFFAOYSA-N ethyl 3,4,13-trimethyl-2-oxa-4,14-diazatetracyclo[8.7.0.03,8.011,15]heptadeca-1(10),11(15),12,16-tetraene-12-carboxylate Chemical compound C1C2=C3C(C(=O)OCC)=C(C)NC3=CC=C2OC2(C)C1CCCN2C XBMIIVQPAWWEQI-UHFFFAOYSA-N 0.000 claims 1
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 7
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 6
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 2
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 2
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 2
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 2
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 2
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 2
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 2
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 2
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 2
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 2
- 101710082514 C-X-C chemokine receptor type 3 Proteins 0.000 description 2
- 101710082513 C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- 102000001327 Chemokine CCL5 Human genes 0.000 description 2
- 108010055166 Chemokine CCL5 Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 108700011778 CCR5 Proteins 0.000 description 1
- 102000004274 CCR5 Receptors Human genes 0.000 description 1
- 108010017088 CCR5 Receptors Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- RINFBAICZVKAOL-UHFFFAOYSA-N ethyl 3,4-diethyl-13-methyl-2-oxa-4,14-diazatetracyclo[8.7.0.03,8.011,15]heptadeca-1(10),11(15),12,16-tetraene-12-carboxylate Chemical compound C1C2=C3C(C(=O)OCC)=C(C)NC3=CC=C2OC2(CC)C1CCCN2CC RINFBAICZVKAOL-UHFFFAOYSA-N 0.000 description 1
- OXXIGOWSWOSXFB-UHFFFAOYSA-N ethyl 3-ethyl-4,13-dimethyl-2-oxa-4,14-diazatetracyclo[8.7.0.03,8.011,15]heptadeca-1(10),11(15),12,16-tetraene-12-carboxylate Chemical compound C1C2=C3C(C(=O)OCC)=C(C)NC3=CC=C2OC2(CC)C1CCCN2C OXXIGOWSWOSXFB-UHFFFAOYSA-N 0.000 description 1
- KKOTWZVRVQPLDT-UHFFFAOYSA-N ethyl 6h-indolo[4,5-g]quinoline-1-carboxylate Chemical compound C1=CC=C2C=C3C4=C(C(=O)OCC)C=NC4=CC=C3CC2=N1 KKOTWZVRVQPLDT-UHFFFAOYSA-N 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/02—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing not further condensed quinolizine ring systems
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
FUNCTIONALIZED HETEROCYCLES AS CHEMOKINE
RECEPTOR MODULATORS
The present invention relates to functionalized heterocycles useful as modulators of the chemokine receptors, including CCR-1, CCR-2, CCR-2A,
CCR-2B, CCR-3, CCR-4, CCR-5, CXCR1, CXCR2, CXCR-3, and/or CXCR4 and to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier. More particularly, the present invention is directed to methods for inhibiting HIV infectivity.
Chemokines mediate a range of proinflammatory effects on leukocytes, such as chemotaxis, degranulation, and intigran activation (Baggiolini et al., Adv.
Immunol, 1994;55:97-179; Oppenheim et al., Annu. Rev. Immunol., 1991; 9:617-48; Miller et al., Crit. Rev. Immunol., 1992;12:17-46). These effects are mediated by binding to the seven-transmembrane-spanning G-protein coupled receptors (Baggiolini et al., Adv. Immunol., 1994;55:97-179; Murphy, Annu. Rev.
Immunol., 1994;12:593-633; Schall et al., Cur Opin. Immunol., 1994;6:865-73;
Gerard et al., Curr. Opin. Immunol. 1994;6;140-5; Mackay, Curr. Bio., In press).
Chemokine receptors also serve as coreceptors for HIV-1 entry into cells. This came from observations that RANTES, MIP-1q, and MIP-1f suppressed infection of susceptible cells in vitro by macrophage-tropic primary HIV-1 isolates (Cocchi et al., Science (Wash. DC), 1995:270:181 1-5). The chemokine receptor
CXCR-4 was found to support infection and cell fusion of CD4% cells by laboratory-adapted, T-tropic HIV-1 strains (Feng et al., Science (Wash. DC), 1996;272:872-7). CCR-5, a RANTES, MIP-1qa, and MIP-1p receptor, was subsequently identified as the principle coreceptor for primary macrophage-tropic strains (Choe et al, Cell, 1996;85:1135-48; Alkhatib et al., Science (Wash. DC), 1996;272:1955-8; Doranz et al., Cell, 1996;85:1149-58; Deng et al., Nature (Lond) 1996;381:661-6; Dragic et al., Nature (Lond), 1996;381:667-3). The importance of CCR-5 for HIV-1 transmission was underscored by the observation that certain individuals who had been repeatedly exposed to HIV-1 but remained uninfected had a defect in CCR-5 expression (Liu et al., Cell, 1996; 86:367-77;
Samson et al., Nature (Lond), 1996;382:722-5; Dean et al., Science (Wash. DC), 1996,273:1856-62; Huang et al., Nature Med., 1996;2:1240-3). These noninfectable individuals were found to be homozygous for a defective CCR-5 allele that contains an internal 32-base pair deletion (CCR-5 A32). The truncated protein encoded by this gene is apparently not expressed at the cell surface.
CCR-5 A32 homozygous individuals comprise ~1% of the Caucasian population and heterozygous individuals comprise ~20%. In studies of about 2700 HIV-1 infected individuals, no A32 homozygotes were found. Individuals who are heterozygous for A32 CCR-5 allele have been shown to progress more slowly to
AIDS than wild-type homozygous individuals (Samson et al., Nature (Lond.), 1996;382:722-5; Dean et al., Science (Wash. DC), 1996;273:1856-62;
Huang et al., Nature Med., 1996;2:1240-3). Thus, the identity of CCR-S5 as the principle coreceptor for primary HIV isolates provides an opportunity to understand disease pathogenesis, and more importantly to identify a new avenue for the treatment of HIV-1 infection. : The instant invention is a series of functionalized heterocycles that block the CD-4/GP-120 interaction with CCR-5 receptor, and thus can be useful in the treatment of HIV infection manifested in AIDS.
The compounds of the invention are useful in a method of modulating chemokine receptor activity in a patient in need of such modulation comprising the administration of an effective amount of the compound.
The present invention is directed to the usc of the foregoing substituted heterocycles as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors, including
CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, CXCR1,
CXCR2, and/or CXCR-4. In particular, the compounds of the present invention are preferred as modulators of the chemokine receptor CCR-5.
The compounds of the instant invention are those of Formula I which may exist in both closed and open form.
Rg Rg chy), cH, ne R43 O _Y 2S R3\ OQ) v
LX | X /
R, Z A rR, z= 4 ring close I ring open or a pharmaceutically acceptable salt thereof wherein:
Ais 0, S, and additionally A is NR| when X is C-Rg;
X1s N when A is NR} or
X 1s C-Rg wherein Ry is halogen, hydrogen, alkyl, -CF3, CHyF, CHF», -(CH2)m-ORy, aryl, arylalkyl, -(CH2),-NR7Rg, or
CH), (CH2)q wherein m is an integer of from 0 to 2 and each occurrence of m is independently an integer of from 0 to 2, q is an integer of from Oto 1, and ris an integer of from 0 to 3;
Y 1s hydrogen, alkyl, arylalkyl, aryl, (CHp),-NR7Rg, -N(R{)-(CH»)y-
C(R7Rg)-aryl, or OR |g wherein Rg 1s hydrogen, alkyl, cycloalkyl, cycloalkyl fuscd to an aryl ring, aryl, (CHp)saryl, -CHCF3, (CH) C(R7Rg)-(CH)), aryl, 0
R R 1
Nail NR,Rg mt OR,
Aryl Any . 0
R n"
PO k% Aryl
R R
NFP NR;Rg NC COR
Y alkyl ye alkyl 0)
R I
Ndi C—NR4Rg ko alkyl 0
Ry — NR-R R —C—OR
Nm 788 Nm c 7 hy cycloalkyl k% cycloalkyl 0]
R I
Cm ENR NC wr cycloalkyl % cCly
Hoy WX \
YW Sc=N, % Sc=cH, 0) , or
N
~
ET Jew, wherein s is an integer of from 1 to 3, tis an integer of from 0 to 3, u is an integer of from 0 to 3, vis an integer of from 1 to 3, and w is an integer of from 0 to 2;
ZisCRorN;
R; 1s hydrogen or alkyl and each occurrence of Rj is independently hydrogen or alkyl;
R and Rj are each independently sclected from: hydrogen, alkyl, halogen, -CN, -NO3», -(CH2);-NR7Rg,
-(CH2)m-COOR7, -(CH2)m-CONR7Rg, 0
EN
CHYZ NT DR,
Oo
I
-(CH)mN-S-R7,
I
0 -(CH2)m-OR7, -(CH3);-SO2NR~Rg, and -(CH2)m-S(O)pR7 wherein each occurrence of R7 and Rg are each independently hydrogen, alkyl, aryl, arylalkyl, -CF3, or Ry and Rg may be taken together to form a cyclic ring of from 3 to 7 atoms which ring may have O, S, or NR] and p is an : 15 integer of from 0 to 2;
R13 1s hydrogen or alkyl;
Rg 1s hydrogen, alkyl, aryl, or aralkyl,
Rs is alkyl, aryl, arylalkyl, acyl; or
R4 and Rg are taken together with the atoms to which they are attached to form a cyclic ring of from 5 to 7 atoms;
Rg 1s hydrogen or alkyl;
R 5 when not taken together with Ry can be taken together with Rg with the atoms to which they are attached to form a ring of from 5 to 7 atoms;
N-Rj is also the corresponding N-oxide,
R11 1s hydrogen or alkyl; nis an integer of from 1 to 3;
J is an integer of from 1 to 2, and j is the integer 0 when Y is hydrogen, alkyl, arylalkyl, or aryl;
with the proviso that pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1- carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, ethyl ester is not included.
Preferred compounds are those of Formula 1 above wherein
Rj is hydrogen.
Other preferred compounds are those of Formula 1 above wherein
Rj is hydrogen and
X is C-Rg.
Still other preferred compounds are those wherein
Rj is hydrogen and
X is C-Rg, wherein Rg is alkyl.
Still other preferred compounds are those wherein
Rj is hydrogen,
X is C-Rg, wherein Rg is alkyl;
R4 and Rs are taken together with the atoms to which they are - attached to form a ring of from 5-7 atoms; and
Y is ORjg.
Still other preferred compounds are those wherein
Rj is hydrogen,
X is C-Rg, wherein Rg is alkyl;
R4 and Rs are taken together to form a 6-membered ring; and
Y is OR wherein R| is alkyl, aryl or (CHp)aryl, -(CH2)t-C(R7Rg)-(CHp)y-aryl.
Still other preferred compounds are those wherein
Rj is hydrogen,
X is C-Rg, wherein Rg is Me;
R4 and Rj are taken together to form a 6-membered ring;
Rg is hydrogen; : nis 2; and
Y is OR} wherein Rj is alkyl, aryl or Ry is -(CH3){-C(R7Rg)- (CHp)y-aryl wherein tis 0, R7 and Rg can each independently be
H, alkyl, -(CH2)yOH or (CH3),,COOR?7, and -(CH3) NR R, where u and v are as defined above.
More preferred compounds are those of Formula 1 and selected from:
Pyrrolo[3°,27:5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,144a,15-decahydro-2-methyl-, methyl ester;
Pyrrolo[3°,27:5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 5-bromo-3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester;
Pyrrolo[3°,2”:5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, propyl ester;
Pyrrolo[3°,2":5,6][1]benzopyrano[3,2-iJquinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-methylpropyl ester;
Pyrrolo[3°,2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2-dimcthylpropyl ester;
Pyrrolo[3°,27:5,6}{ 1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, phenylmethyl cster;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, I-methylethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, cyclopropylmethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(1 -piperidinyl)ethyl ester;
Pyrrolo[3°,27:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-(phenylmethyl)-, ethyl ester;
Pyrrolo[3°,2":5,6](1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 2- ethyl-3,7,8,9,10,12,13,14,14a,15-decahydro-, ethyl ester;
Pyrrolo[3°,27:5,6][1]benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 2- cyclopropyl-3,7,8,9,10,12,13,14,14a,15-decahydro-, ethyl ester;
Pyrrolo[3°,2°:5,6][ 1]benzopyrano|3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-propyl-, ethyl ester;
Pyrrolo[3°,2’:5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,144a,15-decahydro-2-(2-methylpropyl)-, ethyl ester;
Pyrrolo[3°,2’:5,6][ 1 Jbenzopyrano[3,2-i}quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,1-dimethylethyl ester; 2,6a,7-Trimethyl-7,8,9,10,10a,11 -hexahydro-3H,6aH-6-0xa-3,7-diaza- cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; 7-Ethyl-2,6a-dimethyl-7,8,9,10,10a,1 1-hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[ajanthracene-1-carboxylic acid ethyl ester; 6a-Ethyl-2,7-dimethyl-7,8,9,10,10a,1 1-hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; 6a,7-Diethyl-2-methyl-7,8,9,10,10a,1 1-hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; 7-Benzyl-2,6a-dimethyl-7,8,9,10,10a,1 1-hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; 2,7-Dimethyl-6a-phenyl-7,8,9,10,10a,11-hexahydro-3H,6aH-6-oxa- : 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester;
Pyrrolo[3°,2°:5,6][ 1]Jbenzopyrano(3,2-eJindole-1-carboxylic acid, ; 20 8,9,1 1,12,13,13a,14,14a-octahydro-2-methyl-, ethyl ester; 3H,7H-Pyrrolizino[1',8':5,6]pyrano[3,2-e]indole- 1 -acetic acid, 8,9,11,12,12a,13-hexahydro-2-methyl-, ethyl ester; 2-Methyl-8,9,10,10a,11,12, 12a,13-octahydro-3H,6aH,7H-6-0xa-3,6b- diaza-benzo[a]cyclopenta[h}anthracene-1-carboxylic acid ethyl ester; 3H-Pyrido[1",2":1'2"Jazepino[3'2":5,6]pyrano[3,2-¢e]indole-1-acetic acid, 7.8,9,10,12,13,14,15,15a,16-decahydro-2-methyl-, ethyl ester or 7H-Azepino[1",2"":1'2']pyrido[3’,2":5,6]pyrano[3,2-¢)indole-1-acetic acid, 3,8,9,10,11,13,14,15,152a,1 6-decahydro-2-methyl-, ethyl ester;
Pyrrolo[3°,27:5,6][ 1 )benzopyrano[3,2-iJquinolizine- I -carboxamide, 8,9,11,12,13,13a,14,14a-octahydro-2-methyl-N-(phenylmethy!)-;
Pyrrolo[3°,2°:5,6][1]benzopyranof3,2-i]quinolizine-1-carboxamide, N- ethyl-8,9,11,12,13,13a,14,1 4a-octahydro-2-methyl-;
Pyrrolo[3°,2’:5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxaldehyde, 8,9,11,12,13,13a,14,14a-octahydro-2-methyl-;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1- carboxamide, 8,9,11,12,13,13a,14,1 4a-octahydro-N,2-dimethy]-;
Pyrrolo[3°,2’ :5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 8,9,11,12,13,13a,14,14a-octahydro-2-methyl-, (4-fluorophenyl)-methyl ester;
Indazolo[4',5':5,6]pyrano[3,2-/]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester,
Pyrrolo[3',2":5,6][ 1]benzopyrano|3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,12,12-trimethyl-, phenylmethyl ester,
Pyrrolo[3',2"5,6][1 Jbenzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,10,10-trimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine- 1-carboxylic acid, 5-fluoro-3,7,8,9,10,12,13,14, 14a, 15-decahydro-2-methyl-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine- 1-carboxylic acid,
S-fluoro-3,7,8,9,10,12,13,14, 14a,15-decahydro-2-methyl-, phenylmethyl ester; 12H-Furo[3',2":5,6][ 1]benzopyrano(3,2-iJquinolizine-1 -carboxylic acid, 5-fluoro-7,8,9,10,13,14, 14a, 15-octahydro-2-methyl-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 4,5-difluoro-3,7,8,9,10,12,13,14, 14a,15-decahydro-2-methyl-, phenylmethyl ester:
Pyrrolo[3',2":5,6]{1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 4,5-dichloro-3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, phenylmethyl ester;
Pyrrolo[3'.2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-4,5-dimethoxy-2-methyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14, 14a,15-decahydro-2,5-dimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a, 15-decahydro-2,4-dimethyl-, phenylmethyl ester;
Pyrrolo[3',2':5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2,4-dimethyl-, 1 -(4-fluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3- (methoxycarbonyl)phenyl]ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(3-carboxyphenyl)ethyl ester; 1-Propanaminium, N,N,N-trimethyl-, salt with 1-(3-carboxyphenyl)ethyl 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-pyrrolo[3 2"5,6)(1]- benzopyrano[3,2-i]quinolizine-1-carboxylatc (1:1);
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (3-nitrophenyl)methyl ester; } Pyrrolo[3',2":5,6]1 Jbenzopyrano([3,2-i]quinolizine-1-carboxylic acid, : 15 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(3-cyanophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, : x 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3-[(dimethylamino)carbonyl]phenyl]jethyl ester;
Pyrrolo(3',2":5,6][1]benzopyrano[3,2-i]quinolizinc- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3-[(dimethylamino)methyl]- : phenyl]ethyl ester;
Pyrrolo[3°,2":5,6](1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,1 »13,14,14a,15-decahydro-2-methyl-,2-phenylethyl ester;
Pyrrolo[3°,2’:5,6][ 1Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [4-(methoxycarbonyl)phenyl]- methyl ester;
Pyrrolof3°,2’:5,6][1 Jbenzopyrano[3,2-ijquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2,-methyi-, (4-carboxyphenyl)methyl ester; 1-[3-(4-Carboxy-benzyloxycarbonyl)-5 -hydroxy-2-methyl-1H-indol- 4-ylmethyl}-1,2,3,4,6,7,8,9-octahydro-quinolizinylium; chloride;
Pyrrolo[3°,2°:5,6][1 Jbenzopyrano[3,2-iJquinolizine-1-carbox ylic acid, 3,7.8,9,10,12,13,14,14a, 15-decahydro-2-methyl-, [4-(hydroxymethyl)phenyl]- methyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano(3,2-i]quinolizine-2-carboxylic acid, 3,78,9,10,12,1 3,14,14a,15-decahydro-2-methyl-, 2-naphthalenylmethyl ester;
Pyrrolo(3°,2°:5,6][ 1]benzopyrano(3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [3-(methoxycarbonyl)phenyl]- methyl ester;
Pyrrolo[3°,2’:5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [3-(hydroxymethyl)phenyl]- methyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (3-carboxyphenyl)mcthy! ester);
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (3-carboxypheny)- methyl 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methylpyrrolo[3°,2":5,6][1]- benzopyrano[3,2-iJquinolizine-1-carboxylatc (1:1 );
Pyrrolo[3°,2:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [3-[(dimethylamino)methyl]- phenyljmethyl ester;
Pyrrolo[3’,2":5,6]( 1}benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [3-[(dimethylamino)carbonyl]- phenyl]methyl ester; } 20 Pytrolo[3°,2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (2-(4-morpholinyl)ethyl ester;
Pyrrolo[3’,2’:5,6)[ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[1,1°-biphenyl}-4-ylethyl ester;
Pyrrolo[3,2”:5,6][1]benzopyranol3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12.1 3,14,14a,15-decahydro-2-methyl-, (2,6-difluorophenyl)methy! ester;
Pyrrolo[3°,2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1 -phenyl-2,2,2-trifluoro)ethy] ester;
Pyrrolo[3°,2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3.7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3-(trifluoromethyl)phenyl]- ethyl ester;
Pyrmolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(dimethylamino)ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(1 -pyrrolidinyl)ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-( 1-naphthalenyl)ethyl ester;
Pyrrolo[3°,2’:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1 -phenylcyclobutyl ester;
Pyrrolo[3°,2":5,6][1]benzopyrano[3,2-ijquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylcylopropyl ester;
Pyrrolo[3°,2°:5,6][ 1 Jbenzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-pyrazinylethyl cster;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, . 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-quinolinyl)ethy! ester;
Pyrrolo[3°,2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2-pyrimidinyl)ethyl ester;
Pyrrolo[3 *,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1 carboxylic acid, 5-chloro-3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, phenylmethyl ester;
Pyrrolo[3°,2°:5,6][ 1]benzopyrano([3,2-i]quinolizine-1-carboxylic acid, 5-chloro-3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl, 1 -(4-fluorophenyl)ethyl oe ester;
Quinolizinium, 1-[[(4-fluorophenyl)methoxy]carbonyl]-5-hydroxy- 2-methyl-1H-indol-4-yllmethyl]-1,2,3,4,6,7,8,9-octahydro-, chloride;
Pyrrolo[3°,2’:5,6](1]benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-1,2-dimethyl-, (4-fluorophenyl)methyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-mcthyl-, 1-phenylpropyl ester;
Quinolizinium, 1,2,3,4,6,7,8,9-octahydro-1-[[5-hydrox y-2-methyl- 3-[(phenylmethoxy)carbonyl}-1H-indol-4-yl}methyl}-, chloride;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (4-nitrophenyl)methyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano|3,2-i]quinolizine--carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1R)-1-phenylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano|3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-fluorophenyl)ethyl ester;
Pyrrolo(3',2":5,6][ 1]benzopyrano(3,2-i}quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, phenyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano|3,2-i]quinolizine- 1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trifluoro- 1 -phenyl- 1-(trifluoromethyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, bicyclo[2.2.1]hept-2-yl ester;
Pyrrolo[3',2":5,6][ 1]bcnzopyrano(3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(4-fluorophenyl)- 1-methylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylcyclopentyl ester;
Pyrrolo[3',2":5,6][1]}benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylcyclohexyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-(hydroxymethyl)phenyl ester;
Pyrrolo[3',2":5,6][1 Jhenzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (3-hydroxyphenyl)methyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)-1-(4-pyndinyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i}quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (6-(methoxycarbonyl)- 2-pyridinylJmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-pyridinylmethyl ester;
Pyrrolo(3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine- I -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (6-carboxy-2-pyridinyl)methyl ester;
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (6-carboxy- 2-pyridinyl)methyl 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2- : methylpyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1-carbox ylate (1:1);
Pyrrolo[3',2":5,6])[ 1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [5-(methoxycarbonyl)- 3-pyridinyl]methyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (5-carboxy-3-pyridinyl)methyl ester,
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (5-carboxy- 3-pyridinyl)methyl 3,7,8,9,10,12,13,14,14a,15-decahydro-2- methylpyrrolo[3',2':5,6](1]benzopyrano[3,2-ijquinolizine-1 -carboxylate (1:1);
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1 -(4'-methyl[1,1'-biphenyl]- 3-yDethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, ; 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2,6-dimethylphenyl)ethyl . ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (18,2R)-2-(dimethylamino)-
I-phenylpropyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]Jquinolizine-1 -carboxylic acid, 3,7,8,9.10,12,13,14,14a,15-decahydro-2-methyl-, (1R,2S)-2-(dimethylamino)- } 1-phenylpropy] ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,1 4a,15-decahydro-2-methyl-, I-naphthaleny! ester;
Pyrrolo[3',2":5,6](1]benzopyrano[3,2-i]quinolizine-1 ~carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, diphenylmethyl ester;
Pymrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1R)-2,3-dihydro-1H-inden-1-yl ester;
Pyrrolo[3,2":5,6][ 1 ]Jbenzopyrano[3,2-ijquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1,2-dihydro-1-acenaphthylenyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, cyclohexyl(phenyl)methyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 9H-fluoren-9-yl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,2,3,4-tetrahydro-
I-naphthalenyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [(2R,3R)- 3-phenyloxiranyl]methyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano|[3,2-1]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,144,15-decahydro-2-methyl-, 2-oxo-1,2-diphenylethy] ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-1]quinolizine- 1 -carboxylic acid, 3,7,8.9,10,12,13,14,14a,15-decahydro-2-methyl-, 10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5-yl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (2-methylphenyl)phenylmethy! a ester;
Pyrrolo[3',2":5,6](1]benzopyrano|3,2-i)quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, cyclopropyl(4-fluorophenyl)methyl ester;
Pyrrolo[3',2"5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3,4-dihydro-2H-
I-benzothiopyran-4-yl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- I -carbox ylic acid, 3,7.8,9,10,12,13,14,14a,15-dccahydro-2-methyl-, (1S)-1-(2-bromophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trifluoroethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [(2S,3S5)- 3-phenyloxiranyl]methyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trifluoro-1 -methyl- 1-(trifluoromethyl)ethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,1 3,14,14a,15-decahydro-2-methyl-, 2.,2,2-trifluoro- 1-(4-fluorophenyl)-1-(trifluoromethyl)ethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-ilquinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-cyclopentyl-1-phenylethyl ester;
Pyrrolo[3',2":5,6][ 1 ]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-[1,1 "-biphenyl]-4-yl-
I-methylethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-iJquinolizine-1-carboxylic acid, : 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-methyl-1 -phenyl-2-propynyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,1-diphenylethyl ester;
Pyrrolo[3',2":5,6](1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1 -methyl-1,2-diphenylethyl ester;
Pyrrolo[3',2":5,6][ 1 ]benzopyrano[3,2-i}quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(4-fluorophenyl)cyclohexyl ester;
Pyrrolo[3',2"5,6][1 Jbenzopyrano(3,2-i}quinolizine-1 carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,2-diphenylethyl ester;
Pyrrolof3',2":5,6][1 Jbenzopyrano[3,2-ilquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-phenyl-2-propynyl ester;
Pyrrolo[3,2":5,6][1 Joenzopyranof3,2-i]quinclizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, [1,1 "-biphenyl]-4-ylmethyl ester;
Pyrrolof3',2"5,6][1]benzopyrano|3,2-ijquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,144a,15-decahydro-2-methyl-, 4-pyridinylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i)quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,2,3,4-tetrahydro- 7,8-dimethoxy-2-methyl-4-isoquinolinyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3-(dimethylamino)phenyl]- ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,1-dimethyl-2-pyrazinylethyl ester;
Pyrrolo[3',2":5,6][ 1 ]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 4-(dipropylamino)- 1,1-dimethyl-2-butynyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methy}-, (1S)-2,3-dihydro-1H-inden-1-y! cster;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (18,2S)-2-(dimethylamino)- 1-phenylpropyl ester;
Pyrrolo[3',2"5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [4-(trifluoromethyl)phenyl]- methyl ester;
Pyrrolo[3',2"5,6][1]benzopyrano[3,2-ilquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (4-chlorophenyl)methyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-ijquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,1 3,14,14a,15-decahydro-2-methyl-, 2-hydroxyethyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,144,1 5-decahydro-2-methyl-, (3-methylphenyl)mcthyl ester;
Pyrrolo(3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)-1 -phenylethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine- 1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylethyl ester;
Pyrrolo[3',2":5,6][ 1 ]benzopyrano[3,2-i]quinolizine-1-carbothioic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, S-(phenylmethyl) ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i)quinolizine-1 carboxylic acid, 3,7.8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 3-pyridinylmethy] ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i)quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[4-(trifluoromethyl)phenyl]- ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(pentafluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1)benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2,6-difluorophenyl)ethyl p ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine- 1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)-1-(2-furanyl)ethyl este;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i}quinolizine-1 -carboxylic acid, 3,7.8,9,10,12,13,14,143,1 S-decahydro-2-methyl-, 2-(4-morpholinyl)- 1-phenylethyl ester;
Pyrrolo[3',2":5,6][ 1]Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1 R)-1-(2-furanyl)ethyl ester;
Pyrrolo[3',2":5,6][1]Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-methoxy-2-oxo-1-phenylethyl ester;
Pyrrolo[3',2":5,6](1]benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, | -(3-pyridinyl)ethyl ester;
Pyrrolo[3',2':5,6][1]benzopyranol3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (S)-carboxy(phenyl)methyl ester;
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (S)- carboxy(phenyl)methyl, 3,7,8,9,10,12,13,14,14a,15-decahydro-2- methylpyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylate (1:1);
Pyrrolo[3',2':5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1R)-2-methoxy-2-0xo- 1-phenylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano([3,2-i]quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (R)-carboxy(phenyl)methyl ester;
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (R)- carboxy(phenyl)methyl, 3,7,8,9,10,12,13,14,14a,15-decahydro- 2-methylpyrrolo[3',2":5,6][ 1 ]benzopyrano[3,2-i)quinolizine-1-carboxylate (1:1);
Pyrrolof3',2":5,6][1 Jbenzopyrano[3,2-i}quinolizine- | -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 4-pyridinylmcthy! ester;
Pyrrolo[3',2":5,6][1]benzopyrano[ 3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-pyridinyl)ethy! ester;
Pyrrolo[3',2":5,6){ 1]bcnzopyrano[3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2-pyridinyl)ethyi ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-thienylmethyl ester;
Pyrrolo[3',2"5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)-1-(4-fluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1R)-1-(4-fluorophenyl)ethyl ester,
Pyrrolo(3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-pyridinylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-dccahydro-2-methyl-, 2-ethoxy-2-oxoethyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 3-furanylmethyl ester;
~-20-
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (2-nitrophenyl)methyi ester;
Pyrrolo[3',2:5,6]( 1]Jbenzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-furanylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1 -(2-chlorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, carboxymcthyl ester;
Pyrrolo{3',2':5,6][ 1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1 -(2,6-dichlorophenyl)ethy] ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(2-methoxyphenyl)ethyl ester; : Pyrrolo[3',2":5,6][ 1 ]benzopyrano[3,2-i)quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(5-carboxy-3-pyridinyl)ethyl ester, 1,3-Benzenedicarboxylic acid, 5-[({(3,7.8,9,10,12,13,14,14a,15- decahydro-2-methylpyrrolo[3',2":5,6][ 1Jbenzopyrano[3,2-ijquinolizin- 1-yDcarbonylJoxy]methyl]-, diethyl ester; 1,3-Benzenedicarboxylic acid, 5-[[[(3,7,8,9,10,12,13,14,14a,15- : decahydro-2-methylpyrrolo[3',2':5,6][ 1 Jbenzopyrano[3,2-i]quinolizin- 1-yDcarbonylloxy)methyl]-;
Pyrrolo[3',2"5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a, 15-decahydro-2-methyi-, (2-chloro-5-nitrophenyl)methy} ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i)quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (2-chloro-5 -nitrophenyl)methyl ester;
Pyrrolo[3',2":5,6]( 1Jbenzopyranof3,2-iJquinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13, 14,14a,15-decahydro-2-methyl-, (5-amino- 2-chlorophenyl)methy] ester;
Pyrrolo[3',2":5,6){1]benzopyranof3,2-i]quinolizine- 1-acetic acid, 3,7,8,9,10,12,1 3,14,14a,15-decahydro-2-methyl-.alpha.-oxo-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]jquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,4,5-tnimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,1-dimethyl-2-propynyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizinc- 1 -carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trichloro- 1,1-dimethylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, tricyclo[3.3.1.13,7}dec-1-yl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-methyl-1-phenylethyl ester;
Pyrrolo[3',2":5,6][1]Jbenzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-methylcyclohexy! ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano{3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1,1,2-trimcthylpropyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-methylcyclopentyl ester;
Pyrrolof3',2":5,6}{1]benzopyrano[3,2-/]quinolizine-1-carboxylic acid, 3.7,.8,9,10,12,13,14.14a,15-decahydro-2-methyl-, 1-cyclohexyl-i-methylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,4-dimethyl-4-piperidinyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-dccahydro-2-methyl-, 4-fluorophenyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-methylphenyl ester;
Pyrrolo[3',2":5,6]{ 1]benzopyrano|3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-mcthyl-, phenyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-/]quinolizine- 1 -carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-(methoxycarbonyl)phenyl ester,
Claims (22)
1. A compound of Formula] (CH), LT (CH, R 5 ’; 4 0 I : PRY or Ry J Nr S—~——— Xr X AX x Zz A R; rR, <Z nng close y ring open or a pharmaceutically acceptable salt thereof wherein: AsO, S, or NRy; X is CRo, 3 wherein Rg is halogen, hydrogen, alkyl, -CF;, CHF, CHF,, -(CH32);y-OR |, aryl, arylalkyl, -(CH3)m-NR7Rg, or Chay), (CH2)q wherein m is an integer of from 0 to 2 and. each occurrence of m is independently an integer of from 0 to 2, q is an integer of from Oto 1, and r is an integer of from 0 to 3; Y is hydrogen, alkyl, arylalkyl, aryl, (CHp)p,,-NR7Rg, -N(R1)-(CH3)y- C(R7Rg)-aryl, or OR1( wherein Ryo 1s hydrogen, alkyl, cycloalkyl, cycloalkyl fused to an aryl ning, aryl, (CHjp)saryl, -CH, CF, (CH3);C(R7Rg)-(CHy)y aryl, 0 : R il A CTR ES Aryl AMENDED SHEET 2002 -08- 08
R 0 —_— R pL Nm NR;Rg NP C—OR; k% alkyl % alky! 0 R 1 Voce wr alkyl oO Ry — NR-R R —C—OR k% cycloalkyl yy cycloalkyl 0 R I PINAY E% cycloalkyl i cel Mom Horan, EY C=N | Lk C=CH, 0) , or N ~N oT ow, wherein s is an integer of from 1 to 3, tis an integer of from 0 to 3, u is an integer of from Oto 3, v is an integer of from 1 to 3, and w is an integer of from 0 to 2; ZisCR or N; R| is hydrogen or alkyl and each occurrence of Rj is independently hydrogen or alkyl; R and Rj are each independently selected from: hydrogen, alkyl, halogen, -CN, -NO», -(CH2)m-NR7Rg,
-(CH2)-COOR4, -(CH2)-CONR7Rg, 0 a (CH); N R~ 0 ! -(CH2)mN-S-R7, I 0) -(CH2)n-OR 7, -(CH2)m-SO;NR7Rg, and -(CH2)m-S(O)pR7 wherein each occurrence of R7 and Rg are each independently hydrogen, alkyl, aryl, arylalkyl, -CF3, 0rR7 and Rg may be taken together to form a cyclic ring of from 3 to 7 atoms which ring may have O, S, or NRi and pis an integer of from 0 to 2; R3 is hydrogen or alkyl; Ry 1s hydrogen, alkyl, aryl, or aralkyl; Rs is alkyl, aryl, arylalkyl, acyl; or Rg and Rg are taken together with the atoms to which they are attached to form a cyclic ring of from 5 to 7 atoms; Rg is hydrogen or alkyl; Rs when not taken together with R4 can be taken together with Rg with the atoms to which they are attached to form a ring of from 5 to 7 atoms; N-Rj5 is also the corresponding N-oxide; Ry] is hydrogen or alkyl; nis an integer of from 1 to 3; J 1s an integer of from 1 to 2, and j 1s the integer 0 when Y is hydrogen, alkyl, arylalkyl, or aryl;
with the proviso that Pyrrolo[3,2":5,6][1]benzopyrano(3,2-i)quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2- methyl-, ethyl ester is not included.
2. A compound of Formula Nay), : Nc) a £300) IN Ac, QA 5 | RSH Rs > f 40 Ly PRY oC RY xX EE —— 8) X | Xx — A — ’ Ry, Z Ry ZT TA nng close . ring open or a pharmaceutically acceptable salt thereof wherein: Ais NR; XisN; "Y is hydrogen, alkyl, arylalkyl, aryl, (CH) -NR7Rg, -N(R1)-(CH3),- C(R7Rg)-aryl, or OR jg wherein Rjp is hydrogen, alkyl, cycloalkyl, cycloalkyl fused to an aryl ring, aryl, (CHp)garyl, -CH,CFj3, (CH2):C(R7Rg)-(CH3), aryl, 0 R i Nn ORR % Any AMENDED SHEET 2002 -08- 08
. -272a- R m NS 778 NS C—OR,
Y, . ’ Zz alkyl Ny alkyl 0 R ! mito 5% alkyl
@) . R CL R . ! ye cycloalkyl EY cycloalkyl
L. 0 . R I : . (CH) C—NR7Rg pe \ CY Sean yy cycloalkyl 7 3 EO YT c=N | C=CH , =) or = Roy - | (CH). wherein s is an integer of from | to 3, tis an integer of from Oto 3, u is an integer of from 010 3, v is an integer of from } to 3, and wis an integer of from 0 to 2; ZisCRor NN; Ry is hydrogen or alkyl and each occurrence of Rj is independently hydrogen or alkyl; R and Rj are each independently selected from: hydrogen, alkyl, halogen, -CN, -NO», «(CH3)p-NR7Rg, AMENDED SHEET ~~ 2002 -08- g8
B WO 00/42045 PCT/US99/30434 -272b- -(CH2),-COOR 7, -(CH2)m-CONR Rg, 0 Cp,
0 . (CH); N-S-R7, 0 : (CH2)m-ORy, «(CH2)m-SO;NR7Rg, and «(CH2)m-S(O)pR7 wherein each occurrence of Ry and Rg are each independently hydrogen, alkyl, aryl, arylalkyl, -CF3, or Ry and Rg may be taken together to form a cyclic ring of from 3 to 7 atoms which nng may have O, S, or NR and pis an - integer of from 0 to 2: ) R3 is hydrogen or alkyl; Rg 1s hydrogen, alkyl, aryl, or aralkyl: : - Rs is alkyl, aryl, arylalkyl, acyl: or Rg and Rs are taken together with the atoms to which they are attached 10 form a cyclic ring of from 5 to 7 atoms; Rg is hydrogen or alkyl: Rs when not taken together with Rg can be taken together with Rg with the atoms to which they are attached to form a ring of from 5 to 7 atoms; N-Rjs is also the corresponding N-oxide; Ry] is hydrogen or alkyl: nis an integer of from 1 to 3; J Is an integer of from 1] 10 2, and j is the integer 0 when VY js hydrogen, alkyl, arylalkyl, or aryl; AMENDED SHEET 2002 08 08
-272¢- with the proviso that Fymmolo{3",2":5,6]( 1 benzopyrano[3 2-ijauinolizine. I-carboxylic acid, 37.8,9,10,12,13,14,142,15-decahydro-2- methyl-, ethyl ester is not included.
3. A compound according to Claim 1 or 2 wherein: Rj is hydrogen.
4. A compound according to Claim 1 or 2 wherein: Rj is hydrogen and X is C-Rg.
5. A compound according to Claim 1 or 2 wherein: Rj 1s hydrogen and Xs C-Rg, wherein Rg is alkyl.
6. A compound according to Claim 1 or 2 wherein: Rj is hydrogen, Xis C-Rg, wherein Rg is alkyl; Rg and Ry are taken together with the atoms to which they are attached to form a ring of from 5 to 7 atoms; and Y is ORjg.
7. A compound according to Claim 1 or 2 wherein: Rj is hydrogen, Xs C-Rg, wherein Rg is alkyl; R4 and Ry are taken together to form a 6-membered rng; and Y 1s OR wherein Ry is alkyl, aryl or -(CHp)garyl, : -(CH2)i-C(R7Rg)-(CHp)y-aryl.
8. A compound according to Claim 1 or 2 wherein: R15 hydrogen, AMENDED SHEET 9002 08-08
X 1s C-Rg, wherein Rg is Me; R4 and Rj are taken together to form a 6-membered nng; Rg is hydrogen; nis 2; and Y is OR 1g wherein Rip is alkyl, aryl or Rios -(CH2)-C(R7Rg)-(CH3)y- aryl wherein tis 0, R7 and Rg can each independently be H, alkyl, «(CH2)yOH or (CH2),COOR7, and <(CH3), NR) R, where u and v are as defined above. -
9 A compound selected from: Pyrolo[3,2":5,6)(1]benzopyrano|3,2-iJquinolizine- I -carbox yiic acid, 3,7,8,9,10,12,13, 14,14a,15-decahydro-2-methyl-, methyl ester; Pyrrolo[3',2°:5,6][1]benzopyrano(3,2-ijquinolizine-1-carboxylic : acid, 5-bromo-3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl . 15 ester; Pyrolo[3',2":5,6)[1]benzopyrano(3,2-ijquinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, propyl ester; Pymolo[37,2":5,6](1)benzopyrano(3 2-i]quinolizine-1-carbox ylic = acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-methylpropyl ester; Pymolo[3',2":5,6][1]benzopyrano(3,2-iJquinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 2,2-dimcthylpropyl ester; Pymolo[37,2":5,6)(1 )benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, phenylmethyl ester; Pyrrolo[37,2":5,6](1]benzopyrano|3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14,15-decahydro-2-methyl-, I-methylethyl ester; : ) Pymolo[3",2":5,6](1]benzopyrano[3,2-iJquinolizine-1-carboxylic . 30 acid, 3.7.8,9,10,12,13,14,142,15-decahydro-2-methyl-, cyclopropylmethyl ester; AMENDED SHEET ~~ 2002 -08- 08
Pyrrolo[37,27:5,6](1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(1-
piperidinyl)ethyl ester; Pyrrolo[3°,2°:5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-(phenylmethyl)-, ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 2-ethyl-3,7,8,9,10,12,13,14,14a,15-decahydro-, ethyl ester; Pyrrolo[3’,2°:5,6][ 1 ]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 2-cyclopropyl-3,7,8,9,10,12,13,14,14a,15-decahydro-, ethyl ester;
Pyrrolo[3’,2°:5,6][1]benzopyrano|3,2-i]Jquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-propyl-, ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-(2-methylpropyl)-, ethyl ester;
Pyrrolo(3°,2°:5,6](1]benzopyrano(3,2-i]quinolizinc-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,1-dimethylethyl ester;
2,6a,7-Trimethyl-7,8,9,10,10a,11-hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester;
7-Ethyl-2,6a-dimethyl-7,8,9,10,10a,1 1 -hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a)anthracene-1-carboxylic acid ethyl ester;
6a-Ethyl-2,7-dimethyl-7,8,9,10,10a,11-h exahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; 6a,7-Diethyl-2-methyl-7,8,9,10,10a,11-hexahydro-3H,6aH-6-oxa-
3,7-di1aza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester;
7-Benzyl-2,6a-dimethyl-7,8,9,10,10a,11-hexahydro-3H,6aH-6-oxa- 3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; 2,7-Dimethyl-6a-phenyl-7,8,9,10,10a,1 1-hexahydro-3H,6aH- (6-oxa-3,7-diaza-cyclopenta[a]anthracene-1-carboxylic acid ethyl ester; Pyrrolo[3°,2’:5,6][ 1 ]benzopyrano[3,2-eJindole-1-carboxylic acid, 8,9,11,12,13,13a,14,1 4a-octahydro-2-methyl-, ethyl ester;
3H,7H-Pyrrolizino[1',8":5,6]pyrano[3,2-e]indole- 1 -acetic acid, 8,9,11,12,12a,13-hexahydro-2-methyl-, ethyl ester; 2-Methyl-8,9,10,10a,11,12,12a,13-octahydro-3H,6aH, 7H-6-0xa- 3,6b-diaza-benzo[a]cyclopenta[h)anthracene-1-carboxylic acid ethyl ester; 3H-Pyrido[1”",2"": 1'2']azepino[3'2":5,6]pyrano(3,2-¢]indole-1- acetic acid, 7,8,9,10,12,13,14,15,15a,1 6-decahydro-2-methyl-, ethyl ester or 7H-Azepino[1”,2": 1'2']pyndo[3',2":5,6]pyrano[3,2-¢]indole- 1-acetic acid, 3,8,9,10,1 1,13,14,15,15a,16-decahydro-2-methyl-, ethyl ester; Pyrrolo[3°,27:5,6](1]benzopyrano(3,2-i]quinolizine-1-carboxamidc, 8,9,11,12,13,13a,1 4,14a-octahydro-2-methyl-N-(phenylmethyl)-; Pyrrolo[3',2’:5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxamide, N-ethyl-8,9,11,12,13,13a,14,1 4a-octahydro-2-methyl-; Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i}quinolizine-1- carboxaldehyde, 8,9,1 1,12,13,134,14,14a-octahydro-2-mecthyl-; Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1- carboxamide,8,9,11,12,1 3,13a,14,14a-octahydro-N,2-dimethyl-; Pyrrolo[3°,2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carbox ylic acid, 8,9,11,12,13,13a,14,14a-octahydro-2-methyl-, (4-fluorophenyl)- methyl ester;
Indazolo[4',5"5,6]pyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyranc[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2, 12,12-trimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,10,10-trimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1]Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 5-fluoro-3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine- I-carboxylic acid, 5-fluoro-3,7,8,9,10,12,1 3,14,14a,1 5-decahydro-2-methyl-, phenylmethy] ester;
12H-Furo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 5-fluoro-7,8,9,10,13,14,14a,1 5-octahydro-2-methyl-, ethyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- I-carboxylic acid, 4,5-difluoro-3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, phenylmethy! ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i}quinolizine-1-carbox ylic acid, 4,5-dichloro-3,7,8,9,10,12,13,1 4,14a,15 -decahydro-2-methyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-4,5-dimethoxy-2-methyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1-carbox ylic avy, 0,7,0,7,10,12,13,14,144a, | >-decahydro-2,5-dimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6]( 1]benzopyrano[3 ,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13, 14,14a,15-decahydro-2,4-dimethyl-, phenyimethyl ester;
Pyrrolof23',2":5,6](1 Joenzopyrano{3,2-i]quinolizine-1 -carboxyiic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2,4-dimethyl-, 1-(4-fluorophenyl)ethyi ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-ijquinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-[3- (methoxycarbonyl)phenyl]ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(3-carboxyphenyl)ethyl ester;
i 30 1-Propanaminium, N,N,N-trimethyl-, salt with 1-(3-carboxyphenyl)ethyl 3,7,8,9,1 0,12,13,14,14a,1 5-decahydro-2-methyl- pytrolo[3',2":5,6][ 1]-benzopyranof3,2-i]Jquinolizine- 1 -carboxylate (1:1);
Pyrrolo[3',2":5,6][1]benzopyrano([3,2-i1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (3-nitrophenyl)methyl ester;
Pyrrolo[3',2":5,6]{ 1 Joenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(3-cyanophenyl)ethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3-[(dimethylamino)carbonyl]phenyl]ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-[3-[(dimethylamino)methyl]phenyl]ethy! ester;
Pyrrolo[3’,2:5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,1,13,14,14a,15-decahydro-2-methyl-,2-phenylethyl ester;
Pyrrolo[3°.2°:5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [(4-(methoxycarbonyl)phenyl]methyl ester;
Pyrrolo[3°,2°:5,6][ 1]benzopyrano[3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,-methyl-,
(4-carboxyphenyl)methyl ester; 1-[3-(4-Carboxy-benzyloxycarbonyl)-5-hydroxy-2-methyl-1H- indol-4-ylmethyl}-1,2,3,4,6,7,8,9-octahydro-quinolizinylium; chloride;
Pyrrolo{3’,27:5,6][1]benzopyrano[3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-,
[4-(hydroxymethyl)phenyllmethyl ester;
Pyrrolo[3°,27:5,6][ 1]benzopyrano[3,2-i]quinolizine-2-carbox ylic acid, 3,78,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-naphthalenylmethyl ester;
Pyrrolo[37,27:5,6]( 1 Jbenzopyrano(3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [3-(methoxycarbonyl)phenyl]mcthyl ester;
Pyrrolo[3°,2°:5,6][ 1]benzopyrano([3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, [3-(hydroxymethyl)phenyljmethyl ester; Pyrrolo[3°,2’:5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic
5. acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (3-carboxyphenyl)methyl ester); Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (3-carboxypheny)methyl 3,7,8,9,10,12,1 3,14,14a,15-decahydro- 2-methylpyrrolo[3’,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylate (1:1); Pyrrolo[3°,2°:5,6][1 Jbenzopyranof3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (3-[(dimethylamino)methyl]phenyl]methy] ester; Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ~ [3-[(dimethylamino)carbonylJphenyljmethyl cster; : Pyrrolo[3°,2’:5,6]{1]benzopyrano[3,2-i]quinoclizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, [2-(4-morpholinyl)ethyl ester; Pyrrolo[3’,2°:5,6][1]benzopyrano(3,2-i]quinolizine-1 carboxylic acid, 3,7,8,9,10,12,13,14 14a,1 5-decahydro-2-methyi-, 1-[1,1 “-biphenyl]- 4-ylethy] ester; Pyrrolo[3’,2°:5,6][ 1]benzopyrano3 ,2-i]quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (2,6-difluorophenyl)methyl ester; Pyrrolo[3’,2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (1-phenyl-2,2,2- trifluoro)ethyl ester; Pyrrolo[3°,2°:5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-[3-(trifluoromethyl)phenyl)ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(dimethylamino)ethyl ester;
Pyrrolo[3°,27:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(1-pyrrolidinyl)ethyl ester;
Pyrrelo[3°,27:5,6][1]benzopyrano|3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(1-naphthalenyl)ethy] ester;
Pyrrolo[3°,2’:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylcyclobutyl ester;
Pyrrolo[3’,27:5,6][1]benzopyrano[3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, I-phenylcylopropyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano([3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-pyrazinylethyl ester,
Pyrrolo[3°.27:5,6][1]benzopyrano(3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-quinolinyl)ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(2-pyrimidinyl)ethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano(3,2-i)quinolizine-1-carbox ylic acid, 5-chloro-3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, phenylmethyl ester;
Pyrrolo[3°,2°:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 5-chloro-3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl,
1-(4-fluorophenyl)ethy! ester;
Quinolizinium, 1-[[(4-flucrophenyl)methoxy]carbonyl]-5-hydroxy-
2-methyl-1H-1ndol-4-yl)methyl)-1,2,3,4,6,7,8,9-octahydro-, chloride;
Pyrrolo[3°,2’:5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-1,2-dimethyl-, (4-fluorophenyl)methyl ester; Pyrrolo[3',2":5,6][ 1]Jbenzopyrano[3,2-1]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylpropyl ester; Quinolizinium, 1,2,3,4,6,7,8,9-octahydro-1-[[5-hydroxy-2-methy}- 3-[(phenylmethoxy)carbonyl}-1H-indol-4-ylJmethyl]-, chloride; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (4-nitrophenyl)methyl ester; Pyrrolo[3',2":5,6][1]benzopyranof3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,144a,15-decahydro-2-methyl-, (1R)-1-phenylethyl ester; Pyrrolo[3',2":5,6][1]benzopyrano|3,2-ijquinolizine- 1-carbox ylic "acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-fluorophenyl)ethyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, phenyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trifluoro- 1-phenyl-1-(trifluoromethyl)ethyl ester; Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, bicyclo[2.2.1]hept- 2-yl ester; Pyrrolo[3',2":5,6][ 1]Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-fluorophenyl)- 1-methylethyl ester; . Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-ijquinolizine- I -carboxylic 30_ acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylcyclopentyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,1 0,12,13,14,14a,15-decahydro-2-methyl-, 1-phenylcyclohexyl ester, :
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-(hydroxymethyl)pheny! ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine- 1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (3-hydroxyphenyl)methyl ester;
Pyrrolo[3',2":5,6](1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)- 1-(4-pynidinyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,1 4a,15-decahydro-2-methyl-,
[6-(methoxycarbonyl)-2-pyridinyljmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-pyridinylmethyl ester,
Pyrrolo[3',2":5,6]{1]benzopyrano[3,2-1]quinolizine-1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (6-carboxy- 2-pyridinyl)methyl ester;
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (6-carboxy- 2-pynidinylymethyl 3,7,8,9,10,12,13,14,14a,15-decahydro-2- methylpyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylate
(1:1);
Pyrrolo[3',2":5,6]( 1 Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [5-(methoxycarbonyl)-3-pyridinyl]methy] ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (5-carboxy- 3-pyndinyl)methyl ester;
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (5-carboxy- 3-pyndinyl)methyl 3,7,8,9,10,12,13,14,14a,15-decahydro-2-
methylpyrrolo[3',2':5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylate (1:1); Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1 -(4'-methyl[1,1'- biphenyl]-3-yl)ethyl ester; Pyrrolo[3',2':5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2,6-dimethylphenyl)ethy] ester; Pyrrolof3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (1 S,2R)- 2-(dimethylamino)-1-phenylpropyl ester; Pyrrolo[3',2':5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (1 R,2S)- 2-(dimethylamino)-1-phenylpropyl ester; Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid; 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, I-naphthalenyl _ ’ ester; Pyrrolo(3',2":5,6][1 Jbenzopyrano(3,2-i)quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, diphenylmethyl ester; Pyrrolo[3',2":5,6][1 Jjbcnzopyrano(3,2-ijquinoiizine- i -carboxylic acid, 3,7,8,9,10,12,13,14,1 4a,1 5-decahydro-2-methyl-, (1R)-2,3-dihydro- 1H-inden-1-yl ester;
Pyrrolo[3',2":5,6](1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,1 4a,1 5-decahydro-2-methyl-, 1,2-dihydro- I-acenaphthylenyl ester;
Pyrrolo[3',2":5,6)[ 1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, cyclohexyl(phenyl)methyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 9H-fluoren-9-y! ester;
Pyrrolo[3',2":5,6](1]benzopyrano(3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,2,3 4-tetrahydro- 1-naphthaleny! ester;
Pyrrolo([3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [(2R,3R)- 3-phenyloxiranyl)methyl ester;
Pyrrolo[3',2":5,6][ 1 ]Jbenzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-0x0- 1,2-diphenylethy! ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5-yl ester;
Pyrrolo(3',2":5,6][1]benzopyrano{3,2-i}quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-,
(2-methylphenyl)phenylmethyl ester;
Pyrrolo[3',2":5,6](1]benzopyrano(3,2-i]quinolizine- 1 -carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-,
cyclopropyl(4-fluorophenyl)methyl ester; Pyrrolo[3',2":5,6][ 1 ]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,144,1 5-decahydro-2-methyl-, 3,4-dihydro-2H- 1-benzothiopyran-4-yl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)- 1-(2-bromophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trifluoroethyl ester, :
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-iJquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [(2S,35)-
3-phenyloxiranyl]methyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trifluoro- 1-methyl-1-(trifluoromethyl)ethyl ester;
Pymrolo[3',2':5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 2,2,2-trifluoro- 1-(4-fluorophenyl)-1-(trifluoromethyl)ethy] ester;
Pyrrolof3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1 -cyclopentyl- 1-phenylethy! ester;
Pyrrolo[3',2:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1 -[1,1 '_biphenyl]- 4-yl-1-methylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i)quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-m ethyl-, 1-methyl-1-phenyl- 2-propyny] ester;
Pyrmrolo[3',2":5,6][ 1Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1,1-diphenylethyl ester;
— Pyriolo[372775,6][ T]benzopyranol 3,2-1]Jquinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, I-methyl- 1,2-diphenylethyl ester;
Pyrrolo[3',2"5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-m ethyl-, 1-(4-fluorophenyl)cyclohexyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- I-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1,2-diphenylcthyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 S-decahydro-2-methyl-, 1 -phenyl- 2-propynyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [1,1 "-biphenyl]-
4-ylmethyl ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 4-pyridinylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a, 15-decahydro-2-methyl-, 1,2,3,4-tetrahydro-
7,8-dimethoxy-2-methyl-4-isoquinolinyl ester; Pyrrolo[3',2":5,6](1]benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-,
1-[3-(dimethylamino)phenyl]ethyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1,1-dimethy!-
2-pyrazinylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 4-(dipropylamino)- 1,1-dimethyl-2-butynyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)-2,3-dihydro-
1H-inden-1-yl ester;
Pyrrolo(3',2":5,6](1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S,2S)- 2-(dimethylamino)- 1-phenylpropyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13, 14,14a,15-decahydro-2-methyl-, [4-(trifluoromethyl)phenyl)methyl ester;
Pyrrolo[3',2":5,6](1]benzopyrano|3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (4-chlorophenyl)methyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-, phenylmethyl ester; Pyrrolo[3',2":5,6](1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-, cthyl ester; Pyrrolo[3',2":5,6](1]benzopyrano(3,2-i]quinolizine-1-carboxylic } acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-hydroxyethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (3-methylphenyl)methy! ester;
Pyrrolo[3',2":5,6][ 1Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, ( 1S)-1-phenylethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1 -phenylethyl ester;
Pyrrolo[3',2":5,6][1 Ibenzopyrano[3,2-i]quinolizine-1-carbothioic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, S-(phenylmethyl) ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 3-pyridinylmethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl, : 1-[4-(trifluoromethyl)phenyl]ethyl ester;
Pyrrolo[3',2':5,6][1 Jbenzopyrano[3,2-iJquinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a, 15-decahydro-2-methyl-, 1-(pentafluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6](1 jbenzopyrano{3,2-ijquinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(2,6-difluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (18)- 1-(2-furanyl)ethyl este;
Pyrrolo[3',2':5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a 1 5-decahydro-2-methyl-, 2-(4-morpholinyl)- I-phenylethyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,1 3,14,14a,1 5-decahydro-2-methyl-, (IR)- 1-(2-furanyl)ethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-methoxy-2-0xo0- 1-phenylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano|3,2-i}quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(3-pyridinyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (S)- carboxy(phenyl)methyl ester,
Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with (S)- carboxy(phenyl)methyl, 3,7,8,9,10,12,13,14,14a,15-decahydro- 2-methylpyrrolo(3',2":5,6][1 Jbenzopyrano[3,2-i]quinolizine- 1 -carbox ylate (1:1);
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (1R)-2-methoxy- 2-oxo-1-phenylethyl ester;
: Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (R)- carboxy(phenyl)methyl ester;
Ethanaminium, 2-hydroxy-N,N N-trimethyl-, salt with (R)- carboxy(phenyl)methyl, 3,7,8,9,10,12,13,14,14a,15-decahydro- 2-methylpyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carboxylate (1:1);
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 4-pyndinylmethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4-pynidinyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2-pynidinyl)ethyl ester;
Pyrmrolo{3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-thienylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (1S)- 1-(4-fluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano|3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (1R)- 1-(4-fluorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-pyridinylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 2-ethoxy-
2-oxoethyl ester;
Pyrrolo[3',2:5,6][1 Jbenzopyrano(3,2-i]quinolizine-1-carboxylic
: acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 3-furanylmethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, (2-nitrophenyl)methy] ester;
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1 ~carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 2-furanylmethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(2-chlorophenyl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, carboxymethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-(2,6-dichlorophenyl)ethyl ester:
Pyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(2- methoxyphenyl)ethyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(5-carboxy- 3-pyridinyl)ethyl ester; 1,3-Benzenedicarboxyhic acid, 5-[[[(3,7,8,9,10,12,13,14,14a,15- decahydro-2-methylpyrrolo[3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizin- 1-yl)carbonyljoxy]methyl]-, diethyl ester;
1,3-Benzenedicarboxylic acid, 5-[[[(3,7,8,9,10,12,13,14,14a,15- decahydro-2-methylpyrrolo[3',2":5,6][ 1]benzopyrano(3,2-i]quinolizin- 1-yl)carbonyljoxy]methyl]-;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (2-chloro-
5-nitrophenyl)methyl ester;
Pyrrolo[3',2":5,6]{1]benzopyrano[3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (2-chloro- S-nitrophenyl)methyl ester;
Pyrrolo[3',2":5,6]{1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (5-amino- 2-chlorophenyl)methyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-acetic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-.alpha.-oxo-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,4,5-trimethyl-, phenylmethyl ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-dccahydro-2-methyl-, 1,1-dimethyl- 2-propynyl ester;
Pyrrolo{3',2":5,6][1]benzopyrano|3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2,2,2-trichloro- 1,1-dimethylethy! ester;
Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, tricyclo[3.3.1.13,7]dec-1 -yl ester;
Pyrrolo[3',2":5,6]( 1]benzopyrano[ 3,2-i]quinolizinc- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1-methyl- 1-phenylethyl ester;
Pymrolof3',2":5,6][ 1 Jbenzopyrano[3,2-i]quinolizine-1 carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, I-methylcyclohexyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1,1,2-trimethylpropyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-,
1-methylcyclopentyl ester:
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine- 1 -carboxylic . acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 1 -cyclohexyl- I-methylethy! ester; Pyrrolo[3',2":5,6][1 Jbenzopyrano(3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,1 4a,15-decahydro-2-methyl-, 1,4-dimethyl- 4-piperidinyl ester;
Pyrrolo[3',2":5,6][1 Jbenzopyrano|[3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 4-fluorophenyl ester;
Pyrrolo[3',2":5,6]{1]benzopyrano[3 ,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,1 4a,1 5-decahydro-2-methyl-, 3-methylphenyl ester;
Pyrrolo[ 3',2":5,6]( 1]benzopyrano[3,2-i]quinolizine- I-carboxylic acid, 3,7,8,9,10,12,13;14,14a,1 5-decahydro-2-methyl-, phenyl ester;
Pyrrolo[3',2":5,6){ 1]Jbenzopyrano([3,2-i]quinolizine-1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, .3-(methoxycarbonyl)phenyl ester:
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-pyridiny! ester;
Pyrrolo[3',2":5,6][1]benzopyrano(3,2-i]quinolizine- 1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-(trifluoromethyl)-, ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, [5-[(dimethylamino)methyl]-2-furanyl)methyl ester;
Pyrrolo[3',2"5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 2-carboxy- 2-methylpropy! ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1-carbox ylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 3-(dimethylamino)- 2,2-dimethylpropyl ester;
Propanedioic acid, monoanhydride with 3,7,8,9,10,12,13,14,14a,15-dccahydro-2-methylpyrrolo[3',2":5,6)[ 1]- benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 1,1-dimethylethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(dimethylamino)-
2-methylpropyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 2-(1H-1midazol- 1-yl)ethyl ester;
Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, 2-benzofuranylmethyl ester; Pyrrolo[3',2":5,6][ 1]benzopyrano[3,2-/]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1R,25)-2- y (dimethylamino)-1-phenylpropyl ester; Pyrrolo[3',2":5,6][1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (15,2R)-2- (dimethylamino)-1-phenylpropyl ester; and
Pyrrolo[37,2":5,6][1]benzopyrano(3,2-i)quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, 1-(4- fluorophenyljcyclopropyl ester.
10. A compound named Pyrrolo[3’2":5,6][1]benzopyrano(3,2-i)quinolizine, 3,7,8,9,10,12,13,14,14a,15-deczhydro-, or Pyrrolo[37,2":5,6](1)benzopyrano[3,2-i)quinolizine-1-carboxylic acid,
3,7.8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-.
11. A pharmaceutical composition comprising a compound according to Claim 1 or 2 or Pyrrolo[3°.2°:5,6][1]benzopyrano[3,2-i]quinolizine-1 - ] 10 carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, ethyl ester in admixture with a pharmaceutically acceptable excipient, diluent, or carrier.
12. A compound according to Claim 1 or 2 or Pyrrolo[37,27:5,6][1 Jbenzopyrano(3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, ethyl ester or a pharmaceutically acceptable salt thereof for use in a method for modulation of a chemokine receptor activity in a mammal.
13. A compound according to Claim 1 or 2 or Pyrrolo[3°,2°:5,6][1 Jbenzopyrano(3,2-i]quinolizine-1-carboxylic acid,
3,7.8,9,10,12,13,14,14a,1 5-decahydro-2-methyl-, ethyl ester or a pharmaceutically acceptable salt thereof for use in a method for modulation of the CCR-5 chemokine receptor activity in a mammal. AMENDED SHEET 9002 -08- 08
14. A compound according to Claim | or 2 or Pyrrolo[3°.27:5,6](1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid,
3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester or a pharmaceutically acceptable salt thereof for use in a method for preventing infection by HIV, treating infection by HIV, delaying the onset of AIDS, or treating AIDS.
15. A compound according to Claim 1 or 2 or Pyrrolo[37,2":5,6](1 Jbenzopyrano[3,2-i)quinolizine-1-carboxylic acid,
3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester or a pharmaceutically acceptable salt thereof for use in a method of treating inflammatory disease.
16. Use of a compound according to Claim 1 or 2 or
5. Pyrrolo[3°,27:5,6][1 Jbenzopyrano(3,2-i]quinolizine-1-carboxylic acid, 8 | 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester or a pharmaceuticaly acceptable salt thereof in a method of making a medicament for use in a method for modulation of a chemokine receptor activity in a mammal. } 17. Use of a compound according to Claim 1 or 2 or Pyrrolo[37,2%:5,6][1]benzopyrano[3,2-i]quinolizine-1-carboxylic acid, 3,7,8,9,10,12,13,14,14a,] 5-decahydro-2-methyl-, ethyl ester or a pharmaceuticaly acceptable salt thereof in a method of making a medicament for use in a method for modulation of the CCR- 5 chemokine receptor activity in a mammal.
18. Use of a compound according to Claim 1 or 2 or Pyrrolo[3°,2° 15,60] 1]benzopyrano[3,2-i]quinolizine-1 -carboxylic acid,
3,7.8,9,10,12,13.1 4,14a,] 5-decahydro-2-methyl-, ethyl ester or a pharmaceuticaly acceptable salt thereof in a method of making a AMENDED SHEET 2002 -08- 0 8 medicament for use in a method for preventing infection by HIV, treating infection by HIV, delaying the onset of AIDS, or treating AIDS. :
19. Use of a compound according to Claim 1 or 2 or Pyrrolo[3°,2°:5,6](1]benzopyrano[3,2-i]quinolizine- 1 -carboxylic acid, 3,7,8,9,10,12,13,14,14a,15-decahydro-2-methyl-, ethyl ester or a pharmaceuticaly acceptable salt thereof in a method of making a medicament for use in a method of treating inflammatory disease.
20. A combination of a compound of Formula I as defined in Claim 1 or 2 with one or more agents useful in the prevention and/or treatment of AIDS.
21. A compound selected from: Pyridinium, 3-[{[(3,7,8,9,10,12,13,14,14a,15-decahydro- 2-methylpyrrolo[3',2":5,6)[1]benzopyrano(3,2-i]quinolizin- I-yl)carbonyljoxy]jmethyl]-1-methyl-, methanesulfonate; Pyrrolo(3',2':5,6](1]benzopyranal3,2-i]quinolizinium, 3,7,8,9,10,12,13,14,14a,15-decahydro-2,1 l-dimethyl-1-[(S)-(1- phenylethoxy)carbonyl]-, methanesulfonate; and Pyrrolo(3',2:5,6](1]benzopyrano(3,2-i]quinolizine-1-carboxylic acid, 3,7.8,9,10,12,13,14,14a,15-decahydro-2-methyl-, (1S)-1-phenylethyl ester, 11-oxide.
22. A compound named Pyrrolo[3',2':5,6][1]benzopyrano(3,2-i]quinolizine- I-carboxylic acid, 3,7,8,9,10,12,13,1 4,14a,15-decahydro-2-methyl-, anhydride with benzoic acid. 1 AMENDED SHEET 2002 -08- 0 8
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11565499P | 1999-01-13 | 1999-01-13 |
Publications (1)
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|---|---|
| ZA200106592B true ZA200106592B (en) | 2002-08-12 |
Family
ID=22362668
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| ZA200106592A ZA200106592B (en) | 1999-01-13 | 2001-08-10 | Functionalized heterocycles as chemokine receptor modulators. |
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|---|---|
| EP (1) | EP1144415A2 (en) |
| JP (1) | JP2002534526A (en) |
| KR (1) | KR20010086166A (en) |
| CN (1) | CN1344270A (en) |
| AP (1) | AP2001002228A0 (en) |
| AU (1) | AU1940900A (en) |
| BR (1) | BR9916905A (en) |
| CA (1) | CA2372197A1 (en) |
| CZ (1) | CZ20012502A3 (en) |
| EA (1) | EA200100774A1 (en) |
| HK (1) | HK1044539A1 (en) |
| HU (1) | HUP0202932A3 (en) |
| IL (1) | IL144289A0 (en) |
| MX (1) | MXPA01007033A (en) |
| NO (1) | NO20013456L (en) |
| OA (1) | OA11820A (en) |
| PL (1) | PL349348A1 (en) |
| SK (1) | SK9972001A3 (en) |
| WO (1) | WO2000042045A2 (en) |
| ZA (1) | ZA200106592B (en) |
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| EP1377549A1 (en) | 2001-03-12 | 2004-01-07 | Millennium Pharmaceuticals, Inc. | Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor |
| CZ305838B6 (en) * | 2001-03-29 | 2016-04-06 | Eli Lilly And Company | N-(2-arylethyl)benzylamines as 5-HT6 receptor antagonists |
| WO2003035650A1 (en) * | 2001-09-25 | 2003-05-01 | Takeda Chemical Industries, Ltd. | Entry inhibitor |
| TW201018661A (en) | 2003-03-14 | 2010-05-16 | Ono Pharmaceutical Co | Heterocyclic rinf having nitrogen atom derivatives and medicament containing the derivatives as active ingredient |
| WO2004092169A1 (en) | 2003-04-18 | 2004-10-28 | Ono Pharmaceutical Co., Ltd. | Spiropiperidine compound and medicinal use thereof |
| MX2007002886A (en) | 2004-09-13 | 2007-05-16 | Ono Pharmaceutical Co | Nitrogenous heterocyclic derivative and medicine containing the same as an active ingredient. |
| EP1889622A4 (en) | 2005-05-31 | 2009-12-23 | Ono Pharmaceutical Co | Spiropiperidine compound and medicinal use thereof |
| WO2007031838A1 (en) | 2005-09-16 | 2007-03-22 | Ranbaxy Laboratories Limited | Substituted pyrazolo [3,4-b] pyridines as phosphodiesterase inhibitors |
| PL1942108T3 (en) | 2005-10-28 | 2014-03-31 | Ono Pharmaceutical Co | Compound containing basic group and use thereof |
| PT1961744E (en) | 2005-11-18 | 2013-05-15 | Ono Pharmaceutical Co | Basic group-containing compound and use thereof |
| CN101460458A (en) | 2006-02-15 | 2009-06-17 | 阿勒根公司 | Indole-3-carboxylic acid amide, ester, thioamide and thiol ester compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| AU2007214434B2 (en) * | 2006-02-15 | 2012-06-14 | Allergan, Inc. | Indole-3-carboxylic acid amide, ester, thioamide and thiol ester compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| CN101443322A (en) | 2006-03-10 | 2009-05-27 | 小野药品工业株式会社 | Nitrogenated heterocyclic derivative, and pharmaceutical agent comprising the derivative as active ingredient |
| WO2007132846A1 (en) | 2006-05-16 | 2007-11-22 | Ono Pharmaceutical Co., Ltd. | Compound having acidic group which may be protected, and use thereof |
| US8329689B2 (en) | 2006-05-23 | 2012-12-11 | Alexandre Vasilievich Ivachtchenko | Substituted indoles and a method for the production and use thereof |
| US20090325992A1 (en) | 2006-07-31 | 2009-12-31 | Ono Pharmaceutical Co., Ltd. | Compound having cyclic group bound thereto through spiro binding and use thereof |
| US8524917B2 (en) | 2007-01-11 | 2013-09-03 | Allergan, Inc. | 6-substituted indole-3-carboxylic acid amide compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| CN101668741A (en) | 2007-01-11 | 2010-03-10 | 阿勒根公司 | 6-substituted indole-3-carboxylic acid amide compounds having sphingosine-1-phosphate (s1p) receptor antagonist biological activity |
| WO2010129351A1 (en) | 2009-04-28 | 2010-11-11 | Schepens Eye Research Institute | Method to identify and treat age-related macular degeneration |
| JP2013526542A (en) | 2010-05-12 | 2013-06-24 | アッヴィ・インコーポレイテッド | Indazole inhibitor of kinase |
| US20140271680A1 (en) | 2011-08-12 | 2014-09-18 | Universite Paris-Est Creteil Val De Marne | Methods and pharmaceutical compositions for treatment of pulmonary hypertension |
| JO3459B1 (en) | 2012-09-09 | 2020-07-05 | H Lundbeck As | Pharmaceutical compositions for treating alzheimer's disease |
| CN104193669B (en) * | 2014-08-01 | 2016-12-07 | 大连理工大学 | One class Abiduoer analog or its salt, its preparation method and application |
| WO2016112088A1 (en) * | 2015-01-06 | 2016-07-14 | Spero Therapeutics, Inc. | Aryloxyacetylindoles and analogs as antibiotic tolerance inhibitors |
| CN110256324A (en) * | 2019-06-13 | 2019-09-20 | 苏州莱安医药化学技术有限公司 | A kind of preparation method of 2- methyl -5-OHi |
| US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
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| US3549641A (en) * | 1966-06-28 | 1970-12-22 | Warner Lambert Pharmaceutical | Pyrano pyridines and process for their production |
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| US3565903A (en) * | 1967-11-24 | 1971-02-23 | Warner Lambert Pharmaceutical | Pyrano(2,3-b)quinolines and process for their production |
| US5635510A (en) * | 1993-05-06 | 1997-06-03 | Merrell Pharmaceuticals Inc. | Substituted pyrrolidin-3-yl-alkyl-piperidines |
| HRP960352A2 (en) * | 1996-07-26 | 1998-08-31 | Pliva Pharm & Chem Works | Novel coumarin quinoline carboxylic acids |
| PL335484A1 (en) * | 1997-02-26 | 2000-04-25 | Pfizer | Derivatives of heteroarylhexamide, their production and application as selective inhibitors of mip-1a being assimilated by its ccr1 receptor |
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-
1999
- 1999-12-20 KR KR1020017008905A patent/KR20010086166A/en not_active Application Discontinuation
- 1999-12-20 CZ CZ20012502A patent/CZ20012502A3/en unknown
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- 1999-12-20 AU AU19409/00A patent/AU1940900A/en not_active Abandoned
- 1999-12-20 CN CN99816475A patent/CN1344270A/en active Pending
- 1999-12-20 BR BR9916905-3A patent/BR9916905A/en not_active Application Discontinuation
- 1999-12-20 EP EP99963110A patent/EP1144415A2/en not_active Withdrawn
- 1999-12-20 JP JP2000593612A patent/JP2002534526A/en active Pending
- 1999-12-20 EA EA200100774A patent/EA200100774A1/en unknown
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- 1999-12-20 OA OA1200100187A patent/OA11820A/en unknown
- 1999-12-20 PL PL99349348A patent/PL349348A1/en not_active Application Discontinuation
- 1999-12-20 CA CA002372197A patent/CA2372197A1/en not_active Abandoned
- 1999-12-20 HU HU0202932A patent/HUP0202932A3/en unknown
- 1999-12-20 WO PCT/US1999/030434 patent/WO2000042045A2/en not_active Application Discontinuation
- 1999-12-20 IL IL14428999A patent/IL144289A0/en unknown
-
2001
- 2001-07-12 NO NO20013456A patent/NO20013456L/en not_active Application Discontinuation
- 2001-08-10 ZA ZA200106592A patent/ZA200106592B/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| BR9916905A (en) | 2002-01-29 |
| EP1144415A2 (en) | 2001-10-17 |
| CN1344270A (en) | 2002-04-10 |
| JP2002534526A (en) | 2002-10-15 |
| CZ20012502A3 (en) | 2002-03-13 |
| MXPA01007033A (en) | 2003-07-21 |
| OA11820A (en) | 2005-08-17 |
| CA2372197A1 (en) | 2000-07-20 |
| SK9972001A3 (en) | 2002-03-05 |
| HUP0202932A2 (en) | 2002-12-28 |
| NO20013456D0 (en) | 2001-07-12 |
| KR20010086166A (en) | 2001-09-08 |
| HUP0202932A3 (en) | 2003-07-28 |
| AP2001002228A0 (en) | 2001-09-30 |
| NO20013456L (en) | 2001-09-12 |
| EA200100774A1 (en) | 2002-02-28 |
| WO2000042045A3 (en) | 2000-11-09 |
| WO2000042045A2 (en) | 2000-07-20 |
| AU1940900A (en) | 2000-08-01 |
| PL349348A1 (en) | 2002-07-15 |
| IL144289A0 (en) | 2002-05-23 |
| HK1044539A1 (en) | 2002-10-25 |
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