PAGE 1-A
`
`Me
`
`Me
`
`Me
`
`OH
`
`,
`
`MeO
`
`~o
`
`H 0- R
`
`Me
`IE
`
`',
`
`Me
`
`IE
`
`s ~
`
`PAG~ 2-A
`
`Me
`
`~ 157054-82-5 CA
`CN
`Rapamycin, 7-demethoxy-7-(2,4-dimethoxyphenyl)-
`NAME)
`
`(9CI)
`
`(CA INDEX
`
`Absolute stereochemistry.
`qouble bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`~e
`
`Me
`
`Me
`
`Meo·
`
`Me
`
`IE
`
`IE
`
`s ~
`
`~
`
`OH
`
`0
`
`Me
`
`Meo
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157054-83-6 CA
`Rapamycin, 7-demethoxy-7-oxo-
`
`(9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`R
`
`(X OH
`
`_,,/
`
`OMe
`
`H
`
`Me
`
`Me
`
`,.
`Meo·
`
`IE
`
`~ s
`
`OH
`
`Me
`
`PAG~ 2-A
`
`Me
`
`RN
`CN
`
`157054-84-7 CA
`~apamycin, 7-0-demethyl-7-0-ethyl- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond g~ometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`0
`
`OH
`
`Me
`
`Me
`
`,-'
`Meo
`
`Me
`
`s
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157054-85-8 CA
`Rapamycin, 7-0-demethyl-7-0-[(3,4-dimethoxyphenyl)methyl]-
`(CA INDEX NAME)
`
`(9CI)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`0
`
`R
`
`r-,:e (XOH
`
`_,./
`
`OMe
`
`OH
`
`Me
`
`Me
`
`Meo
`
`Me
`
`IE
`
`IE
`
`~
`
`s
`
`'
`
`Meo
`
`OMe
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157054-86-9 CA
`Rapamycin, 7-0-demethyl-7-0-(2-hydroxyethyl}- (9CI}
`
`(CA INDEX NAME'}
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`El
`
`Me
`
`OH
`
`Me
`
`Meo·
`
`~o
`
`Me
`
`IE
`
`s ~
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157054-87-0 CA
`Rapamycin, 7-0-acetyl-7-0-demethyl- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-,..
`
`Me
`
`OH
`
`R
`R ( ; (
`· OMe
`_,./
`
`Me
`
`R
`
`El
`
`Me
`
`OH
`
`Meo , '
`
`~o
`
`Me
`
`H
`
`Aco·
`
`R
`
`Me
`
`IE
`
`IE
`
`~ s
`
`PAGE 2;-A
`
`Me
`
`RN
`CN
`
`157054~88:-l CA
`Rapamycln, 7-demethoxy- {9CI)
`
`{CA INDEX NAME)
`
`iµ>solute stereochemistry.
`Double bond.geometry as shown.
`
`, ~
`
`
`
`

`
`PAGE 1-A
`
`R
`
`r-te a OH
`
`_,,/
`
`OMe
`
`Me
`
`El
`
`Me
`
`MeO
`
`H
`
`Me
`
`IE
`
`IE
`
`s ~
`
`OH
`
`Me
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-33-7 CA
`Rapamycin, 7-demethoxy-7-(methylthio)-, (7R)-
`
`(9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`· OH
`
`/o:OMe
`
`H
`
`Mes·
`
`R
`
`Me
`
`Me
`
`,,
`Meo·
`
`jE
`
`~ s
`
`OH
`
`Me
`
`PAGE 2~A
`
`Me
`
`RN
`CN
`
`157182-34-8 CA
`Rapamycin, 7-demethoxy-7-(phenylthio)-, (7R)-
`
`{9CI)
`
`(CA INDEX NAME1)
`
`Absolute stereochemistry.
`D0uble bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-35-9 CA
`Rapamycin, 7-demethoxy-7-(2,4-dimethoxyphenyl)-, (7R)-
`INDEX NAME)
`
`(9CI)
`
`(CA
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`H
`
`R
`
`MeOnOMe
`
`'OH
`
`0
`
`Me
`
`Me
`
`Me
`
`Meo·
`
`IE
`
`s ~
`
`'.
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-36-0 CA
`Rapamycin, 7-0-demethyl-, (7R) -
`
`(9CI)
`
`(CA INDEX NAME)
`
`A~solute ~~ere?chemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`0
`
`Me
`
`R
`
`El
`
`Me
`
`,•
`
`Meo·
`
`H
`
`HO
`
`R
`
`Me
`
`IE
`
`IE
`
`~ s
`
`OH
`
`Me
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-37-1 CA
`Rapamycin, (7R)-
`
`(9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`R
`
`o: OH
`
`_,,/
`
`OMe
`
`H
`
`R
`
`,.
`
`MeO
`
`Me
`
`IE
`
`El
`
`Meo
`
`OH
`
`Me
`
`IE E
`:::-::-
`
`s
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-38-2 CA
`Rapamycin, 7-0-demethyl-7-0-ethyl-, (7R)-
`
`(9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`R
`
`Me GX OH
`
`_ .. /
`
`OMe
`
`Me
`
`El
`Me
`
`OH
`
`R
`
`Me
`
`Meo
`
`~o
`
`s
`
`H
`
`EtO
`
`Me
`
`IE E
`;;:;.
`
`s
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-39-3 CA
`Rapamycin, 7-0-demethyl-7-0-(2-hydroxyethyl)-, (7R)-
`INDEX NAME)
`
`(9CI)
`
`(CA
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`0
`
`R
`
`Me o: OH
`
`.. -/
`
`OMe
`
`H
`, / R
`./'--....
`HO,
`"-..../
`....... o·
`
`Me
`
`Me
`
`Me
`
`Meo
`
`s
`
`~o
`
`Me
`
`PAGE 2-:A
`
`Me
`
`RN
`CN
`
`15/182-40-6 CA
`Rapamycin, 7-demethoxy-7-(2-furanyl)- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Deuble ~ond geometry as. shown.
`
`
`
`

`
`0
`
`R
`
`Me o: OH
`
`_,./
`
`OMe
`
`PAGE 1-A
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`157182-41-7 CA
`Rapamycin, 7-0-demethyl-7-0-[{3,4-dimethoxyphenyl)methyl]-, {7R)(cid:173)
`{9CI)
`{CA INDEX NAME)
`.
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`Me
`
`,
`
`(X OH
`
`PAGE 1-A
`
`_,,/
`
`OMe
`
`Me
`
`Me
`
`OH
`
`PAG~ 2-A
`
`Me
`
`IT 53123-88-9, Rapamycin
`RL: RCT (Reactant)
`.(reaction of, in prepn. of antifungal, immunosuppressant, and
`neoplasm~nhibitor)
`5312~-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`R}'.l
`CN
`
`Absol1.lte stereochemistry.
`Double ?ond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`OH
`
`s
`
`Me
`
`R
`
`El
`
`Me
`
`Me
`
`Meo·
`
`IE
`
`s ~
`
`OH
`
`Me
`
`PAGE 2-A
`
`Me
`
`DUPLICATE 16
`
`L15 ANSWER 16 OF 51 CA COPYRIGHT 1996 ACS
`AN
`121:73883 CA
`TI
`0-heteroaryl, 0-alkylheteroaryl, O-alkenylheteroaryl and
`0-alkynylheteroarylrapamycin derivatives for treatment of
`autoimmune, inflammatory, and other diseases
`Parsons, William H.; Sinclair, Peter J.; Wong, Frederick; Wyvratt,
`Matthew J.
`PA Merck and Co., Inc., USA
`SO U.S., 34 pp.
`CODEN: USXXAM
`940510
`US 5310901 A
`US 93-26926 930305
`Patent
`English
`MARPAT 121:73883
`
`IN
`
`PI
`AI
`DT
`LA
`OS
`
`
`
`

`
`GI
`
`Meo
`
`Me--- c
`H
`
`Me
`
`R1oVr:
`I ~ 0
`
`0
`
`I
`0
`
`Me
`
`MeQ'
`
`OR2
`
`OMe
`
`H
`
`~ ~ ~
`
`Me
`
`Me
`
`I
`
`AB
`
`RN
`CN
`
`0-heteroaryl, 0-alkylheteroaryl, 0-alkenylheter·oaryl ,and
`(Rl = heteroaryl, substituted
`o-alkynylheteroarylrapamycin derivs. I
`heteroaryl, heteroaryl-Cl-10 alkyl, etc.; R2 = Rl, H, Ph,
`substituted Ph, 1- or 2-naphthyl, etc.) have been prepd. from
`suitable precursors by alkylation and/or arylatin at C-42 and/or
`C-31. These compds. are useful in a mammalian host for the
`treatment of autoimmune diseases and diseases of inflamm(ltion,
`infectious diseases, the prevention of rejection of fbre,.gn.organ
`transplants, and the treatment of solid tumors. Prepn. of s·elected'
`I is included. 42- ( 1-Hydroxyethylindol-5-yl) oxyrapainycin iphib~t9,d,t
`proliferation of T-cells.
`IT 156246-98-9 156246-99-0 156247-00-6
`156247-01-7 156247-02-8 156247-03-9
`156247-04-0 156247-05-1 156247-06-2
`156247-07-3 156247-08-4 156247-09-5
`156247-10-8 156247-11-9 156247-12-0
`156247-13-1
`RL: BIOL (Biological study)
`(for autoimmune or inflammatory or other disease
`·
`treatment)
`156246-98-9 CA
`Rapamycin, 42-0-(1-methyl-lH-indol-5-yl)- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Doµble b~nd geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`N
`I
`Me
`
`Me
`
`s
`
`Me
`
`PAGE 2-A
`
`RN
`CN
`
`156246-99-0 CA
`Rapamycin, 42-0-(1-ethyl-lH-indol-5-yl)- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`Me a
`
`, .. --·
`-
`
`0
`Me
`
`PAGE 1-A
`
`N
`I
`Et
`
`Me
`
`Me
`
`Meo·
`
`s
`
`0
`
`Me
`
`Me
`
`-P~GE 2-:f\
`
`RN
`CN
`
`156247-00-6 CA
`RapalJ.lycin, 31-0-(l-methyl-1H-indol-5-yl)~ (9CI)
`
`(CA INDEX ij~~)
`
`Ab~olute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`Qio l1e er OH
`
`PAGE 1-A
`
`R
`
`H
`
`... /
`
`OMe
`
`s
`
`Me
`
`El
`
`Me
`
`Me
`
`IE
`
`Meo
`
`:;::?' 0
`
`Me
`
`IE
`
`s ~
`
`'
`
`N
`I
`Me
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`156247-01-7 CA
`Rapamycin, 42-0-(1-(2-propenyl)-lH-indol-5-yl)- (9CI)
`NAME)
`
`(CA INDEX
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`Me
`
`Me
`
`Me
`
`s
`
`Me
`
`PAGE 1-A
`
`PAGE 2-A
`
`RN
`CN
`
`15~247-02-8 CA
`Rapamycin, 42-0-(1-propyl-lH-indol-5-yl}- (9CI}
`
`(CA INDEX NAME}
`
`Absolute stereochemistry.
`Doubl~ bond geometry as shown.
`
`~
`
`
`
`

`
`PAGE 1-A
`
`N
`I
`n-Pr
`
`OH
`
`Me
`
`Me
`
`Meo
`
`s
`
`Me
`
`PAGE 2-A
`
`RN
`CN
`
`156247-03-9 CA
`Rapamycin, 31-0-(1-ethyl-lH-indol-5-yl)- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`(40 o:OH
`
`PAGE 1-A
`
`R
`
`H
`
`,,./
`
`OMe
`
`El
`
`Me
`
`Meo
`
`Me
`
`IE
`
`IE
`
`s ~
`
`N
`I
`Et
`
`Me
`
`PAGE,: 2-A
`
`Me
`
`RN
`CN
`
`15624 7-:;-.04,-0 CA
`Rapamy9l~, 31-0-[l-(2-propenyl}-lH-indol-5-yl]- (9CI}
`NAME}
`~·
`
`(CA INDE;K
`
`:r~
`
`Absolute stereochemistry.
`Double bond g~ometry as shown.
`
`''
`
`
`
`

`
`PAGE 1-A
`
`R
`
`Me CXOH
`
`_,,/
`
`OMe
`
`0
`
`s
`
`Me
`
`Me
`
`Meo
`
`IE
`
`~ s
`
`Me
`
`~CH2
`
`Me
`
`PAGE 2-A
`
`RN
`CN
`
`156247-05-1 CA
`Rapamycin, 31-0-(l-propyl-lH-indol-5-yl)- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`a OH
`
`R
`
`_,./
`
`OMe
`
`( l - 0 ~µ
`
`Me
`
`H
`
`R
`
`0
`
`s
`
`N
`I
`n-Pr
`
`Me
`
`s
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`156247-06..::2 CA
`Rapamycin, 42-0-[1-[(4-hydroxyphenyl}methyl]-lH-indol-5-yl]- (9CI}
`(CA INDEX NAME}
`
`Absolute stereochemistry.
`Double b~nd ge~metry as shown.
`
`
`
`

`
`Me ~o
`
`... v ... ·oMe
`
`0
`
`0
`
`PAGE 1-A
`
`Me
`
`Meo· ,-
`
`R
`
`,-'
`
`R
`
`OH
`
`~o
`
`s
`
`Me
`
`IE
`
`IE
`
`~ s
`
`Me
`
`PAGE 1-B
`
`-.......OH
`
`Me
`
`PAGE 2-A
`
`
`
`

`
`RN
`CN
`
`156247-07-3 CA
`Rapamycin, 31-0-(1-((4-hydroxyphenyl)methyl]-lH-indol-5-yl]- (9CI)
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`a OH
`
`R
`
`OMe
`
`PAGE 1-A
`
`N
`
`r-ie
`
`0
`
`, .. /
`
`R
`
`Me
`
`s
`
`Me
`
`Me
`
`Meo·
`
`IE
`
`~ s
`
`Me
`
`OH
`
`RN
`CN
`
`156247~08~4 CA
`Rapamycii;i, 42-0-lH-indol-5-yl- (9CI)
`
`(CA INDEX NAME)
`
`Absolute ster~ochemistry.
`Dop.ble bond ~~ometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`R
`
`El
`
`Me
`
`,.
`Meo·
`
`s
`
`Me
`
`IE
`
`Me
`
`IE
`
`~
`
`Me
`
`PAGE 2-A
`
`RN
`CN
`
`156247-09-5 CA
`Rapamycin, 31-0-lH-indol-5-yl- (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`0
`
`Me
`
`Me
`
`N
`H
`
`Me
`
`PAGE 2-A
`
`Me
`
`RN
`CN
`
`156247-10-8 CA
`Rapamycin, 42-0-(1-(phenylmethyl)-lH-indol-5-yl]-
`NAME)
`
`(9CI)
`
`(CA INDEX
`
`AQsolute stereochemistry.
`Dguble bond gepmetry as shown.
`
`
`
`

`
`Qio
`
`H
`
`R
`
`PAGE 1-A
`
`l Ph
`
`Me
`
`Me
`
`s
`
`Me
`
`PAGE 2-A
`
`RN
`CN
`
`156247-11-9 CA
`Rapamycin, 31-0-(1-(phenylmethyl)-lH-indol-5-yl]- (9CI)
`NAME)
`.
`
`(CA INDEX
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`·- '
`
`0
`
`PAGE 1-A
`
`R
`
`Me o: OH
`
`_,./
`
`OMe
`
`Me
`
`s
`
`Me
`
`Me
`
`Meo
`
`Me
`
`l Ph
`
`PAGE 2-A
`; ..
`
`Me
`
`RN
`CN
`
`156247-12-0 CA
`Rapamycin, 4'2-0-[1-(2-hydroxyethyl)-lH-indol-5-yl]-
`NAME)
`
`(9CI)
`
`(CA INDEX
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`N
`
`~OH
`
`a
`
`0
`s
`
`s
`
`Me
`
`Me
`
`Meo
`
`s
`
`0
`
`Me
`
`Me
`
`PAGE 2-A
`
`RN
`CN
`
`156247-13-1 CA
`Rapamycin, 31-0-(1-(2-hydroxyethyl)-lH-indol-5-yl]- (9CI)
`NAME)
`
`(CA INDEX
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`- - - - - - - - - - - ------·-------
`
`
`
`

`
`0
`
`Me er OH
`
`_,./
`
`OMe
`
`R
`
`PAGE 1-A
`
`Me
`
`El
`
`Me
`
`Meo
`
`Me
`
`IE
`
`IE
`
`~ s
`
`Me
`
`~OH
`
`Me
`
`PAG~ 2-A
`
`IT 53~~3-88-9, Rapamycin
`RL: RGT (,Reactant)
`(reac,tiop of, in rapamyqin deriv. prepn.
`inf lamni~tory or other disease treatment)
`53123-88~9 CA
`Rapamycin (9CI)
`
`1 .•
`
`(CA INDEX NAME)
`
`RN
`CN
`
`Absolute ster~ochemistry.
`Dou~le }?,ond q~ometry as shown.
`
`for autoimmune or
`
`,.: v
`
`
`
`

`
`PAGE 1-A
`
`R
`
`Me er OH
`
`_,,/
`
`OMe
`
`Me
`
`Me
`
`Me
`
`s
`
`PAGE 2-A
`
`Me
`
`L15
`AN
`TI
`
`IN
`PA
`so
`
`PI
`AI
`PRAI
`DT
`LA
`AB
`
`DUPLICATE 17
`
`ANSWER 17 OF 51 CA COPYRIGHT 1996 ACS
`120:236175 CA
`Treatment of immunoinflammatory skin disease with rapamycin and
`cyclosporin A
`Caufield, Craig E.; Musser, John H.; Sehgal, Surendra N.
`American Home Products Corp., USA
`U.S., 4 pp. Cont.-in-part of U.S. Ser. No. 761,120, abandoned.
`CODEN: USXXAM
`940215
`US 5286730 A
`us 92-931242 920817
`us 91-761120 910917
`Patent
`English
`Immunoinf lammatory skin disease is treated in mammals by
`administering rapamycin, alone or in synergistic combination with
`
`
`
`

`
`cyclosporin A, orally, parenterally, intranasally, intrabronchially,
`topically, transdermally, or rectally. Rapamycin, alone or in
`combination with cyclosporin A, is useful in treating skin diseases
`such as psoriasis, atopic dermatitis, contact dermatitis, eczematous
`dermatitis, seborrheic dermatitis, lichen planus, pemphigus, bullous
`pemphigoid, epidermolysis bullosa, urticaria, angioedema,
`vasculitis, erythema, cutaneous eosinophilia, etc. Thus, topical
`application of 0.5 mg rapamycin prevented oxazolone-induced skin
`inflammation in mice.
`IT 53123-88-9, Rapamycin 154325-43-6,
`Rapamycin-cyclosporin A mixt.
`RL: BAC (Biological activity or effector, except adverse); THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(inflammation inhibition by, in skin)
`53123-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`RN
`CN
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`R
`
`Me o:OH
`
`_ .. /
`
`OMe
`
`Me
`
`Me
`
`Me
`
`Meo
`
`s
`
`
`
`

`
`RN
`CN
`
`154325-43-6 CA
`Rapamycin, mixt. with cyclosporin A (9CI)
`
`(CA INDEX NAME)
`
`PAGE 2-A
`
`Me
`
`CM
`
`1
`
`CRN 59865-13-3
`CMF C62 Hlll Nll 012
`CDES *
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`i-Pr
`
`
`
`

`
`PAGE 1-B
`
`Me~ E~
`~ "'-.
`
`i-Bu
`
`0
`
`Me
`
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`
`~~~~N I
`
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`
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`
`R
`
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`
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`
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`
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`
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`
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`,N
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`Me
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`i-Bu
`
`CM
`
`2
`
`CRN 53123-88-9
`CMF C51 H79 N 013
`CDES *
`
`
`
`

`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`R
`
`Me
`
`Me
`
`OH
`
`Me
`
`,
`
`,.
`Meo·
`
`s
`
`Me
`
`PAGE 2-A
`
`DUPLICATE 18
`
`L15 ANSWER 18 OF 51 CA COPYRIGHT 1996 ACS
`AN
`121:221396 CA
`TI
`Rapamycin inhibits production of cytotoxic but not noncytotoxic
`antibodies and preferentially activates T helper 2 cells that
`mediate long-term survival of heart allografts in rats
`Ferraresso, Marianne; Tian, Ling; Ghobrial, Rafik; Stepkowski,
`Stanislaw M.; Kahan, Barry D.
`cs Med. Sch., Univ. Texas, Houston, TX, 77030, USA
`SO
`J. Immunol.
`( 1994) , 153 (7) , 3207-18
`CODEN: JOIMA3; ISSN: 0022-1767
`Journal
`English
`
`AU
`
`DT
`LA
`
`
`
`

`
`AB
`
`RN
`CN
`
`induces unresponsiveness toward heart allografts by
`Rapamycin (RAPA)
`at least two mechanisms: selective prodn. of noncytotoxic
`IgG2c~blocking Ab and preferential activation of Th2 ~cells. RAPA
`(0.8 mg/kg/day) delivered via a 14-day osmotic pump to Wist~r Furth
`(WF; RT-lu) recipients prolongs Buffalo (BUF; RT-lb) heart allograft
`survival from a mean survival time (MST) of 6.5 days to 75.0 days,
`wit~ 6 9f 18 grafts beating for >100 days. Recipient sera or their
`"."
`Ig(;~· but· not IgM fraction, obtained after postgrafting day 40,
`passively tr-ansfer the unresponsive state to sublethally irradi~ted
`secondary recipients in a dose-dependent and immunol.-specific
`fashion. i Sera obtained after untreated WF hosts rejecte~~BUF hearts
`contained ·'IgG moieties of all subclasses that bound to·· c·l~ss I MHC
`In contrast, the unresponsive sera contAine~
`~
`BUF epitopes.
`:predomirnqritly non-C '.-fixing IgG2c and only marginal amts. , of
`activa'ted.'' (C') ffxing IgGl, IgG2a, and IgG2b Ab. The transb~ription
`of IL~2, IL~4, and IL-10 mRNAs was assessed using a PCR method.
`There were similar increases in the levels of IL-2, IL-4d and IL-10
`mRNA.,.in heart allografts from both untreated and RAP~-treated "
`1ecrpients on day 5 postgrafting.
`In contrast, on days 60 and 300
`postgrafting heart allografts from RAPA-treated unrespons,ive
`.
`r\eq4pients showed increased levels of IL-10 and IL-4 "but 'not of ... IL-2
`mRNA, sugg~sting preferential activation of Th2 cells. ~hus, RAPA
`treatment~selectively inhibits the synthesis of C-binding of Ig~ ·
`sugclasses ,, spares the non C-binding blocking IgG2c Ab, and
`·
`preferentially activates Th2 cells.
`IT 53,1-23-88-9, R,?pamy_pin
`RL: THU (Therapeutic use); BIOL (Biological study); USES (Uses)
`(rapamycin inhibits prodn. of cytotoxic antibodies and
`.,,
`activat~s T helper cells mediating long-term survival of heart
`al.loqraf t's)
`53123-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Doubie )?ond geometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`Me
`
`Me
`
`s
`
`PAGE 2-A
`
`Me
`
`DUPLICATE 19
`
`L15 ANSWER 19 OF 51 CA COPYRIGHT 1996 ACS
`AN
`122:122704 CA
`TI Effect of single-dose, late treatment with rapamycin on skin
`allograft survival in ALS- and donor bone marrow cell-treated mice
`De Fazio, S.R.; Plowey, J.; Hartner, W.C.; Gozzo, J.J.
`AU
`cs
`Bouve College of Pharmacy and Health Sciences, Northeastern
`University, Boston, MA, 02115, USA
`so Transplant. Proc. (1994), 26(6), 3102-3
`CODEN: TRPPA8; ISSN: 0041-1345
`Journal
`English
`This study investigated the effect of single doses of rapamycin
`(RAPA) administered 2 wk or more after grafting in mice grafted with
`class I disparate skin and given peritransplant ALS and
`post-transplant BMC. Thus, RAPA is a potent adjunct for the
`
`DT
`LA
`AB
`
`
`
`

`
`A~~hough it
`induction of allograft unresponsiveness by ALS and BMC.
`can be ef~ecti vely administered soon after grafting, it may1' be
`particularly beneficial if given late, up to 4 wk, after ,grafting.
`This agent does not seem to interfere with suppressor"cells-tha~
`actively support continued graft survival. RAPA also has potential
`for t+eating graft rejection.
`53123-88-9, Rapamycin
`RL: BAC (Biological activity or effector, except adverse); THU
`(Therapeutic ·use); BIOL (Biological study); USES (Uses)
`(effect of single-dose, late treatment with rapamyc1n
`on skin allograft survival in ALS- and donor bone
`marrow cell-treated mice)
`,CA
`53123-88-9
`Ra~mycin (9CI)
`.
`Absolute stereo9hem1stry.
`Double bond geometry as shown.
`
`IT
`
`RN
`CN
`
`(CA INDEX NAME)
`
`~·
`
`.PAGE l~A
`
`Me
`
`R
`
`Me
`
`s
`
`l'·
`
`Me
`
`OH
`
`Me
`
`Me
`
`,
`Meo
`
`s
`
`PAG~ 2~-A
`
`Me
`
`
`
`

`
`DUPLICATE 20
`
`L15 ANSWER 20 OF 51 CA COPYRIGHT 1996 ACS
`AN
`122:586 CA
`TI
`Rapamycin inhibits corneal allograft rejection and
`neovascularization
`AU Olsen, Timothy W.; Benegas, Nancy M.; Joplin, Andrea C.;
`Evangelista, Tony; Mindrup, Elizabeth A.; Holland, Edward J.
`cs Department of Ophthalmology, University of Minnesota, Minneapolis,
`MN, USA
`so Arch. Ophthalmol. (Chicago) (1994), 112(11), 1471-5
`CODEN: AROPAW; ISSN: 0003-9950
`Journal
`English
`The immunosuppressive effect of rapamycin in prolonging allograft
`survival in the rat model of orthotopic allogeneic penetrating
`keratoplasty was studied. Thirty inbred Lewis rats received corneal
`allografts from Brown Norway donors. Animals were divided into two
`rapamycin treatment groups and one allogeneic control group. By the
`second week after surgery, all of the control animals had
`experienced allograft failure due to allograft rejection. However,
`allografts in seven of 10 animals in the low-dose treatment group
`and allografts in seven of nine animals in the high-dose treatment
`group remained clear.
`In addn., corneal neovascularization was
`markedly reduced in the treated animals. The systemic
`administration of rapamycin prolongs corneal allograft survival and
`significantly inhibits the neovascular component of rejection in the
`rat model of orthotopic allogeneic penetrating keratoplasty.
`IT 53123-88-9, Rapamycin
`RL: BAC (Biological activity or effector, except adverse); THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(rapamycin inhibition of corneal allograft
`rejection and neovascularization)
`53123-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`DT
`LA
`AB
`
`RN
`CN
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`f.
`
`Ll5
`~
`TI
`
`AU
`cs
`so
`
`DT
`LA
`AB
`
`PAGE 1-A
`
`Me
`
`R
`
`R a OH
`
`__ ./
`
`OMe
`
`OH
`
`s
`
`El
`
`Me
`
`MeO
`
`Me
`
`IE
`
`IE
`
`~ s
`
`OH
`
`Me
`
`PAGE 2-A ..
`
`Me
`
`DUPLICATE 21
`"
`inhibitor of T-cell function, prevents g:raf~
`recipients of allogeneic T-cell-deP,leted d~?r
`
`ANSWER 21 OF 51 CA COPYRIGHT 1996 ACS
`120:12;4~23 CA
`Rapamycin, a potent
`rej~cti?.n in murine
`marrow
`Blazar, ~ruce R.; Taylor, Patricia A.; Sehgal, Suren N.; Vallera,
`Daniel A.
`DeP_. P~diatr., Univ.
`Blood {1994), 83(2),
`CODEN: SLOOAW; ISSN:
`Journal"'
`English
`The autpors investigated the ability of the macrolide antifungal
`q.gent rapamycin (RAPA) to inhibit the rejection of T-celJ-depleted
`(TCD) ~$~or bone marrow (BM) transplanted into major
`~ ·
`-~~
`
`Minnesota Hosp., Minneapolis, MN, 55455, USA
`600-9
`0006-4971
`
`
`
`

`
`histocompatibility complex (MHC)-disparate irradiated recipients.
`RAPA (1.5 mg/kg) was administered for 14 days beginning on the day
`of transplant.
`In the present study, the authors have tested RAPA
`administration in two types of fully allogeneic BM transplantation
`(BMT) systems in which host T cells mediate the rejection of TCD BM
`grafts (DBA/1 transplanted into C57BL/6 and BALB/c transplanted into
`C57BL/6).
`In both instances, RAPA administration prevented the
`rejection of the donor graft, accelerated post-BMT hematopoietic
`recovery, and did not compromise recipient survival. Sequential
`post-BMT fluorescence-activated cell sorter anal. of the spleen
`showed that RAPA administration inhibited host CD4+ and CDS+ T-cell
`expansion that leads to graft rejection. To further investigate the
`effect of RAPA on T-cell subpopulations, the authors used two
`congenic donor mouse stains with isolated MHC class I
`(bml) or class
`II (bm 12) mutations.
`In these studies, the authors showed that
`RAPA administration can inhibit MHC class I-restricted CDS+ or class
`II-restricted CD4+ T-cell-mediated graft rejection without
`compromising recipient survival. The RAPA-facilitated
`alloengraftment is multilineage and durable. The authors have also
`shown that RAPA speeds hematopoietic recovery post BMT. The authors
`conclude that RAPA represents a new therapeutic modality for
`promoting alloengraftment and accelerating hematopoietic recovery.
`IT 53123-88-9, Rapamycin
`RL: BIOL (Biological study)
`(bone marrow graft rejection prevention and
`hematopoietic recovery stimulation by, as immunosuppressant, CD4+
`and CDS+ T-cell inhibition in mechanism of)
`53123-SS-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`RN
`CN
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`
`
`

`
`·PAGE 1-A
`
`Me o: OH
`
`_,,.-~-
`
`0Me
`
`R
`
`a
`
`OH
`
`s
`
`Me
`
`R
`
`El
`
`Me
`
`Meo·
`
`s
`
`Me
`
`IE
`
`IE
`
`s ~
`
`OH
`
`Me
`
`~~GE 2-A
`
`Me
`
`~15
`AN
`rf ~
`IN
`PA
`so
`
`P±
`o's
`AI
`PRAI
`L>T
`LA
`AB
`
`DUPLICATE 22
`
`ANSWER 22 OF 51 CA COPYRIGHT 1996 ACS
`119:247964 CA
`M_ethod of .inducing immunosuppression
`Seqgal, su:ren Nath; Armstrong, Jay Joseph; Eng,· Chee· Ping
`"" Amerdcan Home Products Corp., USA
`.. ,
`~ur. Pat. Appl., 7 pp.
`¢ODEN: .&¥,PXXDW
`EP 5628.53') Al 930929
`R~ AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LI, LU, NL, PT, SE
`EP 93-10t~88 930325
`~
`~
`us 92~858923 920327
`E.atent ~ ·
`Ehglish
`Administration of an anti-rejection effective amt. of
`
`'-
`
`.,,
`
`"....i
`
`.
`
`
`
`

`
`29-demethoxyrapamycin alone or in combination with .gtoreq.1
`anti-rejection chemotherapeutic agents induces immunosuppression and
`is useful for preventing or treating organ or tissue transplant
`rejection. The chemotherapeutic agent is selected from
`azathioprine, corticosteroids, cyclophosphamide, rapamycin,
`cyclosporin A, FK 506, OKT 3, and ATG.
`IT 53123-88-9, Rapamycin
`RL: USES (Uses)
`(immunosuppression from demethoxyraparnycin and, for
`treatinq organ transplant rejection)
`53123-88-9 CA
`Raparnycin (9CI)
`
`(CA INDEX NAME)
`
`RN
`CN
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`s
`
`Me
`
`IE
`
`Meo·
`
`Me
`
`IE
`
`s
`
`~
`
`IT 83482-58-0
`
`PAGE 2-A
`
`Me
`
`
`
`

`
`RL: USES (Uses)
`(immunosuppression from, for treating organ
`transplant rejection)
`83482~58-0 CA
`Rapamycin, 32-demethoxy-
`
`(CA INDEX NAME)
`
`(9CI)
`
`RN
`CN
`
`J!
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`Me
`
`Me
`
`Me
`
`s
`
`PAGE 2'"".~
`
`Me
`
`L15
`/:\N TI
`IN
`
`P:A so
`
`DUPLICATE 23
`ANSWER 23 OF 51 CA COPYRIGHT 1996 ACS
`118,: 198242 CA
`""
`U~~.of ~~pamycin for the manufacture of a medicament for ~he
`treatm~nt of immunoinf lammatory diseases
`Caufiie:1~, Craig Eugene; Musser, John Henry; Sehgal, Surentlra
`roneric~n Home Products Corp., USA
`Eu~~-~ Pa~t. Appl. , 6 pp.
`
`Nat;h
`i-
`
`{
`
`
`
`

`
`CODEN: EPXXDW
`EP 533433 Al 930324
`R: AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LI, LU, NL, PT, SE
`EP 92-308384 920915
`us 91-761120 910917
`Patent
`English
`Pharmaceutical compn. contg. rapamycin (I) alone or in combination
`with cyclosporin A is used for the treatment of immunoinflammatory
`skin or bowel diseases.
`I applied to the ear of mice at 1.0 mg/ear
`significantly prevented an acute inflammation.
`IT 53123-88-9, Rapamycin
`RL: BIOL (Biological study)
`(pharmaceutical compn. contg., as inflammation
`inhibitor)
`53123-88-9 CA
`Rapamycin (9CI)
`
`PI
`DS
`AI
`PRAI
`DT
`LA
`AB
`
`RN
`CN
`
`(CA INDEX NAME)
`
`Absolute stereochemistry.
`Double bond geometry as shown.
`
`PAGE 1-A
`
`Me a OH
`
`,....--
`
`OMe
`
`R
`
`Me
`
`Me
`
`Me
`
`,,
`
`Meo
`
`Me
`
`s
`
`
`
`

`
`Me
`
`DUPLICATE 24
`
`ANSWER 24 OF 51 CA COPYRIGHT 1996 ACS
`118:198240 CA
`~Rapamycin for the treatment of ocular inflammation
`Kulkarni, Prasad s.
`14niv.,ersity of Louisville Research Foundation, Inc., USA
`Can. Pat. ~Appl., 26 pp.
`CODEN: CPXXEB
`GA 2074641 AA 930126
`CA. 92-:-2014,641 920124
`us 91-735604 910725
`Patent
`English
`An ocular inflammation such as uveitis, conjunctivitis,
`epis¢~eritis, scleritis, etc. is treated by oral, parenteral,
`ti'opfc·a1, transdermal, or rectal administration of rapamyein. Thus,
`in rabbits with endotoxin-induced uveitis, rapamycin (10-. mg/,~g f':m.
`twice ·a day} decreased the leukocyte count and prote~n·~ PGEl ,""a.nd
`,LTB4 concns. in the aq. humor by 77, 22, 61, and 30%, resp.
`53.123-88-9, Rapamycin
`'
`RL: BIOL (Biological study)
`(.ocular inflammation treatment with}
`53123 .... 88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`L15
`AN
`TI
`IN
`PA
`so
`
`PI
`AI
`PRAI
`OT
`LA
`AB
`
`IT
`
`RN
`CN
`
`Absolute stereochemistry.
`DQuble bond ge,ometry as shown.
`
`
`
`

`
`PAGE 1-A
`
`0
`
`?-le (X OH
`
`_ .. /
`
`OMe
`
`R
`
`Me
`
`Me
`
`Me
`
`-·
`Meo·
`
`OH
`
`Me
`
`s
`
`PAGE 2-A
`
`Me
`
`DUPLICATE 25
`
`L15 ANSWER 25 OF 51 CA COPYRIGHT 1996 ACS
`AN
`120:45468 CA
`TI
`Inhibition by rapamycin of leukocyte migration and bronchial
`hyperreactivity induced by injection of Sephadex beads to guinea
`pigs
`AU Nogueira de Francischi, Janetti; Conroy, Dolores M.; Maghni, Karim;
`Sirois, Pierre
`Fae. Med., Univ. Sherbrooke, Sherbrooke, PQ, JlH 5N4, Can.
`Br. J. Pharmacol. (1993), 110(4), 1381-6
`CODEN: BJPCBM; ISSN: 0007-1188
`Journal
`English
`The effect of rapamycin (0.001 to 5 mg kg-1) on the increased
`leukocyte counts in bronchoalveolar lavage (BAL) fluid and
`hyperreactivity of isolated bronchial strips to histamine and
`
`CS
`SO
`
`DT
`LA
`AB
`
`
`
`

`
`acetylcholine (ACh) was studied following the i.v. injection of
`Sephadex beads to guinea-pigs. The i.m. (i.m.) injection of
`rap~mycin (0.012 to 5 mg kg-1) dose-dependently inhibited, the
`!ncrease in leukocyte counts in BAL fluid. Rapamycin (5 mg kg-1)
`reduced the nos. of eosinophils neutrophils, marcophages and
`lymphocytes in BAL fluid by 64, 55, 19 and 50% resp.
`In ann.,
`rapa~ycin (0.012 to 5 mg kg-1) significantly inhibited t~e
`Sep}l.atdex-ihduced hyperreactivity of bronchial tissue to both
`histamine and ACh. At a dose of 0.001 mg kgl-1, rapamycfn did not
`significantly reduce leukocyte infiltration or bronchial(cid:173)
`hyperrea~.ftiv,ity. ~ylOSJ?Orin (5.mg kg-1) ~ignificantly r7a';1ced both
`l;ymphocyte and eosinoph!l nos. in BAL fluid of Sephadex-i;_nJected
`guirrea..-Pi_f]:S whereas dexamethasone (1 mg kg-1) significantly reduced
`l~phocyte'· nos. Neither drug affected the bronchial hyperr~,activity
`to~histamine and ACh.
`It is concluded that the new
`~
`_immunc»supp'i:-essi ve drug, rapamycin, is a potent inhib~ tor of
`1.eu~<:>cyte :tm~g.ra~ion and brc,nchial hyperreac:=ti vi t~ obsd. ~-~lo~ing
`f:he .-! • v. ,in) ection of Sephadex beads to guinea-pigs. : Rapam~pin . also
`appears to .be more effective than cyclosporin or dexkmethasehe f'n
`reducing leukocyte counts and bronchial hyperreactivity in th~s
`~odeJ_. The. authors' results suggest that inflammatory Il\e;6hanisi:ns
`which~ are 1'inhibi ted by rapamycin may be important in the~ induc.tion
`:tof S~p~_adex-induc7d hyperreacti vi ty.
`53123-88-9, Rapamycin
`RL: BIOL (Biological study)·
`(leuko~yte migration and bronchial hyperreactivity
`inbiJ)'itiS'n by, inflammatory mechanisms in
`re,latiort to)
`53123-88-9 CA
`Rapamycin {9CI)
`
`(CA INDEX NAME)
`
`IT
`
`RN
`CN
`
`Apsolute s~ereochemistry.
`Double bohd geometry as shown.
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`DUPLICATE 26
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`L15 ANSWER 26 OF 51 CA COPYRIGHT 1996 ACS
`AN
`120:45426 CA
`TI
`Rapamycin treatment depresses intragraft expression of KC/MIP-2,
`granzyme B, and IFN-.gamma. in rat recipients of cardiac allografts
`AU Wieder, Kenneth J.; Hancock, Wayne W.; Schmidbauer, Georg; Corpier,
`Cindy L.; Wieder, Irene; Kobzik, Lester; Strom, Terry B.;
`Kupiec-Weglinski, Jerzy w.
`cs Div. Immunol., Harvard Med. Sch., Boston, MA, 02215, USA
`so
`J. Immunol. (1993}, 151(2), 1158-66
`CODEN: JOIMA3; ISSN: 0022-1767
`Journal
`English
`Rapamycin (RPM} treatment prevents accelerated rejection of cardiac
`allografts in sensitized rats. The prominent feature of this brisk
`24-h rejection, which includes a panoply of both cellular and
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`AB
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`humeral host immune responses, is a massive infiltration of
`rejecting grafts with neutrophils.
`In this study, the authors
`tested the hypothesis that RPM-mediated therapeutic effects on
`accelerated rejection may be linked to decreased expression of
`protein encoded by gro/melanoma-growth stimulatory activity gene
`(KC) and macrophage inflammatory protein-2 (MIP-2) genes, the
`operational, rat homologues of the human intercrine-.alpha. qytokines
`with proint"lammatory IL-8-like neutrophil activation/chem,9tactic
`properties. The induction of these genes was then correlated w.i th
`mRNA profiles encoding for Thl-selective IFN-.gamma. and·
`'
`···
`CTL-specific granzyme B proteins. Northern blot anal. of RNA from
`e~rdiac allografts of sensitized untreated recipients, revealed
`maximal levels of KC and MIP-2 mRNA at 3 to 6 h after
`.tran~plant,ation. In contrast, IFN-.gamma. mRNA, which was at most
`very weakly expressed at 3 h, peaked between 6 to 12 h. As.with
`IFN-.gamma., granzyme B transcripts were undetectable at 3 h, b~t
`peaked around the time of actual graft rejection at 24 h. RPM
`therapy abr6gated accelerated rejection and prolonged cardiac
`~llograft survival to ca. 46 days. This effect was assoc<;} .. · with
`markedly reduce expression of KC and MIP-2 mRNA in the first 24 h as
`well as at 7 and 34 days after transplantation. Moreover, RPM
`completel¥ blocked intragraft appearance of granzyme B and
`IFN-.gamma'. mRNA in long term cardiac allografts.
`Immunohistol.
`anal. has revealed that accelerated rejection was assocd. with
`extensive.neutrophil infiltration, which peaked at 18 to 24 h. At
`this time; leukocytes and endothelium were intensely stained fo+
`IL-8 and IFN-.gamma. antibodies.
`In contrast, the allografts from
`RPM-treat~d hosts showed essentially no neutrophil infiltration and
`minor, focal staining for IL-8 and IFN-.gamma .. This study
`demonstrates an assocn. between the early expression of genes for
`proinflammatory IL-8-dependent neutrophil chemotactic:;: activ~.ty, ang··
`~ater expression of genes assocd. with activation/effector acti-iVity
`o~+ CTL and NK cells. It also documents a novel effect of RPM in
`vivo, which results in the suppression of intragraft IL-87lik,e and
`CTL-dependent mRNA/protein prodn. and diminished neutrophil
`rn~iltratiop; these may contribute to the striking efficacy of RPM
`therapy in sensitized graft recipients.
`IT 53123-88-9, Rapamycin
`RL: BIOL (BJological study)
`(heart ailograft rejection· inhibition by,
`.,
`gene expression and granzyme B and interferon-.ga:nlma. response
`in)
`5312 3'-88-9 CA
`Rapamycin (9CI)
`
`(CA INDEX NAME)
`
`RN
`CN
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`Absolut~ stereochemistry.
`Double b0nd geometry as shown.
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`PAGE 1-A
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`DUPLICATE 27
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`AU
`CS
`SO
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`L15 ANSWER 27 OF 51 CA COPYRIGHT 1996 ACS
`AN
`120:208123 CA
`TI Reduction of Sephadex-induced lung inflammation and bronchial
`hyperreactivity by rapamycin
`Francischi, J. N.; Conroy, D. M.; Cloutier, S.; Sirois, P.
`Dep. Pharmacol., Fae. Med., Sherbrooke, PQ, JlH 5N4, Can.
`Braz. J. Med. Biol. Res. (1993), 26(10), 1105-10
`CODEN: BJMRDK; ISSN: Ol00-879X
`Journal
`English
`The aim of the present work was to det. if rapamycin could affect an
`established inflammatory response. Guinea pigs were injected i.v.
`with Sephadex beads to induce lung inflammation and bronchial
`hyperreactivity. Bronchoalveolar lavage (BAL) fluid was collected
`2, 12 and 24 h after Sephadex administration and the cells were
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`counted. Bronchial tissue was used to construct dos~-contraction
`response curves to histamine and acetylcholine 24 h after~the
`Sephadex injection. Test animals were injected with rapamycin (5
`mg/kg) i.m. 2 or 12 h after Sephadex injection, and BAL fluid was
`collected 24 h after Sephadex administration. ~apamycin~
`administration 2 h after Sephadex reduced